https://me-pedia.org/w/api.php?action=feedcontributions&feedformat=atom&user=DarlaMEpedia - User contributions [en]2026-04-21T08:54:27ZUser contributionsMediaWiki 1.43.8https://me-pedia.org/w/index.php?title=Epstein-Barr_virus&diff=241775Epstein-Barr virus2023-09-14T13:53:32Z<p>Darla:/* Age of infection */ * Notable Studies *</p>
<hr />
<div>The '''Epstein-Barr virus''' or '''EBV''' or Human '''Herpesvirus 4''' or '''HHV-4''' is a [[herpesvirus]].<ref name="CDC" /> It is the most common cause of infectious [[mononucleosis]] or "glandular fever," and infects 90% of adults worldwide.<ref name="Saha2016">{{Cite journal | last1 = Saha | first1 = Abhik | last2 = Robertson | first2 = Erle S | title = Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes | journal =Clinical Cancer Research<br />
| issn = 1557-3265| volume = 17 | issue = 10| pages = 3056–3063 | date = 2011-05-15 | pmid = 21372216 | doi = 10.1158/1078-0432.CCR-10-2578| url = http://clincancerres.aacrjournals.org/content/17/10/3056}}</ref> It has been implicated in numerous immune diseases and chronic illnesses, including [[chronic fatigue syndrome]], [[multiple sclerosis]], [[myasthenia gravis]], and [[systemic lupus erythematosus]]. It is known to turn on "risk genes" for autoimmune disease in the cells it infects.<ref name="Harley2018">{{Cite journal | title = Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity | date = 2018| url = https://www.nature.com/articles/s41588-018-0102-3|journal=Nature Genetics|volume=50|issue=5 | pages = 699–707 | last = Harley | first = John B. | authorlink = | last2 = Chen | first2 = Xiaoting | authorlink2 = | last3 = Pujato | first3 = Mario | authorlink3 = | last4 = Miller | first4 = Daniel | authorlink4 = | last5 = Maddox | first5 = Avery | authorlink5 = | last6 = Forney | first6 = Carmy | authorlink6 = | last7 = Magnusen | first7 = Albert F. | last8 = Lynch | first8 = Arthur | last9 = Chetal | first9 = Kashish | last10 = Yukawa | first10 = Masashi | last11 = Barski | first11 = Artem|language=en|doi=10.1038/s41588-018-0102-3|pmc=|pmid=|access-date=|issn=1546-1718|quote=|via=}}</ref><ref name="NIHNews2018">{{Cite web | url=https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases | title = Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases | last = | first = | date = 16 April 2018 | website = National Institutes of Health|archive-url=|archive-date=|url-status=|access-date=}}</ref><br />
<br />
== Initial infection ==<br />
[[File:Epstein-barr virus (ebv).jpg|thumb|A stained sample of Epstein-Barr virus.]]<br />
Symptoms of EBV infection include: <br />
* [[fatigue]]<br />
* [[fever]]<br />
* [[rash]]<br />
* inflamed [[sore throat|throat]]<br />
* [[swollen lymph nodes]]<br />
* enlarged [[spleen]]<br />
* swollen [[liver]]<ref name="CDC">{{Cite web | url=http://www.cdc.gov/epstein-barr/about-ebv.html | title = Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono | date = 2018-05-10 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-14}}</ref><br />
<br />
===Age of infection===<br />
<br />
Most people acquire EBV before the age of ten. Typically, young children who acquire EBV are either not symptomatic or have mild symptoms that are hard to distinguish from a cold or other other mild, childhood illnesses.<ref>{{Cite book|title=Fields Virology|chapter=Epstein-Barr virus|date=2001|publisher=Lippincott Williams & Wilkins|location=Philadelphia, PA|pages=2575–2627|editor-last=Knipe|editor-first=DM|editor-last2=Howley|editor-first2=PM|last=Rickinson|first=AB|last2=Kieff|first2=E}}</ref> <br />
<br />
In adolescents and young adults, EBV can cause [[infectious mononucleosis]] (IM), also known as glandular fever.<ref name="CDC" /> IM is characterized by [[fever]], [[sore throat]], [[swollen lymph nodes]], [[pain|body aches]], and [[fatigue]]. It generally resolves with rest and only rarely causes serious complications. It typically occurs in people who have not been exposed to EBV in early childhood, and in comparison, is more severe than infection in childhood (i.e., it can last for months). <br />
<br />
Following initial infection, EBV can reactivate and has been shown to have many connections with various chronic illnesses. Relative to initial infections, reactivated EBV is much more severe.<br />
<br />
==Transmission==<br />
<br />
EBV is transmitted through bodily fluids, most commonly through saliva. The first time a person is infected with EBV, the person is contagious for weeks (even when not displaying symptoms). The virus then transitions to the latent or inactive form, and stays in the body. If the virus reactivates, the person will be contagious again.<ref name="CDC" /><br />
<br />
== Diagnosis ==<br />
EBV infection is confirmed with blood tests that detect presence of [[:Category:Antibodies|antibodies]]. Nine out of ten adults have these antibodies, indicating that they have a current or past EBV infection.<ref name="CDC" /><br />
<br />
Anti-VCA (Viral capsid antigen) IgG and EBV nuclear antigen (EBNA) IgG antibodies persist throughout a person's life. Thus, positive results merely indicate a current or past infection. A current EBV infection is diagnosed based on the presence of Anti-VCA IgM and Anti-EA (Early Antigen) IgG. VCA IgM appears early in EBV infection and usually disappears within four to six weeks. Positive VCA IgM suggests current active acute EBV infection. EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. Positive EA IgG can suggest current active EBV infection or EBV re-activation. <ref name="CDC-testing">{{Cite web | url=https://www.cdc.gov/epstein-barr/laboratory-testing.html | title = Epstein-barr {{!}} Mononucleosis {{!}} Laboratory Testing {{!}} Mono | date = 2019-01-28 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-10-08}}</ref><br />
<br />
==Latency==<br />
<br />
In healthy adults, the virus remains latent for life in memory [[B cell]]s. It is estimated that one in every one hundred thousand to one million circulating B cells carry EBV.<ref name="Hsu2000">{{Cite journal | last = Hsu | first = J.L. | last2 = Glaser | first2 = S.L. | date = Apr 2000 | title = Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications |url =https://www.ncbi.nlm.nih.gov/pubmed/10781747/|journal=Critical Reviews in Oncology/Hematology|volume=34|issue=1 | pages = 27–53|issn=1040-8428|pmid=10781747}}</ref> In healthy hosts, EBV populations are kept in check by [[CD4+ T cell|CD4<sup>+</sup>]] and [[CD8|CD8<sup>+</sup>]] [[T cell|T-cell]] responses. <br />
<br />
The equilibrium can be disrupted in individuals with compromised [[immune system]]s such as patients with [[AIDS]] or transplant patients taking immune system suppressing drugs.<ref name="Priatel2014">{{Cite journal | last = Priatel | first = John J | last2 = Chung | first2 = Brian K | last3 = Tsai | first3 = Kevin | last4 = Tan | first4 = Rusung | date = 2014-04-09 | title = Natural killer T cell strategies to combat Epstein–Barr virus infection | url =https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=| pages = e28329|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206|quote=|via=}}</ref> It has been observed that these patients are more susceptible to EBV-related [[cancer]]s, such as certain [[lymphoma]]s and carcinomas.<ref>{{Cite journal | last = Pattle | first = Samuel B. | last2 = Farrell | first2 = Paul J. | date = Nov 2006 | title = The role of Epstein-Barr virus in cancer |url =https://www.ncbi.nlm.nih.gov/pubmed/17049016|journal=Expert Opinion on Biological Therapy|volume=6|issue=11 | pages = 1193–1205|doi=10.1517/14712598.6.11.1193|issn=1744-7682|pmid=17049016|quote=|via=}}</ref> In immunocompromised patients, EBV can induce lymphoproliferation, [[lymphoma]], and hemophagocytic lymphohistiocytosis (HLH).<ref>{{Cite journal | title = Human immunity against EBV—lessons from the clinic | date = 2017-01-20| url = https://doi.org/10.1084/jem.20161846|journal=Journal of Experimental Medicine|volume=214|issue=2 | pages = 269–283 | last = Tangye | first = Stuart G. | last2 = Palendira | first2 = Umaimainthan | last3 = Edwards | first3 = Emily S.J.|doi=10.1084/jem.20161846|issn=0022-1007}}</ref><br />
===Natural killer T cells===<br />
<br />
It is thought that [[natural killer T cell]]s (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of [[CD1d]] expressing cells.<ref name="Priatel2014" /><br />
<br />
==Neuronal infection==<br />
A 2015 study<ref name="JhaHC2015">{{Cite journal | last1 = Jha | first1 = HC | author-link1 = | last2 = Mehta | first2 = D | authorlink2 = | last3 = Lu | first3 = J | authorlink3 = | last4 = El-Naccache | first4 = D | authorlink4 = | last5 = Shukla | first5 = SK | authorlink5 = | last6 = Kovacsics | first6 = C | authorlink6 = | last7 = Kolson | first7 = D | author-link7 = | last8 = Robertson | first8 = ES | author-link8 = | title = Gammaherpesvirus Infection of Human Neuronal Cells| journal = mBio | volume = 6 | issue =6 | pages = e01844-15 | date = 2016-12-01| doi = 10.1128/mBio.01844-15 | pmid = 26628726| url =http://mbio.asm.org/content/6/6/e01844-15 }}</ref> demonstrated that human [[neuron]]al cells could be directly and actively infected with EBV and another [[herpesvirus]], Kaposi's sarcoma-associated herpesvirus (KSHV).<br />
<br />
Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]].<br />
<br />
EBV is known to be linked to many neuronal diseases<ref name="Kleines2011">{{citation | last1 = Kleines | first1 = M | last2 = Schiefer | first2 = J | last3 = Stienen | first3 = A | last4 = Blaum | first4 = M | last5 = Ritter | first5 = K | last6 = Häusler | first6 = M | title = Expanding the spectrum of neurological disease associated with Epstein-Barr virus activity | journal =European Journal of Clinical Microbiology & Infectious Diseases<br />
| issn = 1435-4373| volume = 30 | issue = 12| pages = 1561–1569 | date = 2011-05-15| doi = 10.1007/s10096-011-1261-7| url = http://link.springer.com/article/10.1007/s10096-011-1261-7}}</ref> but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.<br />
<br />
==In human disease==<br />
<br />
Epstein-Barr virus has been associated with a wide number of immune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[systemic lupus erythematosus]],<ref name="Lossius2012">{{Cite journal | title = Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation | date = December 2012| url = https://www.mdpi.com/1999-4915/4/12/3701|journal=Viruses|volume=4|issue=12 | pages = 3701–3730 | last = Lossius | first = Andreas | author-link = | last2 = Johansen | first2 = Jorunn N. | authorlink2 = | last3 = Torkildsen | first3 = Øivind | authorlink3 = | last4 = Vartdal | first4 = Frode | authorlink4 = | last5 = Holmøy | first5 = Trygve | authorlink5 = |language=en|doi=10.3390/v4123701|pmc=PMC3528287|pmid=|issn=1999-4915|via=|quote=}}</ref> c[[Chronic fatigue syndrome|hronic fatigue syndrome]], and [[myasthenia gravis]]. EBV was recently discovered to turn on "risk genes" for autoimmune disease in the cells it infects. [[Epstein-Barr virus nuclear antigen 2|EBNA2]], a protein produced by EBV-infected cells, and its related transcription factors activate half the human genes known to be associated with the risk for lupus as well as genes associated with several other autoimmune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[inflammatory bowel disease]], [[Diabetes#Types|type 1 diabetes]], [[juvenile idiopathic arthritis]] and [[celiac disease]]. EBV activation can thus increase the risk of developing these diseases.<ref name="Harley2018" /><ref name="NIHNews2018" /> <br />
<br />
===Chronic fatigue syndrome===<br />
<br />
A prospective study of 250 primary care patients revealed a higher prevalence of [[chronic fatigue syndrome]] after infectious [[mononucleosis]] (glandular fever) when compared to an ordinary upper respiratory tract infection.<ref name="White1998">{{Cite journal | last = White | first = P.D. | last2 = Thomas | first2 = J.M. | last3 = Amess | first3 = J. | last4 = Crawford | first4 =D.H. | last5 = Grover | first5 = S.A. | last6 = Kangro | first6 = H.O. | last7 = Clare | first7 = A.W. | date = Dec 1998 | title = Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever |url =https://www.ncbi.nlm.nih.gov/pubmed/9926075|journal=The British Journal of Psychiatry: The Journal of Mental Science|volume=173 | pages = 475–481|issn=0007-1250|pmid=9926075|issue=|doi=|pmc=|quote= | author-link = Peter White|via=}}</ref> Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.<ref name="Schmaling1996">{{Cite journal | last = Schmaling | first = K.B. | last2 = Jones | first2 = J.F. | date = Jan 1996 | title = MMPI profiles of patients with chronic fatigue syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1 | pages = 67–74|issn=0022-3999|pmid=8730646}}</ref> A 2006 Australian prospective study found that 12% of subjects infected by EBV met the criteria for [[chronic fatigue syndrome]] six months after their infection, and 9% still had CFS 12 months after infection.<ref name="Hickie2006">{{Cite journal | last = Hickie | first = Ian | author-link = Ian Hickie | last2 = Davenport | first2 = Tracey | authorlink2 = Tracey Davenport | last3 = Wakefield | first3 = Denis | authorlink3 = Denis Wakefield | last4 = Vollmer-Conna | first4 = Ute | authorlink4 = Uté Vollmer-Conna | last5 = Cameron | first5 = Barbara | authorlink5 = | last6 = Vernon | first6 = Suzanne D | authorlink6 = Suzanne Vernon | last7 = Reeves | first7 = William C | author-link8 = William Reeves | last8 = Lloyd | first8 = Andrew | author-link8 = Andrew Lloyd | date = 2006-09-16 | title = Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/|journal=BMJ : British Medical Journal|volume=333|issue=7568 | pages = 575|doi=10.1136/bmj.38933.585764.AE|issn=0959-8138|pmc=1569956|pmid=16950834|access-date=|quote=|via=}}</ref> (The same rate held true for [[Ross River virus]] and [[Q fever]].) In another study sample, 110 of 178 patients with increased antibodies against EBV had a diagnosis of CFS.<ref name="Mikirova2014" /><br />
<br />
=== Long COVID ===<br />
Long COVID may be associated [[herpesvirus]] reactivation such as EBV.<ref>{{Cite journal | last = Proal | first = Amy D. | authorlink = Amy Proal | last2 = VanElzakker | first2 = Michael B. | authorlink2 = Michael VanElzakker | date = 2021 | title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms |url =https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=12|issue= | pages = 698169|doi=10.3389/fmicb.2021.698169|issn=1664-302X}}</ref><ref name=":0">{{Cite journal | title = Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation | date = June 2021| url = https://www.mdpi.com/2076-0817/10/6/763/htm|journal=Pathogens|volume=10|issue=6 | pages = 763 | last = Gold | first = Jeffrey E. | authorlink = | last2 = Okyay | first2 = Ramazan A. | authorlink2 = | last3 = Licht | first3 = Warren E. | author-link3 = | last4 = Hurley | first4 = David J. | author-link4 = | last5 = | first5 = | authorlink5 = | last8 = | first8 = |language=en|doi=10.3390/pathogens10060763|pmc=|pmid=|access-date=|issn=2076-0817|quote=|via=}}</ref><br />
<br />
===Multiple sclerosis===<br />
<br />
Infection later in life, high serum titers against EBV, and [[mononucleosis]] have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.<ref name="Holmoy2008">{{Cite journal | title = Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis | date = 2008-01-01| url = https://www.sciencedirect.com/science/article/pii/S0306987707003167|journal=Medical Hypotheses|volume=70|issue=1 | pages = 66–69 | last = Holmøy | first = Trygve|language=en|doi=10.1016/j.mehy.2007.04.030|issn=0306-9877}}</ref><br />
<br />
Several studies by Alberto Ascherio, MD, DrPH, and his team at the Harvard School of Public Health have suggested that EBV is involved in [[multiple sclerosis]], specifically in people with a certain immune-related gene and high levels of antibodies to EBV in their blood.<ref>{{Cite web | url=https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses | title = Viruses | last = | first = | date = |website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref><br />
<br />
=== Systemic lupus erythematosus ===<br />
In a study of young patients with lupus, 99% had EBV as compared to 70% of healthy controls.<ref name="James1997">{{Cite journal | title = An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. | date = 1997-12-15| url = https://www.jci.org/articles/view/119856|journal=The Journal of Clinical Investigation|volume=100|issue=12 | pages = 3019–3026 | last = James | first = J.A. | last2 = Kaufman | first2 = K.M. | last3 = Farris | first3 = A.D. | last4 = Taylor-Albert | first4 = E. | last5 = Lehman | first5 = T.J. | last6 = Harley | first6 = J.B.|language=en|doi=10.1172/JCI119856|pmid=9399948|issn=0021-9738}}</ref> Another study found that patients with systemic lupus erythematosus had a roughly 40-fold increase in EBV viral loads compared with controls, likely stemming from altered [[t cell]] responses against EBV.<ref>{{Cite journal | title = Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus | date = 2004-01-15| url = https://www.jimmunol.org/content/172/2/1287|journal=The Journal of Immunology|volume=172|issue=2 | pages = 1287–1294 | last = Kang | first = Insoo | last2 = Quan | first2 = Timothy | last3 = Nolasco | first3 = Helena | last4 = Park | first4 = Sung-Hwan | last5 = Hong | first5 = Myung Sun | last6 = Crouch | first6 = Jill | last7 = Pamer | first7 = Eric G. | last8 = Howe | first8 = John Greg | last9 = Craft | first9 = Joe|language=en|doi=10.4049/jimmunol.172.2.1287|pmid=14707107|issn=0022-1767}}</ref><br />
<br />
===Myasthenia gravis===<br />
<br />
[[Myasthenia gravis]] is an [[autoimmune disease]] which has been associated with a large number of different viruses, particularly EBV, [[Human papillomavirus|HPV]], and [[Poliovirus|polioviruses]]. In several studies EBV infection of the thymus has been found in myasthenia gravis patients, but not all studies have found this.<ref name=":1">{{Cite journal | title = A Systematic Review of the Potential Implication of Infectious Agents in Myasthenia Gravis | date = 2021 | url=https://www.frontiersin.org/article/10.3389/fneur.2021.618021|journal=Frontiers in Neurology|volume=12 | last = Leopardi | first = Victoria | last2 = Chang | first2 = Yu-Mei | last3 = Pham | first3 = Andrew | last4 = Luo | first4 = Jie | last5 = Garden | first5 = Oliver A.|doi=10.3389/fneur.2021.618021/full|issn=1664-2295}}</ref> [[B cell|B cells]] from [[myasthenia gravis]] patients stimulated ''in vitro'' by Epstein-Barr virus produced [[acetylcholine]] autoantibodies.<ref>{{Cite journal | last = Brenner | first = T. | last2 = Timore | first2 = Y. | last3 = Wirguin | first3 = I. | last4 = Abramsky | first4 = O. | last5 = Steinitz | first5 = M. | date = Oct 1989 | title = In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis |url =https://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3 | pages = 217–222|issn=0165-5728|pmid=2553772}}</ref> While EBV infection of the [[thymus]] has been posited as a causative agent for the production of [[acetylcholine]] receptor autoantibodies in [[myasthenia gravis]].<ref>{{Cite journal | last = Kaminski | first = Henry J | last2 = Minarovits | first2 = Janos | title = Epstein-barr virus: Trigger for autoimmunity?| url = http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134 | date = 2010 | volume=67|issue=6 | pages = 697-698| doi = | pmc = | pmid = | quote = |access-date=|via=}}</ref>, there is only limited evidence supporting EBV or other viruses as a cause of myasthenia gravis.<ref name=":1" /><br />
<br />
=== Gastrointestinal disease ===<br />
One study of EBV in patients with [[gastritis]], [[Crohn's disease]], and [[ulcerative colitis]] and normal controls found essentially undetectable levels of EBV in normal gastric mucosa. However, EBV was detected in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples.<ref>{{Cite journal | title = Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa | date = 2012-07-01| url = https://doi.org/10.1007/s10620-012-2116-5|journal=Digestive Diseases and Sciences|volume=57|issue=7 | pages = 1887–1898 | last = Ryan | first = Julie L. | last2 = Shen | first2 = You-Jun | last3 = Morgan | first3 = Douglas R. | last4 = Thorne | first4 = Leigh B. | last5 = Kenney | first5 = Shannon C. | last6 = Dominguez | first6 = Ricardo L. | last7 = Gulley | first7 = Margaret L.|language=en|doi=10.1007/s10620-012-2116-5|pmc=PMC3535492|pmid=22410851|issn=1573-2568}}</ref><br />
<br />
===Lyme disease===<br />
Several herpesviruses including Epstein-Barr virus may cause false positives on [[Lyme disease]] tests.<ref name="Goossens1999">{{Cite journal | last1 = Goossens | first1 = HA | last2 = Nohlmans | first2 = MK | last3 = van den Bogaard | first3 = AE | title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis| journal = Infection | date = May-Jun 1999 | volume = 27 | issue = 3| pages =231| doi = 10.1007/BF02561539 | pmid = 10378140| url = https://www.ncbi.nlm.nih.gov/pubmed/10378140}}</ref><br />
<br />
===XMEN disease===<br />
<br />
A 2014 study found chronic Epstein-Barr infection was linked to a magnesium transporter [[magnesium transporter 1|MAGT]] mutation.<ref name="MAGT1">{{Cite web | url=https://www.ncbi.nlm.nih.gov/gene/84061 | title = MAGT1 magnesium transporter 1 [Homo sapiens (human)] | last = | first = | authorlink = | date = | website = NCBI|archive-url=|archive-date=|url-status=|access-date=2022-05-21}}</ref> Dysfunction in this transporter also resulted in decreased NK cell function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Cite journal | last1 = Li | first1 = F.-Y. | author-link1 = | last2 = Chaigne-Delalande | first2 = B | authorlink2 = | last3 = Su | first3 = H | last4 = Matthews | first4 = H | last5 = Lenardo |first5 = M.J. | authorlink3 = | title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. | journal =Blood| date = 2014| doi = 10.1182/blood-2013-11-538686| url = https://ashpublications.org/blood/article/123/14/2148/32463/XMEN-disease-a-new-primary-immunodeficiency|volume=123|issue=14 | pages = 2148–2152|pmc=|pmid=|quote=|via=}}</ref><br />
<br />
This disorder, termed "XMEN" (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. <br />
<br />
Since chronic EBV infection has been associated with chronic fatigue syndrome, this error in [[magnesium]] transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /><ref name="X-men_disease_2">{{Cite journal | title = X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect | date = Dec 2014| url = https://journals.lww.com/co-pediatrics/Abstract/2014/12000/X_linked_immunodeficiency_with_magnesium_defect,.16.aspx|journal=Current Opinion in Pediatrics|volume=26|issue=6 | pages = 713–719 | last = Ravell | first = Juan | author-link = | last2 = Chaigne-Delalande | first2 = Benjamin | authorlink2 = | last3 = Lenardo | first3 = Michael | authorlink3 = |language=en-US|doi=10.1097/MOP.0000000000000156|pmc=PMC4306042|pmid=25313976|access-date=|issn=1040-8703|quote=|via=}}</ref> However, in this disorder, EBV would be seen as an indicator of the illness rather than the cause.<br />
<br />
==Vitamin D==<br />
<br />
Some recent research is finding links between EBV and [[Vitamin D]].<br />
<br />
An EBV protein, EBNA-3, has an affinity for the vitamin D receptor ([[VDR]]) and may actually block the activation of VDR-dependent genes by [[Vitamin D]].<ref>{{Cite journal | last = Yenamandra | first = Surya Pavan | last2 = Hellman | first2 = Ulf | last3 = Kempkes | first3 = Bettina | last4 = Darekar | first4 = Suhas Deoram | last5 = Petermann | first5 = Sabine | last6 = Sculley | first6 = Tom | last7 = Klein | first7 = George | last8 = Kashuba | first8 = Elena | date = Dec 2010 | title = Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes |url =https://www.ncbi.nlm.nih.gov/pubmed/20593215|journal=Cellular and molecular life sciences: CMLS|volume=67|issue=24 | pages = 4249–4256|doi=10.1007/s00018-010-0441-4|issn=1420-9071|pmid=20593215}}</ref><br />
<br />
[[Vitamin D receptor]] may be required for the normal development of [[natural killer T cell]]s that react to cells expressing [[CD1d]], as in cells infected by EBV.<ref>{{Cite journal | last = Yu | first = Sanhong | last2 = Cantorna | first2 = Margherita T. | date = 2008-04-01 | title = The vitamin D receptor is required for iNKT cell development| url = http://www.pnas.org/content/105/13/5207|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=13 | pages = 5207–5212|doi=10.1073/pnas.0711558105|issn=0027-8424|pmid=18364394}}</ref> VDR is expressed on B cells infected with EBV, and bioactive Vitamin D<sub>3</sub> alters T cells to be less detrimental to the immune response.<ref name="Holmoy2008" /><br />
<br />
As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV, and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels<ref>{{Cite journal | last = Ramien | first = Caren | last2 = Pachnio | first2 = Annette | last3 = Sisay | first3 = Sofia | last4 = Begum | first4 = Jusnara | last5 = Leese | first5 = Alison | last6 = Disanto | first6 = Giulio | last7 = Kuhle | first7 = Jens | last8 = Giovannoni | first8 = Gavin | last9 = Rickinson | first9 = Alan | date = May 2014 | title = Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort| url = https://www.ncbi.nlm.nih.gov/pubmed/24192216?dopt=Abstract|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=20|issue=6 | pages = 751–753|doi=10.1177/1352458513509507|issn=1477-0970|pmid=24192216}}</ref> (i.e., above 100 nmol/l).<br />
<br />
==Treatment==<br />
<br />
There is no specific treatment for EBV, only treatment of symptoms, such as taking over-the-counter medications for pain and fever.<ref name="CDC" /> EBV is thought to persistent harmlessly in immunocompetent individuals, but in those with compromised immune systems it has been associated with certain cancers and possibly autoimmune disease. <br />
<br />
===Antivirals===<br />
<br />
Several [[antiviral]]s are active against EBV including [[valganciclovir]], [[valacyclovir]]<ref name="Hoshino2009">{{Cite journal | title = Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers | date = Nov 2009| url = https://pubmed.ncbi.nlm.nih.gov/19740997/|journal=Journal of Virology|volume=83|issue=22 | pages = 11857–11861 | last = Hoshino | first = Yo | author-link = | last2 = Katano | first2 = Harutaka | authorlink2 = | last3 = Zou | first3 = Ping | authorlink3 = | last4 = Hohman | first4 = Patricia | authorlink4 = | last5 = Marques | first5 = Adriana | authorlink5 = | last6 = Tyring | first6 = Stephen K. | author-link6 = | last7 = Follmann | first7 = Dean | last8 = Cohen | first8 = Jeffrey I.|doi=10.1128/JVI.01005-09|pmc=2772668|pmid=19740997|access-date=|issn=1098-5514|quote=|via=}}</ref>, [[acyclovir]]<ref name="Rafaillidis2013">{{Cite journal | title = Antiviral treatment for severe EBV infections in apparently immunocompetent patients | date = Nov 2010| url = https://pubmed.ncbi.nlm.nih.gov/20739216/|journal=Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology|volume=49|issue=3 | pages = 151–157 | last = Rafailidis | first = Petros I. | authorlink = | last2 = Mavros | first2 = Michael N. | authorlink2 = | last3 = Kapaskelis | first3 = Anastasios | authorlink3 = | last4 = Falagas | first4 = Matthew E. | author-link4 = |doi=10.1016/j.jcv.2010.07.008|pmc=|pmid=20739216|access-date=|issn=1873-5967|quote=|via=}}</ref>, and [[spironolactone]].<ref name="Verma2016">{{Cite journal | last1 = Verma | first1 = Dinesh | last2 = Thompson | first2 = Jacob | last3 = Swaminathan | first3 = Sankar| title = Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function | journal =Proceedings of the National Academy of Sciences | issn = 1091-6490 | volume = 113 | issue = 13| pages = 3609–3614 | date = 2016-03-29 | doi = 10.1073/pnas.1523686113 | pmid = 26976570| url = http://www.pnas.org/content/113/13/3609}}</ref><br />
<br />
[[Acyclovir]], an [[antiviral]] drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.<br />
<br />
A theoretical [[immunotherapy]] treatment proposes that inducing [[CD1d]] expression on EBV-infected B cells could prompt effective immune suppression of EBV by natural killer T cells.<ref name="Priatel2014"/><br />
<br />
===Rituximab===<br />
<br />
[[Rituximab]] may be effective in completely eliminating EBV infection from the peripheral blood.<ref>{{Cite journal | last = Diamantopoulos | first = Panagiotis T. | last2 = Polonyfi | first2 = Katerina | last3 = Sofotasiou | first3 = Maria | last4 = Papadopoulou | first4 = Vasiliki | last5 = Kalala | first5 = Fani | last6 = Iliakis | first6 = Theodoros | last7 = Zervakis | first7 = Kostantinos | last8 = Tsilimidos | first8 = Gerassimos | last9 = Kouzis | first9 = Panagiotis | date = Dec 2013 | title = Rituximab in the treatment of EBV-positive low grade B-cell lymphoma| url = https://www.ncbi.nlm.nih.gov/pubmed/24324119|journal=Anticancer Research|volume=33|issue=12 | pages = 5693–5698|issn=1791-7530|pmid=24324119}}</ref> A study of seventeen patients with low-grade [[B cell]] lymphoma found that after three cycles of rituximab, the virus had been completely eliminated from the peripheral blood in all but one patient.<br />
<br />
===Herbs and nutraceuticals===<br />
<br />
Though not tested in clinical trials, licorice derivatives quercetin and isoliquiritigenin inhibit EBV in cell cultures.<ref>{{Cite journal | title = Quercetin-induced apoptosis prevents EBV infection | date = 2015-05-20| url = https://pubmed.ncbi.nlm.nih.gov/26059439|journal=Oncotarget|volume=6|issue=14 | pages = 12603–12624 | last = Lee | first = Minjung | last2 = Son | first2 = Myoungki | last3 = Ryu | first3 = Eunhyun | last4 = Shin | first4 = Yu Su | last5 = Kim | first5 = Jong Gwang | last6 = Kang | first6 = Byung Woog | last7 = Cho | first7 = Hyosun | last8 = Kang | first8 = Hyojeung|doi=10.18632/oncotarget.3687|pmc=4494961|pmid=26059439|issn=1949-2553}}</ref> [[Vitamin C]]<ref name="Mikirova2014">{{Cite journal | title = Effect of high dose vitamin C on Epstein-Barr viral infection | date = 2014-05-03| url = https://pubmed.ncbi.nlm.nih.gov/24793092/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=20 | pages = 725–732 | last = Mikirova | first = Nina | last2 = Hunninghake | first2 = Ronald|doi=10.12659/MSM.890423|pmc=4015650|pmid=24793092|issn=1643-3750}}</ref> and Vitamin D<sub>3</sub><ref name="Rolf2017">{{Cite journal | title = Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis | date = Sep 2018| url = https://pubmed.ncbi.nlm.nih.gov/28731372/|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=24|issue=10 | pages = 1280–1287 | last = Rolf | first = Linda | author-link = | last2 = Muris | first2 = Anne-Hilde | authorlink2 = | last3 = Mathias | first3 = Amandine | authorlink3 = | last4 = Du Pasquier | first4 = Renaud | authorlink4 = | last5 = Koneczny | first5 = Inga | authorlink5 = | last6 = Disanto | first6 = Giulio | authorlink6 = | last7 = Kuhle | first7 = Jens | last8 = Ramagopalan | first8 = Sreeram | last9 = Damoiseaux | first9 = Jan | last10 = Smolders | first10 = Joost | last11 = Hupperts | first11 = Raymond|doi=10.1177/1352458517722646|pmc=6108041|pmid=28731372|access-date=|issn=1477-0970|quote=|via=}}</ref> might also decrease duration and severity of the symptoms of EBV infection.<br />
<br />
===Vaccine===<br />
A [[vaccine]] for the prevention of Epstein-Barr virus is being explored.<ref name="Vaccine2019">{{Cite web | url=https://www.nih.gov/news-events/news-releases/nih-researchers-make-progress-toward-epstein-barr-virus-vaccine | title = NIH researchers make progress toward Epstein-Barr virus vaccine | date = 2019-04-09 | website = National Institutes of Health (NIH)|language=en|access-date=2019-04-10}}</ref><br />
<br />
==Notable studies==<br />
*1996, MMPI profiles of patients with chronic fatigue syndrome<ref name="Schmaling1996" /> - ([[pubmed:8730646|Abstract]])<br />
*1998, Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever<ref name="White1998" /> - ([[pubmed:9926075|Abstract]])<br />
*2006, Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study<ref name="Hickie2006" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full text)]<br />
*2019, EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection<ref name="Asprusten2019">{{Cite journal | last = Asprusten | first = Tarjei Tørre | authorlink = | last2 = Pedersen | first2 = Maria | authorlink2 = Maria Pedersen | last3 = Skovlund | first3 = Eva | authorlink3 = Eva Skovlund | last4 = Wyller | first4 = Vegard Bruun | authorlink4 = Vegard Bruun Wyller | date = 2019 | title=EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection | url =https://www.ncbi.nlm.nih.gov/pubmed/30957026|journal=BMJ paediatrics open|volume=3|issue=1| pages = e000390|doi=10.1136/bmjpo-2018-000390|issn=2399-9772|pmc=|pmid=30957026|quote=|via=}}</ref> - ([[pubmed:30957026|Abstract]])<br />
*2019, Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study<ref name="Pedersen2019a">{{Cite journal | last = Pedersen | first = Maria | author-link = Maria Pedersen | last2 = Asprusten | first2 = Tarjei Tørre | authorlink2 = | last3 = Godang | first3 = Kristin | authorlink3 = Kristin Godang | last4 = Leegaard | first4 = Truls Michael | authorlink4 = | last5 = Osnes | first5 = Liv Toril | authorlink5 = | last6 = Skovlund | first6 = Eva | authorlink6 = Eva Skovlund | last7 = Tjade | first7 = Trygve | author-link7 = | last8 = Øie | first8 = Merete Glenne | author-link8 = | last9 = Wyller | first9 = Vegard Bruun Bratholm | author-link9 = Vegard Bruun Wyller | date = Jan 2019 | title = Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study| url = https://www.ncbi.nlm.nih.gov/pubmed/30261303|journal=Brain, Behavior, and Immunity|volume=75|issue= | pages = 94–100|doi=10.1016/j.bbi.2018.09.023|issn=1090-2139|pmid=30261303|quote=}}</ref> - ([[pubmed:30261303|Abstract]])<br />
*2019, Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later<ref name="Pedersen2019b">{{Cite journal | last = Pedersen | first = Maria | author-link = Maria Pedersen | last2 = Asprusten | first2 = Tarjei Tørre | authorlink2 = Tarjei Tørre Asprusten | last3 = Godang | first3 = Kristin | last4 = Leegaard | first4 = Truls Michael | authorlink4 = | last5 = Osnes | first5 = Liv Toril | authorlink5 = | last6 = Skovlund | first6 = Eva | authorlink6 = Eva Skovlund | last7 = Tjade | first7 = Trygve | last8 = Øie | first8 = Merete Glenne | last9 = Wyller | first9 = Vegard Bruun Bratholm | author-link9 = Vegard Bruun Wyller | date = 2019-01-27 | title = Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later |url =https://www.ncbi.nlm.nih.gov/pubmed/30685875|journal=Acta Paediatrica (Oslo, Norway: 1992)|volume=108|issue=8 | pages = 1521-1526|doi=10.1111/apa.14728|issn=1651-2227|pmid=30685875|quote=|via=}}</ref> - ([[pubmed:30685875|Abstract]])<br />
*2019, Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal | last = Williams | first = Marshall V. | authorlink = | last2 = Cox | first2 = Brandon | authorlink2 = | last3 = Lafuse | first3 = William P. | author-link3 = | last4 = Ariza | first4 = Maria Eugenia | authorlink4 = | authorlink5 = | date = May 2019 | title = Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | url =https://linkinghub.elsevier.com/retrieve/pii/S0149291819301730|journal=Clinical Therapeutics|language=en|volume=41|issue=5 | pages = 848–863|doi=10.1016/j.clinthera.2019.04.009|pmc=6525645|pmid=31040055|quote=|via=}}</ref> - ([https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext Full text)]<br />
*2019, Review article - Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis<ref name="Kerr2019EBV">{{Cite journal | last = Kerr | first = Jonathan R. | authorlink = Jonathan Kerr | date = Feb 2019 | title = Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis | url =https://www.frontiersin.org/articles/10.3389/fped.2019.00059/abstract|journal=Frontiers in Pediatrics|volume=72|issue=10 | pages = 651-8|doi=10.3389/fped.2019.00059|quote=|via= | pmc=|pmid= }}</ref> - [https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full (Full text)]<br />
*2019, Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors<ref name="Kerr2019a">{{Cite journal | last = Kerr | first = Jonathan R | author-link = Jonathan Kerr | date = 2019-07-17 | title = Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors |url =http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205822|journal=Journal of Clinical Pathology|language=en|volume=|issue=| pages=jclinpath–2019–205822|doi=10.1136/jclinpath-2019-205822|issn=0021-9746|quote=|via=}}</ref> - [[pubmed:31315893|(Abstract)]]<br />
*2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal | last = Shikova | first = Evelina | author-link = | last2 = Reshkova | first2 = Valentina | authorlink2 = | last3 = Kumanova | first3 = Аntoniya | authorlink3 = | last4 = Raleva | first4 = Sevdalina | authorlink4 = | last5 = Alexandrova | first5 = Dora | authorlink5 = | last6 = Capo | first6 = Natasa | authorlink6 = | last7 = Murovska | first7 = Modra | date = 2020 | title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome | url =https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=| pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)]<br />
*2021, Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome<ref>{{Cite journal | title = Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome | date = Nov 15, 2021| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/|journal=Frontiers in Immunology|volume=12|issue= | pages = 656797 | last = Ruiz-Pablos | first = Manuel | authorlink = | last2 = Paiva | first2 = Bruno | authorlink2 = | last3 = Monter-Mateo | first3 = Rosario | authorlink3 = | last4 = Garcia | first4 = Nicolas | authorlink4 = | last5 = Zabaleta | first5 = Aintzane | authorlink5 = |doi=10.3389/fimmu.2021.656797|pmc=|pmid=34867935|access-date=June 10, 2022|quote=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/ Full text])<br />
*2021, Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue<ref>{{Cite journal | title = Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue | date = 2021 | url=https://pubmed.ncbi.nlm.nih.gov/34987499|journal=Frontiers in Immunology|volume=12 | pages = 715102 | last = Fevang | first = Børre | last2 = Wyller | first2 = Vegard Bruun Bratholm | last3 = Mollnes | first3 = Tom Eirik | last4 = Pedersen | first4 = Maria | last5 = Asprusten | first5 = Tarjei Tørre | last6 = Michelsen | first6 = Annika | last7 = Ueland | first7 = Thor | last8 = Otterdal | first8 = Kari |doi=10.3389/fimmu.2021.715102|pmc=8721200|pmid=34987499|issn=1664-3224}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721200/ Full text])<br />
*2021, Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation<ref name=":0" /> [https://www.mdpi.com/2076-0817/10/6/763/htm (Full text)]<br />
*2021, Risks for Developing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in College Students Following Infectious Mononucleosis: A Prospective Cohort Study<ref>{{Cite journal|title=Risks for Developing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in College Students Following Infectious Mononucleosis: A Prospective Cohort Study|date=2020-12-25|url=http://dx.doi.org/10.1093/cid/ciaa1886|journal=Clinical Infectious Diseases|volume=73|issue=11|pages=e3740–e3746|last=Jason|first=Leonard A|last2=Cotler|first2=Joseph|last3=Islam|first3=Mohammed F|last4=Sunnquist|first4=Madison|last5=Katz|first5=Ben Z|doi=10.1093/cid/ciaa1886|pmc=8664491|pmid=33367564|issn=1058-4838}}</ref> - ([[pmc:8664491/|Full text]]) <br />
*2022, EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing T<sub>FH</sub> cell differentiation and extrafollicular activities<ref>{{Cite journal | title = EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities | date = 2022-06-08| url = https://insight.jci.org/articles/view/158193|journal=JCI Insight|volume=7|issue=11 | last = Cox | first = Brandon S. | last2 = Alharshawi | first2 = Khaled | last3 = Mena-Palomo | first3 = Irene | last4 = Lafuse | first4 = William P. | last5 = Ariza | first5 = Maria Eugenia|language=en|doi=10.1172/jci.insight.158193|issn=0021-9738}}</ref> - ([https://insight.jci.org/articles/view/158193 Full text])<br />
<br />
== See also ==<br />
* [[List of herpesvirus infection studies]]<br />
* [[Abortive infection theory of ME/CFS]] (Dr. Lerner's theory that abortive herpesviruses cause ME/CFS)<br />
<br />
==Learn more ==<br />
*[https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011487.pub2/full Antiviral agents for infectious mononucleosis (glandular fever) (2016)] - [[Cochrane]] review <br />
* [https://www.nationalmssociety.org/About-the-Society/News/Study-Provides-Strongest-Evidence-Yet-for-the-Role Study Provides Strongest Evidence Yet for the Role of Epstein-Barr Virus in Triggering Multiple Sclerosis (2022)] - Multiple Sclerosis Society<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Infectious agents]]<br />
[[Category:Triggers and risk factors]]<br />
[[Category:Virology]]<br />
[[Category:Viruses]]<br />
[[Category:Herpesviruses]]</div>Darlahttps://me-pedia.org/w/index.php?title=Epstein-Barr_virus&diff=112149Epstein-Barr virus2022-06-29T20:35:52Z<p>Darla:/* Herbs and nutraceuticals */</p>
<hr />
<div>{{Cleanup|reason=Add summary of the Notable studies from 2019 onwards|date=28 July 2020}}<br />
<br />
The '''Epstein-Barr virus''' or '''EBV''' or Human '''Herpesvirus 4''' or '''HHV-4''' is a [[herpesvirus]].<ref name="CDC" /> It is the most common cause of infectious [[mononucleosis]] or "glandular fever," and infects 90% of adults worldwide.<ref name="Saha2016">{{Cite journal | last1 = Saha | first1 = Abhik<br />
| last2 = Robertson | first2 = Erle S<br />
| title = Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes<br />
| journal = Clinical Cancer Research<br />
| issn = 1557-3265| volume = 17| issue = 10| pages = 3056–3063<br />
| date = 2011-05-15<br />
| pmid = 21372216 | doi = 10.1158/1078-0432.CCR-10-2578| url = http://clincancerres.aacrjournals.org/content/17/10/3056}}</ref> It has been implicated in numerous immune diseases and chronic illnesses, including [[chronic fatigue syndrome]], [[multiple sclerosis]], [[myasthenia gravis]], and [[systemic lupus erythematosus]]. It is known to turn on "risk genes" for autoimmune disease in the cells it infects.<ref name="Harley2018">{{Cite journal|title=Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity|date=2018|url=https://www.nature.com/articles/s41588-018-0102-3|journal=Nature Genetics|volume=50|issue=5|pages=699–707|last=Harley|first=John B.|author-link=|last2=Chen|first2=Xiaoting|author-link2=|last3=Pujato|first3=Mario|author-link3=|last4=Miller|first4=Daniel|author-link4=|last5=Maddox|first5=Avery|author-link5=|last6=Forney|first6=Carmy|author-link6=|last7=Magnusen|first7=Albert F.|last8=Lynch|first8=Arthur|last9=Chetal|first9=Kashish|last10=Yukawa|first10=Masashi|last11=Barski|first11=Artem|language=en|doi=10.1038/s41588-018-0102-3|pmc=|pmid=|access-date=|issn=1546-1718|quote=|via=}}</ref><ref name="NIHNews2018">{{Cite web|url=https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases|title=Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases|last=|first=|date=16 April 2018|website=National Institutes of Health|archive-url=|archive-date=|url-status=|access-date=}}</ref><br />
<br />
== Initial infection ==<br />
[[File:Epstein-barr virus (ebv).jpg|thumb|A stained sample of Epstein-Barr virus.]]<br />
Symptoms of EBV infection include: <br />
* [[fatigue]]<br />
* [[fever]]<br />
* [[rash]]<br />
* inflamed [[sore throat|throat]]<br />
* [[swollen lymph nodes]]<br />
* enlarged [[spleen]]<br />
* swollen [[liver]]<ref name="CDC">{{Cite web|url=http://www.cdc.gov/epstein-barr/about-ebv.html|title=Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono |date=2018-05-10|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-14}}</ref><br />
<br />
===Age of infection===<br />
<br />
Most people acquire EBV in early childhood. Typically, young children who acquire EBV are either not symptomatic or have mild symptoms that are hard to distinguish from a cold or other other mild, childhood illnesses. <br />
<br />
In adolescents and young adults, EBV can cause [[infectious mononucleosis]] (IM), also known as glandular fever.<ref name="CDC" /> IM is characterized by [[fever]], [[sore throat]], [[swollen lymph nodes]], [[pain|body aches]], and [[fatigue]]. It generally resolves with rest and only rarely causes serious complications. It typically occurs in people who have not been exposed to EBV in early childhood, and in comparison, is more severe than infection in childhood (i.e., it can last for months). <br />
<br />
Following initial infection, EBV can reactivate and has been shown to have many connections with various chronic illnesses. Relative to initial infections, reactivated EBV is much more severe.<br />
<br />
==Transmission==<br />
<br />
EBV is transmitted through bodily fluids, most commonly through saliva. The first time a person is infected with EBV, the person is contagious for weeks (even when not displaying symptoms). The virus then transitions to the latent or inactive form, and stays in the body. If the virus reactivates, the person will be contagious again.<ref name="CDC" /><br />
<br />
== Diagnosis ==<br />
EBV infection is confirmed with blood tests that detect presence of [[:Category:Antibodies|antibodies]]. Nine out of ten adults have these antibodies, indicating that they have a current or past EBV infection.<ref name="CDC" /><br />
<br />
Anti-VCA (Viral capsid antigen) IgG and EBV nuclear antigen (EBNA) IgG antibodies persist throughout a person's life. Thus, positive results merely indicate a current or past infection. A current EBV infection is diagnosed based on the presence of Anti-VCA IgM and Anti-EA (Early Antigen) IgG. VCA IgM appears early in EBV infection and usually disappears within four to six weeks. Positive VCA IgM suggests current active acute EBV infection. EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. Positive EA IgG can suggest current active EBV infection or EBV re-activation. <ref name="CDC-testing">{{Cite web|url=https://www.cdc.gov/epstein-barr/laboratory-testing.html|title=Epstein-barr {{!}} Mononucleosis {{!}} Laboratory Testing {{!}} Mono|date=2019-01-28|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-10-08}}</ref><br />
<br />
==Latency==<br />
<br />
In healthy adults, the virus remains latent for life in memory [[B cell]]s. It is estimated that 1 in every one hundred thousand to one million circulating B cells carry EBV.<ref name="Hsu2000">{{Cite journal|last=Hsu|first=J. L.|last2=Glaser|first2=S. L.|date=Apr 2000|title=Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications|url=https://www.ncbi.nlm.nih.gov/pubmed/10781747/|journal=Critical Reviews in Oncology/Hematology|volume=34|issue=1|pages=27–53|issn=1040-8428|pmid=10781747}}</ref> In healthy hosts, EBV populations are kept in check by [[CD4+ T cell|CD4<sup>+</sup>]] and [[CD8|CD8<sup>+</sup>]] [[T cell|T-cell]] responses. <br />
<br />
The equilibrium can be disrupted in individuals with compromised [[immune system]]s such as patients with [[AIDS]] or transplant patients taking immune system suppressing drugs.<ref name="Priatel2014">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=4|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206|quote=|via=}}</ref> It has been observed that these patients are more susceptible to EBV-related [[cancer]]s, such as certain [[lymphoma]]s and carcinomas.<ref>{{Cite journal|last=Pattle|first=Samuel B.|last2=Farrell|first2=Paul J.|date=Nov 2006|title=The role of Epstein-Barr virus in cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/17049016|journal=Expert Opinion on Biological Therapy|volume=6|issue=11|pages=1193–1205|doi=10.1517/14712598.6.11.1193|issn=1744-7682|pmid=17049016|quote=|via=}}</ref> In immunocompromised patients, EBV can induce lymphoproliferation, [[lymphoma]], and hemophagocytic lymphohistiocytosis (HLH).<ref>{{Cite journal|title=Human immunity against EBV—lessons from the clinic|date=2017-01-20|url=https://doi.org/10.1084/jem.20161846|journal=Journal of Experimental Medicine|volume=214|issue=2|pages=269–283|last=Tangye|first=Stuart G.|last2=Palendira|first2=Umaimainthan|last3=Edwards|first3=Emily S.J.|doi=10.1084/jem.20161846|issn=0022-1007}}</ref><br />
===Natural killer T cells===<br />
<br />
It is thought that [[natural killer T cell]]s (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of [[CD1d]] expressing cells.<ref name="Priatel2014" /><br />
<br />
==Neuronal infection==<br />
A 2015 study<ref name="JhaHC2015">{{Cite journal | last1 = Jha | first1 = HC | authorlink1 = <br />
| last2 = Mehta | first2 = D | authorlink2 = <br />
| last3 = Lu | first3 = J | authorlink3 = <br />
| last4 = El-Naccache | first4 = D | authorlink4 = <br />
| last5 = Shukla | first5 = SK | authorlink5 =<br />
| last6 = Kovacsics | first6 = C | authorlink6 =<br />
| last7 = Kolson | first7 = D | authorlink7 = <br />
| last8 = Robertson | first8 = ES | authorlink8 =<br />
| title = Gammaherpesvirus Infection of Human Neuronal Cells| journal = mBio | volume = 6 | issue =6 | pages = e01844-15| date = 2016-12-01| doi = 10.1128/mBio.01844-15 | pmid = 26628726| url =http://mbio.asm.org/content/6/6/e01844-15<br />
}}</ref> demonstrated that human [[neuron]]al cells could be directly and actively infected with EBV and another [[herpesvirus]], Kaposi's sarcoma-associated herpesvirus (KSHV).<br />
<br />
Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]].<br />
<br />
EBV is known to be linked to many neuronal diseases<ref name="Kleines2011">{{citation<br />
| last1 = Kleines | first1 = M<br />
| last2 = Schiefer | first2 = J<br />
| last3 = Stienen | first3 = A<br />
| last4 = Blaum | first4 = M<br />
| last5 = Ritter | first5 = K<br />
| last6 = Häusler | first6 = M<br />
| title = Expanding the spectrum of neurological disease associated with Epstein-Barr virus activity<br />
| journal = European Journal of Clinical Microbiology & Infectious Diseases<br />
| issn = 1435-4373| volume = 30| issue = 12| pages = 1561–1569<br />
| date = 2011-05-15| doi = 10.1007/s10096-011-1261-7| url = http://link.springer.com/article/10.1007/s10096-011-1261-7}}</ref> but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.<br />
<br />
==In human disease==<br />
<br />
Epstein-Barr virus has been associated with a wide number of immune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[systemic lupus erythematosus]],<ref name="Lossius2012">{{Cite journal|title=Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation|date=December 2012|url=https://www.mdpi.com/1999-4915/4/12/3701|journal=Viruses|volume=4|issue=12|pages=3701–3730|last=Lossius|first=Andreas|author-link=|last2=Johansen|first2=Jorunn N.|author-link2=|last3=Torkildsen|first3=Øivind|author-link3=|last4=Vartdal|first4=Frode|author-link4=|last5=Holmøy|first5=Trygve|author-link5=|language=en|doi=10.3390/v4123701|pmc=PMC3528287|pmid=|issn=1999-4915|via=|quote=}}</ref> [[Chronic fatigue syndrome]], and [[myasthenia gravis]]. EBV was recently discovered to turn on "risk genes" for autoimmune disease in the cells it infects. [[Epstein-Barr virus nuclear antigen 2|EBNA2]], a protein produced by EBV-infected cells, and its related transcription factors activate half the human genes known to be associated with the risk for lupus as well as genes associated with several other autoimmune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[inflammatory bowel disease]], [[Diabetes#Types|type 1 diabetes]], [[juvenile idiopathic arthritis]] and [[celiac disease]]. EBV activation can thus increase the risk of developing these diseases.<ref name="Harley2018" /><ref name="NIHNews2018" /> <br />
<br />
===Chronic fatigue syndrome===<br />
<br />
A prospective study of 250 primary care patients revealed a higher prevalence of [[chronic fatigue syndrome]] after infectious [[mononucleosis]] (glandular fever) when compared to an ordinary upper respiratory tract infection.<ref name="White1998">{{Cite journal|last=White|first=P. D.|last2=Thomas|first2=J. M.|last3=Amess|first3=J.|last4=Crawford|first4=D. H.|last5=Grover|first5=S. A.|last6=Kangro|first6=H. O.|last7=Clare|first7=A. W.|date=Dec 1998|title=Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever|url=https://www.ncbi.nlm.nih.gov/pubmed/9926075|journal=The British Journal of Psychiatry: The Journal of Mental Science|volume=173|pages=475–481|issn=0007-1250|pmid=9926075|issue=|doi=|pmc=|quote=|author-link=Peter White|via=}}</ref> Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.<ref name="Schmaling1996">{{Cite journal|last=Schmaling|first=K. B.|last2=Jones|first2=J. F.|date=Jan 1996|title=MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1|pages=67–74|issn=0022-3999|pmid=8730646}}</ref> A 2006 Australian prospective study found that 12% of subjects infected by EBV met the criteria for [[chronic fatigue syndrome]] six months after their infection, and 9% still had CFS 12 months after infection.<ref name="Hickie2006">{{Cite journal|last=Hickie|first=Ian|author-link=Ian Hickie|last2=Davenport|first2=Tracey|author-link2=Tracey Davenport|last3=Wakefield|first3=Denis|author-link3=Denis Wakefield|last4=Vollmer-Conna|first4=Ute|author-link4=Uté Vollmer-Conna|last5=Cameron|first5=Barbara|author-link5=|last6=Vernon|first6=Suzanne D|author-link6=Suzanne Vernon|last7=Reeves|first7=William C|author-link7=William Reeves|last8=Lloyd|first8=Andrew|author-link8=Andrew Lloyd|date=2006-09-16|title=Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/|journal=BMJ : British Medical Journal|volume=333|issue=7568|pages=575|doi=10.1136/bmj.38933.585764.AE|issn=0959-8138|pmc=1569956|pmid=16950834|access-date=|quote=|via=}}</ref> (The same rate held true for [[Ross River virus]] and [[Q fever]]). In another study sample, 110 of 178 patients with increased antibodies against EBV had a diagnosis of CFS.<ref name="Mikirova2014" /><br />
<br />
=== Long COVID ===<br />
Long COVID may be associated [[herpesvirus]] reactivation such as EBV.<ref>{{Cite journal|last=Proal|first=Amy D.|author-link=Amy Proal|last2=VanElzakker|first2=Michael B.|author-link2=Michael VanElzakker|date=2021|title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms|url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=12|issue=|pages=698169|doi=10.3389/fmicb.2021.698169|issn=1664-302X}}</ref><ref name=":0">{{Cite journal|title=Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation|date=June 2021|url=https://www.mdpi.com/2076-0817/10/6/763/htm|journal=Pathogens|volume=10|issue=6|pages=763|last=Gold|first=Jeffrey E.|author-link=|last2=Okyay|first2=Ramazan A.|author-link2=|last3=Licht|first3=Warren E.|author-link3=|last4=Hurley|first4=David J.|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|language=en|doi=10.3390/pathogens10060763|pmc=|pmid=|access-date=|issn=2076-0817|quote=|via=}}</ref><br />
<br />
===Multiple sclerosis===<br />
<br />
Infection later in life, high serum titers against EBV, and [[mononucleosis]] have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.<ref name="Holmoy2008">{{Cite journal|title=Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis|date=2008-01-01|url=https://www.sciencedirect.com/science/article/pii/S0306987707003167|journal=Medical Hypotheses|volume=70|issue=1|pages=66–69|last=Holmøy|first=Trygve|language=en|doi=10.1016/j.mehy.2007.04.030|issn=0306-9877}}</ref><br />
<br />
Several studies by Alberto Ascherio, MD, DrPH, and his team at the Harvard School of Public Health have suggested that EBV is involved in [[multiple sclerosis]], specifically in people with a certain immune-related gene and high levels of antibodies to EBV in their blood.<ref>{{Cite web|url=https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses|title=Viruses|last=|first=|date=|website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref><br />
<br />
=== Systemic lupus erythematosus ===<br />
In a study of young patients with lupus, 99% had EBV as compared to 70% of healthy controls.<ref name="James1997">{{Cite journal|title=An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus.|date=1997-12-15|url=https://www.jci.org/articles/view/119856|journal=The Journal of Clinical Investigation|volume=100|issue=12|pages=3019–3026|last=James|first=J. A.|last2=Kaufman|first2=K. M.|last3=Farris|first3=A. D.|last4=Taylor-Albert|first4=E.|last5=Lehman|first5=T. J.|last6=Harley|first6=J. B.|language=en|doi=10.1172/JCI119856|pmid=9399948|issn=0021-9738}}</ref> Another study found that patients with systemic lupus erythematosus had a roughly 40-fold increase in EBV viral loads compared with controls, likely stemming from altered [[t cell]] responses against EBV.<ref>{{Cite journal|title=Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus|date=2004-01-15|url=https://www.jimmunol.org/content/172/2/1287|journal=The Journal of Immunology|volume=172|issue=2|pages=1287–1294|last=Kang|first=Insoo|last2=Quan|first2=Timothy|last3=Nolasco|first3=Helena|last4=Park|first4=Sung-Hwan|last5=Hong|first5=Myung Sun|last6=Crouch|first6=Jill|last7=Pamer|first7=Eric G.|last8=Howe|first8=John Greg|last9=Craft|first9=Joe|language=en|doi=10.4049/jimmunol.172.2.1287|pmid=14707107|issn=0022-1767}}</ref><br />
<br />
===Myasthenia gravis===<br />
<br />
[[Myasthenia gravis]] is an [[autoimmune disease]] which has been associated with a large number of different viruses, particularly EBV, [[Human papillomavirus|HPV]], and [[Poliovirus|polioviruses]]. In several studies EBV infection of the thymus has been found in myasthenia gravis patients, but not all studies have found this.<ref name=":1">{{Cite journal|title=A Systematic Review of the Potential Implication of Infectious Agents in Myasthenia Gravis|date=2021|url=https://www.frontiersin.org/article/10.3389/fneur.2021.618021|journal=Frontiers in Neurology|volume=12|last=Leopardi|first=Victoria|last2=Chang|first2=Yu-Mei|last3=Pham|first3=Andrew|last4=Luo|first4=Jie|last5=Garden|first5=Oliver A.|doi=10.3389/fneur.2021.618021/full|issn=1664-2295}}</ref> [[B cell|B cells]] from [[myasthenia gravis]] patients stimulated ''in vitro'' by Epstein-Barr virus produced [[acetylcholine]] autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=https://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> While EBV infection of the [[thymus]] has been posited as a causative agent for the production of [[acetylcholine]] receptor autoantibodies in [[myasthenia gravis]].<ref>{{Cite journal|last=Kaminski|first=Henry J|last2=Minarovits|first2=Janos|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134|date=2010|volume=67|issue=6|pages=697-698|doi=|pmc=|pmid=|quote=|access-date=|via=}}</ref>, there is only limited evidence supporting EBV or other viruses as a cause of myasthenia gravis.<ref name=":1" /><br />
<br />
=== Gastrointestinal disease ===<br />
One study of EBV in patients with [[gastritis]], [[Crohn's disease]], and [[ulcerative colitis]] and normal controls found essentially undetectable levels of EBV in normal gastric mucosa. However, EBV was detected in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples.<ref>{{Cite journal|title=Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa|date=2012-07-01|url=https://doi.org/10.1007/s10620-012-2116-5|journal=Digestive Diseases and Sciences|volume=57|issue=7|pages=1887–1898|last=Ryan|first=Julie L.|last2=Shen|first2=You-Jun|last3=Morgan|first3=Douglas R.|last4=Thorne|first4=Leigh B.|last5=Kenney|first5=Shannon C.|last6=Dominguez|first6=Ricardo L.|last7=Gulley|first7=Margaret L.|language=en|doi=10.1007/s10620-012-2116-5|pmc=PMC3535492|pmid=22410851|issn=1573-2568}}</ref><br />
<br />
===Lyme disease===<br />
Several herpesviruses including Epstein-Barr virus may cause false positives on [[Lyme disease]] tests.<ref name="Goossens1999">{{Cite journal | last1 = Goossens | first1 = HA<br />
| last2 = Nohlmans | first2 = MK <br />
| last3 = van den Bogaard | first3 = AE<br />
| title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis| journal = Infection | date = May-Jun 1999 | volume = 27 | issue = 3| pages =231| doi = 10.1007/BF02561539|pmid = 10378140| url = https://www.ncbi.nlm.nih.gov/pubmed/10378140}}</ref><br />
<br />
===XMEN disease===<br />
<br />
A 2014 study found chronic Epstein-Barr infection was linked to a magnesium transporter [[magnesium transporter 1|MAGT]] mutation.<ref name="MAGT1">{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/84061|title=MAGT1 magnesium transporter 1 [Homo sapiens (human)]|last=|first=|authorlink=|date=|website=NCBI|archive-url=|archive-date=|url-status=|access-date=2022-05-21}}</ref> Dysfunction in this transporter also resulted in decreased NK cell function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Cite journal |last1 = Li |first1 = F.-Y. |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Su<br />
| first3 = H<br />
| last4 = Matthews<br />
| first4 = H |last5 = Lenardo |first5 = M.J. |authorlink3 = <br />
| title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. <br />
| journal = Blood| date = 2014| doi = 10.1182/blood-2013-11-538686|url=https://ashpublications.org/blood/article/123/14/2148/32463/XMEN-disease-a-new-primary-immunodeficiency|volume=123|issue=14|pages=2148–2152|pmc=|pmid=|quote=|via=}}</ref><br />
<br />
This disorder, termed "XMEN" (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. <br />
<br />
Since chronic EBV infection has been associated with chronic fatigue syndrome, this error in [[magnesium]] transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /><ref name="X-men_disease_2">{{Cite journal|title=X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect|date=Dec 2014|url=https://journals.lww.com/co-pediatrics/Abstract/2014/12000/X_linked_immunodeficiency_with_magnesium_defect,.16.aspx|journal=Current Opinion in Pediatrics|volume=26|issue=6|pages=713–719|last=Ravell|first=Juan|author-link=|last2=Chaigne-Delalande|first2=Benjamin|author-link2=|last3=Lenardo|first3=Michael|author-link3=|language=en-US|doi=10.1097/MOP.0000000000000156|pmc=PMC4306042|pmid=25313976|access-date=|issn=1040-8703|quote=|via=}}</ref> However, in this disorder, EBV would be seen as an indicator of the illness rather than the cause.<br />
<br />
==Vitamin D==<br />
<br />
Some recent research is finding links between EBV and [[Vitamin D]].<br />
<br />
An EBV protein, EBNA-3, has an affinity for the vitamin D receptor ([[VDR]]) and may actually block the activation of VDR-dependent genes by [[Vitamin D]].<ref>{{Cite journal|last=Yenamandra|first=Surya Pavan|last2=Hellman|first2=Ulf|last3=Kempkes|first3=Bettina|last4=Darekar|first4=Suhas Deoram|last5=Petermann|first5=Sabine|last6=Sculley|first6=Tom|last7=Klein|first7=George|last8=Kashuba|first8=Elena|date=Dec 2010|title=Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes|url=https://www.ncbi.nlm.nih.gov/pubmed/20593215|journal=Cellular and molecular life sciences: CMLS|volume=67|issue=24|pages=4249–4256|doi=10.1007/s00018-010-0441-4|issn=1420-9071|pmid=20593215}}</ref><br />
<br />
[[Vitamin D receptor]] may be required for the normal development of [[natural killer T cell]]s that react to cells expressing [[CD1d]], as in cells infected by EBV.<ref>{{Cite journal|last=Yu|first=Sanhong|last2=Cantorna|first2=Margherita T.|date=2008-04-01|title=The vitamin D receptor is required for iNKT cell development|url=http://www.pnas.org/content/105/13/5207|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=13|pages=5207–5212|doi=10.1073/pnas.0711558105|issn=0027-8424|pmid=18364394}}</ref> VDR is expressed on B cells infected with EBV, and bioactive Vitamin D<sub>3</sub> alters T cells to be less detrimental to the immune response.<ref name="Holmoy2008" /><br />
<br />
As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV, and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels<ref>{{Cite journal|last=Ramien|first=Caren|last2=Pachnio|first2=Annette|last3=Sisay|first3=Sofia|last4=Begum|first4=Jusnara|last5=Leese|first5=Alison|last6=Disanto|first6=Giulio|last7=Kuhle|first7=Jens|last8=Giovannoni|first8=Gavin|last9=Rickinson|first9=Alan|date=May 2014|title=Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort|url=https://www.ncbi.nlm.nih.gov/pubmed/24192216?dopt=Abstract|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=20|issue=6|pages=751–753|doi=10.1177/1352458513509507|issn=1477-0970|pmid=24192216}}</ref> (i.e., above 100 nmol/l).<br />
<br />
==Treatment==<br />
<br />
There is no specific treatment for EBV, only treatment of symptoms, such as taking over-the-counter medications for pain and fever.<ref name="CDC" /> EBV is thought to persistent harmlessly in immunocompetent individuals, but in those with compromised immune systems it has been associated with certain cancers and possibly autoimmune disease. <br />
<br />
===Antivirals===<br />
<br />
Several [[antiviral]]s are active against EBV including [[valganciclovir]], [[valacyclovir]]<ref name="Hoshino2009">{{Cite journal|title=Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers|date=Nov 2009|url=https://pubmed.ncbi.nlm.nih.gov/19740997/|journal=Journal of Virology|volume=83|issue=22|pages=11857–11861|last=Hoshino|first=Yo|author-link=|last2=Katano|first2=Harutaka|author-link2=|last3=Zou|first3=Ping|author-link3=|last4=Hohman|first4=Patricia|author-link4=|last5=Marques|first5=Adriana|author-link5=|last6=Tyring|first6=Stephen K.|author-link6=|last7=Follmann|first7=Dean|last8=Cohen|first8=Jeffrey I.|doi=10.1128/JVI.01005-09|pmc=2772668|pmid=19740997|access-date=|issn=1098-5514|quote=|via=}}</ref>, [[acyclovir]]<ref name="Rafaillidis2013">{{Cite journal|title=Antiviral treatment for severe EBV infections in apparently immunocompetent patients|date=Nov 2010|url=https://pubmed.ncbi.nlm.nih.gov/20739216/|journal=Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology|volume=49|issue=3|pages=151–157|last=Rafailidis|first=Petros I.|author-link=|last2=Mavros|first2=Michael N.|author-link2=|last3=Kapaskelis|first3=Anastasios|author-link3=|last4=Falagas|first4=Matthew E.|author-link4=|doi=10.1016/j.jcv.2010.07.008|pmc=|pmid=20739216|access-date=|issn=1873-5967|quote=|via=}}</ref>, and [[spironolactone]].<ref name="Verma2016">{{Cite journal | last1 = Verma | first1 = Dinesh<br />
| last2 = Thompson | first2 = Jacob<br />
| last3 = Swaminathan | first3 = Sankar| title = Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function<br />
| journal = Proceedings of the National Academy of Sciences | issn = 1091-6490 | volume = 113| issue = 13| pages = 3609–3614<br />
| date = 2016-03-29<br />
| doi = 10.1073/pnas.1523686113 | pmid = 26976570| url = http://www.pnas.org/content/113/13/3609}}</ref><br />
<br />
[[Acyclovir]], an [[antiviral]] drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.<br />
<br />
A theoretical [[immunotherapy]] treatment proposes that inducing [[CD1d]] expression on EBV-infected B cells could prompt effective immune suppression of EBV by natural killer T cells.<ref name="Priatel2014">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206}}</ref><br />
<br />
===Rituximab===<br />
<br />
[[Rituximab]] may be effective in completely eliminating EBV infection from the peripheral blood.<ref>{{Cite journal|last=Diamantopoulos|first=Panagiotis T.|last2=Polonyfi|first2=Katerina|last3=Sofotasiou|first3=Maria|last4=Papadopoulou|first4=Vasiliki|last5=Kalala|first5=Fani|last6=Iliakis|first6=Theodoros|last7=Zervakis|first7=Kostantinos|last8=Tsilimidos|first8=Gerassimos|last9=Kouzis|first9=Panagiotis|date=Dec 2013|title=Rituximab in the treatment of EBV-positive low grade B-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/24324119|journal=Anticancer Research|volume=33|issue=12|pages=5693–5698|issn=1791-7530|pmid=24324119}}</ref> A study of seventeen patients with low-grade [[B cell]] lymphoma found that after three cycles of rituximab, the virus had been completely eliminated from the peripheral blood in all but one patient.<br />
<br />
===Herbs and nutraceuticals===<br />
<br />
Though not tested in clinical trials, licorice derivatives quercetin and isoliquiritigenin inhibit EBV in cell cultures.<ref>{{Cite journal|title=Quercetin-induced apoptosis prevents EBV infection|date=2015-05-20|url=https://pubmed.ncbi.nlm.nih.gov/26059439|journal=Oncotarget|volume=6|issue=14|pages=12603–12624|last=Lee|first=Minjung|last2=Son|first2=Myoungki|last3=Ryu|first3=Eunhyun|last4=Shin|first4=Yu Su|last5=Kim|first5=Jong Gwang|last6=Kang|first6=Byung Woog|last7=Cho|first7=Hyosun|last8=Kang|first8=Hyojeung|doi=10.18632/oncotarget.3687|pmc=4494961|pmid=26059439|issn=1949-2553}}</ref> [[Vitamin C]]<ref name="Mikirova2014">{{Cite journal|title=Effect of high dose vitamin C on Epstein-Barr viral infection|date=2014-05-03|url=https://pubmed.ncbi.nlm.nih.gov/24793092/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=20|pages=725–732|last=Mikirova|first=Nina|last2=Hunninghake|first2=Ronald|doi=10.12659/MSM.890423|pmc=4015650|pmid=24793092|issn=1643-3750}}</ref> and Vitamin D<sub>3</sub><ref name="Rolf2017">{{Cite journal|title=Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis|date=Sep 2018|url=https://pubmed.ncbi.nlm.nih.gov/28731372/|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=24|issue=10|pages=1280–1287|last=Rolf|first=Linda|author-link=|last2=Muris|first2=Anne-Hilde|author-link2=|last3=Mathias|first3=Amandine|author-link3=|last4=Du Pasquier|first4=Renaud|author-link4=|last5=Koneczny|first5=Inga|author-link5=|last6=Disanto|first6=Giulio|author-link6=|last7=Kuhle|first7=Jens|last8=Ramagopalan|first8=Sreeram|last9=Damoiseaux|first9=Jan|last10=Smolders|first10=Joost|last11=Hupperts|first11=Raymond|doi=10.1177/1352458517722646|pmc=6108041|pmid=28731372|access-date=|issn=1477-0970|quote=|via=}}</ref> might also decrease duration and severity of the symptoms of EBV infection.<br />
<br />
===Vaccine===<br />
A [[vaccine]] for the prevention of Epstein-Barr virus is being explored.<ref name="Vaccine2019">{{Cite web|url=https://www.nih.gov/news-events/news-releases/nih-researchers-make-progress-toward-epstein-barr-virus-vaccine|title=NIH researchers make progress toward Epstein-Barr virus vaccine|date=2019-04-09|website=National Institutes of Health (NIH)|language=en|access-date=2019-04-10}}</ref><br />
<br />
==Notable studies==<br />
*1996, MMPI profiles of patients with chronic fatigue syndrome<ref name="Schmaling1996" /> - ([[pubmed:8730646|Abstract]])<br />
*1998, Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever<ref name="White1998" /> - ([[pubmed:9926075|Abstract]])<br />
*2006, Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study<ref name="Hickie2006" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full text)]<br />
*2019, EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection<ref name="Asprusten2019">{{Cite journal|last=Asprusten|first=Tarjei Tørre|author-link=|last2=Pedersen|first2=Maria|author-link2=Maria Pedersen|last3=Skovlund|first3=Eva|author-link3=Eva Skovlund|last4=Wyller|first4=Vegard Bruun|author-link4=Vegard Bruun Wyller|date=2019|title=EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection|url=https://www.ncbi.nlm.nih.gov/pubmed/30957026|journal=BMJ paediatrics open|volume=3|issue=1|pages=e000390|doi=10.1136/bmjpo-2018-000390|issn=2399-9772|pmc=|pmid=30957026|quote=|via=}}</ref> - ([[pubmed:30957026|Abstract]])<br />
*2019, Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study<ref name="Pedersen2019a">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=|last3=Godang|first3=Kristin|author-link3=Kristin Godang|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|author-link7=|last8=Øie|first8=Merete Glenne|author-link8=|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=Jan 2019|title=Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pubmed/30261303|journal=Brain, Behavior, and Immunity|volume=75|issue=|pages=94–100|doi=10.1016/j.bbi.2018.09.023|issn=1090-2139|pmid=30261303|quote=}}</ref> - ([[pubmed:30261303|Abstract]])<br />
*2019, Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later<ref name="Pedersen2019b">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=Tarjei Tørre Asprusten|last3=Godang|first3=Kristin|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|last8=Øie|first8=Merete Glenne|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=2019-01-27|title=Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later|url=https://www.ncbi.nlm.nih.gov/pubmed/30685875|journal=Acta Paediatrica (Oslo, Norway: 1992)|volume=108|issue=8|pages=1521-1526|doi=10.1111/apa.14728|issn=1651-2227|pmid=30685875|quote=|via=}}</ref> - ([[pubmed:30685875|Abstract]])<br />
*2019, Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Williams|first=Marshall V.|author-link=|last2=Cox|first2=Brandon|author-link2=|last3=Lafuse|first3=William P.|author-link3=|last4=Ariza|first4=Maria Eugenia|author-link4=|author-link5=|date=May 2019|title=Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0149291819301730|journal=Clinical Therapeutics|language=en|volume=41|issue=5|pages=848–863|doi=10.1016/j.clinthera.2019.04.009|pmc=6525645|pmid=31040055|quote=|via=}}</ref> - ([https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext Full text)]<br />
*2019, Review article - Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis<ref name="Kerr2019EBV">{{Cite journal|last=Kerr|first=Jonathan R.|author-link=Jonathan Kerr|date=Feb 2019|title=Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00059/abstract|journal=Frontiers in Pediatrics|volume=72|issue=10|pages=651-8|doi=10.3389/fped.2019.00059|quote=|via=|last2=|first2=|pmc=|pmid=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full (Full text)]<br />
*2019, Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors<ref name="Kerr2019a">{{Cite journal|last=Kerr|first=Jonathan R|author-link=Jonathan Kerr|author-link2=|date=2019-07-17|title=Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors|url=http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205822|journal=Journal of Clinical Pathology|language=en|volume=|issue=|pages=jclinpath–2019–205822|doi=10.1136/jclinpath-2019-205822|issn=0021-9746|quote=|via=}}</ref> - [[pubmed:31315893|(Abstract)]]<br />
*2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal|last=Shikova|first=Evelina|author-link=|last2=Reshkova|first2=Valentina|author-link2=|last3=Kumanova|first3=Аntoniya|author-link3=|last4=Raleva|first4=Sevdalina|author-link4=|last5=Alexandrova|first5=Dora|author-link5=|last6=Capo|first6=Natasa|author-link6=|last7=Murovska|first7=Modra|date=2020|title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=|pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)]<br />
*2021, Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome<ref>{{Cite journal|title=Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|date=Nov 15, 2021|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/|journal=Frontiers in Immunology|volume=12|issue=|pages=656797|last=Ruiz-Pablos|first=Manuel|author-link=|last2=Paiva|first2=Bruno|author-link2=|last3=Monter-Mateo|first3=Rosario|author-link3=|last4=Garcia|first4=Nicolas|author-link4=|last5=Zabaleta|first5=Aintzane|author-link5=|doi=10.3389/fimmu.2021.656797|pmc=|pmid=34867935|access-date=June 10, 2022|quote=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/ Full text])<br />
*2021, Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue<ref>{{Cite journal|title=Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue|date=2021|url=https://pubmed.ncbi.nlm.nih.gov/34987499|journal=Frontiers in Immunology|volume=12|pages=715102|last=Fevang|first=Børre|last2=Wyller|first2=Vegard Bruun Bratholm|last3=Mollnes|first3=Tom Eirik|last4=Pedersen|first4=Maria|last5=Asprusten|first5=Tarjei Tørre|last6=Michelsen|first6=Annika|last7=Ueland|first7=Thor|last8=Otterdal|first8=Kari|doi=10.3389/fimmu.2021.715102|pmc=8721200|pmid=34987499|issn=1664-3224}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721200/ Full text])<br />
*2021, Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation<ref name=":0" /> [https://www.mdpi.com/2076-0817/10/6/763/htm (Full text)]<br />
*2022, EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing T<sub>FH</sub> cell differentiation and extrafollicular activities<ref>{{Cite journal|title=EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities|date=2022-06-08|url=https://insight.jci.org/articles/view/158193|journal=JCI Insight|volume=7|issue=11|last=Cox|first=Brandon S.|last2=Alharshawi|first2=Khaled|last3=Mena-Palomo|first3=Irene|last4=Lafuse|first4=William P.|last5=Ariza|first5=Maria Eugenia|language=en|doi=10.1172/jci.insight.158193|issn=0021-9738}}</ref> - ([https://insight.jci.org/articles/view/158193 Full text])<br />
<br />
== See also ==<br />
* [[List of herpesvirus infection studies]]<br />
<br />
==Learn more ==<br />
*[https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011487.pub2/full Antiviral agents for infectious mononucleosis (glandular fever) (2016)] - [[Cochrane]] review <br />
* [https://www.nationalmssociety.org/About-the-Society/News/Study-Provides-Strongest-Evidence-Yet-for-the-Role Study Provides Strongest Evidence Yet for the Role of Epstein-Barr Virus in Triggering Multiple Sclerosis (2022)] - Multiple Sclerosis Society<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Infectious agents]]<br />
[[Category:Triggers and risk factors]]<br />
[[Category:Virology]]<br />
[[Category:Viruses]]</div>Darlahttps://me-pedia.org/w/index.php?title=Epstein-Barr_virus&diff=112141Epstein-Barr virus2022-06-29T11:06:53Z<p>Darla:/* Vitamin D */</p>
<hr />
<div>{{Cleanup|reason=Add summary of the Notable studies from 2019 onwards|date=28 July 2020}}<br />
<br />
The '''Epstein-Barr virus''' or '''EBV''' or Human '''Herpesvirus 4''' or '''HHV-4''' is a [[herpesvirus]].<ref name="CDC" /> It is the most common cause of infectious [[mononucleosis]] or "glandular fever," and infects 90% of adults worldwide.<ref name="Saha2016">{{Cite journal | last1 = Saha | first1 = Abhik<br />
| last2 = Robertson | first2 = Erle S<br />
| title = Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes<br />
| journal = Clinical Cancer Research<br />
| issn = 1557-3265| volume = 17| issue = 10| pages = 3056–3063<br />
| date = 2011-05-15<br />
| pmid = 21372216 | doi = 10.1158/1078-0432.CCR-10-2578| url = http://clincancerres.aacrjournals.org/content/17/10/3056}}</ref> It has been implicated in numerous immune diseases and chronic illnesses, including [[chronic fatigue syndrome]], [[multiple sclerosis]], [[myasthenia gravis]], and [[systemic lupus erythematosus]]. It is known to turn on "risk genes" for autoimmune disease in the cells it infects.<ref name="Harley2018">{{Cite journal|title=Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity|date=2018|url=https://www.nature.com/articles/s41588-018-0102-3|journal=Nature Genetics|volume=50|issue=5|pages=699–707|last=Harley|first=John B.|author-link=|last2=Chen|first2=Xiaoting|author-link2=|last3=Pujato|first3=Mario|author-link3=|last4=Miller|first4=Daniel|author-link4=|last5=Maddox|first5=Avery|author-link5=|last6=Forney|first6=Carmy|author-link6=|last7=Magnusen|first7=Albert F.|last8=Lynch|first8=Arthur|last9=Chetal|first9=Kashish|last10=Yukawa|first10=Masashi|last11=Barski|first11=Artem|language=en|doi=10.1038/s41588-018-0102-3|pmc=|pmid=|access-date=|issn=1546-1718|quote=|via=}}</ref><ref name="NIHNews2018">{{Cite web|url=https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases|title=Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases|last=|first=|date=16 April 2018|website=National Institutes of Health|archive-url=|archive-date=|url-status=|access-date=}}</ref><br />
<br />
== Initial infection ==<br />
[[File:Epstein-barr virus (ebv).jpg|thumb|A stained sample of Epstein-Barr virus.]]<br />
Symptoms of EBV infection include: <br />
* [[fatigue]]<br />
* [[fever]]<br />
* [[rash]]<br />
* inflamed [[sore throat|throat]]<br />
* [[swollen lymph nodes]]<br />
* enlarged [[spleen]]<br />
* swollen [[liver]]<ref name="CDC">{{Cite web|url=http://www.cdc.gov/epstein-barr/about-ebv.html|title=Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono |date=2018-05-10|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-14}}</ref><br />
<br />
===Age of infection===<br />
<br />
Most people acquire EBV in early childhood. Typically, young children who acquire EBV are either not symptomatic or have mild symptoms that are hard to distinguish from a cold or other other mild, childhood illnesses. <br />
<br />
In adolescents and young adults, EBV can cause [[infectious mononucleosis]] (IM), also known as glandular fever.<ref name="CDC" /> IM is characterized by [[fever]], [[sore throat]], [[swollen lymph nodes]], [[pain|body aches]], and [[fatigue]]. It generally resolves with rest and only rarely causes serious complications. It typically occurs in people who have not been exposed to EBV in early childhood, and in comparison, is more severe than infection in childhood (i.e., it can last for months). <br />
<br />
Following initial infection, EBV can reactivate and has been shown to have many connections with various chronic illnesses. Relative to initial infections, reactivated EBV is much more severe.<br />
<br />
==Transmission==<br />
<br />
EBV is transmitted through bodily fluids, most commonly through saliva. The first time a person is infected with EBV, the person is contagious for weeks (even when not displaying symptoms). The virus then transitions to the latent or inactive form, and stays in the body. If the virus reactivates, the person will be contagious again.<ref name="CDC" /><br />
<br />
== Diagnosis ==<br />
EBV infection is confirmed with blood tests that detect presence of [[:Category:Antibodies|antibodies]]. Nine out of ten adults have these antibodies, indicating that they have a current or past EBV infection.<ref name="CDC" /><br />
<br />
Anti-VCA (Viral capsid antigen) IgG and EBV nuclear antigen (EBNA) IgG antibodies persist throughout a person's life. Thus, positive results merely indicate a current or past infection. A current EBV infection is diagnosed based on the presence of Anti-VCA IgM and Anti-EA (Early Antigen) IgG. VCA IgM appears early in EBV infection and usually disappears within four to six weeks. Positive VCA IgM suggests current active acute EBV infection. EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. Positive EA IgG can suggest current active EBV infection or EBV re-activation. <ref name="CDC-testing">{{Cite web|url=https://www.cdc.gov/epstein-barr/laboratory-testing.html|title=Epstein-barr {{!}} Mononucleosis {{!}} Laboratory Testing {{!}} Mono|date=2019-01-28|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-10-08}}</ref><br />
<br />
==Latency==<br />
<br />
In healthy adults, the virus remains latent for life in memory [[B cell]]s. It is estimated that 1 in every one hundred thousand to one million circulating B cells carry EBV.<ref name="Hsu2000">{{Cite journal|last=Hsu|first=J. L.|last2=Glaser|first2=S. L.|date=Apr 2000|title=Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications|url=https://www.ncbi.nlm.nih.gov/pubmed/10781747/|journal=Critical Reviews in Oncology/Hematology|volume=34|issue=1|pages=27–53|issn=1040-8428|pmid=10781747}}</ref> In healthy hosts, EBV populations are kept in check by [[CD4+ T cell|CD4<sup>+</sup>]] and [[CD8|CD8<sup>+</sup>]] [[T cell|T-cell]] responses. <br />
<br />
The equilibrium can be disrupted in individuals with compromised [[immune system]]s such as patients with [[AIDS]] or transplant patients taking immune system suppressing drugs.<ref name="Priatel2014">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=4|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206|quote=|via=}}</ref> It has been observed that these patients are more susceptible to EBV-related [[cancer]]s, such as certain [[lymphoma]]s and carcinomas.<ref>{{Cite journal|last=Pattle|first=Samuel B.|last2=Farrell|first2=Paul J.|date=Nov 2006|title=The role of Epstein-Barr virus in cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/17049016|journal=Expert Opinion on Biological Therapy|volume=6|issue=11|pages=1193–1205|doi=10.1517/14712598.6.11.1193|issn=1744-7682|pmid=17049016|quote=|via=}}</ref> In immunocompromised patients, EBV can induce lymphoproliferation, [[lymphoma]], and hemophagocytic lymphohistiocytosis (HLH).<ref>{{Cite journal|title=Human immunity against EBV—lessons from the clinic|date=2017-01-20|url=https://doi.org/10.1084/jem.20161846|journal=Journal of Experimental Medicine|volume=214|issue=2|pages=269–283|last=Tangye|first=Stuart G.|last2=Palendira|first2=Umaimainthan|last3=Edwards|first3=Emily S.J.|doi=10.1084/jem.20161846|issn=0022-1007}}</ref><br />
===Natural killer T cells===<br />
<br />
It is thought that [[natural killer T cell]]s (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of [[CD1d]] expressing cells.<ref name="Priatel2014" /><br />
<br />
==Neuronal infection==<br />
A 2015 study<ref name="JhaHC2015">{{Cite journal | last1 = Jha | first1 = HC | authorlink1 = <br />
| last2 = Mehta | first2 = D | authorlink2 = <br />
| last3 = Lu | first3 = J | authorlink3 = <br />
| last4 = El-Naccache | first4 = D | authorlink4 = <br />
| last5 = Shukla | first5 = SK | authorlink5 =<br />
| last6 = Kovacsics | first6 = C | authorlink6 =<br />
| last7 = Kolson | first7 = D | authorlink7 = <br />
| last8 = Robertson | first8 = ES | authorlink8 =<br />
| title = Gammaherpesvirus Infection of Human Neuronal Cells| journal = mBio | volume = 6 | issue =6 | pages = e01844-15| date = 2016-12-01| doi = 10.1128/mBio.01844-15 | pmid = 26628726| url =http://mbio.asm.org/content/6/6/e01844-15<br />
}}</ref> demonstrated that human [[neuron]]al cells could be directly and actively infected with EBV and another [[herpesvirus]], Kaposi's sarcoma-associated herpesvirus (KSHV).<br />
<br />
Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]].<br />
<br />
EBV is known to be linked to many neuronal diseases<ref name="Kleines2011">{{citation<br />
| last1 = Kleines | first1 = M<br />
| last2 = Schiefer | first2 = J<br />
| last3 = Stienen | first3 = A<br />
| last4 = Blaum | first4 = M<br />
| last5 = Ritter | first5 = K<br />
| last6 = Häusler | first6 = M<br />
| title = Expanding the spectrum of neurological disease associated with Epstein-Barr virus activity<br />
| journal = European Journal of Clinical Microbiology & Infectious Diseases<br />
| issn = 1435-4373| volume = 30| issue = 12| pages = 1561–1569<br />
| date = 2011-05-15| doi = 10.1007/s10096-011-1261-7| url = http://link.springer.com/article/10.1007/s10096-011-1261-7}}</ref> but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.<br />
<br />
==In human disease==<br />
<br />
Epstein-Barr virus has been associated with a wide number of immune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[systemic lupus erythematosus]],<ref name="Lossius2012">{{Cite journal|title=Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation|date=December 2012|url=https://www.mdpi.com/1999-4915/4/12/3701|journal=Viruses|volume=4|issue=12|pages=3701–3730|last=Lossius|first=Andreas|author-link=|last2=Johansen|first2=Jorunn N.|author-link2=|last3=Torkildsen|first3=Øivind|author-link3=|last4=Vartdal|first4=Frode|author-link4=|last5=Holmøy|first5=Trygve|author-link5=|language=en|doi=10.3390/v4123701|pmc=PMC3528287|pmid=|issn=1999-4915|via=|quote=}}</ref> [[Chronic fatigue syndrome]], and [[myasthenia gravis]]. EBV was recently discovered to turn on "risk genes" for autoimmune disease in the cells it infects. [[Epstein-Barr virus nuclear antigen 2|EBNA2]], a protein produced by EBV-infected cells, and its related transcription factors activate half the human genes known to be associated with the risk for lupus as well as genes associated with several other autoimmune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[inflammatory bowel disease]], [[Diabetes#Types|type 1 diabetes]], [[juvenile idiopathic arthritis]] and [[celiac disease]]. EBV activation can thus increase the risk of developing these diseases.<ref name="Harley2018" /><ref name="NIHNews2018" /> <br />
<br />
===Chronic fatigue syndrome===<br />
<br />
A prospective study of 250 primary care patients revealed a higher prevalence of [[chronic fatigue syndrome]] after infectious [[mononucleosis]] (glandular fever) when compared to an ordinary upper respiratory tract infection.<ref name="White1998">{{Cite journal|last=White|first=P. D.|last2=Thomas|first2=J. M.|last3=Amess|first3=J.|last4=Crawford|first4=D. H.|last5=Grover|first5=S. A.|last6=Kangro|first6=H. O.|last7=Clare|first7=A. W.|date=Dec 1998|title=Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever|url=https://www.ncbi.nlm.nih.gov/pubmed/9926075|journal=The British Journal of Psychiatry: The Journal of Mental Science|volume=173|pages=475–481|issn=0007-1250|pmid=9926075|issue=|doi=|pmc=|quote=|author-link=Peter White|via=}}</ref> Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.<ref name="Schmaling1996">{{Cite journal|last=Schmaling|first=K. B.|last2=Jones|first2=J. F.|date=Jan 1996|title=MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1|pages=67–74|issn=0022-3999|pmid=8730646}}</ref> A 2006 Australian prospective study found that 12% of subjects infected by EBV met the criteria for [[chronic fatigue syndrome]] six months after their infection, and 9% still had CFS 12 months after infection.<ref name="Hickie2006">{{Cite journal|last=Hickie|first=Ian|author-link=Ian Hickie|last2=Davenport|first2=Tracey|author-link2=Tracey Davenport|last3=Wakefield|first3=Denis|author-link3=Denis Wakefield|last4=Vollmer-Conna|first4=Ute|author-link4=Uté Vollmer-Conna|last5=Cameron|first5=Barbara|author-link5=|last6=Vernon|first6=Suzanne D|author-link6=Suzanne Vernon|last7=Reeves|first7=William C|author-link7=William Reeves|last8=Lloyd|first8=Andrew|author-link8=Andrew Lloyd|date=2006-09-16|title=Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/|journal=BMJ : British Medical Journal|volume=333|issue=7568|pages=575|doi=10.1136/bmj.38933.585764.AE|issn=0959-8138|pmc=1569956|pmid=16950834|access-date=|quote=|via=}}</ref> (The same rate held true for [[Ross River virus]] and [[Q fever]]). In another study sample, 110 of 178 patients with increased antibodies against EBV had a diagnosis of CFS.<ref name="Mikirova2014" /><br />
<br />
=== Long COVID ===<br />
Long COVID may be associated [[herpesvirus]] reactivation such as EBV.<ref>{{Cite journal|last=Proal|first=Amy D.|author-link=Amy Proal|last2=VanElzakker|first2=Michael B.|author-link2=Michael VanElzakker|date=2021|title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms|url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=12|issue=|pages=698169|doi=10.3389/fmicb.2021.698169|issn=1664-302X}}</ref><ref name=":0">{{Cite journal|title=Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation|date=June 2021|url=https://www.mdpi.com/2076-0817/10/6/763/htm|journal=Pathogens|volume=10|issue=6|pages=763|last=Gold|first=Jeffrey E.|author-link=|last2=Okyay|first2=Ramazan A.|author-link2=|last3=Licht|first3=Warren E.|author-link3=|last4=Hurley|first4=David J.|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|language=en|doi=10.3390/pathogens10060763|pmc=|pmid=|access-date=|issn=2076-0817|quote=|via=}}</ref><br />
<br />
===Multiple sclerosis===<br />
<br />
Infection later in life, high serum titers against EBV, and [[mononucleosis]] have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.<ref name="Holmoy2008">{{Cite journal|title=Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis|date=2008-01-01|url=https://www.sciencedirect.com/science/article/pii/S0306987707003167|journal=Medical Hypotheses|volume=70|issue=1|pages=66–69|last=Holmøy|first=Trygve|language=en|doi=10.1016/j.mehy.2007.04.030|issn=0306-9877}}</ref><br />
<br />
Several studies by Alberto Ascherio, MD, DrPH, and his team at the Harvard School of Public Health have suggested that EBV is involved in [[multiple sclerosis]], specifically in people with a certain immune-related gene and high levels of antibodies to EBV in their blood.<ref>{{Cite web|url=https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses|title=Viruses|last=|first=|date=|website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref><br />
<br />
=== Systemic lupus erythematosus ===<br />
In a study of young patients with lupus, 99% had EBV as compared to 70% of healthy controls.<ref name="James1997">{{Cite journal|title=An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus.|date=1997-12-15|url=https://www.jci.org/articles/view/119856|journal=The Journal of Clinical Investigation|volume=100|issue=12|pages=3019–3026|last=James|first=J. A.|last2=Kaufman|first2=K. M.|last3=Farris|first3=A. D.|last4=Taylor-Albert|first4=E.|last5=Lehman|first5=T. J.|last6=Harley|first6=J. B.|language=en|doi=10.1172/JCI119856|pmid=9399948|issn=0021-9738}}</ref> Another study found that patients with systemic lupus erythematosus had a roughly 40-fold increase in EBV viral loads compared with controls, likely stemming from altered [[t cell]] responses against EBV.<ref>{{Cite journal|title=Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus|date=2004-01-15|url=https://www.jimmunol.org/content/172/2/1287|journal=The Journal of Immunology|volume=172|issue=2|pages=1287–1294|last=Kang|first=Insoo|last2=Quan|first2=Timothy|last3=Nolasco|first3=Helena|last4=Park|first4=Sung-Hwan|last5=Hong|first5=Myung Sun|last6=Crouch|first6=Jill|last7=Pamer|first7=Eric G.|last8=Howe|first8=John Greg|last9=Craft|first9=Joe|language=en|doi=10.4049/jimmunol.172.2.1287|pmid=14707107|issn=0022-1767}}</ref><br />
<br />
===Myasthenia gravis===<br />
<br />
[[Myasthenia gravis]] is an [[autoimmune disease]] which has been associated with a large number of different viruses, particularly EBV, [[Human papillomavirus|HPV]], and [[Poliovirus|polioviruses]]. In several studies EBV infection of the thymus has been found in myasthenia gravis patients, but not all studies have found this.<ref name=":1">{{Cite journal|title=A Systematic Review of the Potential Implication of Infectious Agents in Myasthenia Gravis|date=2021|url=https://www.frontiersin.org/article/10.3389/fneur.2021.618021|journal=Frontiers in Neurology|volume=12|last=Leopardi|first=Victoria|last2=Chang|first2=Yu-Mei|last3=Pham|first3=Andrew|last4=Luo|first4=Jie|last5=Garden|first5=Oliver A.|doi=10.3389/fneur.2021.618021/full|issn=1664-2295}}</ref> [[B cell|B cells]] from [[myasthenia gravis]] patients stimulated ''in vitro'' by Epstein-Barr virus produced [[acetylcholine]] autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=https://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> While EBV infection of the [[thymus]] has been posited as a causative agent for the production of [[acetylcholine]] receptor autoantibodies in [[myasthenia gravis]].<ref>{{Cite journal|last=Kaminski|first=Henry J|last2=Minarovits|first2=Janos|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134|date=2010|volume=67|issue=6|pages=697-698|doi=|pmc=|pmid=|quote=|access-date=|via=}}</ref>, there is only limited evidence supporting EBV or other viruses as a cause of myasthenia gravis.<ref name=":1" /><br />
<br />
=== Gastrointestinal disease ===<br />
One study of EBV in patients with [[gastritis]], [[Crohn's disease]], and [[ulcerative colitis]] and normal controls found essentially undetectable levels of EBV in normal gastric mucosa. However, EBV was detected in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples.<ref>{{Cite journal|title=Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa|date=2012-07-01|url=https://doi.org/10.1007/s10620-012-2116-5|journal=Digestive Diseases and Sciences|volume=57|issue=7|pages=1887–1898|last=Ryan|first=Julie L.|last2=Shen|first2=You-Jun|last3=Morgan|first3=Douglas R.|last4=Thorne|first4=Leigh B.|last5=Kenney|first5=Shannon C.|last6=Dominguez|first6=Ricardo L.|last7=Gulley|first7=Margaret L.|language=en|doi=10.1007/s10620-012-2116-5|pmc=PMC3535492|pmid=22410851|issn=1573-2568}}</ref><br />
<br />
===Lyme disease===<br />
Several herpesviruses including Epstein-Barr virus may cause false positives on [[Lyme disease]] tests.<ref name="Goossens1999">{{Cite journal | last1 = Goossens | first1 = HA<br />
| last2 = Nohlmans | first2 = MK <br />
| last3 = van den Bogaard | first3 = AE<br />
| title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis| journal = Infection | date = May-Jun 1999 | volume = 27 | issue = 3| pages =231| doi = 10.1007/BF02561539|pmid = 10378140| url = https://www.ncbi.nlm.nih.gov/pubmed/10378140}}</ref><br />
<br />
===XMEN disease===<br />
<br />
A 2014 study found chronic Epstein-Barr infection was linked to a magnesium transporter [[magnesium transporter 1|MAGT]] mutation.<ref name="MAGT1">{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/84061|title=MAGT1 magnesium transporter 1 [Homo sapiens (human)]|last=|first=|authorlink=|date=|website=NCBI|archive-url=|archive-date=|url-status=|access-date=2022-05-21}}</ref> Dysfunction in this transporter also resulted in decreased NK cell function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Cite journal |last1 = Li |first1 = F.-Y. |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Su<br />
| first3 = H<br />
| last4 = Matthews<br />
| first4 = H |last5 = Lenardo |first5 = M.J. |authorlink3 = <br />
| title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. <br />
| journal = Blood| date = 2014| doi = 10.1182/blood-2013-11-538686|url=https://ashpublications.org/blood/article/123/14/2148/32463/XMEN-disease-a-new-primary-immunodeficiency|volume=123|issue=14|pages=2148–2152|pmc=|pmid=|quote=|via=}}</ref><br />
<br />
This disorder, termed "XMEN" (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. <br />
<br />
Since chronic EBV infection has been associated with chronic fatigue syndrome, this error in [[magnesium]] transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /><ref name="X-men_disease_2">{{Cite journal|title=X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect|date=Dec 2014|url=https://journals.lww.com/co-pediatrics/Abstract/2014/12000/X_linked_immunodeficiency_with_magnesium_defect,.16.aspx|journal=Current Opinion in Pediatrics|volume=26|issue=6|pages=713–719|last=Ravell|first=Juan|author-link=|last2=Chaigne-Delalande|first2=Benjamin|author-link2=|last3=Lenardo|first3=Michael|author-link3=|language=en-US|doi=10.1097/MOP.0000000000000156|pmc=PMC4306042|pmid=25313976|access-date=|issn=1040-8703|quote=|via=}}</ref> However, in this disorder, EBV would be seen as an indicator of the illness rather than the cause.<br />
<br />
==Vitamin D==<br />
<br />
Some recent research is finding links between EBV and [[Vitamin D]].<br />
<br />
An EBV protein, EBNA-3, has an affinity for the vitamin D receptor ([[VDR]]) and may actually block the activation of VDR-dependent genes by [[Vitamin D]].<ref>{{Cite journal|last=Yenamandra|first=Surya Pavan|last2=Hellman|first2=Ulf|last3=Kempkes|first3=Bettina|last4=Darekar|first4=Suhas Deoram|last5=Petermann|first5=Sabine|last6=Sculley|first6=Tom|last7=Klein|first7=George|last8=Kashuba|first8=Elena|date=Dec 2010|title=Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes|url=https://www.ncbi.nlm.nih.gov/pubmed/20593215|journal=Cellular and molecular life sciences: CMLS|volume=67|issue=24|pages=4249–4256|doi=10.1007/s00018-010-0441-4|issn=1420-9071|pmid=20593215}}</ref><br />
<br />
[[Vitamin D receptor]] may be required for the normal development of [[natural killer T cell]]s that react to cells expressing [[CD1d]], as in cells infected by EBV.<ref>{{Cite journal|last=Yu|first=Sanhong|last2=Cantorna|first2=Margherita T.|date=2008-04-01|title=The vitamin D receptor is required for iNKT cell development|url=http://www.pnas.org/content/105/13/5207|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=13|pages=5207–5212|doi=10.1073/pnas.0711558105|issn=0027-8424|pmid=18364394}}</ref> VDR is expressed on B cells infected with EBV, and bioactive Vitamin D<sub>3</sub> alters T cells to be less detrimental to the immune response.<ref name="Holmoy2008" /><br />
<br />
As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV, and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels<ref>{{Cite journal|last=Ramien|first=Caren|last2=Pachnio|first2=Annette|last3=Sisay|first3=Sofia|last4=Begum|first4=Jusnara|last5=Leese|first5=Alison|last6=Disanto|first6=Giulio|last7=Kuhle|first7=Jens|last8=Giovannoni|first8=Gavin|last9=Rickinson|first9=Alan|date=May 2014|title=Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort|url=https://www.ncbi.nlm.nih.gov/pubmed/24192216?dopt=Abstract|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=20|issue=6|pages=751–753|doi=10.1177/1352458513509507|issn=1477-0970|pmid=24192216}}</ref> (i.e., above 100 nmol/l).<br />
<br />
==Treatment==<br />
<br />
There is no specific treatment for EBV, only treatment of symptoms, such as taking over-the-counter medications for pain and fever.<ref name="CDC" /> EBV is thought to persistent harmlessly in immunocompetent individuals, but in those with compromised immune systems it has been associated with certain cancers and possibly autoimmune disease. <br />
<br />
===Antivirals===<br />
<br />
Several [[antiviral]]s are active against EBV including [[valganciclovir]], [[valacyclovir]]<ref name="Hoshino2009">{{Cite journal|title=Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers|date=Nov 2009|url=https://pubmed.ncbi.nlm.nih.gov/19740997/|journal=Journal of Virology|volume=83|issue=22|pages=11857–11861|last=Hoshino|first=Yo|author-link=|last2=Katano|first2=Harutaka|author-link2=|last3=Zou|first3=Ping|author-link3=|last4=Hohman|first4=Patricia|author-link4=|last5=Marques|first5=Adriana|author-link5=|last6=Tyring|first6=Stephen K.|author-link6=|last7=Follmann|first7=Dean|last8=Cohen|first8=Jeffrey I.|doi=10.1128/JVI.01005-09|pmc=2772668|pmid=19740997|access-date=|issn=1098-5514|quote=|via=}}</ref>, [[acyclovir]]<ref name="Rafaillidis2013">{{Cite journal|title=Antiviral treatment for severe EBV infections in apparently immunocompetent patients|date=Nov 2010|url=https://pubmed.ncbi.nlm.nih.gov/20739216/|journal=Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology|volume=49|issue=3|pages=151–157|last=Rafailidis|first=Petros I.|author-link=|last2=Mavros|first2=Michael N.|author-link2=|last3=Kapaskelis|first3=Anastasios|author-link3=|last4=Falagas|first4=Matthew E.|author-link4=|doi=10.1016/j.jcv.2010.07.008|pmc=|pmid=20739216|access-date=|issn=1873-5967|quote=|via=}}</ref>, and [[spironolactone]].<ref name="Verma2016">{{Cite journal | last1 = Verma | first1 = Dinesh<br />
| last2 = Thompson | first2 = Jacob<br />
| last3 = Swaminathan | first3 = Sankar| title = Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function<br />
| journal = Proceedings of the National Academy of Sciences | issn = 1091-6490 | volume = 113| issue = 13| pages = 3609–3614<br />
| date = 2016-03-29<br />
| doi = 10.1073/pnas.1523686113 | pmid = 26976570| url = http://www.pnas.org/content/113/13/3609}}</ref><br />
<br />
[[Acyclovir]], an [[antiviral]] drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.<br />
<br />
A theoretical [[immunotherapy]] treatment proposes that inducing [[CD1d]] expression on EBV-infected B cells could prompt effective immune suppression of EBV by natural killer T cells.<ref name="Priatel2014">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206}}</ref><br />
<br />
===Rituximab===<br />
<br />
[[Rituximab]] may be effective in completely eliminating EBV infection from the peripheral blood.<ref>{{Cite journal|last=Diamantopoulos|first=Panagiotis T.|last2=Polonyfi|first2=Katerina|last3=Sofotasiou|first3=Maria|last4=Papadopoulou|first4=Vasiliki|last5=Kalala|first5=Fani|last6=Iliakis|first6=Theodoros|last7=Zervakis|first7=Kostantinos|last8=Tsilimidos|first8=Gerassimos|last9=Kouzis|first9=Panagiotis|date=Dec 2013|title=Rituximab in the treatment of EBV-positive low grade B-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/24324119|journal=Anticancer Research|volume=33|issue=12|pages=5693–5698|issn=1791-7530|pmid=24324119}}</ref> A study of seventeen patients with low-grade [[B cell]] lymphoma found that after three cycles of rituximab, the virus had been completely eliminated from the peripheral blood in all but one patient.<br />
<br />
===Herbs and nutraceuticals===<br />
<br />
Herbs shown to have antiviral properties against EBV including [[licorice|licorice.]]<ref>{{Cite journal|last=Lin|first=Jung-Chung|last2=Cherng|first2=Jaw-Ming|last3=Hung|first3=Man-Shan|last4=Baltina|first4=Lidia A.|last5=Baltina|first5=Lia|last6=Kondratenko|first6=Rimma|date=Jul 2008|title=Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: structure-activity relationships|url=https://www.ncbi.nlm.nih.gov/pubmed/18423902|journal=Antiviral Research|volume=79|issue=1|pages=6–11|doi=10.1016/j.antiviral.2008.01.160|issn=0166-3542|pmid=18423902}}</ref> [[Vitamin C]] and Vitamin D<ref name="Rolf2017">{{Cite journal|title=Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis|date=Sep 2018|url=https://pubmed.ncbi.nlm.nih.gov/28731372/|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=24|issue=10|pages=1280–1287|last=Rolf|first=Linda|author-link=|last2=Muris|first2=Anne-Hilde|author-link2=|last3=Mathias|first3=Amandine|author-link3=|last4=Du Pasquier|first4=Renaud|author-link4=|last5=Koneczny|first5=Inga|author-link5=|last6=Disanto|first6=Giulio|author-link6=|last7=Kuhle|first7=Jens|last8=Ramagopalan|first8=Sreeram|last9=Damoiseaux|first9=Jan|last10=Smolders|first10=Joost|last11=Hupperts|first11=Raymond|doi=10.1177/1352458517722646|pmc=6108041|pmid=28731372|access-date=|issn=1477-0970|quote=|via=}}</ref> might also decrease duration and severity of the symptoms of EBV infection.<ref name="Mikirova2014">{{Cite journal|title=Effect of high dose vitamin C on Epstein-Barr viral infection|date=2014-05-03|url=https://pubmed.ncbi.nlm.nih.gov/24793092/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=20|pages=725–732|last=Mikirova|first=Nina|last2=Hunninghake|first2=Ronald|doi=10.12659/MSM.890423|pmc=4015650|pmid=24793092|issn=1643-3750}}</ref><br />
<br />
===Vaccine===<br />
A [[vaccine]] for the prevention of Epstein-Barr virus is being explored.<ref name="Vaccine2019">{{Cite web|url=https://www.nih.gov/news-events/news-releases/nih-researchers-make-progress-toward-epstein-barr-virus-vaccine|title=NIH researchers make progress toward Epstein-Barr virus vaccine|date=2019-04-09|website=National Institutes of Health (NIH)|language=en|access-date=2019-04-10}}</ref><br />
<br />
==Notable studies==<br />
*1996, MMPI profiles of patients with chronic fatigue syndrome<ref name="Schmaling1996" /> - ([[pubmed:8730646|Abstract]])<br />
*1998, Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever<ref name="White1998" /> - ([[pubmed:9926075|Abstract]])<br />
*2006, Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study<ref name="Hickie2006" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full text)]<br />
*2019, EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection<ref name="Asprusten2019">{{Cite journal|last=Asprusten|first=Tarjei Tørre|author-link=|last2=Pedersen|first2=Maria|author-link2=Maria Pedersen|last3=Skovlund|first3=Eva|author-link3=Eva Skovlund|last4=Wyller|first4=Vegard Bruun|author-link4=Vegard Bruun Wyller|date=2019|title=EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection|url=https://www.ncbi.nlm.nih.gov/pubmed/30957026|journal=BMJ paediatrics open|volume=3|issue=1|pages=e000390|doi=10.1136/bmjpo-2018-000390|issn=2399-9772|pmc=|pmid=30957026|quote=|via=}}</ref> - ([[pubmed:30957026|Abstract]])<br />
*2019, Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study<ref name="Pedersen2019a">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=|last3=Godang|first3=Kristin|author-link3=Kristin Godang|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|author-link7=|last8=Øie|first8=Merete Glenne|author-link8=|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=Jan 2019|title=Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pubmed/30261303|journal=Brain, Behavior, and Immunity|volume=75|issue=|pages=94–100|doi=10.1016/j.bbi.2018.09.023|issn=1090-2139|pmid=30261303|quote=}}</ref> - ([[pubmed:30261303|Abstract]])<br />
*2019, Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later<ref name="Pedersen2019b">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=Tarjei Tørre Asprusten|last3=Godang|first3=Kristin|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|last8=Øie|first8=Merete Glenne|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=2019-01-27|title=Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later|url=https://www.ncbi.nlm.nih.gov/pubmed/30685875|journal=Acta Paediatrica (Oslo, Norway: 1992)|volume=108|issue=8|pages=1521-1526|doi=10.1111/apa.14728|issn=1651-2227|pmid=30685875|quote=|via=}}</ref> - ([[pubmed:30685875|Abstract]])<br />
*2019, Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Williams|first=Marshall V.|author-link=|last2=Cox|first2=Brandon|author-link2=|last3=Lafuse|first3=William P.|author-link3=|last4=Ariza|first4=Maria Eugenia|author-link4=|author-link5=|date=May 2019|title=Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0149291819301730|journal=Clinical Therapeutics|language=en|volume=41|issue=5|pages=848–863|doi=10.1016/j.clinthera.2019.04.009|pmc=6525645|pmid=31040055|quote=|via=}}</ref> - ([https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext Full text)]<br />
*2019, Review article - Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis<ref name="Kerr2019EBV">{{Cite journal|last=Kerr|first=Jonathan R.|author-link=Jonathan Kerr|date=Feb 2019|title=Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00059/abstract|journal=Frontiers in Pediatrics|volume=72|issue=10|pages=651-8|doi=10.3389/fped.2019.00059|quote=|via=|last2=|first2=|pmc=|pmid=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full (Full text)]<br />
*2019, Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors<ref name="Kerr2019a">{{Cite journal|last=Kerr|first=Jonathan R|author-link=Jonathan Kerr|author-link2=|date=2019-07-17|title=Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors|url=http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205822|journal=Journal of Clinical Pathology|language=en|volume=|issue=|pages=jclinpath–2019–205822|doi=10.1136/jclinpath-2019-205822|issn=0021-9746|quote=|via=}}</ref> - [[pubmed:31315893|(Abstract)]]<br />
*2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal|last=Shikova|first=Evelina|author-link=|last2=Reshkova|first2=Valentina|author-link2=|last3=Kumanova|first3=Аntoniya|author-link3=|last4=Raleva|first4=Sevdalina|author-link4=|last5=Alexandrova|first5=Dora|author-link5=|last6=Capo|first6=Natasa|author-link6=|last7=Murovska|first7=Modra|date=2020|title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=|pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)]<br />
*2021, Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome<ref>{{Cite journal|title=Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|date=Nov 15, 2021|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/|journal=Frontiers in Immunology|volume=12|issue=|pages=656797|last=Ruiz-Pablos|first=Manuel|author-link=|last2=Paiva|first2=Bruno|author-link2=|last3=Monter-Mateo|first3=Rosario|author-link3=|last4=Garcia|first4=Nicolas|author-link4=|last5=Zabaleta|first5=Aintzane|author-link5=|doi=10.3389/fimmu.2021.656797|pmc=|pmid=34867935|access-date=June 10, 2022|quote=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/ Full text])<br />
*2021, Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue<ref>{{Cite journal|title=Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue|date=2021|url=https://pubmed.ncbi.nlm.nih.gov/34987499|journal=Frontiers in Immunology|volume=12|pages=715102|last=Fevang|first=Børre|last2=Wyller|first2=Vegard Bruun Bratholm|last3=Mollnes|first3=Tom Eirik|last4=Pedersen|first4=Maria|last5=Asprusten|first5=Tarjei Tørre|last6=Michelsen|first6=Annika|last7=Ueland|first7=Thor|last8=Otterdal|first8=Kari|doi=10.3389/fimmu.2021.715102|pmc=8721200|pmid=34987499|issn=1664-3224}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721200/ Full text])<br />
*2021, Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation<ref name=":0" /> [https://www.mdpi.com/2076-0817/10/6/763/htm (Full text)]<br />
*2022, EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing T<sub>FH</sub> cell differentiation and extrafollicular activities<ref>{{Cite journal|title=EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities|date=2022-06-08|url=https://insight.jci.org/articles/view/158193|journal=JCI Insight|volume=7|issue=11|last=Cox|first=Brandon S.|last2=Alharshawi|first2=Khaled|last3=Mena-Palomo|first3=Irene|last4=Lafuse|first4=William P.|last5=Ariza|first5=Maria Eugenia|language=en|doi=10.1172/jci.insight.158193|issn=0021-9738}}</ref> - ([https://insight.jci.org/articles/view/158193 Full text])<br />
<br />
== See also ==<br />
* [[List of herpesvirus infection studies]]<br />
<br />
==Learn more ==<br />
*[https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011487.pub2/full Antiviral agents for infectious mononucleosis (glandular fever) (2016)] - [[Cochrane]] review <br />
* [https://www.nationalmssociety.org/About-the-Society/News/Study-Provides-Strongest-Evidence-Yet-for-the-Role Study Provides Strongest Evidence Yet for the Role of Epstein-Barr Virus in Triggering Multiple Sclerosis (2022)] - Multiple Sclerosis Society<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Infectious agents]]<br />
[[Category:Triggers and risk factors]]<br />
[[Category:Virology]]<br />
[[Category:Viruses]]</div>Darlahttps://me-pedia.org/w/index.php?title=Epstein-Barr_virus&diff=112140Epstein-Barr virus2022-06-29T10:57:25Z<p>Darla:/* Chronic fatigue syndrome */</p>
<hr />
<div>{{Cleanup|reason=Add summary of the Notable studies from 2019 onwards|date=28 July 2020}}<br />
<br />
The '''Epstein-Barr virus''' or '''EBV''' or Human '''Herpesvirus 4''' or '''HHV-4''' is a [[herpesvirus]].<ref name="CDC" /> It is the most common cause of infectious [[mononucleosis]] or "glandular fever," and infects 90% of adults worldwide.<ref name="Saha2016">{{Cite journal | last1 = Saha | first1 = Abhik<br />
| last2 = Robertson | first2 = Erle S<br />
| title = Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes<br />
| journal = Clinical Cancer Research<br />
| issn = 1557-3265| volume = 17| issue = 10| pages = 3056–3063<br />
| date = 2011-05-15<br />
| pmid = 21372216 | doi = 10.1158/1078-0432.CCR-10-2578| url = http://clincancerres.aacrjournals.org/content/17/10/3056}}</ref> It has been implicated in numerous immune diseases and chronic illnesses, including [[chronic fatigue syndrome]], [[multiple sclerosis]], [[myasthenia gravis]], and [[systemic lupus erythematosus]]. It is known to turn on "risk genes" for autoimmune disease in the cells it infects.<ref name="Harley2018">{{Cite journal|title=Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity|date=2018|url=https://www.nature.com/articles/s41588-018-0102-3|journal=Nature Genetics|volume=50|issue=5|pages=699–707|last=Harley|first=John B.|author-link=|last2=Chen|first2=Xiaoting|author-link2=|last3=Pujato|first3=Mario|author-link3=|last4=Miller|first4=Daniel|author-link4=|last5=Maddox|first5=Avery|author-link5=|last6=Forney|first6=Carmy|author-link6=|last7=Magnusen|first7=Albert F.|last8=Lynch|first8=Arthur|last9=Chetal|first9=Kashish|last10=Yukawa|first10=Masashi|last11=Barski|first11=Artem|language=en|doi=10.1038/s41588-018-0102-3|pmc=|pmid=|access-date=|issn=1546-1718|quote=|via=}}</ref><ref name="NIHNews2018">{{Cite web|url=https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases|title=Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases|last=|first=|date=16 April 2018|website=National Institutes of Health|archive-url=|archive-date=|url-status=|access-date=}}</ref><br />
<br />
== Initial infection ==<br />
[[File:Epstein-barr virus (ebv).jpg|thumb|A stained sample of Epstein-Barr virus.]]<br />
Symptoms of EBV infection include: <br />
* [[fatigue]]<br />
* [[fever]]<br />
* [[rash]]<br />
* inflamed [[sore throat|throat]]<br />
* [[swollen lymph nodes]]<br />
* enlarged [[spleen]]<br />
* swollen [[liver]]<ref name="CDC">{{Cite web|url=http://www.cdc.gov/epstein-barr/about-ebv.html|title=Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono |date=2018-05-10|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-14}}</ref><br />
<br />
===Age of infection===<br />
<br />
Most people acquire EBV in early childhood. Typically, young children who acquire EBV are either not symptomatic or have mild symptoms that are hard to distinguish from a cold or other other mild, childhood illnesses. <br />
<br />
In adolescents and young adults, EBV can cause [[infectious mononucleosis]] (IM), also known as glandular fever.<ref name="CDC" /> IM is characterized by [[fever]], [[sore throat]], [[swollen lymph nodes]], [[pain|body aches]], and [[fatigue]]. It generally resolves with rest and only rarely causes serious complications. It typically occurs in people who have not been exposed to EBV in early childhood, and in comparison, is more severe than infection in childhood (i.e., it can last for months). <br />
<br />
Following initial infection, EBV can reactivate and has been shown to have many connections with various chronic illnesses. Relative to initial infections, reactivated EBV is much more severe.<br />
<br />
==Transmission==<br />
<br />
EBV is transmitted through bodily fluids, most commonly through saliva. The first time a person is infected with EBV, the person is contagious for weeks (even when not displaying symptoms). The virus then transitions to the latent or inactive form, and stays in the body. If the virus reactivates, the person will be contagious again.<ref name="CDC" /><br />
<br />
== Diagnosis ==<br />
EBV infection is confirmed with blood tests that detect presence of [[:Category:Antibodies|antibodies]]. Nine out of ten adults have these antibodies, indicating that they have a current or past EBV infection.<ref name="CDC" /><br />
<br />
Anti-VCA (Viral capsid antigen) IgG and EBV nuclear antigen (EBNA) IgG antibodies persist throughout a person's life. Thus, positive results merely indicate a current or past infection. A current EBV infection is diagnosed based on the presence of Anti-VCA IgM and Anti-EA (Early Antigen) IgG. VCA IgM appears early in EBV infection and usually disappears within four to six weeks. Positive VCA IgM suggests current active acute EBV infection. EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. Positive EA IgG can suggest current active EBV infection or EBV re-activation. <ref name="CDC-testing">{{Cite web|url=https://www.cdc.gov/epstein-barr/laboratory-testing.html|title=Epstein-barr {{!}} Mononucleosis {{!}} Laboratory Testing {{!}} Mono|date=2019-01-28|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-10-08}}</ref><br />
<br />
==Latency==<br />
<br />
In healthy adults, the virus remains latent for life in memory [[B cell]]s. It is estimated that 1 in every one hundred thousand to one million circulating B cells carry EBV.<ref name="Hsu2000">{{Cite journal|last=Hsu|first=J. L.|last2=Glaser|first2=S. L.|date=Apr 2000|title=Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications|url=https://www.ncbi.nlm.nih.gov/pubmed/10781747/|journal=Critical Reviews in Oncology/Hematology|volume=34|issue=1|pages=27–53|issn=1040-8428|pmid=10781747}}</ref> In healthy hosts, EBV populations are kept in check by [[CD4+ T cell|CD4<sup>+</sup>]] and [[CD8|CD8<sup>+</sup>]] [[T cell|T-cell]] responses. <br />
<br />
The equilibrium can be disrupted in individuals with compromised [[immune system]]s such as patients with [[AIDS]] or transplant patients taking immune system suppressing drugs.<ref name="Priatel2014">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=4|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206|quote=|via=}}</ref> It has been observed that these patients are more susceptible to EBV-related [[cancer]]s, such as certain [[lymphoma]]s and carcinomas.<ref>{{Cite journal|last=Pattle|first=Samuel B.|last2=Farrell|first2=Paul J.|date=Nov 2006|title=The role of Epstein-Barr virus in cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/17049016|journal=Expert Opinion on Biological Therapy|volume=6|issue=11|pages=1193–1205|doi=10.1517/14712598.6.11.1193|issn=1744-7682|pmid=17049016|quote=|via=}}</ref> In immunocompromised patients, EBV can induce lymphoproliferation, [[lymphoma]], and hemophagocytic lymphohistiocytosis (HLH).<ref>{{Cite journal|title=Human immunity against EBV—lessons from the clinic|date=2017-01-20|url=https://doi.org/10.1084/jem.20161846|journal=Journal of Experimental Medicine|volume=214|issue=2|pages=269–283|last=Tangye|first=Stuart G.|last2=Palendira|first2=Umaimainthan|last3=Edwards|first3=Emily S.J.|doi=10.1084/jem.20161846|issn=0022-1007}}</ref><br />
===Natural killer T cells===<br />
<br />
It is thought that [[natural killer T cell]]s (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of [[CD1d]] expressing cells.<ref name="Priatel2014" /><br />
<br />
==Neuronal infection==<br />
A 2015 study<ref name="JhaHC2015">{{Cite journal | last1 = Jha | first1 = HC | authorlink1 = <br />
| last2 = Mehta | first2 = D | authorlink2 = <br />
| last3 = Lu | first3 = J | authorlink3 = <br />
| last4 = El-Naccache | first4 = D | authorlink4 = <br />
| last5 = Shukla | first5 = SK | authorlink5 =<br />
| last6 = Kovacsics | first6 = C | authorlink6 =<br />
| last7 = Kolson | first7 = D | authorlink7 = <br />
| last8 = Robertson | first8 = ES | authorlink8 =<br />
| title = Gammaherpesvirus Infection of Human Neuronal Cells| journal = mBio | volume = 6 | issue =6 | pages = e01844-15| date = 2016-12-01| doi = 10.1128/mBio.01844-15 | pmid = 26628726| url =http://mbio.asm.org/content/6/6/e01844-15<br />
}}</ref> demonstrated that human [[neuron]]al cells could be directly and actively infected with EBV and another [[herpesvirus]], Kaposi's sarcoma-associated herpesvirus (KSHV).<br />
<br />
Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]].<br />
<br />
EBV is known to be linked to many neuronal diseases<ref name="Kleines2011">{{citation<br />
| last1 = Kleines | first1 = M<br />
| last2 = Schiefer | first2 = J<br />
| last3 = Stienen | first3 = A<br />
| last4 = Blaum | first4 = M<br />
| last5 = Ritter | first5 = K<br />
| last6 = Häusler | first6 = M<br />
| title = Expanding the spectrum of neurological disease associated with Epstein-Barr virus activity<br />
| journal = European Journal of Clinical Microbiology & Infectious Diseases<br />
| issn = 1435-4373| volume = 30| issue = 12| pages = 1561–1569<br />
| date = 2011-05-15| doi = 10.1007/s10096-011-1261-7| url = http://link.springer.com/article/10.1007/s10096-011-1261-7}}</ref> but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.<br />
<br />
==In human disease==<br />
<br />
Epstein-Barr virus has been associated with a wide number of immune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[systemic lupus erythematosus]],<ref name="Lossius2012">{{Cite journal|title=Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation|date=December 2012|url=https://www.mdpi.com/1999-4915/4/12/3701|journal=Viruses|volume=4|issue=12|pages=3701–3730|last=Lossius|first=Andreas|author-link=|last2=Johansen|first2=Jorunn N.|author-link2=|last3=Torkildsen|first3=Øivind|author-link3=|last4=Vartdal|first4=Frode|author-link4=|last5=Holmøy|first5=Trygve|author-link5=|language=en|doi=10.3390/v4123701|pmc=PMC3528287|pmid=|issn=1999-4915|via=|quote=}}</ref> [[Chronic fatigue syndrome]], and [[myasthenia gravis]]. EBV was recently discovered to turn on "risk genes" for autoimmune disease in the cells it infects. [[Epstein-Barr virus nuclear antigen 2|EBNA2]], a protein produced by EBV-infected cells, and its related transcription factors activate half the human genes known to be associated with the risk for lupus as well as genes associated with several other autoimmune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[inflammatory bowel disease]], [[Diabetes#Types|type 1 diabetes]], [[juvenile idiopathic arthritis]] and [[celiac disease]]. EBV activation can thus increase the risk of developing these diseases.<ref name="Harley2018" /><ref name="NIHNews2018" /> <br />
<br />
===Chronic fatigue syndrome===<br />
<br />
A prospective study of 250 primary care patients revealed a higher prevalence of [[chronic fatigue syndrome]] after infectious [[mononucleosis]] (glandular fever) when compared to an ordinary upper respiratory tract infection.<ref name="White1998">{{Cite journal|last=White|first=P. D.|last2=Thomas|first2=J. M.|last3=Amess|first3=J.|last4=Crawford|first4=D. H.|last5=Grover|first5=S. A.|last6=Kangro|first6=H. O.|last7=Clare|first7=A. W.|date=Dec 1998|title=Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever|url=https://www.ncbi.nlm.nih.gov/pubmed/9926075|journal=The British Journal of Psychiatry: The Journal of Mental Science|volume=173|pages=475–481|issn=0007-1250|pmid=9926075|issue=|doi=|pmc=|quote=|author-link=Peter White|via=}}</ref> Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.<ref name="Schmaling1996">{{Cite journal|last=Schmaling|first=K. B.|last2=Jones|first2=J. F.|date=Jan 1996|title=MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1|pages=67–74|issn=0022-3999|pmid=8730646}}</ref> A 2006 Australian prospective study found that 12% of subjects infected by EBV met the criteria for [[chronic fatigue syndrome]] six months after their infection, and 9% still had CFS 12 months after infection.<ref name="Hickie2006">{{Cite journal|last=Hickie|first=Ian|author-link=Ian Hickie|last2=Davenport|first2=Tracey|author-link2=Tracey Davenport|last3=Wakefield|first3=Denis|author-link3=Denis Wakefield|last4=Vollmer-Conna|first4=Ute|author-link4=Uté Vollmer-Conna|last5=Cameron|first5=Barbara|author-link5=|last6=Vernon|first6=Suzanne D|author-link6=Suzanne Vernon|last7=Reeves|first7=William C|author-link7=William Reeves|last8=Lloyd|first8=Andrew|author-link8=Andrew Lloyd|date=2006-09-16|title=Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/|journal=BMJ : British Medical Journal|volume=333|issue=7568|pages=575|doi=10.1136/bmj.38933.585764.AE|issn=0959-8138|pmc=1569956|pmid=16950834|access-date=|quote=|via=}}</ref> (The same rate held true for [[Ross River virus]] and [[Q fever]]). In another study sample, 110 of 178 patients with increased antibodies against EBV had a diagnosis of CFS.<ref name="Mikirova2014" /><br />
<br />
=== Long COVID ===<br />
Long COVID may be associated [[herpesvirus]] reactivation such as EBV.<ref>{{Cite journal|last=Proal|first=Amy D.|author-link=Amy Proal|last2=VanElzakker|first2=Michael B.|author-link2=Michael VanElzakker|date=2021|title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms|url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=12|issue=|pages=698169|doi=10.3389/fmicb.2021.698169|issn=1664-302X}}</ref><ref name=":0">{{Cite journal|title=Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation|date=June 2021|url=https://www.mdpi.com/2076-0817/10/6/763/htm|journal=Pathogens|volume=10|issue=6|pages=763|last=Gold|first=Jeffrey E.|author-link=|last2=Okyay|first2=Ramazan A.|author-link2=|last3=Licht|first3=Warren E.|author-link3=|last4=Hurley|first4=David J.|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|language=en|doi=10.3390/pathogens10060763|pmc=|pmid=|access-date=|issn=2076-0817|quote=|via=}}</ref><br />
<br />
===Multiple sclerosis===<br />
<br />
Infection later in life, high serum titers against EBV, and [[mononucleosis]] have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.<ref name="Holmoy2008">{{Cite journal|title=Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis|date=2008-01-01|url=https://www.sciencedirect.com/science/article/pii/S0306987707003167|journal=Medical Hypotheses|volume=70|issue=1|pages=66–69|last=Holmøy|first=Trygve|language=en|doi=10.1016/j.mehy.2007.04.030|issn=0306-9877}}</ref><br />
<br />
Several studies by Alberto Ascherio, MD, DrPH, and his team at the Harvard School of Public Health have suggested that EBV is involved in [[multiple sclerosis]], specifically in people with a certain immune-related gene and high levels of antibodies to EBV in their blood.<ref>{{Cite web|url=https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses|title=Viruses|last=|first=|date=|website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref><br />
<br />
=== Systemic lupus erythematosus ===<br />
In a study of young patients with lupus, 99% had EBV as compared to 70% of healthy controls.<ref name="James1997">{{Cite journal|title=An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus.|date=1997-12-15|url=https://www.jci.org/articles/view/119856|journal=The Journal of Clinical Investigation|volume=100|issue=12|pages=3019–3026|last=James|first=J. A.|last2=Kaufman|first2=K. M.|last3=Farris|first3=A. D.|last4=Taylor-Albert|first4=E.|last5=Lehman|first5=T. J.|last6=Harley|first6=J. B.|language=en|doi=10.1172/JCI119856|pmid=9399948|issn=0021-9738}}</ref> Another study found that patients with systemic lupus erythematosus had a roughly 40-fold increase in EBV viral loads compared with controls, likely stemming from altered [[t cell]] responses against EBV.<ref>{{Cite journal|title=Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus|date=2004-01-15|url=https://www.jimmunol.org/content/172/2/1287|journal=The Journal of Immunology|volume=172|issue=2|pages=1287–1294|last=Kang|first=Insoo|last2=Quan|first2=Timothy|last3=Nolasco|first3=Helena|last4=Park|first4=Sung-Hwan|last5=Hong|first5=Myung Sun|last6=Crouch|first6=Jill|last7=Pamer|first7=Eric G.|last8=Howe|first8=John Greg|last9=Craft|first9=Joe|language=en|doi=10.4049/jimmunol.172.2.1287|pmid=14707107|issn=0022-1767}}</ref><br />
<br />
===Myasthenia gravis===<br />
<br />
[[Myasthenia gravis]] is an [[autoimmune disease]] which has been associated with a large number of different viruses, particularly EBV, [[Human papillomavirus|HPV]], and [[Poliovirus|polioviruses]]. In several studies EBV infection of the thymus has been found in myasthenia gravis patients, but not all studies have found this.<ref name=":1">{{Cite journal|title=A Systematic Review of the Potential Implication of Infectious Agents in Myasthenia Gravis|date=2021|url=https://www.frontiersin.org/article/10.3389/fneur.2021.618021|journal=Frontiers in Neurology|volume=12|last=Leopardi|first=Victoria|last2=Chang|first2=Yu-Mei|last3=Pham|first3=Andrew|last4=Luo|first4=Jie|last5=Garden|first5=Oliver A.|doi=10.3389/fneur.2021.618021/full|issn=1664-2295}}</ref> [[B cell|B cells]] from [[myasthenia gravis]] patients stimulated ''in vitro'' by Epstein-Barr virus produced [[acetylcholine]] autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=https://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> While EBV infection of the [[thymus]] has been posited as a causative agent for the production of [[acetylcholine]] receptor autoantibodies in [[myasthenia gravis]].<ref>{{Cite journal|last=Kaminski|first=Henry J|last2=Minarovits|first2=Janos|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134|date=2010|volume=67|issue=6|pages=697-698|doi=|pmc=|pmid=|quote=|access-date=|via=}}</ref>, there is only limited evidence supporting EBV or other viruses as a cause of myasthenia gravis.<ref name=":1" /><br />
<br />
=== Gastrointestinal disease ===<br />
One study of EBV in patients with [[gastritis]], [[Crohn's disease]], and [[ulcerative colitis]] and normal controls found essentially undetectable levels of EBV in normal gastric mucosa. However, EBV was detected in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples.<ref>{{Cite journal|title=Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa|date=2012-07-01|url=https://doi.org/10.1007/s10620-012-2116-5|journal=Digestive Diseases and Sciences|volume=57|issue=7|pages=1887–1898|last=Ryan|first=Julie L.|last2=Shen|first2=You-Jun|last3=Morgan|first3=Douglas R.|last4=Thorne|first4=Leigh B.|last5=Kenney|first5=Shannon C.|last6=Dominguez|first6=Ricardo L.|last7=Gulley|first7=Margaret L.|language=en|doi=10.1007/s10620-012-2116-5|pmc=PMC3535492|pmid=22410851|issn=1573-2568}}</ref><br />
<br />
===Lyme disease===<br />
Several herpesviruses including Epstein-Barr virus may cause false positives on [[Lyme disease]] tests.<ref name="Goossens1999">{{Cite journal | last1 = Goossens | first1 = HA<br />
| last2 = Nohlmans | first2 = MK <br />
| last3 = van den Bogaard | first3 = AE<br />
| title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis| journal = Infection | date = May-Jun 1999 | volume = 27 | issue = 3| pages =231| doi = 10.1007/BF02561539|pmid = 10378140| url = https://www.ncbi.nlm.nih.gov/pubmed/10378140}}</ref><br />
<br />
===XMEN disease===<br />
<br />
A 2014 study found chronic Epstein-Barr infection was linked to a magnesium transporter [[magnesium transporter 1|MAGT]] mutation.<ref name="MAGT1">{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/84061|title=MAGT1 magnesium transporter 1 [Homo sapiens (human)]|last=|first=|authorlink=|date=|website=NCBI|archive-url=|archive-date=|url-status=|access-date=2022-05-21}}</ref> Dysfunction in this transporter also resulted in decreased NK cell function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Cite journal |last1 = Li |first1 = F.-Y. |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Su<br />
| first3 = H<br />
| last4 = Matthews<br />
| first4 = H |last5 = Lenardo |first5 = M.J. |authorlink3 = <br />
| title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. <br />
| journal = Blood| date = 2014| doi = 10.1182/blood-2013-11-538686|url=https://ashpublications.org/blood/article/123/14/2148/32463/XMEN-disease-a-new-primary-immunodeficiency|volume=123|issue=14|pages=2148–2152|pmc=|pmid=|quote=|via=}}</ref><br />
<br />
This disorder, termed "XMEN" (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. <br />
<br />
Since chronic EBV infection has been associated with chronic fatigue syndrome, this error in [[magnesium]] transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /><ref name="X-men_disease_2">{{Cite journal|title=X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect|date=Dec 2014|url=https://journals.lww.com/co-pediatrics/Abstract/2014/12000/X_linked_immunodeficiency_with_magnesium_defect,.16.aspx|journal=Current Opinion in Pediatrics|volume=26|issue=6|pages=713–719|last=Ravell|first=Juan|author-link=|last2=Chaigne-Delalande|first2=Benjamin|author-link2=|last3=Lenardo|first3=Michael|author-link3=|language=en-US|doi=10.1097/MOP.0000000000000156|pmc=PMC4306042|pmid=25313976|access-date=|issn=1040-8703|quote=|via=}}</ref> However, in this disorder, EBV would be seen as an indicator of the illness rather than the cause.<br />
<br />
==Vitamin D==<br />
<br />
Some recent research is finding links between EBV and [[Vitamin D]].<br />
<br />
An Epstein-Barr virus protein EBNA-3 has an affinity for [[VDR]] and may actually block the activation of VDR-dependent genes by [[Vitamin D]].<ref>{{Cite journal|last=Yenamandra|first=Surya Pavan|last2=Hellman|first2=Ulf|last3=Kempkes|first3=Bettina|last4=Darekar|first4=Suhas Deoram|last5=Petermann|first5=Sabine|last6=Sculley|first6=Tom|last7=Klein|first7=George|last8=Kashuba|first8=Elena|date=Dec 2010|title=Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes|url=https://www.ncbi.nlm.nih.gov/pubmed/20593215|journal=Cellular and molecular life sciences: CMLS|volume=67|issue=24|pages=4249–4256|doi=10.1007/s00018-010-0441-4|issn=1420-9071|pmid=20593215}}</ref><br />
<br />
[[Vitamin D receptor]] may be required for the normal development of [[natural killer T cell]]s that react to cells expressing [[CD1d]], as in cells infected by EBV.<ref>{{Cite journal|last=Yu|first=Sanhong|last2=Cantorna|first2=Margherita T.|date=2008-04-01|title=The vitamin D receptor is required for iNKT cell development|url=http://www.pnas.org/content/105/13/5207|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=13|pages=5207–5212|doi=10.1073/pnas.0711558105|issn=0027-8424|pmid=18364394}}</ref><br />
<br />
As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV, and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels<ref>{{Cite journal|last=Ramien|first=Caren|last2=Pachnio|first2=Annette|last3=Sisay|first3=Sofia|last4=Begum|first4=Jusnara|last5=Leese|first5=Alison|last6=Disanto|first6=Giulio|last7=Kuhle|first7=Jens|last8=Giovannoni|first8=Gavin|last9=Rickinson|first9=Alan|date=May 2014|title=Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort|url=https://www.ncbi.nlm.nih.gov/pubmed/24192216?dopt=Abstract|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=20|issue=6|pages=751–753|doi=10.1177/1352458513509507|issn=1477-0970|pmid=24192216}}</ref> (i.e., above 100 nmol/l).<br />
<br />
==Treatment==<br />
<br />
There is no specific treatment for EBV, only treatment of symptoms, such as taking over-the-counter medications for pain and fever.<ref name="CDC" /> EBV is thought to persistent harmlessly in immunocompetent individuals, but in those with compromised immune systems it has been associated with certain cancers and possibly autoimmune disease. <br />
<br />
===Antivirals===<br />
<br />
Several [[antiviral]]s are active against EBV including [[valganciclovir]], [[valacyclovir]]<ref name="Hoshino2009">{{Cite journal|title=Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers|date=Nov 2009|url=https://pubmed.ncbi.nlm.nih.gov/19740997/|journal=Journal of Virology|volume=83|issue=22|pages=11857–11861|last=Hoshino|first=Yo|author-link=|last2=Katano|first2=Harutaka|author-link2=|last3=Zou|first3=Ping|author-link3=|last4=Hohman|first4=Patricia|author-link4=|last5=Marques|first5=Adriana|author-link5=|last6=Tyring|first6=Stephen K.|author-link6=|last7=Follmann|first7=Dean|last8=Cohen|first8=Jeffrey I.|doi=10.1128/JVI.01005-09|pmc=2772668|pmid=19740997|access-date=|issn=1098-5514|quote=|via=}}</ref>, [[acyclovir]]<ref name="Rafaillidis2013">{{Cite journal|title=Antiviral treatment for severe EBV infections in apparently immunocompetent patients|date=Nov 2010|url=https://pubmed.ncbi.nlm.nih.gov/20739216/|journal=Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology|volume=49|issue=3|pages=151–157|last=Rafailidis|first=Petros I.|author-link=|last2=Mavros|first2=Michael N.|author-link2=|last3=Kapaskelis|first3=Anastasios|author-link3=|last4=Falagas|first4=Matthew E.|author-link4=|doi=10.1016/j.jcv.2010.07.008|pmc=|pmid=20739216|access-date=|issn=1873-5967|quote=|via=}}</ref>, and [[spironolactone]].<ref name="Verma2016">{{Cite journal | last1 = Verma | first1 = Dinesh<br />
| last2 = Thompson | first2 = Jacob<br />
| last3 = Swaminathan | first3 = Sankar| title = Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function<br />
| journal = Proceedings of the National Academy of Sciences | issn = 1091-6490 | volume = 113| issue = 13| pages = 3609–3614<br />
| date = 2016-03-29<br />
| doi = 10.1073/pnas.1523686113 | pmid = 26976570| url = http://www.pnas.org/content/113/13/3609}}</ref><br />
<br />
[[Acyclovir]], an [[antiviral]] drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.<br />
<br />
A theoretical [[immunotherapy]] treatment proposes that inducing [[CD1d]] expression on EBV-infected B cells could prompt effective immune suppression of EBV by natural killer T cells.<ref name="Priatel2014">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206}}</ref><br />
<br />
===Rituximab===<br />
<br />
[[Rituximab]] may be effective in completely eliminating EBV infection from the peripheral blood.<ref>{{Cite journal|last=Diamantopoulos|first=Panagiotis T.|last2=Polonyfi|first2=Katerina|last3=Sofotasiou|first3=Maria|last4=Papadopoulou|first4=Vasiliki|last5=Kalala|first5=Fani|last6=Iliakis|first6=Theodoros|last7=Zervakis|first7=Kostantinos|last8=Tsilimidos|first8=Gerassimos|last9=Kouzis|first9=Panagiotis|date=Dec 2013|title=Rituximab in the treatment of EBV-positive low grade B-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/24324119|journal=Anticancer Research|volume=33|issue=12|pages=5693–5698|issn=1791-7530|pmid=24324119}}</ref> A study of seventeen patients with low-grade [[B cell]] lymphoma found that after three cycles of rituximab, the virus had been completely eliminated from the peripheral blood in all but one patient.<br />
<br />
===Herbs and nutraceuticals===<br />
<br />
Herbs shown to have antiviral properties against EBV including [[licorice|licorice.]]<ref>{{Cite journal|last=Lin|first=Jung-Chung|last2=Cherng|first2=Jaw-Ming|last3=Hung|first3=Man-Shan|last4=Baltina|first4=Lidia A.|last5=Baltina|first5=Lia|last6=Kondratenko|first6=Rimma|date=Jul 2008|title=Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: structure-activity relationships|url=https://www.ncbi.nlm.nih.gov/pubmed/18423902|journal=Antiviral Research|volume=79|issue=1|pages=6–11|doi=10.1016/j.antiviral.2008.01.160|issn=0166-3542|pmid=18423902}}</ref> [[Vitamin C]] and Vitamin D<ref name="Rolf2017">{{Cite journal|title=Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis|date=Sep 2018|url=https://pubmed.ncbi.nlm.nih.gov/28731372/|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=24|issue=10|pages=1280–1287|last=Rolf|first=Linda|author-link=|last2=Muris|first2=Anne-Hilde|author-link2=|last3=Mathias|first3=Amandine|author-link3=|last4=Du Pasquier|first4=Renaud|author-link4=|last5=Koneczny|first5=Inga|author-link5=|last6=Disanto|first6=Giulio|author-link6=|last7=Kuhle|first7=Jens|last8=Ramagopalan|first8=Sreeram|last9=Damoiseaux|first9=Jan|last10=Smolders|first10=Joost|last11=Hupperts|first11=Raymond|doi=10.1177/1352458517722646|pmc=6108041|pmid=28731372|access-date=|issn=1477-0970|quote=|via=}}</ref> might also decrease duration and severity of the symptoms of EBV infection.<ref name="Mikirova2014">{{Cite journal|title=Effect of high dose vitamin C on Epstein-Barr viral infection|date=2014-05-03|url=https://pubmed.ncbi.nlm.nih.gov/24793092/|journal=Medical Science Monitor: International Medical Journal of Experimental and Clinical Research|volume=20|pages=725–732|last=Mikirova|first=Nina|last2=Hunninghake|first2=Ronald|doi=10.12659/MSM.890423|pmc=4015650|pmid=24793092|issn=1643-3750}}</ref><br />
<br />
===Vaccine===<br />
A [[vaccine]] for the prevention of Epstein-Barr virus is being explored.<ref name="Vaccine2019">{{Cite web|url=https://www.nih.gov/news-events/news-releases/nih-researchers-make-progress-toward-epstein-barr-virus-vaccine|title=NIH researchers make progress toward Epstein-Barr virus vaccine|date=2019-04-09|website=National Institutes of Health (NIH)|language=en|access-date=2019-04-10}}</ref><br />
<br />
==Notable studies==<br />
*1996, MMPI profiles of patients with chronic fatigue syndrome<ref name="Schmaling1996" /> - ([[pubmed:8730646|Abstract]])<br />
*1998, Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever<ref name="White1998" /> - ([[pubmed:9926075|Abstract]])<br />
*2006, Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study<ref name="Hickie2006" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full text)]<br />
*2019, EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection<ref name="Asprusten2019">{{Cite journal|last=Asprusten|first=Tarjei Tørre|author-link=|last2=Pedersen|first2=Maria|author-link2=Maria Pedersen|last3=Skovlund|first3=Eva|author-link3=Eva Skovlund|last4=Wyller|first4=Vegard Bruun|author-link4=Vegard Bruun Wyller|date=2019|title=EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection|url=https://www.ncbi.nlm.nih.gov/pubmed/30957026|journal=BMJ paediatrics open|volume=3|issue=1|pages=e000390|doi=10.1136/bmjpo-2018-000390|issn=2399-9772|pmc=|pmid=30957026|quote=|via=}}</ref> - ([[pubmed:30957026|Abstract]])<br />
*2019, Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study<ref name="Pedersen2019a">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=|last3=Godang|first3=Kristin|author-link3=Kristin Godang|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|author-link7=|last8=Øie|first8=Merete Glenne|author-link8=|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=Jan 2019|title=Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pubmed/30261303|journal=Brain, Behavior, and Immunity|volume=75|issue=|pages=94–100|doi=10.1016/j.bbi.2018.09.023|issn=1090-2139|pmid=30261303|quote=}}</ref> - ([[pubmed:30261303|Abstract]])<br />
*2019, Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later<ref name="Pedersen2019b">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=Tarjei Tørre Asprusten|last3=Godang|first3=Kristin|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|last8=Øie|first8=Merete Glenne|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=2019-01-27|title=Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later|url=https://www.ncbi.nlm.nih.gov/pubmed/30685875|journal=Acta Paediatrica (Oslo, Norway: 1992)|volume=108|issue=8|pages=1521-1526|doi=10.1111/apa.14728|issn=1651-2227|pmid=30685875|quote=|via=}}</ref> - ([[pubmed:30685875|Abstract]])<br />
*2019, Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Williams|first=Marshall V.|author-link=|last2=Cox|first2=Brandon|author-link2=|last3=Lafuse|first3=William P.|author-link3=|last4=Ariza|first4=Maria Eugenia|author-link4=|author-link5=|date=May 2019|title=Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0149291819301730|journal=Clinical Therapeutics|language=en|volume=41|issue=5|pages=848–863|doi=10.1016/j.clinthera.2019.04.009|pmc=6525645|pmid=31040055|quote=|via=}}</ref> - ([https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext Full text)]<br />
*2019, Review article - Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis<ref name="Kerr2019EBV">{{Cite journal|last=Kerr|first=Jonathan R.|author-link=Jonathan Kerr|date=Feb 2019|title=Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00059/abstract|journal=Frontiers in Pediatrics|volume=72|issue=10|pages=651-8|doi=10.3389/fped.2019.00059|quote=|via=|last2=|first2=|pmc=|pmid=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full (Full text)]<br />
*2019, Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors<ref name="Kerr2019a">{{Cite journal|last=Kerr|first=Jonathan R|author-link=Jonathan Kerr|author-link2=|date=2019-07-17|title=Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors|url=http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205822|journal=Journal of Clinical Pathology|language=en|volume=|issue=|pages=jclinpath–2019–205822|doi=10.1136/jclinpath-2019-205822|issn=0021-9746|quote=|via=}}</ref> - [[pubmed:31315893|(Abstract)]]<br />
*2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal|last=Shikova|first=Evelina|author-link=|last2=Reshkova|first2=Valentina|author-link2=|last3=Kumanova|first3=Аntoniya|author-link3=|last4=Raleva|first4=Sevdalina|author-link4=|last5=Alexandrova|first5=Dora|author-link5=|last6=Capo|first6=Natasa|author-link6=|last7=Murovska|first7=Modra|date=2020|title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=|pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)]<br />
*2021, Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome<ref>{{Cite journal|title=Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|date=Nov 15, 2021|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/|journal=Frontiers in Immunology|volume=12|issue=|pages=656797|last=Ruiz-Pablos|first=Manuel|author-link=|last2=Paiva|first2=Bruno|author-link2=|last3=Monter-Mateo|first3=Rosario|author-link3=|last4=Garcia|first4=Nicolas|author-link4=|last5=Zabaleta|first5=Aintzane|author-link5=|doi=10.3389/fimmu.2021.656797|pmc=|pmid=34867935|access-date=June 10, 2022|quote=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/ Full text])<br />
*2021, Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue<ref>{{Cite journal|title=Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue|date=2021|url=https://pubmed.ncbi.nlm.nih.gov/34987499|journal=Frontiers in Immunology|volume=12|pages=715102|last=Fevang|first=Børre|last2=Wyller|first2=Vegard Bruun Bratholm|last3=Mollnes|first3=Tom Eirik|last4=Pedersen|first4=Maria|last5=Asprusten|first5=Tarjei Tørre|last6=Michelsen|first6=Annika|last7=Ueland|first7=Thor|last8=Otterdal|first8=Kari|doi=10.3389/fimmu.2021.715102|pmc=8721200|pmid=34987499|issn=1664-3224}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721200/ Full text])<br />
*2021, Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation<ref name=":0" /> [https://www.mdpi.com/2076-0817/10/6/763/htm (Full text)]<br />
*2022, EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing T<sub>FH</sub> cell differentiation and extrafollicular activities<ref>{{Cite journal|title=EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities|date=2022-06-08|url=https://insight.jci.org/articles/view/158193|journal=JCI Insight|volume=7|issue=11|last=Cox|first=Brandon S.|last2=Alharshawi|first2=Khaled|last3=Mena-Palomo|first3=Irene|last4=Lafuse|first4=William P.|last5=Ariza|first5=Maria Eugenia|language=en|doi=10.1172/jci.insight.158193|issn=0021-9738}}</ref> - ([https://insight.jci.org/articles/view/158193 Full text])<br />
<br />
== See also ==<br />
* [[List of herpesvirus infection studies]]<br />
<br />
==Learn more ==<br />
*[https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011487.pub2/full Antiviral agents for infectious mononucleosis (glandular fever) (2016)] - [[Cochrane]] review <br />
* [https://www.nationalmssociety.org/About-the-Society/News/Study-Provides-Strongest-Evidence-Yet-for-the-Role Study Provides Strongest Evidence Yet for the Role of Epstein-Barr Virus in Triggering Multiple Sclerosis (2022)] - Multiple Sclerosis Society<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Infectious agents]]<br />
[[Category:Triggers and risk factors]]<br />
[[Category:Virology]]<br />
[[Category:Viruses]]</div>Darlahttps://me-pedia.org/w/index.php?title=Neuroinflammation&diff=112138Neuroinflammation2022-06-27T11:14:12Z<p>Darla:/* Talks and interviews */</p>
<hr />
<div>[[File:Microglia and Astrocyte Dysfunction.png|thumb|Possible mechanism showing the decline of microglia and astrocyte function and structure.]]<br />
'''Neuroinflammation''' is a term used to describe activation of the resident immune cells in the [[central nervous system]] (CNS),<ref name=":10">{{Cite journal|last=Aguzzi|first=Adriano|last2=Barres|first2=Ben A.|last3=Bennett|first3=Mariko L.|date=2013-01-11|title=Microglia: Scapegoat, Saboteur, or Something Else?|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431634/|journal=Science (New York, N.Y.)|volume=339|issue=6116|pages=156–161|doi=10.1126/science.1227901|issn=0036-8075|pmc=4431634|pmid=23307732}}</ref><ref>{{Cite journal|last=Mrak|first=Robert E.|last2=Griffin|first2=W. Sue T.|date=2004-04-20|title=Welcome to the Journal of Neuroinflammation!|url=https://doi.org/10.1186/1742-2094-1-1|journal=Journal of Neuroinflammation|volume=1|issue=1|pages=1|doi=10.1186/1742-2094-1-1|issn=1742-2094|pmc=483051|pmid=15285806}}</ref> it involves [[Neuron|neurons]], [[Microglia|microglial]] and [[Macroglia|macroglial]] cells.<ref>{{Cite journal|title=Role of Neuroinflammation in Autism Spectrum Disorder and the Emergence of Brain Histaminergic System. Lessons Also for BPSD?|date=2020|url=https://www.frontiersin.org/article/10.3389/fphar.2020.00886|journal=Frontiers in Pharmacology|volume=11|pages=886|last=Eissa|first=Nermin|last2=Sadeq|first2=Adel|last3=Sasse|first3=Astrid|last4=Sadek|first4=Bassem|doi=10.3389/fphar.2020.00886|issn=1663-9812}}</ref> This contrasts with classical Greco-Roman [[inflammation]], which was originally defined as swelling, redness, heat, and pain, but has come to mean infiltration of tissues by blood-borne immune cells. Unlike classical inflammation, neuroinflammation does not imply infiltration of tissues by blood-borne immune cells. As such, the term “neuroinflammation” must not be confused with the term “[[encephalitis]]”, which implies classical inflammation. Because of this distinction, the relatively recent term “neuroinflammation” has generated considerable confusion in the scientific community.<ref name=":0">{{Cite journal|last=Graeber|first=Manuel B.|last2=Li|first2=Wei|last3=Rodriguez|first3=Michael L.|date=2011-12-01|title=Role of microglia in CNS inflammation|url=https://www.ncbi.nlm.nih.gov/pubmed/21889505|journal=FEBS letters|volume=585|issue=23|pages=3798–3805|doi=10.1016/j.febslet.2011.08.033|issn=1873-3468|pmid=21889505}}</ref><br />
<br />
The immune cells activated in neuroinflammation are the tissue-resident [[Macrophage|macrophages]] of the CNS, which, for historical reasons, are called [[microglia]].<ref name=":10" /><ref>{{Cite journal|last=Ginhoux|first=Florent|last2=Greter|first2=Melanie|last3=Leboeuf|first3=Marylene|last4=Nandi|first4=Sayan|last5=See|first5=Peter|last6=Gokhan|first6=Solen|last7=Mehler|first7=Mark F.|last8=Conway|first8=Simon J.|last9=Ng|first9=Lai Guan|date=2010-11-05|title=Fate mapping analysis reveals that adult microglia derive from primitive macrophages|url=https://www.ncbi.nlm.nih.gov/pubmed/20966214|journal=Science (New York, N.Y.)|volume=330|issue=6005|pages=841–845|doi=10.1126/science.1194637|issn=1095-9203|pmc=3719181|pmid=20966214}}</ref> Like other macrophages, microglia fight infections and repair tissue damage.<ref name=":1">{{Cite journal|last=DiSabato|first=Damon J.|last2=Quan|first2=Ning|last3=Godbout|first3=Jonathan P.|date=Oct 2016|title=Neuroinflammation: the devil is in the details|url=https://www.ncbi.nlm.nih.gov/pubmed/26990767|journal=Journal of Neurochemistry|volume=139 |issue =Suppl 2|pages=136–153|doi=10.1111/jnc.13607|issn=1471-4159|pmc=5025335|pmid=26990767}}</ref> In the case of minor infections or minor tissue damage, microglia can often resolve the situation on their own. In more serious situations, the microglia will secrete [[cytokine]]s to attract help from blood-borne immune cells. <br />
<br />
==Diseases associated with neuroinflammation==<br />
Neuroinflammation is a symptom of many diseases and thought to be a part of ME. [[Alzheimer's disease]], [[Parkinson's disease]], and [[multiple sclerosis]] are illnesses in which the brain experiences decline in structure and function, and also where it shows clear signs of neuroinflammation. [[Inflammation]] of the [[brain]] is linked to activated [[microglia]], [[cytokine]] presence in the brain,<ref>{{Cite journal|last=Chen|first=Wei-Wei|last2=Zhang|first2=Xia|last3=Huang|first3=Wen-Juan|date=Apr 2016|title=Role of neuroinflammation in neurodegenerative diseases (Review)|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805095/|journal=Molecular Medicine Reports|volume=13|issue=4|pages=3391–3396|doi=10.3892/mmr.2016.4948|issn=1791-2997|pmc=4805095|pmid=26935478}}</ref> and changes in the neurochemicals produced by the brain.<ref name=":2">{{Cite journal|last=Albrecht|first=Daniel S.|last2=Granziera|first2=Cristina|last3=Hooker|first3=Jacob M.|last4=Loggia|first4=Marco L.|date=2016-04-20|title=In Vivo Imaging of Human Neuroinflammation|url=https://www.ncbi.nlm.nih.gov/pubmed/26985861|journal=ACS chemical neuroscience|volume=7|issue=4|pages=470–483|doi=10.1021/acschemneuro.6b00056|issn=1948-7193|pmc=5433433|pmid=26985861}}</ref> These effects also occur in [[Myalgic encephalomyelitis|ME]] which is why researchers are searching to more strongly show neuroinflammation in these patients.<br />
<br />
==Causes==<br />
<br />
=== Microglia activation ===<br />
The [[blood brain barrier]] (BBB), a membrane that separates the brain from the rest of the body, may become compromised in [[Myalgic encephalomyelitis|ME]] patients. If there are [[Cytokine|cytokines]] circulating in the bloodstream, they may get into the brain through opened sections of the BBB<ref name=":3">{{Cite journal|last=Morris|first=Gerwyn|last2=Maes|first2=Michael|date=Dec 2013|title=A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/22718491|journal=Metabolic Brain Disease|volume=28|issue=4|pages=523–540|doi=10.1007/s11011-012-9324-8|issn=1573-7365|pmid=22718491}}</ref>. While this initially starts as a normal brain response so that the brain can get the body back to normal, healthy functioning, this process can be predisposed to dysfunction and activation may be sustained longer than usual.<br />
<br />
[[Microglia]] are cells that can act as the brain’s primary immune response. If cytokines or immune cells from outside the [[Central nervous system|CNS]] enter the brain through the BBB, the microglia will respond to the immune threat and attempt to clear the infiltrators out. However, this process increases neuron activation and the release of more cytokines potentially leading to a cycle of neuroinflammation<ref name=":3" />. <br />
<br />
One study used a radioligand, a tracer that lights up in the presence of a specific molecule, in a positron emission tomography (PET) scanner in search of activated microglia in ME patients’ brains. Activated microglia cells are believed to be correlated to neuroinflammation. Increased radioligand presence in ME subjects’ brains was observed; however, further analysis of these data and replication of their results are needed<ref>{{Cite journal|last=Nakatomi|first=Yasuhito|last2=Mizuno|first2=Kei|last3=Ishii|first3=Akira|last4=Wada|first4=Yasuhiro|last5=Tanaka|first5=Masaaki|last6=Tazawa|first6=Shusaku|last7=Onoe|first7=Kayo|last8=Fukuda|first8=Sanae|last9=Kawabe|first9=Joji|date=Jun 2014|title=Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study|url=https://www.ncbi.nlm.nih.gov/pubmed/24665088|journal=Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine|volume=55|issue=6|pages=945–950|doi=10.2967/jnumed.113.131045|issn=1535-5667|pmid=24665088}}</ref>.<br />
<br />
===<span id="ONS_pathway">Oxidative and nitrosative stress</span>===<br />
The '''oxidative and nitrosative stress pathway''' or '''O&NS pathway''' results in tissue damage which could lead to neuroimflammation in [[ME/CFS]].<br />
[[File:CauseofCFSME.jpg|thumb|403x403px|Scheme of cascade events in CFS/ME/SEID showing O&N pathway.Source: Eur Jrnl of Translational Myology 28(3).<ref>{{Cite journal|last=Pietrangelo|first=Tiziana|last2=Fulle|first2=Stefania|last3=Coscia|first3=Francesco|last4=Gigliotti|first4=Paola Virginia|last5=Fanò-Illic|first5=Giorgio|date=2018-09-07|title=Old muscle in young body: an aphorism describing the Chronic Fatigue Syndrome|url=http://dx.doi.org/10.4081/ejtm.2018.7688|journal=European Journal of Translational Myology|volume=28|issue=3|doi=10.4081/ejtm.2018.7688|issn=2037-7460}}</ref> License: CC-BY-NC-4.0]]<br />
Neuroinflammation may also be related to excess [[oxygen]] and nitrogen molecules in tissues. This can cause oxidative or nitrosative stress (O&NS), leading to tissue damage. The O&NS pathway helps maintain the blood brain barrier, an important membrane keeping the brain protected from harmful substances present in the blood. When the pathway is dysfunctional, the blood-brain barrier becomes less effective at keeping out particles. Breakdown of this barrier could lead to immune cells entering the brain and trigger an immune response, leading to neuroinflammation. Researchers propose a link between the dysfunction of brain tissues in ME/CFS and the breakdown of the oxidative and nitrosative stress pathway.<ref name=":3" /><br />
{{See also|Nitrogen hypothesis}}<br />
<br />
=== Activation of cyclical neuroinflammation: A self-perpetuating cycle ===<br />
When a patient gets an infection, the body attempts to return homeostasis. The immune system has regulatory structures called toll-like receptors (TLRs). High amounts of stress or a previous injury can predispose an individual’s TLRs to be more sensitive, releasing inflammatory molecules more readily in response to an immune stressor.<ref>{{Cite journal|last=Gárate|first=Iciar|last2=Garcia-Bueno|first2=Borja|last3=Madrigal|first3=Jose Luis Muñoz|last4=Caso|first4=Javier Rubén|last5=Alou|first5=Luis|last6=Gomez-Lus|first6=Marisa L.|last7=Micó|first7=Juan Antonio|last8=Leza|first8=Juan Carlos|date=2013-01-01|title=Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway|url=https://www.ncbi.nlm.nih.gov/pubmed/22906518|journal=Biological Psychiatry|volume=73|issue=1|pages=32–43|doi=10.1016/j.biopsych.2012.07.005|issn=1873-2402|pmid=22906518}}</ref> One of the downstream pathways of TLRs, the oxidative and nitrosative stress pathway (O&NS) can get activated. If this pathway is overstimulated, the body will produce a larger-scale response in an effort to return to normal.<ref>{{Cite journal|last=Liu|first=JiaJun|last2=Buisman-Pijlman|first2=Femke|last3=Hutchinson|first3=Mark R.|date=2014|title=Toll-like receptor 4: innate immune regulator of neuroimmune and neuroendocrine interactions in stress and major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/25324715|journal=Frontiers in Neuroscience|volume=8|pages=309|doi=10.3389/fnins.2014.00309|issn=1662-4548|pmc=4179746|pmid=25324715}}</ref> In this attempt, a chemical called damage-associated molecular patterns (DAMPs) triggers the release of more inflammatory molecules, some of which activate the TLRs<ref>{{Cite journal|last=Morris|first=Gerwyn|last2=Berk|first2=Michael|last3=Walder|first3=Ken|last4=Maes|first4=Michael|date=2015-02-06|title=Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses|url=https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0259-2|journal=BMC Medicine|language=en|volume=13|issue=1|doi=10.1186/s12916-014-0259-2|issn=1741-7015|pmc=4320458|pmid=25856766}}</ref> (Morris et al., 2015). The process of activation from TLRs to the O&NS pathway to the production of more inflammatory molecules then becomes a cycle.<ref name=":4">{{Cite journal|last=Chaudhuri|first=A.|last2=Condon|first2=B. R.|last3=Gow|first3=J. W.|last4=Brennan|first4=D.|last5=Hadley|first5=D. M.|date=2003-02-10|title=Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12598734|journal=Neuroreport|volume=14|issue=2|pages=225–228|doi=10.1097/01.wnr.0000054960.21656.64|issn=0959-4965|pmid=12598734}}</ref><br />
<br />
== Possible neurological biomarkers of ME ==<br />
When the brain is going through challenges such as neuroinflammation or neurodegeneration, several chemicals become dysregulated. These changes are able to be recorded using a special function of magnetic resonance (MR) scanners. Because each chemical has a distinct molecular structure, the magnetic field formed by the scanner will bounce off of each chemical in unique ways. This allows the technician to measure the amounts of these chemicals in the brain.<br />
<br />
Several neurochemicals have been studied in relation to ME patients. Myo-inositol is thought to be involved in astrocyte function (Albrecht et al. 2016) and trended to be higher in ME patients compared to controls.<ref name=":5">{{Cite journal|last=Brooks|first=J. C.|last2=Roberts|first2=N.|last3=Whitehouse|first3=G.|last4=Majeed|first4=T.|date=Nov 2000|title=Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11144799|journal=The British Journal of Radiology|volume=73|issue=875|pages=1206–1208|doi=10.1259/bjr.73.875.11144799|issn=0007-1285|pmid=11144799}}</ref><br />
<br />
N-acetylacetate (NAA) shows neuron density, which has been found in other neurological disorders<ref name=":2" /> and has been shown to be lower in ME patients,<ref name=":4" /><ref name=":5" /> but this was not found in all studies.<ref>{{Cite journal|last=Puri|first=B. K.|last2=Counsell|first2=S. J.|last3=Zaman|first3=R.|last4=Main|first4=J.|last5=Collins|first5=A. G.|last6=Hajnal|first6=J. V.|last7=Davey|first7=N. J.|date=Nov 2002|title=Relative increase in choline in the occipital cortex in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12197861|journal=Acta Psychiatrica Scandinavica|volume=106|issue=3|pages=224–226|issn=0001-690X|pmid=12197861}}</ref><ref name=":6">{{Cite journal|last=Tomoda|first=A.|last2=Miike|first2=T.|last3=Yamada|first3=E.|last4=Honda|first4=H.|last5=Moroi|first5=T.|last6=Ogawa|first6=M.|last7=Ohtani|first7=Y.|last8=Morishita|first8=S.|date=Jan 2000|title=Chronic fatigue syndrome in childhood|url=https://www.ncbi.nlm.nih.gov/pubmed/10761837|journal=Brain & Development|volume=22|issue=1|pages=60–64|issn=0387-7604|pmid=10761837}}</ref><br />
<br />
[[Choline]] is linked to activation of glia, loss of energy and expression of macrophages in the brain<ref name=":2" /> and has been shown to change compared to controls.<ref name=":4" /><ref name=":5" /><ref name=":6" /> <ref>{{Cite journal|last=Puri|first=B. K.|last2=Agour|first2=M.|last3=Gunatilake|first3=K. D. R.|last4=Fernando|first4=K. a. C.|last5=Gurusinghe|first5=A. I.|last6=Treasaden|first6=I. H.|date=Nov 2009|title=An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)|url=https://www.ncbi.nlm.nih.gov/pubmed/19906518|journal=Prostaglandins, Leukotrienes, and Essential Fatty Acids|volume=81|issue=5-6|pages=303–305|doi=10.1016/j.plefa.2009.10.002|issn=1532-2823|pmid=19906518}}</ref><br />
<br />
Lactate increases when more energy is being expended and has been shown to be higher than controls,<ref name=":7">{{Cite journal|last=Mathew|first=Sanjay J.|last2=Mao|first2=Xiangling|last3=Keegan|first3=Kathryn A.|last4=Levine|first4=Susan M.|last5=Smith|first5=Eric L. P.|last6=Heier|first6=Linda A.|last7=Otcheretko|first7=Viktor|last8=Coplan|first8=Jeremy D.|last9=Shungu|first9=Dikoma C.|date=Apr 2009|title=Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study|url=https://www.ncbi.nlm.nih.gov/pubmed/18942064|journal=NMR in biomedicine|volume=22|issue=3|pages=251–258|doi=10.1002/nbm.1315|issn=0952-3480|pmid=18942064}}</ref><ref>{{Cite journal|last=Shungu|first=Dikoma C.|last2=Weiduschat|first2=Nora|last3=Murrough|first3=James W.|last4=Mao|first4=Xiangling|last5=Pillemer|first5=Sarah|last6=Dyke|first6=Jonathan P.|last7=Medow|first7=Marvin S.|last8=Natelson|first8=Benjamin H.|last9=Stewart|first9=Julian M.|date=Sep 2012|title=Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology|url=https://www.ncbi.nlm.nih.gov/pubmed/22281935|journal=NMR in biomedicine|volume=25|issue=9|pages=1073–1087|doi=10.1002/nbm.2772|issn=1099-1492|pmc=3896084|pmid=22281935}}</ref><ref name=":8">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Vu|first2=Diana|last3=Coplan|first3=Jeremy D.|last4=Mao|first4=Xiangling|last5=Blate|first5=Michelle|last6=Kang|first6=Guoxin|last7=Soto|first7=Eli|last8=Kapusuz|first8=Tolga|last9=Shungu|first9=Dikoma C.|date=2017|title=Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pubmed/29308330|journal=Fatigue: Biomedicine, Health & Behavior|volume=5|issue=1|pages=15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=5754037|pmid=29308330}}</ref><ref name=":9">{{Cite journal|last=Murrough|first=James W.|last2=Mao|first2=Xiangling|last3=Collins|first3=Katherine A.|last4=Kelly|first4=Chris|last5=Andrade|first5=Gizely|last6=Nestadt|first6=Paul|last7=Levine|first7=Susan M.|last8=Mathew|first8=Sanjay J.|last9=Shungu|first9=Dikoma C.|date=Jul 2010|title=Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/20661876|journal=NMR in biomedicine|volume=23|issue=6|pages=643–650|doi=10.1002/nbm.1512|issn=1099-1492|pmid=20661876}}</ref> and significantly differs from lactate levels in people with psychological disorders.<ref name=":7" /><ref name=":9" /> Both ME patients and [[fibromyalgia]] patients were found to have similar levels of elevated lactate, so more tests would be needed to differentiate the two.<ref name=":8" /><br />
<br />
Though contrasts were found between ME people and controls in many of these [[Diagnostic biomarker|biomarker]] studies, researchers are not sure what the changes mean specifically because the metabolites are used in multiple brain processes. Furthermore, the results shown by these papers has not been largely replicated. However, if repeated, these biomarkers could potentially become an objective measure for diagnosing ME.<br />
<br />
==Notable studies==<br />
*2010, Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways<ref name="Twisk, 2010">{{Cite journal|last1=Twisk|first1=Frank|authorlink1= Frank Twisk|last2=Maes|first2=Michael|authorlink2=Michael Maes|title=Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways|journal=BMC Medicine|volume=8|issue=35|page=|date=2010|url= https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901228/pdf/1741-7015-8-35.pdf}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901228/pdf/1741-7015-8-35.pdf (Full text)]<br />
*2011, Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome<ref>{{Cite journal|last=Maes|first=Michael|author-link=Michael Maes|last2=Twisk|first2=Frank N.M.|author-link2=Frank Twisk|last3=Kubera|first3=Marta|author-link3=|last4=Ringel|first4=Karl|author-link4=|last5=Leunis|first5=Jean-Claude|author-link5=|last6=Geffard|first6=Michel|author-link6=|date=Feb 2012|title=Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0165032711005362|journal=Journal of Affective Disorders|language=en|volume=136|issue=3|pages=909–917|doi=10.1016/j.jad.2011.09.010|quote=|via=}}</ref> - [[pubmed:21967891|(Abstract)]]<br />
*2010, Autopsies of four deceased ME patients showed various pathological phenomena in the CNS and [[peripheral nervous system]]s.<ref>{{Cite web|url=https://www.meassociation.org.uk/2011/01/pathology-of-mecfs-pilot-study-of-four-autopsy-reports/|title=Pathology of ME/CFS: pilot study of four autopsy reports|last=|first=|date=Jan 2011|website=[[The ME Association]]|language=en-US|archive-url=|archive-date=|access-date=2018-08-10}}</ref><br />
*2013, Daily cytokine fluctuations, driven by [[leptin]], are associated with fatigue severity in [[chronic fatigue syndrome]]: Evidence of inflammatory pathology<ref name="stanfordleptin">{{Cite journal <br />
| last1 = Stringer | first1 = EA <br />
| last2 = Baker | first2 = KS <br />
| last3 = Carrol | first3 = IR <br />
| last4 = Montoya | first4 = JG | authorlink4 = Jose Montoya<br />
| last5 = Chu | first5 = L | authorlink5 = Lily Chu <br />
| last6 = Maeker | first6 = HT <br />
| last7 = Younger | first7 = JW | authorlink7 = Jarred Younger| title = Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: Evidence of inflammatory pathology | journal = J Transl Med.| date = Apr 9, 2013 | pmid = 23570606 | pmc = 3637529 | doi = 10.1186/1479-5876-11-93| url = http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-11-93 }}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637529/ (Full Text)] <br />
* 2014, A Japanese PET study looked at neuroinflammation in 9 patients with ME/CFS and 10 controls. They measured a protein expressed by activated [[microglia]], and found that values in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%–199% higher in ME/CFS patients than in healthy controls. The values in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the values in the cingulate cortex and thalamus positively correlated with pain score, and the value in the hippocampus positively correlated with depression score.<ref name="Nakatomi2014">{{Cite journal <br />
| last1 = Nakatomi | first1 = Yasuhito | authorlink1 = <br />
| last2 = Mizuno | first2 = Kei | authorlink2 = <br />
| last3 = Ishii | first3 = Akira | authorlink3 = <br />
| last4 = Wada | first4 = Yasuhiro | authorlink4 = <br />
| last5 = Tanaka | first5 = Masaaki | authorlink5 = <br />
| last6 = Tazawa | first6 = Shusaku | authorlink6 = <br />
| last7 = Onoe | first7 = Kayo | authorlink7 = <br />
| last8 = Fukuda | first8 = Sanae | authorlink8 = <br />
| last9 = Kawabe | first9 = Joji | authorlink9 = <br />
| last10 = Takahashi | first10= Kazuhiro | authorlink10= <br />
| last11 = Kataoka | first11= Yosky | authorlink11= <br />
| last12 = Shiomi | first12= Susumu | authorlink12= <br />
| last13 = Yamaguti | first13= Kouzi | authorlink13= <br />
| last14 = Inaba | first14= Masaaki | authorlink14= <br />
| last15 = Kuratsune | first15= Hirohiko | authorlink15= <br />
| last16 = Watanabe | first16= Yasuyoshi | authorlink16= Yasuyoshi Watanabe<br />
| title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study<br />
| journal = Journal of Nuclear Medicine | volume = 55|issue =6 | page = 945-50<br />
| date = 2014-03-24| pmid = 24665088 | doi = 10.2967/jnumed.113.131045| url =http://jnm.snmjournals.org/content/55/6/945.long }}</ref><br />
*2015, Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome<ref name="Zeineh2015">{{Cite journal|last=Zeineh|first=Michael M.|author-link=Michael Zeineh|last2=Kang|first2=James|author-link2=|last3=Atlas|first3=Scott W.|author-link3=|last4=Raman|first4=Mira M.|author-link4=|last5=Reiss|first5=Allan L.|author-link5=|last6=Norris|first6=Jane L.|author-link6=Jane Norris|last7=Valencia|first7=Ian|author-link7=Ian Valencia|last8=Montoya|first8=Jose G.|author-link8=Jose Montoya|date=2015|title=Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome|url=https://pubs.rsna.org/doi/abs/10.1148/radiol.14141079|journal=Radiology|language=en|volume=274|issue=2|pages=517–526|doi=10.1148/radiol.14141079|issn=0033-8419|via=|quote=}}</ref><br />
*2016, [https://doi.org/10.1038/nature16549 Schizophrenia risk from complex variation of complement component 4]<ref name="Sekar2016">{{Cite journal|last=Sekar|first=Aswin|last2=Bialas|first2=Allison R.|last3=de Rivera|first3=Heather|last4=Davis|first4=Avery|last5=Hammond|first5=Timothy R.|last6=Kamitaki|first6=Nolan|last7=Tooley|first7=Katherine|last8=Presumey|first8=Jessy|last9=Baum|first9=Matthew|date=2016-02-11|title=Schizophrenia risk from complex variation of complement component 4|url=https://www.ncbi.nlm.nih.gov/pubmed/26814963|journal=Nature|volume=530|issue=7589|pages=177–183|doi=10.1038/nature16549|issn=1476-4687|pmc=4752392|pmid=26814963}}</ref><br />
* 2016, [https://doi.org/10.18632/aging.100981 Reversal of cognitive decline in Alzheimer’s disease]<ref>{{Cite journal|last=Bredesen|first=Dale E.|last2=Amos|first2=Edwin C.|last3=Canick|first3=Jonathan|last4=Ackerley|first4=Mary|last5=Raji|first5=Cyrus|last6=Fiala|first6=Milan|last7=Ahdidan|first7=Jamila|date=Jun 2016|title=Reversal of cognitive decline in Alzheimer's disease|url=https://www.ncbi.nlm.nih.gov/pubmed/27294343|journal=Aging|volume=8|issue=6|pages=1250–1258|doi=10.18632/aging.100981|issn=1945-4589|pmc=4931830|pmid=27294343}}</ref><br />
* 2017, [https://doi.org/10.1016/j.biopsych.2017.08.005 Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study]<ref>{{Cite journal|last=Holmes|first=Sophie E.|last2=Hinz|first2=Rainer|last3=Conen|first3=Silke|last4=Gregory|first4=Catherine J.|last5=Matthews|first5=Julian C.|last6=Anton-Rodriguez|first6=Jose M.|last7=Gerhard|first7=Alexander|last8=Talbot|first8=Peter S.|date=2018-01-01|title=Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study|url=https://www.ncbi.nlm.nih.gov/pubmed/28939116|journal=Biological Psychiatry|volume=83|issue=1|pages=61–69|doi=10.1016/j.biopsych.2017.08.005|issn=1873-2402|pmid=28939116}}</ref><br />
* 2019, [[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]<ref name="Mueller2019">{{Cite journal|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=Mueller|first=Christina|authorlink=Christina Mueller|last2=Lin|first2=Joanne C|authorlink2=Joanne Lin|date=2019|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger|last3=Sheriff|last4=Maudsley|last5=Younger|first3=Sulaiman|first4=Andrew A|first5=Jarred W|volume=14|issue=2|pages=562-572|journal=Brain Imaging and Behavior}}</ref> <br />
*2019, Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation<ref>{{Cite journal|last=Albrecht|first=Daniel S.|author-link=Daniel Albrecht|last2=Forsberg|first2=Anton|author-link2=|last3=Sandström|first3=Angelica|author-link3=|last4=Bergan|first4=Courtney|author-link4=|last5=Kadetoff|first5=Diana|author-link5=|last6=Protsenko|first6=Ekaterina|author-link6=|last7=Lampa|first7=Jon|last8=Lee|first8=Yvonne C.|last9=Höglund|first9=Caroline Olgart|date=2019-01-01|title=Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation|url=http://www.sciencedirect.com/science/article/pii/S0889159118302423|journal=Brain, Behavior, and Immunity|language=en|volume=75|issue=|pages=72–83|doi=10.1016/j.bbi.2018.09.018|issn=0889-1591|pmc=|pmid=|access-date=|quote=|via=|last10=Catana|first10=Ciprian|first11=Simon|last11=Cervenka|last12=Akeju|first12=Oluwaseun|last13=Lekander|first13=Mats|last14=Cohen|first14=George|last15=Halldin|first15=Christer|last16=Taylor|first16=Norman|last17=Minhae|first17=Kim|last18=Hooker|first18=Jacob M.|last19=Edwards|first19=Robert R.|last20=Napadow|first20=Vitaly|last21=Kosek|first21=Eva|last22=Loggia|first22=Marco L.}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0889159118302423 (Full text)]<br />
*2020, In-vivo imaging of neuroinflammation in veterans with Gulf War illness<ref name="Loggia2020">{{Cite journal|last=Alshelh|first=Zeynab|author-link=|last2=Albrecht|first2=Daniel S.|author-link2=|last3=Bergan|first3=Courtney|author-link3=|last4=Akeju|first4=Oluwaseun|author-link4=|last5=Clauw|first5=Daniel J.|author-link5=Daniel Clauw|last6=Conboy|first6=Lisa|author-link6=|last7=Edwards|first7=Robert R.|last8=Kim|first8=Minhae|last9=Lee|first9=Yvonne C.|date=2020-02-04|title=In-vivo imaging of neuroinflammation in veterans with Gulf War illness|url=http://www.sciencedirect.com/science/article/pii/S0889159119313340|journal=Brain, Behavior, and Immunity|language=en|volume=87|issue=|pages=498-507|doi=10.1016/j.bbi.2020.01.020|issn=0889-1591|pmc=|pmid=|access-date=|quote=|via=|last10=Protsenko|first10=Ekaterina|last11=Napadow|first11=Vitaly|last12=Sullivan|first12=Kimberly|author-link12=Kimberly Sullivan|author-link13=Marco Loggia|last13=Loggia|first13=Marco F.}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0889159119313340 (Full text)]<br />
<br />
==Talks and interviews==<br />
*2016, [https://www.youtube.com/watch?v=_ijlkRwORfM What is neuroinflammation?]<ref>{{Cite web|url=https://www.youtube.com/watch?v=_ijlkRwORfM|title=What is neuroinflammation?|last=Younger|first=Jarred|date=Apr 4, 2016|website=YouTube|via=Younger Lab|archive-url=|archive-date=|access-date=}}</ref> - Jarred Younger<br />
*2016, [https://www.youtube.com/watch?v=1p6UojKL010 Do you have a hot brain?]<ref>{{Cite web|url=https://www.youtube.com/watch?v=1p6UojKL010|title=Do you have a hot brain?|last=Younger|first=Jarred|date=Apr 25, 2016|website=YouTube|via=Younger Lab|archive-url=|archive-date=|access-date=}}</ref> - Jarred Younger<br />
*2017, [https://www.betterhealthguy.com/episode49 Brain on Fire with Dr. Mary Ackerley, MD]<br />
*2017, [https://www.moldillnessmadesimple.com/brain-on-fire-brain-changes-in-mold-illness-with-dr-ackerley/ Brain on Fire Webinar - Brain Changes in Mold Illness with Dr. Mary Ackerley]<br />
* 2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study]<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|archive-url=|archive-date=|publisher=SolveCFS}}</ref> - SolveCFS<br />
* 2022, [https://www.youtube.com/results?search_query=solve+me%2Fcfs+jarred+younger+june+23 Dr. Jarred Younger Presents: How We Can See ME/CFS Inflammation in the Brain - Solve ME Webinar]<br />
<br />
== See also ==<br />
*[[Brain]]<br />
*[[Neurology of ME/CFS]]<br />
*[[Autopsy]]<br />
*[[Microglia]]<br />
*[[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]<br />
*[[Jarred Younger]]<br />
*[[Chronic pain]]<br />
<br />
==Learn more==<br />
*[https://www.healthrising.org/blog/2020/05/02/fibromyalgia-chronic-fatigue-syndrome-gulf-war-illness-neuroinflammation/? Fibromyalgia, Chronic Fatigue Syndrome, Gulf War Illness – the Widespread Neuroinflammation Diseases] - Cort Johnson<br />
* 2018, [https://www.healthrising.org/blog/2018/09/24/brain-fire-neuroinflammation-found-chronic-fatigue-syndrome-me-cfs/ Brain on Fire: Widespread Neuroinflammation Found in Chronic Fatigue Syndrome (ME/CFS)]<ref>{{Cite news|url=https://www.healthrising.org/blog/2018/09/24/brain-fire-neuroinflammation-found-chronic-fatigue-syndrome-me-cfs/|title=Brain on Fire: Widespread Neuroinflammation Found in Chronic Fatigue Syndrome (ME/CFS) - Health Rising|last=Johnson|first=Cort|date=2018-09-24|work=Health Rising|access-date=2018-09-26|archive-url=|archive-date=|language=en-US}}</ref> - Cort Johnson<br />
:<blockquote>[[Jarred Younger|Younger’s]] new approach looked at the entire [[brain]] and found signs of [[inflammation]] almost everywhere. When asked what could cause that, Younger said that any neurodegenerative/ neuroinflammatory disorder like [[Multiple sclerosis|MS]] or a severe brain injury that tweaks the [[microglia]] (immune cells in the brain) enough to produce a sustained period of inflammation, burns up the oxygen in the system. Once that happens, the cells resort to [[anerobic metabolism]] and lactate builds up just as it does in the [[muscle]]s during [[exercise]].</blockquote><br />
*2015, [http://med.stanford.edu/news/all-news/2014/10/study-finds-brain-abnormalities-in-chronic-fatigue-patients.html Study finds brain abnormalities in chronic fatigue patients] - Stanford University <br />
*2014, [http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/ Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder] - NY Times Well article by [[David Tuller]] on the [[brain scans]] of [[ME/CFS]] patients researched by [[Stanford ME/CFS Initiative]] <br />
*2014, [http://paradigmchange.me/wp/fire/ Brain on Fire - The Role of Toxic Mold in Triggering Psychiatric Symptoms] - Paradigm Change <br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Body systems]]<br />
[[Category:Neurology]]<br />
[[Category:Immunology]]</div>Darlahttps://me-pedia.org/w/index.php?title=Jarred_Younger&diff=112137Jarred Younger2022-06-27T11:11:17Z<p>Darla:/* Talks and interviews */</p>
<hr />
<div>[[File:Younger.jpg|200px|right]]<br />
'''Jarred W. Younger''' B.A. PhD. is an American researcher who leads the Neuroinflammation, Pain and Fatigue lab at the University of Birmingham, Alabama, [[United States]].<ref name="uab-profile">https://www.uab.edu/cas/psychology/people/faculty/jarred-younger</ref> He previously worked at the [[Stanford ME/CFS Initiative]] with [[Jose Montoya]], as an Assistant Professor involved in a notable study highlighting [[leptin]] levels and [[ME/CFS]].<ref name="stanfordleptin" /><ref name="pandoravideo">{{Cite web|title=Pandora Research Report: Jarred Younger - Leptin in the Role of Neuroinflammation, Pain and Fatigue|date=Jan 24, 2015|url=https://www.youtube.com/watch?v=bFwAyrb5p34|language=en|access-date=2019-09-12}}</ref><br />
<br />
He is currently funded by the U.S. [[National Institutes of Health]] and Department of Defense to study new techniques for diagnosing and treating [[neuroinflammation]] in ME/CFS, [[fibromyalgia]] and [[Gulf War Illness]]. In particular his work focuses on the role of [[microglia]].<br />
<br />
==Awards==<br />
*2016 [[Ramsay Award]] Program grant recipient, sponsored by the [[Solve ME/CFS Initiative]] for Advanced Non-Invasive Analysis in ME/CFS Diagnosis and Treatment Decisions<ref>{{Cite web|url=https://solvecfs.org/2016-ramsay-award-program-results/|title=2016 Ramsay Award Program Results|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-09-12}}</ref><ref>{{Cite web|url=https://solvecfs.org/advanced-non-invasive-analysis-in-mecfs-diagnosis-and-treatment-decisions/|title=Advanced Non-Invasive Analysis in ME/CFS Diagnosis and Treatment Decisions|date=2016-12-07|website=Solve ME/CFS Initiative|language=en-US|access-date=2020-02-18}}</ref><br />
<br />
==Committees and boards==<br />
===ME/CFS Collaborative Research Center===<br />
Dr. Younger is a member of the Working Group which offers their expertise and resources to the [[ME/CFS Collaborative Research Center at Stanford University]].<ref>{{Cite web|url=https://bos.etapestry.com/prod/viewEmailAsPage.do?erRef=773.0.423082047&databaseId=OMF&mailingId=34274682&jobRef=773.0.506425459&key=b6b9237b3ebd1e462a5d11dbc5c4dae&personaRef=773.0.423082048&memberId=1348639685|title=OMF grants $1.2M to Ramp Up Collaborative Research Center at Stanford University|website=bos.etapestry.com|access-date=2019-09-12}}</ref> <br />
<br />
===ME/CFS Common Data Element (CDE) Project===<br />
Chair (Overall/Cognitive) of the Neurologic/Cognitive/CNS Imaging Working Group of the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Common Data Element (CDE) Project sponsored by the [[National Institute of Neurological Disorders and Stroke]] (NINDS) and the [[Centers for Disease Control and Prevention]] (CDC).<ref>{{Cite web|url=https://www.commondataelements.ninds.nih.gov/Myalgic%20Encephalomyelitis/Chronic%20Fatigue%20Syndrome#pane-138|title=Complete Myalgic Encephalomyelitis/Chronic Fatigue Syndrome CDE Roster|last=|first=|authorlink=|date=|website=NIH|archive-url=|archive-date=|access-date=2019-10-11}}</ref><br />
<br />
==Notable studies==<br />
*2010, [[Low dose naltrexone]] for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels<ref name="Younger2013">{{Cite journal|last=Younger|first=Jarred|author-link=Jarred Younger|last2=Noor|first2=Noorulain|author-link2=|last3=McCue|first3=Rebecca|author-link3=|last4=Mackey|first4=Sean|author-link4=|date=Feb 2013|title=Low-dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels|url=http://doi.wiley.com/10.1002/art.37734|journal=Arthritis & Rheumatism|language=en|volume=65|issue=2|pages=529–538|doi=10.1002/art.37734|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.37734 (Full Text)]<br />
*2009, Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study<ref name="Younger2009">{{Cite journal|last=Younger|first=Jarred|author-link=Jarred Younger|last2=Mackey|first2=Sean|author-link2=|date=May 2009|title=Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study|url=https://academic.oup.com/painmedicine/article-lookup/doi/10.1111/j.1526-4637.2009.00613.x|journal=Pain Medicine|language=en|volume=10|issue=4|pages=663–672|doi=10.1111/j.1526-4637.2009.00613.x|issn=1526-2375|pmc=2891387|pmid=19453963|access-date=|quote=|via=}}</ref> - [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891387/ (Full Text)] <br />
*2013, Daily cytokine fluctuations, driven by [[leptin]], are associated with fatigue severity in [[chronic fatigue syndrome]]: Evidence of inflammatory pathology<ref name="stanfordleptin">{{Cite journal <br />
| last1 = Stringer | first1 = EA <br />
| last2 = Baker | first2 = KS <br />
| last3 = Carrol | first3 = IR <br />
| last4 = Montoya | first4 = JG | authorlink4 = Jose Montoya<br />
| last5 = Chu | first5 = L | authorlink5 = Lily Chu <br />
| last6 = Maeker | first6 = HT <br />
| last7 = Younger | first7 = JW | authorlink7 = Jarred Younger| title = Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: Evidence of inflammatory pathology | journal = J Transl Med.| date = Apr 9, 2013 | pmid = 23570606 | pmc = 3637529 | doi = 10.1186/1479-5876-11-93| url = http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-11-93 }}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637529/ (Full Text)] <br />
*2017, Cytokine signature associated with disease severity in chronic fatigue syndrome patients<ref name="Montoya, 2017">{{Cite journal <br />
| last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya<br />
| last2 = Holmes | first2 = Tyson H. | authorlink2 = <br />
| last3 = Anderson | first3 = Jill N. | authorlink3 = <br />
| last4 = Maecker | first4 = Holden T. | authorlink4 = <br />
| last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = <br />
| last6 = Valencia | first6 = Ian J. | authorlink6 = Ian Valencia <br />
| last7 = Chu | first7 = Lily | authorlink7 = Lily Chu<br />
| last8 = Younger | first8 = Jarred W. | authorlink8 = Jarred Younger<br />
| last9 = Tato | first9 = Cristina M. | authorlink9 = <br />
| last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis| title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | page = E7150-E7158| date = 2017| pmid = | doi = 10.1073/pnas.1710519114 }}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576836/ (Full Text)]<br />
*2019, Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy<ref name="Meuller2019">{{Cite journal|last=Mueller|first=Christina|author-link=|last2=Lin|first2=Joanne C.|author-link2=|last3=Sheriff|first3=Sulaiman|author-link3=|last4=Maudsley|first4=Andrew A.|author-link4=|last5=Younger|first5=Jarred W.|author-link5=Jarred Younger|date=2019-01-07|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|url=http://link.springer.com/10.1007/s11682-018-0029-4|journal=Brain Imaging and Behavior|language=en|volume=|issue=|pages=|doi=10.1007/s11682-018-0029-4|issn=1931-7557|quote=|via=}}</ref> - [[pubmed:30617782|(Abstract)]]<br />
<br />
==Talks and interviews==<br />
*2011, [https://www.youtube.com/watch?v=ma_lY7NFLQk Chronic Pain in Women]<br />
*2014, [https://www.youtube.com/watch?v=NoGfOsrarlY ME/CFS Alerts Episode 68: Jarred Younger Interviewed by Deborah Waroff]<br />
*2015, [https://www.youtube.com/watch?v=TOqBYZg6Nmo Dr Jarred Younger - LDN Scientist - Low Dose Naltrexone]<br />
*2015, [https://www.youtube.com/watch?v=bFwAyrb5p34 Pandora Research Report: Jarred Younger - Leptin in the Role of Neuroinflammation, Pain and Fatigue] (see [[Leptin]])<br />
*2015, [https://www.youtube.com/watch?v=TH_upgDgLQ8 Jarred Younger, Ph.D. - Microglial Modulation in the Treatment of Fibromyalgia]<br />
*2015, [[Spoonie Radio]] [https://www.youtube.com/watch?v=9UqkB6TBQ-A Ep 15: Jarred Younger] (see also [[Courtney Craig]]) <br />
*2016, [https://www.youtube.com/watch?v=wJB95m4FLa0 Chronic Fatigue Syndrome & Myalgic Encephalomyelitis: Can We Find Answers in the Brain? - Solve CFS Webinar]<br />
*2016, [https://www.youtube.com/channel/UCoVoOvIX90IMEZCbBf_ycEA Younger Lab YouTube Channel: Series of ongoing talks on the work of the lab]<br />
*2016, [http://selfhacked.com/2016/03/29/dr-jared-younger-cutting-edge-research-on-cfs-neuroinflammation-pain-and-fatigue/ Dr. Jarred Younger: Cutting Edge Research on CFS, Neuroinflammation, Pain, and Fatigue]<br />
* 2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study]<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|archive-url=|archive-date=|publisher=SolveCFS}}</ref><br />
* 29 Sep 2018, ''How Brain Inflammation Causes ME/CFS'', given at Second Annual [[Community Symposium on the Molecular Basis of ME/CFS - 2017|Community Symposium on the Molecular Basis of ME/CFS]], sponsored by [[Open Medicine Foundation]] - [https://www.youtube.com/watch?v=8XrdSlpUQTE&list=PLl4AfLZNZEQPxjqF4ojAO3wdCFMeriNBK&index=14 (Video)]<br />
*2019, [https://www.youtube.com/watch?v=JW-JYCcAnUg Dr. Jarred Younger - Neuroinflammation in ME/CFS]<br />
*2022, [https://www.youtube.com/results?search_query=solve+me%2Fcfs+jarred+younger+june+23 Dr. Jarred Younger Presents: How We Can See ME/CFS Inflammation in the Brain - Solve ME Webinar]<br />
<br />
==Articles and blogs==<br />
*2015, [http://www.cortjohnson.org/blog/2015/07/15/the-neuroinflammation-man-jarred-younger-on-inflammation-fibromyalgia-and-chronic-fatigue-syndrome/ The Neuroinflammation Man: Jarred Younger on Inflammation, Fibromyalgia and Chronic Fatigue Syndrome] ([[Cort Johnson]])<br />
*2015, [http://www.cortjohnson.org/blog/2015/01/09/younger-chronic-fatigue-fibromyalgia-lab/ New Chronic Fatigue Syndrome and Fibromyalgia Lab Opens: Jarred Younger Talks] (Cort Johnson)<br />
*2016, [http://www.uab.edu/uabmagazine/features/prisoners-of-pain Prisoners of Pain - UAB magazine (Spring 2016)]<br />
*2016, [https://selfhacked.com/2016/03/29/dr-jared-younger-cutting-edge-research-on-cfs-neuroinflammation-pain-and-fatigue/ Self Hacked on Dr Younger]<br />
*2016, [https://www.youtube.com/channel/UCoVoOvIX90IMEZCbBf_ycEA/ Younger Lab YouTube Channel]<br />
*2016, [http://www.cortjohnson.org/blog/2016/03/08/fibromyalgia-chronic-fatigue-syndrome-neuroinflammation-pain-fatigue-lab-makes-good/ Fibromyalgia and Chronic Fatigue Syndrome (ME/CFS) Research Center Makes Good] (Cort Johnson)<br />
*2018, [https://www.healthrising.org/blog/2018/09/24/brain-fire-neuroinflammation-found-chronic-fatigue-syndrome-me-cfs/ Brain on Fire: Widespread Neuroinflammation Found in Chronic Fatigue Syndrome (ME/CFS)](Cort Johnson)<br />
<blockquote>Younger's new approach looked at the entire [[brain]] and found signs of [[inflammation]] almost everywhere. When asked what could cause that, Younger said that any neurodegenerative/ neuroinflammatory disorder like [[Multiple sclerosis|MS]] or a severe brain injury that tweaks the [[microglia]] (immune cells in the brain) enough to produce a sustained period of inflammation, burns up the [[oxygen]] in the system. Once that happens, the cells resort to [[anaerobic metabolism]] and lactate builds up just as it does in the [[Muscle|muscles]] during [[exercise]].</blockquote><br />
<br />
==See also==<br />
*[[Fibromyalgia]]<br />
*[[Gulf War Illness]]<br />
*[[Chronic fatigue syndrome]]<br />
*[[Leptin]]<br />
*[[Low dose naltrexone]]<br />
*[[Microglia]]<br />
*[[Neuroinflammation]]<br />
<br />
==Learn more==<br />
*[https://www.ncbi.nlm.nih.gov/pubmed/?term=Younger%20J%5BAuthor%5D&cauthor=true&cauthor_uid=24526250 Publications on the PubMed register - Jarred Younger]<br />
*[https://sites.uab.edu/younger/ UAB Departmental Website]<br />
*[https://www.uab.edu/cas/psychology/people/faculty/jarred-younger Biography at UAB]<br />
*[https://www.facebook.com/Neuroinflammation-Pain-and-Fatigue-Laboratory-at-UAB-1543963919214695/ Facebook page for Younger Lab at UAB]<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Researchers]]<br />
[[Category:US researchers]]</div>Darlahttps://me-pedia.org/w/index.php?title=Epstein-Barr_virus&diff=112095Epstein-Barr virus2022-06-14T11:00:43Z<p>Darla:/* Notable studies */</p>
<hr />
<div>{{Cleanup|reason=Add summary of the Notable studies from 2019 onwards|date=28 July 2020}}<br />
<br />
[[The 3Ps model|The]] '''Epstein-Barr virus''' (EBV) or HHV4 is a [[herpesvirus]]. It is the most common cause of infectious [[mononucleosis]] or "glandular fever," and infects 90% of adults worldwide.<ref name="Saha2016">{{Cite journal <br />
| last1 = Saha | first1 = Abhik<br />
| last2 = Robertson | first2 = Erle S<br />
| title = Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes<br />
| journal = Clinical Cancer Research<br />
| issn = 1557-3265| volume = 17| issue = 10| pages = 3056–3063<br />
| date = 2011-05-15<br />
| pmid = 21372216 | doi = 10.1158/1078-0432.CCR-10-2578| url = http://clincancerres.aacrjournals.org/content/17/10/3056}}</ref> It has been implicated in numerous immune diseases and chronic illnesses, including [[chronic fatigue syndrome]], [[multiple sclerosis]], [[myasthenia gravis]], and [[systemic lupus erythematosus]]. It is known to turn on "risk genes" for autoimmune disease in the cells it infects.<ref name=":0">{{Cite journal|last=Harley|first=John|date= 16 April 2018|title=Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity|url=https://www.nature.com/articles/s41588-018-0102-3|journal=Nature genetics|volume=|pages=|issue=|via=|quote=}}</ref><ref name=":1">{{Cite web|url=https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases|title=Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases|last=|first=|date=16 April 2018|website=National Institutes of Health|archive-url=|archive-date=|url-status=|access-date=}}</ref><br />
<br />
== Initial infection ==<br />
[[File:Epstein-barr virus (ebv).jpg|thumb|A stained sample of Epstein-Barr virus.]]<br />
Symptoms of EBV infection include: <br />
* [[fatigue]]<br />
<br />
* [[fever]]<br />
* [[rash]]<br />
* inflamed [[sore throat|throat]]<br />
* [[swollen lymph nodes]]<br />
* enlarged [[spleen]]<br />
* swollen [[liver]]<ref name=":2">{{Cite web|url=http://www.cdc.gov/epstein-barr/about-ebv.html|title=Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono {{!}} CDC|date=2018-05-10|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-14}}</ref><br />
<br />
===Age of infection===<br />
<br />
Most people acquire EBV in early childhood. Typically, young children who acquire EBV are either not symptomatic or have mild symptoms that are hard to distinguish from a cold or other other mild, childhood illnesses. <br />
<br />
In adolescents and young adults, EBV can cause [[infectious mononucleosis]] (IM), also known as glandular fever.<ref name=":2" /> IM is characterized by [[fever]], [[sore throat]], [[swollen lymph nodes]], [[pain|body aches]], and [[fatigue]]. It generally resolves with rest and only rarely causes serious complications. It typically occurs in people who have not been exposed to EBV in early childhood, and in comparison, is more severe than infection in childhood (i.e., it can last for months). <br />
<br />
Following initial infection, EBV can reactivate and has been shown to have many connections with various chronic illnesses. Relative to initial infections, reactivated EBV is much more severe.<br />
<br />
==Transmission==<br />
<br />
EBV is transmitted through bodily fluids, most commonly through saliva. The first time a person is infected with EBV, the person is contagious for weeks (even when not displaying symptoms). The virus then transitions to the latent or inactive form, and stays in the body. If the virus reactivates, the person will be contagious again.<ref name=":2" /><br />
<br />
== Diagnosis ==<br />
EBV infection is confirmed with blood tests that detect presence of [[:Category:Antibodies|antibodies]]. Nine out of ten adults have these antibodies, indicating that they have a current or past EBV infection.<ref name=":2" /><br />
<br />
Anti-VCA (Viral capsid antigen) IgG and EBV nuclear antigen (EBNA) IgG antibodies persist throughout a person's life. Thus, positive results merely indicate a current or past infection. A current EBV infection is diagnosed based on the presence of Anti-VCA IgM and Anti-EA (Early Antigen) IgG. VCA IgM appears early in EBV infection and usually disappears within four to six weeks. Positive VCA IgM suggests current active acute EBV infection. EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. Positive EA IgG can suggest current active EBV infection or EBV re-activation. <ref>{{Cite web|url=https://www.cdc.gov/epstein-barr/laboratory-testing.html|title=Epstein-barr {{!}} Mononucleosis {{!}} Laboratory Testing {{!}} Mono {{!}} CDC|date=2019-01-28|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-10-08}}</ref><br />
<br />
==Latency==<br />
<br />
In healthy adults, the virus remains latent for life in memory [[B cell]]s. It is estimated that 1 in every one hundred thousand to one million circulating B cells carry EBV.<ref>{{Cite journal|last=Hsu|first=J. L.|last2=Glaser|first2=S. L.|date=Apr 2000|title=Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications|url=https://www.ncbi.nlm.nih.gov/pubmed/10781747/|journal=Critical Reviews in Oncology/Hematology|volume=34|issue=1|pages=27–53|issn=1040-8428|pmid=10781747}}</ref> In healthy hosts, EBV populations are kept in check by [[CD4+ T cell|CD4<sup>+</sup>]] and [[CD8|CD8<sup>+</sup>]] [[T cell|T-cell]] responses. <br />
<br />
The equilibrium can be disrupted in individuals with compromised [[immune system]]s such as patients with [[AIDS]] or transplant patients taking immune system suppressing drugs.<ref name=":3">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206|issue=|pages=4|quote=|via=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=}}</ref> It has been observed that these patients are more susceptible to EBV-related [[cancer]]s, such as certain [[lymphoma]]s and carcinomas.<ref>{{Cite journal|last=Pattle|first=Samuel B.|last2=Farrell|first2=Paul J.|date=Nov 2006|title=The role of Epstein-Barr virus in cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/17049016|journal=Expert Opinion on Biological Therapy|volume=6|issue=11|pages=1193–1205|doi=10.1517/14712598.6.11.1193|issn=1744-7682|pmid=17049016|quote=|via=}}</ref> In immunocompromised patients, EBV can induce lymphoproliferation, [[lymphoma]], and hemophagocytic lymphohistiocytosis (HLH).<ref>{{Cite journal|last=Tangye|first=Stuart|date=January 20, 2017|title=Human immunity against EBV—lessons from the clinic|url=http://jem.rupress.org/content/214/2/269|journal=Journal of Experimental Medicine|volume=|pages=|issue=|via=|quote=}}</ref><br />
===Natural killer T cells===<br />
<br />
It is thought that [[natural killer T cell]]s (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of [[CD1d]] expressing cells.<ref name=":3" /><br />
<br />
==Neuronal infection==<br />
A 2015 study<ref name="JhaHC2015">{{Cite journal <br />
| last1 = Jha | first1 = HC | authorlink1 = <br />
| last2 = Mehta | first2 = D | authorlink2 = <br />
| last3 = Lu | first3 = J | authorlink3 = <br />
| last4 = El-Naccache | first4 = D | authorlink4 = <br />
| last5 = Shukla | first5 = SK | authorlink5 =<br />
| last6 = Kovacsics | first6 = C | authorlink6 =<br />
| last7 = Kolson | first7 = D | authorlink7 = <br />
| last8 = Robertson | first8 = ES | authorlink8 =<br />
| title = Gammaherpesvirus Infection of Human Neuronal Cells<br />
| journal = mBio | volume = 6 | issue =6 | pages = <br />
| date = 2016-12-01<br />
| doi = 10.1128/mBio.01844-15 | pmid = 26628726<br />
| url = http://mbio.asm.org/content/6/6/e01844-15<br />
}}</ref> demonstrated that human [[neuron]]al cells could be directly and actively infected with EBV and another [[herpesvirus]], Kaposi's sarcoma-associated herpesvirus (KSHV).<br />
<br />
Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]].<br />
<br />
EBV is known to be linked to many neuronal diseases<ref name="Kleines2011">{{citation<br />
| last1 = Kleines | first1 = M<br />
| last2 = Schiefer | first2 = J<br />
| last3 = Stienen | first3 = A<br />
| last4 = Blaum | first4 = M<br />
| last5 = Ritter | first5 = K<br />
| last6 = Häusler | first6 = M<br />
| title = Expanding the spectrum of neurological disease associated with Epstein-Barr virus activity<br />
| journal = European Journal of Clinical Microbiology & Infectious Diseases<br />
| issn = 1435-4373| volume = 30| issue = 12| pages = 1561–1569<br />
| date = 2011-05-15| doi = 10.1007/s10096-011-1261-7| url = http://link.springer.com/article/10.1007/s10096-011-1261-7}}</ref> but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.<br />
<br />
==In human disease==<br />
<br />
Epstein-Barr virus has been associated with a wide number of immune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[systemic lupus erythematosus]],<ref>{{Cite journal|last=Lossius|first=Andreas|date=December 2012|title=Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528287/|journal=Virus|volume=|pages=|issue=|via=|quote=}}</ref> [[Chronic fatigue syndrome]], and [[myasthenia gravis]]. EBV was recently discovered to turn on "risk genes" for autoimmune disease in the cells it infects. [[Epstein-Barr virus nuclear antigen 2|EBNA2]], a protein produced by EBV-infected cells, and its related transcription factors activate half the human genes known to be associated with the risk for lupus as well as genes associated with several other autoimmune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[inflammatory bowel disease]], [[Diabetes#Types|type 1 diabetes]], [[juvenile idiopathic arthritis]] and [[celiac disease]]. EBV activation can thus increase the risk of developing these diseases.<ref name=":0" /><ref name=":1" /> <br />
<br />
===Chronic fatigue syndrome===<br />
<br />
A prospective study of 250 primary care patients revealed a higher prevalence of [[chronic fatigue syndrome]] after infectious [[mononucleosis]] (glandular fever) when compared to an ordinary upper respiratory tract infection.<ref name=":4">{{Cite journal|last=White|first=P. D.|last2=Thomas|first2=J. M.|last3=Amess|first3=J.|last4=Crawford|first4=D. H.|last5=Grover|first5=S. A.|last6=Kangro|first6=H. O.|last7=Clare|first7=A. W.|date=Dec 1998|title=Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever|url=https://www.ncbi.nlm.nih.gov/pubmed/9926075|journal=The British Journal of Psychiatry: The Journal of Mental Science|volume=173|pages=475–481|issn=0007-1250|pmid=9926075}}</ref> Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.<ref name=":5">{{Cite journal|last=Schmaling|first=K. B.|last2=Jones|first2=J. F.|date=Jan 1996|title=MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1|pages=67–74|issn=0022-3999|pmid=8730646}}</ref> A 2006 Australian prospective study found that 12% of subjects infected by EBV met the criteria for [[Chronic fatigue syndrome]] six months after their infection, and 9% still had CFS 12 months after infection.<ref name=":6">{{Cite journal|last=Hickie|first=Ian|author-link=Ian Hickie|last2=Davenport|first2=Tracey|author-link2=Tracey Davenport|last3=Wakefield|first3=Denis|author-link3=Denis Wakefield|last4=Vollmer-Conna|first4=Ute|author-link4=Uté Vollmer-Conna|last5=Cameron|first5=Barbara|author-link5=|last6=Vernon|first6=Suzanne D|author-link6=Suzanne Vernon|last7=Reeves|first7=William C|author-link7=William Reeves|last8=Lloyd|first8=Andrew|author-link8=Andrew Lloyd|date=2006-09-16|title=Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/|journal=BMJ : British Medical Journal|volume=333|issue=7568|pages=575|doi=10.1136/bmj.38933.585764.AE|issn=0959-8138|pmc=1569956|pmid=16950834|access-date=|quote=|via=}}</ref> (The same rate held true for [[Ross River virus]] and [[Q fever]]).<br />
<br />
=== Long COVID ===<br />
Long COVID may be associated [[herpesvirus]] reactivation such as Epstein-Barr Virus.<ref>{{Cite journal|last=Proal|first=Amy D.|author-link=Amy Proal|last2=VanElzakker|first2=Michael B.|author-link2=Michael VanElzakker|date=2021|title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms|url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=12|issue=|pages=698169|doi=10.3389/fmicb.2021.698169|issn=1664-302X}}</ref><br />
<br />
===Multiple sclerosis===<br />
<br />
Infection later in life, high serum titers against EBV, and [[mononucleosis]] have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.<ref>{{Cite journal|last=Holmøy|first=Trygve|date=2008|title=Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis|url=http://www.sciencedirect.com/science/article/pii/S0306987707003167|journal=Medical Hypotheses|volume=70|issue=|pages=|via=}}</ref><br />
<br />
Several studies by Alberto Ascherio, MD, DrPH, and his team at the Harvard School of Public Health have suggested that Epstein-Barr virus is involved in [[multiple sclerosis]], specifically in people with a certain immune-related gene and high levels of antibodies to EBV in their blood.<ref>{{Cite web|url=https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses|title=Viruses|last=|first=|date=|website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref><br />
<br />
=== Systemic lupus erythematosus ===<br />
In a study of young patients with lupus, 99% had EBV as compared to 70% of healthy controls.<ref>{{Cite journal|last=James|first=JA|date=1997-12-15|title=An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus|url=https://www.jci.org/articles/view/119856|journal=The Journal of Clinical Investigation|volume=|issue=|pages=|via=}}</ref> Another study found that patients with SLE had a roughly 40-fold increase in EBV viral loads compared with controls, likely stemming from altered [[t cell]] responses against EBV.<ref>{{Cite journal|last=Kang|first=Insoo|date=15 January 2004|title=Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus|url=http://www.jimmunol.org/content/172/2/1287.short|journal=The Journal of Immunology|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Myasthenia gravis===<br />
<br />
[[B cell]]s from [[myasthenia gravis]] patient stimulated ''in vitro'' by Epstein-Barr virus produced [[acetylcholine]] autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=https://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> Ongoing EBV infection of the [[thymus]] has been posited as a causative agent for the production of [[acetylcholine]] receptor autoantibodies in [[myasthenia gravis]].<ref>{{Cite journal|last=Kaminski|first=Henry J|last2=Minarovits|first2=Janos|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134|date=2010|volume=67|issue=6|pages=697-698|doi=|pmc=|pmid=|quote=|access-date=|via=}}</ref><ref>http://journals.lww.com/neurologynow/_layouts/15/oaks.journals.mobile/post.aspx?blogId=2&postId=10</ref><br />
<br />
=== Gastrointestinal disease ===<br />
One study of EBV in patients with [[gastritis]], [[Crohn's disease]], and [[ulcerative colitis]] and normal controls found essentially undetectable levels of EBV in normal gastric mucosa. However, EBV was detected in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples.<ref>{{Cite journal|last=Ryan|first=Julie|date=2013|title=Epstein-Barr Virus Infection is Common in Inflamed Gastrointestinal Mucosa|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535492/|journal=Dig Dis Sci.|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Lyme disease===<br />
Several herpesviruses including Epstein-Barr virus<ref name="Goossens1999">{{Cite journal <br />
| last1 = Goossens | first1 = HA<br />
| last2 = Nohlmans | first2 = MK <br />
| last3 = van den Bogaard | first3 = AE<br />
| title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis| journal = Infection | issue = 1999 | volume = 27 | pages =231| pmid = 10378140| url = https://www.ncbi.nlm.nih.gov/pubmed/10378140}}</ref> may cause false positives on [[Lyme disease]] tests.<br />
<br />
===XMEN disease===<br />
<br />
A 2014 study found chronic Epstein-Barr infection was linked to a magnesium transporter [[MAGT-1]] mutation.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/84061|title=MAGT1 magnesium transporter 1 [Homo sapiens (human)] - Gene|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NCBI|archive-url=|archive-date=|url-status=|access-date=2022-05-21}}</ref> Dysfunction in this transporter also resulted in decreased NK cell function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Cite journal |last1 = Li |first1 = F.-Y. |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Su<br />
| first3 = H<br />
| last4 = Matthews<br />
| first4 = H |last5 = Lenardo |first5 = M.J. |authorlink3 = <br />
| title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. <br />
| journal = Blood| date = 2014| doi = 10.1182/blood-2013-11-538686|url=https://ashpublications.org/blood/article/123/14/2148/32463/XMEN-disease-a-new-primary-immunodeficiency|issue=14|pages=2148–2152|pmc=|pmid=|quote=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|access-date=|author-link4=|author-link5=|author-link6=|via=|volume=123}}</ref><br />
<br />
This disorder, termed 'XMEN' (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. <br />
<br />
Since chronic Epstein-Barr virus infection has been associated with chronic fatigue syndrome, this error in [[magnesium]] transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /><ref name="X-men_disease_2">{{Cite journal |last1 = Ravell |first1 = J |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Lenardo<br />
| first3 = M| title = XMEN disease: a combined immune deficiency with magnesium defect. <br />
| journal = Current Opinion in Pediatrics<br />
| date = 2014| doi = 10.1097/MOP.0000000000000156}}</ref> However, in this disorder, EBV would be seen as an indicator of the illness rather than the cause.<br />
<br />
==Vitamin D==<br />
<br />
Some recent research is finding links between EBV and [[Vitamin D]]<br />
<br />
An Epstein-Barr virus protein EBNA-3 has an affinity for [[VDR]] and may actually block the activation of VDR-dependent genes by [[Vitamin D]].<ref>{{Cite journal|last=Yenamandra|first=Surya Pavan|last2=Hellman|first2=Ulf|last3=Kempkes|first3=Bettina|last4=Darekar|first4=Suhas Deoram|last5=Petermann|first5=Sabine|last6=Sculley|first6=Tom|last7=Klein|first7=George|last8=Kashuba|first8=Elena|date=Dec 2010|title=Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes|url=https://www.ncbi.nlm.nih.gov/pubmed/20593215|journal=Cellular and molecular life sciences: CMLS|volume=67|issue=24|pages=4249–4256|doi=10.1007/s00018-010-0441-4|issn=1420-9071|pmid=20593215}}</ref><br />
<br />
[[Vitamin D receptor]] may be required for the normal development of [[natural killer T cell]]s that react to cells expressing [[CD1d]], as in cells infected by EBV.<ref>{{Cite journal|last=Yu|first=Sanhong|last2=Cantorna|first2=Margherita T.|date=2008-04-01|title=The vitamin D receptor is required for iNKT cell development|url=http://www.pnas.org/content/105/13/5207|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=13|pages=5207–5212|doi=10.1073/pnas.0711558105|issn=0027-8424|pmid=18364394}}</ref><br />
<br />
As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels<ref>{{Cite journal|last=Ramien|first=Caren|last2=Pachnio|first2=Annette|last3=Sisay|first3=Sofia|last4=Begum|first4=Jusnara|last5=Leese|first5=Alison|last6=Disanto|first6=Giulio|last7=Kuhle|first7=Jens|last8=Giovannoni|first8=Gavin|last9=Rickinson|first9=Alan|date=May 2014|title=Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort|url=https://www.ncbi.nlm.nih.gov/pubmed/24192216?dopt=Abstract|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=20|issue=6|pages=751–753|doi=10.1177/1352458513509507|issn=1477-0970|pmid=24192216}}</ref> (i.e., above 100 nmol/l).<br />
<br />
==Treatment==<br />
<br />
There is no specific treatment for EBV, only treatment of symptoms, such as taking over-the-counter medications for pain and fever.<ref name=":2" /> EBV is thought to persistent harmlessly in immunocompetent individuals, but in those with compromised immune systems it has been associated with certain cancers and possibly autoimmune disease. <br />
<br />
===Antivirals===<br />
<br />
Several [[antiviral]]s are active against EBV including [[valganciclovir|valganciclovir,]] [[valacyclovir]]<ref>{{Cite journal|last=Hoshino|first=Yo|date=|title=Long-Term Administration of Valacyclovir Reduces the Number of Epstein-Barr Virus (EBV)-Infected B Cells but Not the Number of EBV DNA Copies per B Cell in Healthy Volunteers|url=http://jvi.asm.org/content/83/22/11857.full|journal=Journal of Virology|volume=|issue=|pages=|via=}}</ref>, [[acyclovir]]<ref>{{Cite journal|last=Rafaillidis|first=Pl|date=Nov 2013|title=Antiviral treatment for severe EBV infections in apparently immunocompetent patients|url=https://www.ncbi.nlm.nih.gov/pubmed/20739216|journal=Journal of Clinical Virology|volume=|issue=|pages=|via=}}</ref>, and [[spironolactone]].<ref name="Verma2016">{{Cite journal <br />
| last1 = Verma | first1 = Dinesh<br />
| last2 = Thompson | first2 = Jacob<br />
| last3 = Swaminathan | first3 = Sankar| title = Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function<br />
| journal = Proceedings of the National Academy of Sciences | issn = 1091-6490 | volume = 113| issue = 13| pages = 3609–3614<br />
| date = 2016-03-29<br />
| doi = 10.1073/pnas.1523686113 | pmid = 26976570| url = http://www.pnas.org/content/113/13/3609}}</ref><br />
<br />
[[Acyclovir]], an [[antiviral]] drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.<br />
<br />
A theoretical [[immunotherapy]] treatment proposes that inducing [[CD1d]] expression on EBV-infected B cells could prompt effective immune suppression of EBV by NKT cells.<ref>{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206}}</ref><br />
<br />
===Rituximab===<br />
<br />
[[Rituximab]] may be effective in completely eliminating Epstein-Barr virus infection from the peripheral blood.<ref>{{Cite journal|last=Diamantopoulos|first=Panagiotis T.|last2=Polonyfi|first2=Katerina|last3=Sofotasiou|first3=Maria|last4=Papadopoulou|first4=Vasiliki|last5=Kalala|first5=Fani|last6=Iliakis|first6=Theodoros|last7=Zervakis|first7=Kostantinos|last8=Tsilimidos|first8=Gerassimos|last9=Kouzis|first9=Panagiotis|date=Dec 2013|title=Rituximab in the treatment of EBV-positive low grade B-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/24324119|journal=Anticancer Research|volume=33|issue=12|pages=5693–5698|issn=1791-7530|pmid=24324119}}</ref> A study of seventeen patients with low-grade [[B cell]] lymphoma found that after three cycles of Rituximab, the virus had been completely eliminated from the peripheral blood in all but one patient.<br />
<br />
===Herbs and nutraceuticals===<br />
<br />
Herbs shown to have antiviral properties against EBV including [[licorice|licorice.]]<ref>{{Cite journal|last=Lin|first=Jung-Chung|last2=Cherng|first2=Jaw-Ming|last3=Hung|first3=Man-Shan|last4=Baltina|first4=Lidia A.|last5=Baltina|first5=Lia|last6=Kondratenko|first6=Rimma|date=Jul 2008|title=Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: structure-activity relationships|url=https://www.ncbi.nlm.nih.gov/pubmed/18423902|journal=Antiviral Research|volume=79|issue=1|pages=6–11|doi=10.1016/j.antiviral.2008.01.160|issn=0166-3542|pmid=18423902}}</ref> [[Vitamin C]] and Vitamin D<ref>{{Cite journal|last=Rolf|first=L|date=July 2017|title=Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis|url=https://www.ncbi.nlm.nih.gov/pubmed/28731372|journal=Multiple Sclerosis|volume=|issue=|pages=|via=}}</ref> might also decrease duration and severity of the symptoms of EBV infection.<ref>{{Cite journal|last=Mikirova|first=N|date=May 2014|title=Effect of high dose vitamin C on Epstein-Barr viral infection|url=https://www.ncbi.nlm.nih.gov/pubmed/24793092|journal=Med Sci Monit|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Vaccine===<br />
A [[vaccine]] for the prevention of Epstein-Barr virus is being explored.<ref>{{Cite web|url=https://www.nih.gov/news-events/news-releases/nih-researchers-make-progress-toward-epstein-barr-virus-vaccine|title=NIH researchers make progress toward Epstein-Barr virus vaccine|date=2019-04-09|website=National Institutes of Health (NIH)|language=en|access-date=2019-04-10}}</ref><br />
<br />
==Notable studies==<br />
*1996, MMPI profiles of patients with chronic fatigue syndrome<ref name=":5" /> - ([[pubmed:8730646|Abstract]])<br />
*1998, Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever<ref name=":4" /> - ([[pubmed:9926075|Abstract]])<br />
*2006, Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study<ref name=":6" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full text)]<br />
*2019, EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection<ref name="Asprusten2019">{{Cite journal|last=Asprusten|first=Tarjei Tørre|author-link=|last2=Pedersen|first2=Maria|author-link2=Maria Pedersen|last3=Skovlund|first3=Eva|author-link3=Eva Skovlund|last4=Wyller|first4=Vegard Bruun|author-link4=Vegard Bruun Wyller|date=2019|title=EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection|url=https://www.ncbi.nlm.nih.gov/pubmed/30957026|journal=BMJ paediatrics open|volume=3|issue=1|pages=e000390|doi=10.1136/bmjpo-2018-000390|issn=2399-9772|pmc=|pmid=30957026|quote=|via=}}</ref> - ([[pubmed:30957026|Abstract]])<br />
*2019, Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study<ref name="Pedersen2019a">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=|last3=Godang|first3=Kristin|author-link3=Kristin Godang|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|author-link7=|last8=Øie|first8=Merete Glenne|author-link8=|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=Jan 2019|title=Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pubmed/30261303|journal=Brain, Behavior, and Immunity|volume=75|issue=|pages=94–100|doi=10.1016/j.bbi.2018.09.023|issn=1090-2139|pmid=30261303|quote=}}</ref> - ([[pubmed:30261303|Abstract]])<br />
*2019, Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later<ref name="Pedersen2019b">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=Tarjei Tørre Asprusten|last3=Godang|first3=Kristin|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|last8=Øie|first8=Merete Glenne|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=2019-01-27|title=Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later|url=https://www.ncbi.nlm.nih.gov/pubmed/30685875|journal=Acta Paediatrica (Oslo, Norway: 1992)|volume=108|issue=8|pages=1521-1526|doi=10.1111/apa.14728|issn=1651-2227|pmid=30685875|quote=|via=}}</ref> - ([[pubmed:30685875|Abstract]])<br />
*2019, Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Williams|first=Marshall V.|author-link=|last2=Cox|first2=Brandon|author-link2=|last3=Lafuse|first3=William P.|author-link3=|last4=Ariza|first4=Maria Eugenia|author-link4=|author-link5=|date=May 2019|title=Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0149291819301730|journal=Clinical Therapeutics|language=en|volume=41|issue=5|pages=848–863|doi=10.1016/j.clinthera.2019.04.009|pmc=6525645|pmid=31040055|quote=|via=}}</ref> - ([https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext Full text)]<br />
*2019, Review article - Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis<ref name="Kerr2019EBV">{{Cite journal|last=Kerr|first=Jonathan R.|author-link=Jonathan Kerr|date=Feb 2019|title=Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00059/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00059|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full (Full text)]<br />
*2019, Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors<ref name="Kerr2019a">{{Cite journal|last=Kerr|first=Jonathan R|author-link=Jonathan Kerr|author-link2=|date=2019-07-17|title=Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors|url=http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205822|journal=Journal of Clinical Pathology|language=en|volume=|issue=|pages=jclinpath–2019–205822|doi=10.1136/jclinpath-2019-205822|issn=0021-9746|quote=|via=}}</ref> - [[pubmed:31315893|(Abstract)]]<br />
*2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal|last=Shikova|first=Evelina|author-link=|last2=Reshkova|first2=Valentina|author-link2=|last3=Kumanova|first3=Аntoniya|author-link3=|last4=Raleva|first4=Sevdalina|author-link4=|last5=Alexandrova|first5=Dora|author-link5=|last6=Capo|first6=Natasa|author-link6=|last7=Murovska|first7=Modra|date=2020|title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=|pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)]<br />
*2021, Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome<ref>{{Cite journal|title=Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|date=Nov 15, 2021|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/|journal=Frontiers in Immunology|volume=12|issue=|pages=656797|last=Ruiz-Pablos|first=Manuel|author-link=https://pubmed.ncbi.nlm.nih.gov/?term=Ruiz-Pablos%20M%5BAuthor%5D|last2=Paiva|first2=Bruno|author-link2=https://pubmed.ncbi.nlm.nih.gov/?term=Paiva%20B%5BAuthor%5D|last3=Monter-Mateo|first3=Rosario|author-link3=https://pubmed.ncbi.nlm.nih.gov/?term=Montero-Mateo%20R%5BAuthor%5D|last4=Garcia|first4=Nicolas|author-link4=https://pubmed.ncbi.nlm.nih.gov/?term=Garcia%20N%5BAuthor%5D|last5=Zabaleta|first5=Aintzane|author-link5=https://pubmed.ncbi.nlm.nih.gov/?term=Zabaleta%20A%5BAuthor%5D|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|doi=10.3389/fimmu.2021.656797|pmc=|pmid=34867935|access-date=June 10, 2022|quote=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/ Full text])<br />
*2021, Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue<ref>{{Cite journal|title=Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue|date=2021|url=https://pubmed.ncbi.nlm.nih.gov/34987499|journal=Frontiers in Immunology|volume=12|pages=715102|last=Fevang|first=Børre|last2=Wyller|first2=Vegard Bruun Bratholm|last3=Mollnes|first3=Tom Eirik|last4=Pedersen|first4=Maria|last5=Asprusten|first5=Tarjei Tørre|last6=Michelsen|first6=Annika|last7=Ueland|first7=Thor|last8=Otterdal|first8=Kari|doi=10.3389/fimmu.2021.715102|pmc=8721200|pmid=34987499|issn=1664-3224}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721200/ Full text])<br />
*2022, EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing T<sub>FH</sub> cell differentiation and extrafollicular activities<ref>{{Cite journal|title=EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities|date=2022-06-08|url=https://insight.jci.org/articles/view/158193|journal=JCI Insight|volume=7|issue=11|last=Cox|first=Brandon S.|last2=Alharshawi|first2=Khaled|last3=Mena-Palomo|first3=Irene|last4=Lafuse|first4=William P.|last5=Ariza|first5=Maria Eugenia|language=en|doi=10.1172/jci.insight.158193|issn=0021-9738}}</ref> - ([https://insight.jci.org/articles/view/158193 Full text])<br />
<br />
== See also ==<br />
* [[List of herpesvirus infection studies]]<br />
<br />
==Learn more ==<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Infectious agents]]<br />
[[Category:Triggers and risk factors]]<br />
[[Category:Virology]]<br />
[[Category:Viruses]]</div>Darlahttps://me-pedia.org/w/index.php?title=Talk:Epstein-Barr_virus&diff=112094Talk:Epstein-Barr virus2022-06-14T10:54:46Z<p>Darla:added suggestion to remove source 16</p>
<hr />
<div>Studies to add to this page:<br />
<br />
* 2009, [https://www.tandfonline.com/doi/abs/10.1080/08916930500484849 Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus] - [https://www.tandfonline.com/doi/abs/10.1080/08916930500484849 (Full text)]<br />
<br />
* 1988, [https://www.tandfonline.com/doi/abs/10.1080/08916930500484849 The chronic mononucleosis syndrome (mainly for historic value)] - [https://www.ncbi.nlm.nih.gov/pubmed/2830340 (Full text)]<br />
<br />
///<br />
Darla's comment 1: Probably should delete the text "Long COVID may be associated herpesvirus reactivation such as Epstein-Barr Virus.[16]," which implies EBV is a herpesvirus and seems to be missing the word "with." The source cited there is cited nowhere else on the EBV page.<br />
Darla's comment 2: I will work on applying Dr M Guthridge's suggestions.<br />
///<br />
<br />
////////////////////////<br />
@Dr_M_Guthridge comments/info:<br />
<br />
Jen Brea has made a wonderful contribution by setting up this EBV page. I (@Dr_M_Guthridge) have pasted some info and possible suggestions that might be useful below. I just dont have the time or energy to do it myself. So, would someone else like to edit and integrate with the current EBV page? Happy for anyone to have a go. <br />
<br />
DISCLAIMER: The information I have provided below is of a general nature and should not be used to diagnose, treat or manage any illness or condition. A professional healthcare provider should always be consulted for any diagnosis, treatment or therapy. <br />
<br />
COMMENT ON EXISTING MEpedia EBV PAGE: Jen Brea has done a terrific job on the current EBV page. My only comment about the existing information is that I would remove the reference that licorice, vitamin c and vitamin D having antiviral activity. There is little scientific evidence that they have any anti-EBV activity. While there is some evidence that vitamin D deficiency is associated with increased EBV-associated autoimmune diseases, that is quite different to using Vitamin D to treat an EBV infection. <br />
<br />
Below is info and numbered (1-6) references that might be included on the EBV page:<br />
<br />
EBV incidence and epidemiology<br />
The Epstein-Barr virus (EBV) is a member of the herpes family and causes a disease called Infectious Mononucleosis.1,2 Its incidence varies but it is estimated that approximately 500 cases/100 000 persons/year contract EBV in developed countries with most people contracting the disease between 15-24.2 <br />
<br />
In the developing world, most children are infected within the first 3 years of life and EBV seropositivity reaches 100% within the first 10 years. These early primary infections are nearly always asymptomatic. In contrast, in the developed world, up to 50% of children are EBV seronegative at the end of their first decade and then become infected through intimate oral contact during teenage years or in early adulthood. 3 As many as half of these delayed primary infections are symptomatic, presenting after an incubation period of 4–7 weeks as acute infectious mononucleosis (AIM or glandular fever), with symptoms that include fever, fatigue, malaise, pharyngitis and lymphadenopathy. 3<br />
<br />
Cell Types Infected by EBV. <br />
EBV is capable of infecting B lymphocytes, squamous epithelial cells, glandular epithelial cells, myoepithelial cells, smooth muscle cells, T cells, NK cells, plasma cells, and follicular dendritic cells. 4 This wide spectrum of susceptible cell types was determined because of pathological lesions in which EBV is localized to these cells, whereas healthy carriers seem to harbor EBV almost exclusively in B lymphocytes. 4 The importance of B cells in the life cycle of EBV is emphasized by the inability of infection to take hold in children with Bruton’s agammaglobulinemia, a rare genetic disorder in which B cells are absent.4<br />
<br />
EBV and B-lymphocytes <br />
Resting memory B cells are thought to be the site of persistence of EBV within the body. Shedding of EBV from the oropharynx (throat) can be abolished in patients treated with anti-retroviral therapies (ART) such as acyclovir, whereas the number of EBV infected B cells in the circulation remains the same as before treatment.1 Thus, while ART may be effective in medical conditions caused by serious acute EBV infections or chronic active EBV (CA-EBV) infections (see below), it may not be effective in the resolution of pathologies associated with latent infections such as ME/CFS. In addition, the observation that EBV can be eradicated in bone marrow–transplant recipients who have received therapy that ablates their hematopoietic cells, but not their oropharyngeal cells, further evidence that B-cells provide a ‘sanctuary’ for EBV persistence.1<br />
<br />
Acute Infectious Mononucleosis (AIM or Glandular Fever)<br />
Primary infection of adults and adolescents with EBV frequently gives rise to acute infectious mononucleosis (AIM), a self-limiting lymphoproliferative disease. In the acute phase (usually <3 weeks), AIM patients are often bed-ridden and have symptoms that include sore throat (pharyngitis and palatal petechiae), fever, enlarged lymph nodes (lymphadenopathy), fatigue, liver enlargement (hepatomegaly) and spleen enlargement (splenomegaly).2 <br />
<br />
While less common, severe complications during the initial acute phase of infection require hospitalization due to hemolytic anemia (low red cells), thrombocytopenia (low platelets), aplastic anemia (low red cells), myocarditis (inflammation of the heart), hepatitis (decreased liver function), genital ulcers, rupture of the spleen, and neurologic complications such as Guillain–Barré syndrome, encephalitis, and meningitis.1,2 Thus, the severity of symptoms and the course of disease can vary significantly between patients. <br />
<br />
Diagnosis of EBV infection and EBV-induced diseases (squelae) <br />
Possible diagnostic tests2 used in the differential diagnosis of primary EBV infection and/or EBV-induced diseases are:<br />
• Heterophile antibody test (also known as the Monospot test) <br />
• Serology of EBV viral capsid antigen (VCA) IgM/IgG <br />
• Serology of EBV nuclear antigen (EBNA) IgM/IgG antibodies measured with different assays including multiplexed bead-based assay (BBA), enzyme immunoassay (EIA) and immunofluorescence assay (IFA) <br />
• PCR measurement of EBV viral load (EBV-VL) in peripheral blood <br />
• Reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of EBV expressed genes <br />
• Peripheral blood counts including neutrophil/lymphocyte/monocyte counts <br />
• Inflammatory markers including C-reactive protein (CRP) and/or Erythrocyte Sedimenation Rate (ESR)<br />
<br />
However, interpretation of the above pathology tests is not always simple. In particular, interpretation can be difficult when VCA-IgG, VCA-IgM and IgG-EBNA-1-antibodies are detected. In such cases, careful consideration of the limitations of each test used, the time after disease onset that the test was performed and other associated symptoms is required.<br />
<br />
EBV in patients with immunodeficiency: <br />
Patients that have latent EBV and who are also immunodeficient are at high risk of developing a number of potentially serious diseases. For example, late-stage HIV who are immune suppressed are at particular risk for developing hairy leukoplakia, lymphoid interstitial pneumonitis and non-Hodgkin’s lymphoma.5 Transplant patients who are on immunosuppressive treatments are also at significant risk of developing EBV-induced post-transplant lymphoproliferative disease (PTLD). Furthermore, EBV infection may prove fatal in male patients with a rare inherited immunologic abnormality, known as the X-linked lymphoproliferative disease, or Duncan syndrome. EBV is also associated with several cancers, including nasopharyngeal carcinoma, Burkitt’s lymphoma and Hodgkin’s disease.5<br />
<br />
Chronic Active EBV (CA-EBV) disease<br />
Rare persons infected with EBV develop a life-threatening condition termed chronic active EBV (CA-EBV) disease.6 CA-EBV is a distinct disease with differing eitiology and diagnostic criteria although misdiagnosis between CA-EBV and ME/CFS can occur. It is more common in Asia than in western countries and is characterized by persistent or recurrent AIM-like symptoms for at least 6 months along with atypical serology (high titers against several latent and lytic antigens) and high EBV viral load in the absence of immunosuppression. Levels of EBV DNA in blood mononuclear cells correlate with CA-EBV disease severity.4 Symptoms of CA-CBV resemble AIM and may include fever, lymphocytosis, fatigue, hepatic dysfunction, splenomegaly, thrombocytopenia and anemia.6 <br />
<br />
Treatment for EBV <br />
Treatment of AIM is mainly supportive. Specifically, acetaminophen or nonsteroidal anti-inflammatory agents (NSAIDs) are usually used in order to manage fever, throat discomfort, and malaise. Corticosteroids can shorten the duration of major symptoms in AIM; however, they are generally not recommended for the treatment of uncomplicated disease and have been associated with increases in certain complications.2<br />
<br />
* 1. 2000, EPSTEIN–BARR VIRUS INFECTION - [http://www.columbia.edu/itc/hs/medical/pathophys/immunology/2004/misc/articles/NEJM_EBV_review.pdf (Full text)]<br />
* 2. 2012, Current diagnosis and management of infectious mononucleosis - [https://www.ncbi.nlm.nih.gov/pubmed/22123662 (Abstract)]<br />
* 3. 2014, Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clinical & translational immunology - [https://onlinelibrary.wiley.com/doi/pdf/10.1038/cti.2014.25 (Full text)]<br />
* 4. 2008, Laboratory assays for Epstein-Barr virus-related disease. The Journal of molecular diagnostics - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2438195/ (Full text)]<br />
* 5. 2010, Rafailidis, P.I., Mavros, M.N., Kapaskelis, A. & Falagas, M.E. Antiviral treatment for severe EBV infections in apparently immunocompetent patients - [https://europepmc.org/article/med/20739216 (Abstract)]<br />
* 6. 2011, Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States - [https://www.researchgate.net/profile/V_Koneti_Rao/publication/50939678_Characterization_and_treatment_of_chronic_active_Epstein-Barr_virus_disease_A_28-year_experience_in_the_United_States/links/0deec516c68d232343000000.pdf (Full text)]<br />
/// End comments by Dr M Guthridge</div>Darlahttps://me-pedia.org/w/index.php?title=Epstein-Barr_virus&diff=111983Epstein-Barr virus2022-06-10T11:18:23Z<p>Darla:/* Notable studies */</p>
<hr />
<div>{{Cleanup|reason=Add summary of the Notable studies from 2019 onwards|date=28 July 2020}}<br />
<br />
[[The 3Ps model|The]] '''Epstein-Barr virus''' (EBV) or HHV4 is a [[herpesvirus]]. It is the most common cause of infectious [[mononucleosis]] or "glandular fever," and infects 90% of adults worldwide.<ref name="Saha2016">{{Cite journal <br />
| last1 = Saha | first1 = Abhik<br />
| last2 = Robertson | first2 = Erle S<br />
| title = Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes<br />
| journal = Clinical Cancer Research<br />
| issn = 1557-3265| volume = 17| issue = 10| pages = 3056–3063<br />
| date = 2011-05-15<br />
| pmid = 21372216 | doi = 10.1158/1078-0432.CCR-10-2578| url = http://clincancerres.aacrjournals.org/content/17/10/3056}}</ref> It has been implicated in numerous immune diseases and chronic illnesses, including [[chronic fatigue syndrome]], [[multiple sclerosis]], [[myasthenia gravis]], and [[systemic lupus erythematosus]]. It is known to turn on "risk genes" for autoimmune disease in the cells it infects.<ref name=":0">{{Cite journal|last=Harley|first=John|date= 16 April 2018|title=Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity|url=https://www.nature.com/articles/s41588-018-0102-3|journal=Nature genetics|volume=|pages=|issue=|via=|quote=}}</ref><ref name=":1">{{Cite web|url=https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases|title=Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases|last=|first=|date=16 April 2018|website=National Institutes of Health|archive-url=|archive-date=|url-status=|access-date=}}</ref><br />
<br />
== Initial infection ==<br />
[[File:Epstein-barr virus (ebv).jpg|thumb|A stained sample of Epstein-Barr virus.]]<br />
Symptoms of EBV infection include: <br />
* [[fatigue]]<br />
<br />
* [[fever]]<br />
* [[rash]]<br />
* inflamed [[sore throat|throat]]<br />
* [[swollen lymph nodes]]<br />
* enlarged [[spleen]]<br />
* swollen [[liver]]<ref name=":2">{{Cite web|url=http://www.cdc.gov/epstein-barr/about-ebv.html|title=Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono {{!}} CDC|date=2018-05-10|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-14}}</ref><br />
<br />
===Age of infection===<br />
<br />
Most people acquire EBV in early childhood. Typically, young children who acquire EBV are either not symptomatic or have mild symptoms that are hard to distinguish from a cold or other other mild, childhood illnesses. <br />
<br />
In adolescents and young adults, EBV can cause [[infectious mononucleosis]] (IM), also known as glandular fever.<ref name=":2" /> IM is characterized by [[fever]], [[sore throat]], [[swollen lymph nodes]], [[pain|body aches]], and [[fatigue]]. It generally resolves with rest and only rarely causes serious complications. It typically occurs in people who have not been exposed to EBV in early childhood, and in comparison, is more severe than infection in childhood (i.e., it can last for months). <br />
<br />
Following initial infection, EBV can reactivate and has been shown to have many connections with various chronic illnesses. Relative to initial infections, reactivated EBV is much more severe.<br />
<br />
==Transmission==<br />
<br />
EBV is transmitted through bodily fluids, most commonly through saliva. The first time a person is infected with EBV, the person is contagious for weeks (even when not displaying symptoms). The virus then transitions to the latent or inactive form, and stays in the body. If the virus reactivates, the person will be contagious again.<ref name=":2" /><br />
<br />
== Diagnosis ==<br />
EBV infection is confirmed with blood tests that detect presence of [[:Category:Antibodies|antibodies]]. Nine out of ten adults have these antibodies, indicating that they have a current or past EBV infection.<ref name=":2" /><br />
<br />
Anti-VCA (Viral capsid antigen) IgG and EBV nuclear antigen (EBNA) IgG antibodies persist throughout a person's life. Thus, positive results merely indicate a current or past infection. A current EBV infection is diagnosed based on the presence of Anti-VCA IgM and Anti-EA (Early Antigen) IgG. VCA IgM appears early in EBV infection and usually disappears within four to six weeks. Positive VCA IgM suggests current active acute EBV infection. EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. Positive EA IgG can suggest current active EBV infection or EBV re-activation. <ref>{{Cite web|url=https://www.cdc.gov/epstein-barr/laboratory-testing.html|title=Epstein-barr {{!}} Mononucleosis {{!}} Laboratory Testing {{!}} Mono {{!}} CDC|date=2019-01-28|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-10-08}}</ref><br />
<br />
==Latency==<br />
<br />
In healthy adults, the virus remains latent for life in memory [[B cell]]s. It is estimated that 1 in every one hundred thousand to one million circulating B cells carry EBV.<ref>{{Cite journal|last=Hsu|first=J. L.|last2=Glaser|first2=S. L.|date=Apr 2000|title=Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications|url=https://www.ncbi.nlm.nih.gov/pubmed/10781747/|journal=Critical Reviews in Oncology/Hematology|volume=34|issue=1|pages=27–53|issn=1040-8428|pmid=10781747}}</ref> In healthy hosts, EBV populations are kept in check by [[CD4+ T cell|CD4<sup>+</sup>]] and [[CD8|CD8<sup>+</sup>]] [[T cell|T-cell]] responses. <br />
<br />
The equilibrium can be disrupted in individuals with compromised [[immune system]]s such as patients with [[AIDS]] or transplant patients taking immune system suppressing drugs.<ref name=":3">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206|issue=|pages=4|quote=|via=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=}}</ref> It has been observed that these patients are more susceptible to EBV-related [[cancer]]s, such as certain [[lymphoma]]s and carcinomas.<ref>{{Cite journal|last=Pattle|first=Samuel B.|last2=Farrell|first2=Paul J.|date=Nov 2006|title=The role of Epstein-Barr virus in cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/17049016|journal=Expert Opinion on Biological Therapy|volume=6|issue=11|pages=1193–1205|doi=10.1517/14712598.6.11.1193|issn=1744-7682|pmid=17049016|quote=|via=}}</ref> In immunocompromised patients, EBV can induce lymphoproliferation, [[lymphoma]], and hemophagocytic lymphohistiocytosis (HLH).<ref>{{Cite journal|last=Tangye|first=Stuart|date=January 20, 2017|title=Human immunity against EBV—lessons from the clinic|url=http://jem.rupress.org/content/214/2/269|journal=Journal of Experimental Medicine|volume=|pages=|issue=|via=|quote=}}</ref><br />
===Natural killer T cells===<br />
<br />
It is thought that [[natural killer T cell]]s (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of [[CD1d]] expressing cells.<ref name=":3" /><br />
<br />
==Neuronal infection==<br />
A 2015 study<ref name="JhaHC2015">{{Cite journal <br />
| last1 = Jha | first1 = HC | authorlink1 = <br />
| last2 = Mehta | first2 = D | authorlink2 = <br />
| last3 = Lu | first3 = J | authorlink3 = <br />
| last4 = El-Naccache | first4 = D | authorlink4 = <br />
| last5 = Shukla | first5 = SK | authorlink5 =<br />
| last6 = Kovacsics | first6 = C | authorlink6 =<br />
| last7 = Kolson | first7 = D | authorlink7 = <br />
| last8 = Robertson | first8 = ES | authorlink8 =<br />
| title = Gammaherpesvirus Infection of Human Neuronal Cells<br />
| journal = mBio | volume = 6 | issue =6 | pages = <br />
| date = 2016-12-01<br />
| doi = 10.1128/mBio.01844-15 | pmid = 26628726<br />
| url = http://mbio.asm.org/content/6/6/e01844-15<br />
}}</ref> demonstrated that human [[neuron]]al cells could be directly and actively infected with EBV and another [[herpesvirus]], Kaposi's sarcoma-associated herpesvirus (KSHV).<br />
<br />
Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]].<br />
<br />
EBV is known to be linked to many neuronal diseases<ref name="Kleines2011">{{citation<br />
| last1 = Kleines | first1 = M<br />
| last2 = Schiefer | first2 = J<br />
| last3 = Stienen | first3 = A<br />
| last4 = Blaum | first4 = M<br />
| last5 = Ritter | first5 = K<br />
| last6 = Häusler | first6 = M<br />
| title = Expanding the spectrum of neurological disease associated with Epstein-Barr virus activity<br />
| journal = European Journal of Clinical Microbiology & Infectious Diseases<br />
| issn = 1435-4373| volume = 30| issue = 12| pages = 1561–1569<br />
| date = 2011-05-15| doi = 10.1007/s10096-011-1261-7| url = http://link.springer.com/article/10.1007/s10096-011-1261-7}}</ref> but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.<br />
<br />
==In human disease==<br />
<br />
Epstein-Barr virus has been associated with a wide number of immune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[systemic lupus erythematosus]],<ref>{{Cite journal|last=Lossius|first=Andreas|date=December 2012|title=Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528287/|journal=Virus|volume=|pages=|issue=|via=|quote=}}</ref> [[Chronic fatigue syndrome]], and [[myasthenia gravis]]. EBV was recently discovered to turn on "risk genes" for autoimmune disease in the cells it infects. [[Epstein-Barr virus nuclear antigen 2|EBNA2]], a protein produced by EBV-infected cells, and its related transcription factors activate half the human genes known to be associated with the risk for lupus as well as genes associated with several other autoimmune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[inflammatory bowel disease]], [[Diabetes#Types|type 1 diabetes]], [[juvenile idiopathic arthritis]] and [[celiac disease]]. EBV activation can thus increase the risk of developing these diseases.<ref name=":0" /><ref name=":1" /> <br />
<br />
===Chronic fatigue syndrome===<br />
<br />
A prospective study of 250 primary care patients revealed a higher prevalence of [[chronic fatigue syndrome]] after infectious [[mononucleosis]] (glandular fever) when compared to an ordinary upper respiratory tract infection.<ref name=":4">{{Cite journal|last=White|first=P. D.|last2=Thomas|first2=J. M.|last3=Amess|first3=J.|last4=Crawford|first4=D. H.|last5=Grover|first5=S. A.|last6=Kangro|first6=H. O.|last7=Clare|first7=A. W.|date=Dec 1998|title=Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever|url=https://www.ncbi.nlm.nih.gov/pubmed/9926075|journal=The British Journal of Psychiatry: The Journal of Mental Science|volume=173|pages=475–481|issn=0007-1250|pmid=9926075}}</ref> Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.<ref name=":5">{{Cite journal|last=Schmaling|first=K. B.|last2=Jones|first2=J. F.|date=Jan 1996|title=MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1|pages=67–74|issn=0022-3999|pmid=8730646}}</ref> A 2006 Australian prospective study found that 12% of subjects infected by EBV met the criteria for [[Chronic fatigue syndrome]] six months after their infection, and 9% still had CFS 12 months after infection.<ref name=":6">{{Cite journal|last=Hickie|first=Ian|author-link=Ian Hickie|last2=Davenport|first2=Tracey|author-link2=Tracey Davenport|last3=Wakefield|first3=Denis|author-link3=Denis Wakefield|last4=Vollmer-Conna|first4=Ute|author-link4=Uté Vollmer-Conna|last5=Cameron|first5=Barbara|author-link5=|last6=Vernon|first6=Suzanne D|author-link6=Suzanne Vernon|last7=Reeves|first7=William C|author-link7=William Reeves|last8=Lloyd|first8=Andrew|author-link8=Andrew Lloyd|date=2006-09-16|title=Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/|journal=BMJ : British Medical Journal|volume=333|issue=7568|pages=575|doi=10.1136/bmj.38933.585764.AE|issn=0959-8138|pmc=1569956|pmid=16950834|access-date=|quote=|via=}}</ref> (The same rate held true for [[Ross River virus]] and [[Q fever]]).<br />
<br />
=== Long COVID ===<br />
Long COVID may be associated [[herpesvirus]] reactivation such as Epstein-Barr Virus.<ref>{{Cite journal|last=Proal|first=Amy D.|author-link=Amy Proal|last2=VanElzakker|first2=Michael B.|author-link2=Michael VanElzakker|date=2021|title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms|url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=12|issue=|pages=698169|doi=10.3389/fmicb.2021.698169|issn=1664-302X}}</ref><br />
<br />
===Multiple sclerosis===<br />
<br />
Infection later in life, high serum titers against EBV, and [[mononucleosis]] have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.<ref>{{Cite journal|last=Holmøy|first=Trygve|date=2008|title=Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis|url=http://www.sciencedirect.com/science/article/pii/S0306987707003167|journal=Medical Hypotheses|volume=70|issue=|pages=|via=}}</ref><br />
<br />
Several studies by Alberto Ascherio, MD, DrPH, and his team at the Harvard School of Public Health have suggested that Epstein-Barr virus is involved in [[multiple sclerosis]], specifically in people with a certain immune-related gene and high levels of antibodies to EBV in their blood.<ref>{{Cite web|url=https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses|title=Viruses|last=|first=|date=|website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref><br />
<br />
=== Systemic lupus erythematosus ===<br />
In a study of young patients with lupus, 99% had EBV as compared to 70% of healthy controls.<ref>{{Cite journal|last=James|first=JA|date=1997-12-15|title=An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus|url=https://www.jci.org/articles/view/119856|journal=The Journal of Clinical Investigation|volume=|issue=|pages=|via=}}</ref> Another study found that patients with SLE had a roughly 40-fold increase in EBV viral loads compared with controls, likely stemming from altered [[t cell]] responses against EBV.<ref>{{Cite journal|last=Kang|first=Insoo|date=15 January 2004|title=Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus|url=http://www.jimmunol.org/content/172/2/1287.short|journal=The Journal of Immunology|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Myasthenia gravis===<br />
<br />
[[B cell]]s from [[myasthenia gravis]] patient stimulated ''in vitro'' by Epstein-Barr virus produced [[acetylcholine]] autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=https://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> Ongoing EBV infection of the [[thymus]] has been posited as a causative agent for the production of [[acetylcholine]] receptor autoantibodies in [[myasthenia gravis]].<ref>{{Cite journal|last=Kaminski|first=Henry J|last2=Minarovits|first2=Janos|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134|date=2010|volume=67|issue=6|pages=697-698|doi=|pmc=|pmid=|quote=|access-date=|via=}}</ref><ref>http://journals.lww.com/neurologynow/_layouts/15/oaks.journals.mobile/post.aspx?blogId=2&postId=10</ref><br />
<br />
=== Gastrointestinal disease ===<br />
One study of EBV in patients with [[gastritis]], [[Crohn's disease]], and [[ulcerative colitis]] and normal controls found essentially undetectable levels of EBV in normal gastric mucosa. However, EBV was detected in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples.<ref>{{Cite journal|last=Ryan|first=Julie|date=2013|title=Epstein-Barr Virus Infection is Common in Inflamed Gastrointestinal Mucosa|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535492/|journal=Dig Dis Sci.|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Lyme disease===<br />
Several herpesviruses including Epstein-Barr virus<ref name="Goossens1999">{{Cite journal <br />
| last1 = Goossens | first1 = HA<br />
| last2 = Nohlmans | first2 = MK <br />
| last3 = van den Bogaard | first3 = AE<br />
| title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis| journal = Infection | issue = 1999 | volume = 27 | pages =231| pmid = 10378140| url = https://www.ncbi.nlm.nih.gov/pubmed/10378140}}</ref> may cause false positives on [[Lyme disease]] tests.<br />
<br />
===XMEN disease===<br />
<br />
A 2014 study found chronic Epstein-Barr infection was linked to a magnesium transporter [[MAGT-1]] mutation.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/84061|title=MAGT1 magnesium transporter 1 [Homo sapiens (human)] - Gene|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NCBI|archive-url=|archive-date=|url-status=|access-date=2022-05-21}}</ref> Dysfunction in this transporter also resulted in decreased NK cell function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Cite journal |last1 = Li |first1 = F.-Y. |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Su<br />
| first3 = H<br />
| last4 = Matthews<br />
| first4 = H |last5 = Lenardo |first5 = M.J. |authorlink3 = <br />
| title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. <br />
| journal = Blood| date = 2014| doi = 10.1182/blood-2013-11-538686|url=https://ashpublications.org/blood/article/123/14/2148/32463/XMEN-disease-a-new-primary-immunodeficiency|issue=14|pages=2148–2152|pmc=|pmid=|quote=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|access-date=|author-link4=|author-link5=|author-link6=|via=|volume=123}}</ref><br />
<br />
This disorder, termed 'XMEN' (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. <br />
<br />
Since chronic Epstein-Barr virus infection has been associated with chronic fatigue syndrome, this error in [[magnesium]] transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /><ref name="X-men_disease_2">{{Cite journal |last1 = Ravell |first1 = J |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Lenardo<br />
| first3 = M| title = XMEN disease: a combined immune deficiency with magnesium defect. <br />
| journal = Current Opinion in Pediatrics<br />
| date = 2014| doi = 10.1097/MOP.0000000000000156}}</ref> However, in this disorder, EBV would be seen as an indicator of the illness rather than the cause.<br />
<br />
==Vitamin D==<br />
<br />
Some recent research is finding links between EBV and [[Vitamin D]]<br />
<br />
An Epstein-Barr virus protein EBNA-3 has an affinity for [[VDR]] and may actually block the activation of VDR-dependent genes by [[Vitamin D]].<ref>{{Cite journal|last=Yenamandra|first=Surya Pavan|last2=Hellman|first2=Ulf|last3=Kempkes|first3=Bettina|last4=Darekar|first4=Suhas Deoram|last5=Petermann|first5=Sabine|last6=Sculley|first6=Tom|last7=Klein|first7=George|last8=Kashuba|first8=Elena|date=Dec 2010|title=Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes|url=https://www.ncbi.nlm.nih.gov/pubmed/20593215|journal=Cellular and molecular life sciences: CMLS|volume=67|issue=24|pages=4249–4256|doi=10.1007/s00018-010-0441-4|issn=1420-9071|pmid=20593215}}</ref><br />
<br />
[[Vitamin D receptor]] may be required for the normal development of [[natural killer T cell]]s that react to cells expressing [[CD1d]], as in cells infected by EBV.<ref>{{Cite journal|last=Yu|first=Sanhong|last2=Cantorna|first2=Margherita T.|date=2008-04-01|title=The vitamin D receptor is required for iNKT cell development|url=http://www.pnas.org/content/105/13/5207|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=13|pages=5207–5212|doi=10.1073/pnas.0711558105|issn=0027-8424|pmid=18364394}}</ref><br />
<br />
As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels<ref>{{Cite journal|last=Ramien|first=Caren|last2=Pachnio|first2=Annette|last3=Sisay|first3=Sofia|last4=Begum|first4=Jusnara|last5=Leese|first5=Alison|last6=Disanto|first6=Giulio|last7=Kuhle|first7=Jens|last8=Giovannoni|first8=Gavin|last9=Rickinson|first9=Alan|date=May 2014|title=Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort|url=https://www.ncbi.nlm.nih.gov/pubmed/24192216?dopt=Abstract|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=20|issue=6|pages=751–753|doi=10.1177/1352458513509507|issn=1477-0970|pmid=24192216}}</ref> (i.e., above 100 nmol/l).<br />
<br />
==Treatment==<br />
<br />
There is no specific treatment for EBV, only treatment of symptoms, such as taking over-the-counter medications for pain and fever.<ref name=":2" /> EBV is thought to persistent harmlessly in immunocompetent individuals, but in those with compromised immune systems it has been associated with certain cancers and possibly autoimmune disease. <br />
<br />
===Antivirals===<br />
<br />
Several [[antiviral]]s are active against EBV including [[valganciclovir|valganciclovir,]] [[valacyclovir]]<ref>{{Cite journal|last=Hoshino|first=Yo|date=|title=Long-Term Administration of Valacyclovir Reduces the Number of Epstein-Barr Virus (EBV)-Infected B Cells but Not the Number of EBV DNA Copies per B Cell in Healthy Volunteers|url=http://jvi.asm.org/content/83/22/11857.full|journal=Journal of Virology|volume=|issue=|pages=|via=}}</ref>, [[acyclovir]]<ref>{{Cite journal|last=Rafaillidis|first=Pl|date=Nov 2013|title=Antiviral treatment for severe EBV infections in apparently immunocompetent patients|url=https://www.ncbi.nlm.nih.gov/pubmed/20739216|journal=Journal of Clinical Virology|volume=|issue=|pages=|via=}}</ref> and [[spironolactone]].<ref name="Verma2016">{{Cite journal <br />
| last1 = Verma | first1 = Dinesh<br />
| last2 = Thompson | first2 = Jacob<br />
| last3 = Swaminathan | first3 = Sankar| title = Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function<br />
| journal = Proceedings of the National Academy of Sciences | issn = 1091-6490 | volume = 113| issue = 13| pages = 3609–3614<br />
| date = 2016-03-29<br />
| doi = 10.1073/pnas.1523686113 | pmid = 26976570| url = http://www.pnas.org/content/113/13/3609}}</ref><br />
<br />
[[Acyclovir]], an [[antiviral]] drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.<br />
<br />
A theoretical [[immunotherapy]] treatment proposes that inducing [[CD1d]] expression on EBV-infected B cells could prompt effective immune suppression of EBV by NKT cells.<ref>{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206}}</ref><br />
<br />
===Rituximab===<br />
<br />
[[Rituximab]] may be effective in completely eliminating Epstein-Barr virus infection from the peripheral blood.<ref>{{Cite journal|last=Diamantopoulos|first=Panagiotis T.|last2=Polonyfi|first2=Katerina|last3=Sofotasiou|first3=Maria|last4=Papadopoulou|first4=Vasiliki|last5=Kalala|first5=Fani|last6=Iliakis|first6=Theodoros|last7=Zervakis|first7=Kostantinos|last8=Tsilimidos|first8=Gerassimos|last9=Kouzis|first9=Panagiotis|date=Dec 2013|title=Rituximab in the treatment of EBV-positive low grade B-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/24324119|journal=Anticancer Research|volume=33|issue=12|pages=5693–5698|issn=1791-7530|pmid=24324119}}</ref> A study of seventeen patients with low-grade [[B cell]] lymphoma found that after three cycles of Rituximab, the virus had been completely eliminated from the peripheral blood in all but one patient.<br />
<br />
===Herbs and nutraceuticals===<br />
<br />
Herbs shown to have antiviral properties against EBV including [[licorice|licorice.]]<ref>{{Cite journal|last=Lin|first=Jung-Chung|last2=Cherng|first2=Jaw-Ming|last3=Hung|first3=Man-Shan|last4=Baltina|first4=Lidia A.|last5=Baltina|first5=Lia|last6=Kondratenko|first6=Rimma|date=Jul 2008|title=Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: structure-activity relationships|url=https://www.ncbi.nlm.nih.gov/pubmed/18423902|journal=Antiviral Research|volume=79|issue=1|pages=6–11|doi=10.1016/j.antiviral.2008.01.160|issn=0166-3542|pmid=18423902}}</ref> [[Vitamin C]] and Vitamin D<ref>{{Cite journal|last=Rolf|first=L|date=July 2017|title=Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis|url=https://www.ncbi.nlm.nih.gov/pubmed/28731372|journal=Multiple Sclerosis|volume=|issue=|pages=|via=}}</ref> might also decrease duration and severity of the symptoms of EBV infection.<ref>{{Cite journal|last=Mikirova|first=N|date=May 2014|title=Effect of high dose vitamin C on Epstein-Barr viral infection|url=https://www.ncbi.nlm.nih.gov/pubmed/24793092|journal=Med Sci Monit|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Vaccine===<br />
A [[vaccine]] for the prevention of Epstein-Barr virus is being explored.<ref>{{Cite web|url=https://www.nih.gov/news-events/news-releases/nih-researchers-make-progress-toward-epstein-barr-virus-vaccine|title=NIH researchers make progress toward Epstein-Barr virus vaccine|date=2019-04-09|website=National Institutes of Health (NIH)|language=en|access-date=2019-04-10}}</ref><br />
<br />
==Notable studies==<br />
*1996, MMPI profiles of patients with chronic fatigue syndrome<ref name=":5" /> - ([[pubmed:8730646|Abstract]])<br />
*1998, Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever<ref name=":4" /> - ([[pubmed:9926075|Abstract]])<br />
*2006, Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study<ref name=":6" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full text)]<br />
*2019, EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection<ref name="Asprusten2019">{{Cite journal|last=Asprusten|first=Tarjei Tørre|author-link=|last2=Pedersen|first2=Maria|author-link2=Maria Pedersen|last3=Skovlund|first3=Eva|author-link3=Eva Skovlund|last4=Wyller|first4=Vegard Bruun|author-link4=Vegard Bruun Wyller|date=2019|title=EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection|url=https://www.ncbi.nlm.nih.gov/pubmed/30957026|journal=BMJ paediatrics open|volume=3|issue=1|pages=e000390|doi=10.1136/bmjpo-2018-000390|issn=2399-9772|pmc=|pmid=30957026|quote=|via=}}</ref> - ([[pubmed:30957026|Abstract]])<br />
*2019, Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study<ref name="Pedersen2019a">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=|last3=Godang|first3=Kristin|author-link3=Kristin Godang|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|author-link7=|last8=Øie|first8=Merete Glenne|author-link8=|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=Jan 2019|title=Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pubmed/30261303|journal=Brain, Behavior, and Immunity|volume=75|issue=|pages=94–100|doi=10.1016/j.bbi.2018.09.023|issn=1090-2139|pmid=30261303|quote=}}</ref> - ([[pubmed:30261303|Abstract]])<br />
*2019, Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later<ref name="Pedersen2019b">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=Tarjei Tørre Asprusten|last3=Godang|first3=Kristin|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|last8=Øie|first8=Merete Glenne|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=2019-01-27|title=Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later|url=https://www.ncbi.nlm.nih.gov/pubmed/30685875|journal=Acta Paediatrica (Oslo, Norway: 1992)|volume=108|issue=8|pages=1521-1526|doi=10.1111/apa.14728|issn=1651-2227|pmid=30685875|quote=|via=}}</ref> - ([[pubmed:30685875|Abstract]])<br />
*2019, Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Williams|first=Marshall V.|author-link=|last2=Cox|first2=Brandon|author-link2=|last3=Lafuse|first3=William P.|author-link3=|last4=Ariza|first4=Maria Eugenia|author-link4=|author-link5=|date=May 2019|title=Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0149291819301730|journal=Clinical Therapeutics|language=en|volume=41|issue=5|pages=848–863|doi=10.1016/j.clinthera.2019.04.009|pmc=6525645|pmid=31040055|quote=|via=}}</ref> - ([https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext Full text)]<br />
*2019, Review article - [[Epstein-Barr virus]] induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis<ref name="Kerr2019EBV">{{Cite journal|last=Kerr|first=Jonathan R.|author-link=Jonathan Kerr|date=Feb 2019|title=Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00059/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00059|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full (Full text)]<br />
*2019, Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors<ref name="Kerr2019a">{{Cite journal|last=Kerr|first=Jonathan R|author-link=Jonathan Kerr|author-link2=|date=2019-07-17|title=Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors|url=http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205822|journal=Journal of Clinical Pathology|language=en|volume=|issue=|pages=jclinpath–2019–205822|doi=10.1136/jclinpath-2019-205822|issn=0021-9746|quote=|via=}}</ref> - [[pubmed:31315893|(Abstract)]]<br />
*2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal|last=Shikova|first=Evelina|author-link=|last2=Reshkova|first2=Valentina|author-link2=|last3=Kumanova|first3=Аntoniya|author-link3=|last4=Raleva|first4=Sevdalina|author-link4=|last5=Alexandrova|first5=Dora|author-link5=|last6=Capo|first6=Natasa|author-link6=|last7=Murovska|first7=Modra|date=2020|title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=|pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)]<br />
*2021, Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome<ref>{{Cite journal|title=Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|date=Nov 15, 2021|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/|journal=Frontiers in Immunology|volume=12|issue=|pages=656797|last=Ruiz-Pablos|first=Manuel|author-link=https://pubmed.ncbi.nlm.nih.gov/?term=Ruiz-Pablos%20M%5BAuthor%5D|last2=Paiva|first2=Bruno|author-link2=https://pubmed.ncbi.nlm.nih.gov/?term=Paiva%20B%5BAuthor%5D|last3=Monter-Mateo|first3=Rosario|author-link3=https://pubmed.ncbi.nlm.nih.gov/?term=Montero-Mateo%20R%5BAuthor%5D|last4=Garcia|first4=Nicolas|author-link4=https://pubmed.ncbi.nlm.nih.gov/?term=Garcia%20N%5BAuthor%5D|last5=Zabaleta|first5=Aintzane|author-link5=https://pubmed.ncbi.nlm.nih.gov/?term=Zabaleta%20A%5BAuthor%5D|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|doi=10.3389/fimmu.2021.656797|pmc=|pmid=34867935|access-date=June 10, 2022|quote=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/ Full text])<br />
*2022, EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities<ref>{{Cite journal|title=EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities|date=2022-06-08|url=https://insight.jci.org/articles/view/158193|journal=JCI Insight|volume=7|issue=11|last=Cox|first=Brandon S.|last2=Alharshawi|first2=Khaled|last3=Mena-Palomo|first3=Irene|last4=Lafuse|first4=William P.|last5=Ariza|first5=Maria Eugenia|language=en|doi=10.1172/jci.insight.158193|issn=0021-9738}}</ref> - ([https://insight.jci.org/articles/view/158193 Full text])<br />
<br />
== See also ==<br />
* [[List of herpesvirus infection studies]]<br />
<br />
==Learn more ==<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Infectious agents]]<br />
[[Category:Triggers and risk factors]]<br />
[[Category:Virology]]<br />
[[Category:Viruses]]</div>Darlahttps://me-pedia.org/w/index.php?title=Epstein-Barr_virus&diff=111982Epstein-Barr virus2022-06-10T10:57:27Z<p>Darla:/* Notable studies */</p>
<hr />
<div>{{Cleanup|reason=Add summary of the Notable studies from 2019 onwards|date=28 July 2020}}<br />
<br />
[[The 3Ps model|The]] '''Epstein-Barr virus''' (EBV) or HHV4 is a [[herpesvirus]]. It is the most common cause of infectious [[mononucleosis]] or "glandular fever," and infects 90% of adults worldwide.<ref name="Saha2016">{{Cite journal <br />
| last1 = Saha | first1 = Abhik<br />
| last2 = Robertson | first2 = Erle S<br />
| title = Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes<br />
| journal = Clinical Cancer Research<br />
| issn = 1557-3265| volume = 17| issue = 10| pages = 3056–3063<br />
| date = 2011-05-15<br />
| pmid = 21372216 | doi = 10.1158/1078-0432.CCR-10-2578| url = http://clincancerres.aacrjournals.org/content/17/10/3056}}</ref> It has been implicated in numerous immune diseases and chronic illnesses, including [[chronic fatigue syndrome]], [[multiple sclerosis]], [[myasthenia gravis]], and [[systemic lupus erythematosus]]. It is known to turn on "risk genes" for autoimmune disease in the cells it infects.<ref name=":0">{{Cite journal|last=Harley|first=John|date= 16 April 2018|title=Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity|url=https://www.nature.com/articles/s41588-018-0102-3|journal=Nature genetics|volume=|pages=|issue=|via=|quote=}}</ref><ref name=":1">{{Cite web|url=https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases|title=Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases|last=|first=|date=16 April 2018|website=National Institutes of Health|archive-url=|archive-date=|url-status=|access-date=}}</ref><br />
<br />
== Initial infection ==<br />
[[File:Epstein-barr virus (ebv).jpg|thumb|A stained sample of Epstein-Barr virus.]]<br />
Symptoms of EBV infection include: <br />
* [[fatigue]]<br />
<br />
* [[fever]]<br />
* [[rash]]<br />
* inflamed [[sore throat|throat]]<br />
* [[swollen lymph nodes]]<br />
* enlarged [[spleen]]<br />
* swollen [[liver]]<ref name=":2">{{Cite web|url=http://www.cdc.gov/epstein-barr/about-ebv.html|title=Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono {{!}} CDC|date=2018-05-10|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-14}}</ref><br />
<br />
===Age of infection===<br />
<br />
Most people acquire EBV in early childhood. Typically, young children who acquire EBV are either not symptomatic or have mild symptoms that are hard to distinguish from a cold or other other mild, childhood illnesses. <br />
<br />
In adolescents and young adults, EBV can cause [[infectious mononucleosis]] (IM), also known as glandular fever.<ref name=":2" /> IM is characterized by [[fever]], [[sore throat]], [[swollen lymph nodes]], [[pain|body aches]], and [[fatigue]]. It generally resolves with rest and only rarely causes serious complications. It typically occurs in people who have not been exposed to EBV in early childhood, and in comparison, is more severe than infection in childhood (i.e., it can last for months). <br />
<br />
Following initial infection, EBV can reactivate and has been shown to have many connections with various chronic illnesses. Relative to initial infections, reactivated EBV is much more severe.<br />
<br />
==Transmission==<br />
<br />
EBV is transmitted through bodily fluids, most commonly through saliva. The first time a person is infected with EBV, the person is contagious for weeks (even when not displaying symptoms). The virus then transitions to the latent or inactive form, and stays in the body. If the virus reactivates, the person will be contagious again.<ref name=":2" /><br />
<br />
== Diagnosis ==<br />
EBV infection is confirmed with blood tests that detect presence of [[:Category:Antibodies|antibodies]]. Nine out of ten adults have these antibodies, indicating that they have a current or past EBV infection.<ref name=":2" /><br />
<br />
Anti-VCA (Viral capsid antigen) IgG and EBV nuclear antigen (EBNA) IgG antibodies persist throughout a person's life. Thus, positive results merely indicate a current or past infection. A current EBV infection is diagnosed based on the presence of Anti-VCA IgM and Anti-EA (Early Antigen) IgG. VCA IgM appears early in EBV infection and usually disappears within four to six weeks. Positive VCA IgM suggests current active acute EBV infection. EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. Positive EA IgG can suggest current active EBV infection or EBV re-activation. <ref>{{Cite web|url=https://www.cdc.gov/epstein-barr/laboratory-testing.html|title=Epstein-barr {{!}} Mononucleosis {{!}} Laboratory Testing {{!}} Mono {{!}} CDC|date=2019-01-28|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-10-08}}</ref><br />
<br />
==Latency==<br />
<br />
In healthy adults, the virus remains latent for life in memory [[B cell]]s. It is estimated that 1 in every one hundred thousand to one million circulating B cells carry EBV.<ref>{{Cite journal|last=Hsu|first=J. L.|last2=Glaser|first2=S. L.|date=Apr 2000|title=Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications|url=https://www.ncbi.nlm.nih.gov/pubmed/10781747/|journal=Critical Reviews in Oncology/Hematology|volume=34|issue=1|pages=27–53|issn=1040-8428|pmid=10781747}}</ref> In healthy hosts, EBV populations are kept in check by [[CD4+ T cell|CD4<sup>+</sup>]] and [[CD8|CD8<sup>+</sup>]] [[T cell|T-cell]] responses. <br />
<br />
The equilibrium can be disrupted in individuals with compromised [[immune system]]s such as patients with [[AIDS]] or transplant patients taking immune system suppressing drugs.<ref name=":3">{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206|issue=|pages=4|quote=|via=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=}}</ref> It has been observed that these patients are more susceptible to EBV-related [[cancer]]s, such as certain [[lymphoma]]s and carcinomas.<ref>{{Cite journal|last=Pattle|first=Samuel B.|last2=Farrell|first2=Paul J.|date=Nov 2006|title=The role of Epstein-Barr virus in cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/17049016|journal=Expert Opinion on Biological Therapy|volume=6|issue=11|pages=1193–1205|doi=10.1517/14712598.6.11.1193|issn=1744-7682|pmid=17049016|quote=|via=}}</ref> In immunocompromised patients, EBV can induce lymphoproliferation, [[lymphoma]], and hemophagocytic lymphohistiocytosis (HLH).<ref>{{Cite journal|last=Tangye|first=Stuart|date=January 20, 2017|title=Human immunity against EBV—lessons from the clinic|url=http://jem.rupress.org/content/214/2/269|journal=Journal of Experimental Medicine|volume=|pages=|issue=|via=|quote=}}</ref><br />
===Natural killer T cells===<br />
<br />
It is thought that [[natural killer T cell]]s (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of [[CD1d]] expressing cells.<ref name=":3" /><br />
<br />
==Neuronal infection==<br />
A 2015 study<ref name="JhaHC2015">{{Cite journal <br />
| last1 = Jha | first1 = HC | authorlink1 = <br />
| last2 = Mehta | first2 = D | authorlink2 = <br />
| last3 = Lu | first3 = J | authorlink3 = <br />
| last4 = El-Naccache | first4 = D | authorlink4 = <br />
| last5 = Shukla | first5 = SK | authorlink5 =<br />
| last6 = Kovacsics | first6 = C | authorlink6 =<br />
| last7 = Kolson | first7 = D | authorlink7 = <br />
| last8 = Robertson | first8 = ES | authorlink8 =<br />
| title = Gammaherpesvirus Infection of Human Neuronal Cells<br />
| journal = mBio | volume = 6 | issue =6 | pages = <br />
| date = 2016-12-01<br />
| doi = 10.1128/mBio.01844-15 | pmid = 26628726<br />
| url = http://mbio.asm.org/content/6/6/e01844-15<br />
}}</ref> demonstrated that human [[neuron]]al cells could be directly and actively infected with EBV and another [[herpesvirus]], Kaposi's sarcoma-associated herpesvirus (KSHV).<br />
<br />
Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]].<br />
<br />
EBV is known to be linked to many neuronal diseases<ref name="Kleines2011">{{citation<br />
| last1 = Kleines | first1 = M<br />
| last2 = Schiefer | first2 = J<br />
| last3 = Stienen | first3 = A<br />
| last4 = Blaum | first4 = M<br />
| last5 = Ritter | first5 = K<br />
| last6 = Häusler | first6 = M<br />
| title = Expanding the spectrum of neurological disease associated with Epstein-Barr virus activity<br />
| journal = European Journal of Clinical Microbiology & Infectious Diseases<br />
| issn = 1435-4373| volume = 30| issue = 12| pages = 1561–1569<br />
| date = 2011-05-15| doi = 10.1007/s10096-011-1261-7| url = http://link.springer.com/article/10.1007/s10096-011-1261-7}}</ref> but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.<br />
<br />
==In human disease==<br />
<br />
Epstein-Barr virus has been associated with a wide number of immune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[systemic lupus erythematosus]],<ref>{{Cite journal|last=Lossius|first=Andreas|date=December 2012|title=Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528287/|journal=Virus|volume=|pages=|issue=|via=|quote=}}</ref> [[Chronic fatigue syndrome]], and [[myasthenia gravis]]. EBV was recently discovered to turn on "risk genes" for autoimmune disease in the cells it infects. [[Epstein-Barr virus nuclear antigen 2|EBNA2]], a protein produced by EBV-infected cells, and its related transcription factors activate half the human genes known to be associated with the risk for lupus as well as genes associated with several other autoimmune diseases including [[multiple sclerosis]], [[rheumatoid arthritis]], [[inflammatory bowel disease]], [[Diabetes#Types|type 1 diabetes]], [[juvenile idiopathic arthritis]] and [[celiac disease]]. EBV activation can thus increase the risk of developing these diseases.<ref name=":0" /><ref name=":1" /> <br />
<br />
===Chronic fatigue syndrome===<br />
<br />
A prospective study of 250 primary care patients revealed a higher prevalence of [[chronic fatigue syndrome]] after infectious [[mononucleosis]] (glandular fever) when compared to an ordinary upper respiratory tract infection.<ref name=":4">{{Cite journal|last=White|first=P. D.|last2=Thomas|first2=J. M.|last3=Amess|first3=J.|last4=Crawford|first4=D. H.|last5=Grover|first5=S. A.|last6=Kangro|first6=H. O.|last7=Clare|first7=A. W.|date=Dec 1998|title=Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever|url=https://www.ncbi.nlm.nih.gov/pubmed/9926075|journal=The British Journal of Psychiatry: The Journal of Mental Science|volume=173|pages=475–481|issn=0007-1250|pmid=9926075}}</ref> Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.<ref name=":5">{{Cite journal|last=Schmaling|first=K. B.|last2=Jones|first2=J. F.|date=Jan 1996|title=MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1|pages=67–74|issn=0022-3999|pmid=8730646}}</ref> A 2006 Australian prospective study found that 12% of subjects infected by EBV met the criteria for [[Chronic fatigue syndrome]] six months after their infection, and 9% still had CFS 12 months after infection.<ref name=":6">{{Cite journal|last=Hickie|first=Ian|author-link=Ian Hickie|last2=Davenport|first2=Tracey|author-link2=Tracey Davenport|last3=Wakefield|first3=Denis|author-link3=Denis Wakefield|last4=Vollmer-Conna|first4=Ute|author-link4=Uté Vollmer-Conna|last5=Cameron|first5=Barbara|author-link5=|last6=Vernon|first6=Suzanne D|author-link6=Suzanne Vernon|last7=Reeves|first7=William C|author-link7=William Reeves|last8=Lloyd|first8=Andrew|author-link8=Andrew Lloyd|date=2006-09-16|title=Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/|journal=BMJ : British Medical Journal|volume=333|issue=7568|pages=575|doi=10.1136/bmj.38933.585764.AE|issn=0959-8138|pmc=1569956|pmid=16950834|access-date=|quote=|via=}}</ref> (The same rate held true for [[Ross River virus]] and [[Q fever]]).<br />
<br />
=== Long COVID ===<br />
Long COVID may be associated [[herpesvirus]] reactivation such as Epstein-Barr Virus.<ref>{{Cite journal|last=Proal|first=Amy D.|author-link=Amy Proal|last2=VanElzakker|first2=Michael B.|author-link2=Michael VanElzakker|date=2021|title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms|url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=12|issue=|pages=698169|doi=10.3389/fmicb.2021.698169|issn=1664-302X}}</ref><br />
<br />
===Multiple sclerosis===<br />
<br />
Infection later in life, high serum titers against EBV, and [[mononucleosis]] have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.<ref>{{Cite journal|last=Holmøy|first=Trygve|date=2008|title=Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis|url=http://www.sciencedirect.com/science/article/pii/S0306987707003167|journal=Medical Hypotheses|volume=70|issue=|pages=|via=}}</ref><br />
<br />
Several studies by Alberto Ascherio, MD, DrPH, and his team at the Harvard School of Public Health have suggested that Epstein-Barr virus is involved in [[multiple sclerosis]], specifically in people with a certain immune-related gene and high levels of antibodies to EBV in their blood.<ref>{{Cite web|url=https://www.nationalmssociety.org/What-is-MS/What-Causes-MS/Viruses|title=Viruses|last=|first=|date=|website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=2018-11-14}}</ref><br />
<br />
=== Systemic lupus erythematosus ===<br />
In a study of young patients with lupus, 99% had EBV as compared to 70% of healthy controls.<ref>{{Cite journal|last=James|first=JA|date=1997-12-15|title=An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus|url=https://www.jci.org/articles/view/119856|journal=The Journal of Clinical Investigation|volume=|issue=|pages=|via=}}</ref> Another study found that patients with SLE had a roughly 40-fold increase in EBV viral loads compared with controls, likely stemming from altered [[t cell]] responses against EBV.<ref>{{Cite journal|last=Kang|first=Insoo|date=15 January 2004|title=Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus|url=http://www.jimmunol.org/content/172/2/1287.short|journal=The Journal of Immunology|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Myasthenia gravis===<br />
<br />
[[B cell]]s from [[myasthenia gravis]] patient stimulated ''in vitro'' by Epstein-Barr virus produced [[acetylcholine]] autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=https://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> Ongoing EBV infection of the [[thymus]] has been posited as a causative agent for the production of [[acetylcholine]] receptor autoantibodies in [[myasthenia gravis]].<ref>{{Cite journal|last=Kaminski|first=Henry J|last2=Minarovits|first2=Janos|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134|date=2010|volume=67|issue=6|pages=697-698|doi=|pmc=|pmid=|quote=|access-date=|via=}}</ref><ref>http://journals.lww.com/neurologynow/_layouts/15/oaks.journals.mobile/post.aspx?blogId=2&postId=10</ref><br />
<br />
=== Gastrointestinal disease ===<br />
One study of EBV in patients with [[gastritis]], [[Crohn's disease]], and [[ulcerative colitis]] and normal controls found essentially undetectable levels of EBV in normal gastric mucosa. However, EBV was detected in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples.<ref>{{Cite journal|last=Ryan|first=Julie|date=2013|title=Epstein-Barr Virus Infection is Common in Inflamed Gastrointestinal Mucosa|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535492/|journal=Dig Dis Sci.|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Lyme disease===<br />
Several herpesviruses including Epstein-Barr virus<ref name="Goossens1999">{{Cite journal <br />
| last1 = Goossens | first1 = HA<br />
| last2 = Nohlmans | first2 = MK <br />
| last3 = van den Bogaard | first3 = AE<br />
| title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis| journal = Infection | issue = 1999 | volume = 27 | pages =231| pmid = 10378140| url = https://www.ncbi.nlm.nih.gov/pubmed/10378140}}</ref> may cause false positives on [[Lyme disease]] tests.<br />
<br />
===XMEN disease===<br />
<br />
A 2014 study found chronic Epstein-Barr infection was linked to a magnesium transporter [[MAGT-1]] mutation.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/84061|title=MAGT1 magnesium transporter 1 [Homo sapiens (human)] - Gene|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NCBI|archive-url=|archive-date=|url-status=|access-date=2022-05-21}}</ref> Dysfunction in this transporter also resulted in decreased NK cell function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Cite journal |last1 = Li |first1 = F.-Y. |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Su<br />
| first3 = H<br />
| last4 = Matthews<br />
| first4 = H |last5 = Lenardo |first5 = M.J. |authorlink3 = <br />
| title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. <br />
| journal = Blood| date = 2014| doi = 10.1182/blood-2013-11-538686|url=https://ashpublications.org/blood/article/123/14/2148/32463/XMEN-disease-a-new-primary-immunodeficiency|issue=14|pages=2148–2152|pmc=|pmid=|quote=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|access-date=|author-link4=|author-link5=|author-link6=|via=|volume=123}}</ref><br />
<br />
This disorder, termed 'XMEN' (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. <br />
<br />
Since chronic Epstein-Barr virus infection has been associated with chronic fatigue syndrome, this error in [[magnesium]] transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /><ref name="X-men_disease_2">{{Cite journal |last1 = Ravell |first1 = J |authorlink1 = |last2 = Chaigne-Delalande |first2 = B |authorlink2 = <br />
| last3 = Lenardo<br />
| first3 = M| title = XMEN disease: a combined immune deficiency with magnesium defect. <br />
| journal = Current Opinion in Pediatrics<br />
| date = 2014| doi = 10.1097/MOP.0000000000000156}}</ref> However, in this disorder, EBV would be seen as an indicator of the illness rather than the cause.<br />
<br />
==Vitamin D==<br />
<br />
Some recent research is finding links between EBV and [[Vitamin D]]<br />
<br />
An Epstein-Barr virus protein EBNA-3 has an affinity for [[VDR]] and may actually block the activation of VDR-dependent genes by [[Vitamin D]].<ref>{{Cite journal|last=Yenamandra|first=Surya Pavan|last2=Hellman|first2=Ulf|last3=Kempkes|first3=Bettina|last4=Darekar|first4=Suhas Deoram|last5=Petermann|first5=Sabine|last6=Sculley|first6=Tom|last7=Klein|first7=George|last8=Kashuba|first8=Elena|date=Dec 2010|title=Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes|url=https://www.ncbi.nlm.nih.gov/pubmed/20593215|journal=Cellular and molecular life sciences: CMLS|volume=67|issue=24|pages=4249–4256|doi=10.1007/s00018-010-0441-4|issn=1420-9071|pmid=20593215}}</ref><br />
<br />
[[Vitamin D receptor]] may be required for the normal development of [[natural killer T cell]]s that react to cells expressing [[CD1d]], as in cells infected by EBV.<ref>{{Cite journal|last=Yu|first=Sanhong|last2=Cantorna|first2=Margherita T.|date=2008-04-01|title=The vitamin D receptor is required for iNKT cell development|url=http://www.pnas.org/content/105/13/5207|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=13|pages=5207–5212|doi=10.1073/pnas.0711558105|issn=0027-8424|pmid=18364394}}</ref><br />
<br />
As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels<ref>{{Cite journal|last=Ramien|first=Caren|last2=Pachnio|first2=Annette|last3=Sisay|first3=Sofia|last4=Begum|first4=Jusnara|last5=Leese|first5=Alison|last6=Disanto|first6=Giulio|last7=Kuhle|first7=Jens|last8=Giovannoni|first8=Gavin|last9=Rickinson|first9=Alan|date=May 2014|title=Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort|url=https://www.ncbi.nlm.nih.gov/pubmed/24192216?dopt=Abstract|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=20|issue=6|pages=751–753|doi=10.1177/1352458513509507|issn=1477-0970|pmid=24192216}}</ref> (i.e., above 100 nmol/l).<br />
<br />
==Treatment==<br />
<br />
There is no specific treatment for EBV, only treatment of symptoms, such as taking over-the-counter medications for pain and fever.<ref name=":2" /> EBV is thought to persistent harmlessly in immunocompetent individuals, but in those with compromised immune systems it has been associated with certain cancers and possibly autoimmune disease. <br />
<br />
===Antivirals===<br />
<br />
Several [[antiviral]]s are active against EBV including [[valganciclovir|valganciclovir,]] [[valacyclovir]]<ref>{{Cite journal|last=Hoshino|first=Yo|date=|title=Long-Term Administration of Valacyclovir Reduces the Number of Epstein-Barr Virus (EBV)-Infected B Cells but Not the Number of EBV DNA Copies per B Cell in Healthy Volunteers|url=http://jvi.asm.org/content/83/22/11857.full|journal=Journal of Virology|volume=|issue=|pages=|via=}}</ref>, [[acyclovir]]<ref>{{Cite journal|last=Rafaillidis|first=Pl|date=Nov 2013|title=Antiviral treatment for severe EBV infections in apparently immunocompetent patients|url=https://www.ncbi.nlm.nih.gov/pubmed/20739216|journal=Journal of Clinical Virology|volume=|issue=|pages=|via=}}</ref> and [[spironolactone]].<ref name="Verma2016">{{Cite journal <br />
| last1 = Verma | first1 = Dinesh<br />
| last2 = Thompson | first2 = Jacob<br />
| last3 = Swaminathan | first3 = Sankar| title = Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function<br />
| journal = Proceedings of the National Academy of Sciences | issn = 1091-6490 | volume = 113| issue = 13| pages = 3609–3614<br />
| date = 2016-03-29<br />
| doi = 10.1073/pnas.1523686113 | pmid = 26976570| url = http://www.pnas.org/content/113/13/3609}}</ref><br />
<br />
[[Acyclovir]], an [[antiviral]] drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.<br />
<br />
A theoretical [[immunotherapy]] treatment proposes that inducing [[CD1d]] expression on EBV-infected B cells could prompt effective immune suppression of EBV by NKT cells.<ref>{{Cite journal|last=Priatel|first=John J|last2=Chung|first2=Brian K|last3=Tsai|first3=Kevin|last4=Tan|first4=Rusung|date=2014-04-09|title=Natural killer T cell strategies to combat Epstein–Barr virus infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063158/|journal=Oncoimmunology|volume=3|issue=|pages=|doi=10.4161/onci.28329|issn=2162-4011|pmc=4063158|pmid=25050206}}</ref><br />
<br />
===Rituximab===<br />
<br />
[[Rituximab]] may be effective in completely eliminating Epstein-Barr virus infection from the peripheral blood.<ref>{{Cite journal|last=Diamantopoulos|first=Panagiotis T.|last2=Polonyfi|first2=Katerina|last3=Sofotasiou|first3=Maria|last4=Papadopoulou|first4=Vasiliki|last5=Kalala|first5=Fani|last6=Iliakis|first6=Theodoros|last7=Zervakis|first7=Kostantinos|last8=Tsilimidos|first8=Gerassimos|last9=Kouzis|first9=Panagiotis|date=Dec 2013|title=Rituximab in the treatment of EBV-positive low grade B-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/24324119|journal=Anticancer Research|volume=33|issue=12|pages=5693–5698|issn=1791-7530|pmid=24324119}}</ref> A study of seventeen patients with low-grade [[B cell]] lymphoma found that after three cycles of Rituximab, the virus had been completely eliminated from the peripheral blood in all but one patient.<br />
<br />
===Herbs and nutraceuticals===<br />
<br />
Herbs shown to have antiviral properties against EBV including [[licorice|licorice.]]<ref>{{Cite journal|last=Lin|first=Jung-Chung|last2=Cherng|first2=Jaw-Ming|last3=Hung|first3=Man-Shan|last4=Baltina|first4=Lidia A.|last5=Baltina|first5=Lia|last6=Kondratenko|first6=Rimma|date=Jul 2008|title=Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: structure-activity relationships|url=https://www.ncbi.nlm.nih.gov/pubmed/18423902|journal=Antiviral Research|volume=79|issue=1|pages=6–11|doi=10.1016/j.antiviral.2008.01.160|issn=0166-3542|pmid=18423902}}</ref> [[Vitamin C]] and Vitamin D<ref>{{Cite journal|last=Rolf|first=L|date=July 2017|title=Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis|url=https://www.ncbi.nlm.nih.gov/pubmed/28731372|journal=Multiple Sclerosis|volume=|issue=|pages=|via=}}</ref> might also decrease duration and severity of the symptoms of EBV infection.<ref>{{Cite journal|last=Mikirova|first=N|date=May 2014|title=Effect of high dose vitamin C on Epstein-Barr viral infection|url=https://www.ncbi.nlm.nih.gov/pubmed/24793092|journal=Med Sci Monit|volume=|issue=|pages=|via=}}</ref><br />
<br />
===Vaccine===<br />
A [[vaccine]] for the prevention of Epstein-Barr virus is being explored.<ref>{{Cite web|url=https://www.nih.gov/news-events/news-releases/nih-researchers-make-progress-toward-epstein-barr-virus-vaccine|title=NIH researchers make progress toward Epstein-Barr virus vaccine|date=2019-04-09|website=National Institutes of Health (NIH)|language=en|access-date=2019-04-10}}</ref><br />
<br />
==Notable studies==<br />
*1996, MMPI profiles of patients with chronic fatigue syndrome<ref name=":5" /> - ([[pubmed:8730646|Abstract]])<br />
*1998, Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever<ref name=":4" /> - ([[pubmed:9926075|Abstract]])<br />
*2006, Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study<ref name=":6" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full text)]<br />
*2019, EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection<ref name="Asprusten2019">{{Cite journal|last=Asprusten|first=Tarjei Tørre|author-link=|last2=Pedersen|first2=Maria|author-link2=Maria Pedersen|last3=Skovlund|first3=Eva|author-link3=Eva Skovlund|last4=Wyller|first4=Vegard Bruun|author-link4=Vegard Bruun Wyller|date=2019|title=EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection|url=https://www.ncbi.nlm.nih.gov/pubmed/30957026|journal=BMJ paediatrics open|volume=3|issue=1|pages=e000390|doi=10.1136/bmjpo-2018-000390|issn=2399-9772|pmc=|pmid=30957026|quote=|via=}}</ref> - ([[pubmed:30957026|Abstract]])<br />
*2019, Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study<ref name="Pedersen2019a">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=|last3=Godang|first3=Kristin|author-link3=Kristin Godang|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|author-link7=|last8=Øie|first8=Merete Glenne|author-link8=|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=Jan 2019|title=Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study|url=https://www.ncbi.nlm.nih.gov/pubmed/30261303|journal=Brain, Behavior, and Immunity|volume=75|issue=|pages=94–100|doi=10.1016/j.bbi.2018.09.023|issn=1090-2139|pmid=30261303|quote=}}</ref> - ([[pubmed:30261303|Abstract]])<br />
*2019, Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later<ref name="Pedersen2019b">{{Cite journal|last=Pedersen|first=Maria|author-link=Maria Pedersen|last2=Asprusten|first2=Tarjei Tørre|author-link2=Tarjei Tørre Asprusten|last3=Godang|first3=Kristin|last4=Leegaard|first4=Truls Michael|author-link4=|last5=Osnes|first5=Liv Toril|author-link5=|last6=Skovlund|first6=Eva|author-link6=Eva Skovlund|last7=Tjade|first7=Trygve|last8=Øie|first8=Merete Glenne|last9=Wyller|first9=Vegard Bruun Bratholm|author-link9=Vegard Bruun Wyller|date=2019-01-27|title=Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later|url=https://www.ncbi.nlm.nih.gov/pubmed/30685875|journal=Acta Paediatrica (Oslo, Norway: 1992)|volume=108|issue=8|pages=1521-1526|doi=10.1111/apa.14728|issn=1651-2227|pmid=30685875|quote=|via=}}</ref> - ([[pubmed:30685875|Abstract]])<br />
*2019, Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Williams|first=Marshall V.|author-link=|last2=Cox|first2=Brandon|author-link2=|last3=Lafuse|first3=William P.|author-link3=|last4=Ariza|first4=Maria Eugenia|author-link4=|author-link5=|date=May 2019|title=Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0149291819301730|journal=Clinical Therapeutics|language=en|volume=41|issue=5|pages=848–863|doi=10.1016/j.clinthera.2019.04.009|pmc=6525645|pmid=31040055|quote=|via=}}</ref> - ([https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext Full text)]<br />
*2019, Review article - [[Epstein-Barr virus]] induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis<ref name="Kerr2019EBV">{{Cite journal|last=Kerr|first=Jonathan R.|author-link=Jonathan Kerr|date=Feb 2019|title=Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00059/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00059|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full (Full text)]<br />
*2019, Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors<ref name="Kerr2019a">{{Cite journal|last=Kerr|first=Jonathan R|author-link=Jonathan Kerr|author-link2=|date=2019-07-17|title=Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors|url=http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205822|journal=Journal of Clinical Pathology|language=en|volume=|issue=|pages=jclinpath–2019–205822|doi=10.1136/jclinpath-2019-205822|issn=0021-9746|quote=|via=}}</ref> - [[pubmed:31315893|(Abstract)]]<br />
*2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal|last=Shikova|first=Evelina|author-link=|last2=Reshkova|first2=Valentina|author-link2=|last3=Kumanova|first3=Аntoniya|author-link3=|last4=Raleva|first4=Sevdalina|author-link4=|last5=Alexandrova|first5=Dora|author-link5=|last6=Capo|first6=Natasa|author-link6=|last7=Murovska|first7=Modra|date=2020|title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=|pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)]<br />
*2022, EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities<ref>{{Cite journal|title=EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities|date=2022-06-08|url=https://insight.jci.org/articles/view/158193|journal=JCI Insight|volume=7|issue=11|last=Cox|first=Brandon S.|last2=Alharshawi|first2=Khaled|last3=Mena-Palomo|first3=Irene|last4=Lafuse|first4=William P.|last5=Ariza|first5=Maria Eugenia|language=en|doi=10.1172/jci.insight.158193|issn=0021-9738}}</ref> - ([https://insight.jci.org/articles/view/158193 Full text])<br />
<br />
== See also ==<br />
* [[List of herpesvirus infection studies]]<br />
<br />
==Learn more ==<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Infectious agents]]<br />
[[Category:Triggers and risk factors]]<br />
[[Category:Virology]]<br />
[[Category:Viruses]]</div>Darlahttps://me-pedia.org/w/index.php?title=Gastrointestinal_system&diff=97266Gastrointestinal system2022-03-02T12:11:12Z<p>Darla:/* Malabsorption */ and /* Dysbyosis */ citations</p>
<hr />
<div>The '''gastrointestinal system''' is an organ system which takes in food, digests it to extract and absorb energy and nutrients, and expels the remaining waste as feces. It consists of the esophagus, stomach, and intestines, and is divided into the upper and lower gastrointestinal tracts.<br />
<br />
[[Autonomic nervous system]] dysfunction of the gut, [[dysmotility]], [[dysbiosis]], and potentially, gut [[pathogen]]s, are all thought to contribute to the symptoms of [[ME]].<br />
<br />
== Evidence of gastrointestinal dysfunction in CFS ==<br />
<br />
=== Dysbiosis ===<br />
<br />
{{main|page_name =Dysbiosis}}<br />
<br />
There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. On average, ME/CFS patients have lower levels of ''[[Bifidobacteria]]'', ''[[Escherichia coli]]'' and higher levels of [[aerobic bacteria]],<ref name=":0">{{Cite journal|last=Logan|first=Alan C|last2=Venket Rao|first2=A|last3=Irani|first3=Dinaz|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=http://www.medical-hypotheses.com/article/S0306-9877(03)00096-3/abstract|journal=Medical Hypotheses|language=English|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|issn=0306-9877}}</ref> in particular ''[[Enterococcus]]'' and ''[[Streptococcus]]'' species.<ref>{{Cite journal|last=Sheedy|first=John R.|last2=Wettenhall|first2=Richard E. H.|last3=Scanlon|first3=Denis|last4=Gooley|first4=Paul R.|last5=Lewis|first5=Donald P.|last6=McGregor|first6=Neil|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|last9=DE Meirleir|first9=Kenny L.|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=http://www.ncbi.nlm.nih.gov/pubmed/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|issn=0258-851X|pmid=19567398}}</ref> The latter produce [[D-lactate]], a form of lactic acid only produced by non-human cells that is poorly metabolized in humans. [[D lactate]] is associated with a wide variety of cognitive and neurological symptoms, such as in patients who suffer from [[Lactic acidosis|D-lactic acidosis]]. A study found that higher levels of enterococcus bacteria in CFS patients were associated with more severe neurological and cognitive dysfunction.<ref>https://getinfo.de/en/search/id/BLCP%3ACN055885616/%60Bacterial-Colonosis-in-Patients-with-Persistent/</ref><br />
<br />
CFS patients may suffer from [[small intestinal bacterial overgrowth]] (SIBO).<ref name=":0" /><br />
<br />
One hypothesized consequence of dysobiosis is an overproduction of [[hydrogen sulfide]] (H2S) by pathogenic bacteria. H2S can inhibit [[Mitochondrion|mitochondria]]l respiration by blocking [[cytochrome c oxidase]].{{Citation needed}}<br />
<br />
A study of Norwegian and Belgian patients found significantly decreased proportions of [[Firmicutes]] genera ''[[Holdemania]]'' and increased proportions of [[Bacteroidetes]] genera ''[[Alistipes]]'' in the Norwegian but not the Belgian sample. Significantly increased proportions of [[Firmicutes]] genera ''[[Lactonifactor]]'' were found in both.<ref>{{Cite journal|date=2013-08-01|title=High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients|url=https://www.sciencedirect.com/science/article/pii/S1075996413000929|journal=Anaerobe|language=en|volume=22|pages=50–56|doi=10.1016/j.anaerobe.2013.06.002|issn=1075-9964}}</ref><br />
<br />
=== Intestinal permeability ===<br />
<br />
{{main|page_name =Intestinal permeability}}<br />
<br />
In a healthy digestive tract, the intestinal walls provide a tight, selective barrier to allow the absorption of nutrients prevent the entry of bacteria or pathogens. However, in CFS patients, there is evidence of increased [[intestinal permeability]] or "leaky gut." Intestinal permeability can allow for the [[translocation]] of bacteria across the mucosal lining and inside the blood stream. <br />
<br />
One study found higher levels of serum [[Immunoglobulin A|IgA]] and [[Immunoglobulin M|IgM]] against [[lipopolysaccharides]] (LPS), a major component of the outer membrane of [[gram-negative]] bacteria, indicating translocation.<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=Apr 2007|title=Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut–intestinal permeability|url=http://www.jad-journal.com/article/S0165-0327(06)00355-7/abstract|journal=Journal of Affective Disorders|language=English|volume=99|issue=1-3|pages=237–240|doi=10.1016/j.jad.2006.08.021|issn=0165-0327}}</ref> Serum IgA was significantly correlated to the severity of illness.<br />
<br />
=== Malabsorption ===<br />
CFS patients may have malabsorption of micronutrients. Lactic acid bacteria have therapeutic potential in malabsorption of micronutrients by supporting the intestinal epithelial barrier.<ref name=":0" /><br />
<br />
==Learn more==<br />
*[[Gastroparesis]]<br />
*[[Irritable bowel syndrome]]<br />
<br />
==See also==<br />
*[[Antibiotics]]<br />
*[[Fecal bacteriotherapy]]<br />
*[[Helminthic therapy]]<br />
*[[Hygiene hypothesis]]<br />
*[[Microbiome]]<br />
*[[Probiotics]]<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Body systems]]<br />
[[Category:Digestive system]]</div>Darlahttps://me-pedia.org/w/index.php?title=Gastrointestinal_system&diff=97265Gastrointestinal system2022-03-02T12:06:04Z<p>Darla:/* Dysbiosis */ and /* Malabsorption */</p>
<hr />
<div>The '''gastrointestinal system''' is an organ system which takes in food, digests it to extract and absorb energy and nutrients, and expels the remaining waste as feces. It consists of the esophagus, stomach, and intestines, and is divided into the upper and lower gastrointestinal tracts.<br />
<br />
[[Autonomic nervous system]] dysfunction of the gut, [[dysmotility]], [[dysbiosis]], and potentially, gut [[pathogen]]s, are all thought to contribute to the symptoms of [[ME]].<br />
<br />
== Evidence of gastrointestinal dysfunction in CFS ==<br />
<br />
=== Dysbiosis ===<br />
<br />
{{main|page_name =Dysbiosis}}<br />
<br />
There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. On average, ME/CFS patients have lower levels of ''[[Bifidobacteria]]'', ''[[Escherichia coli]]'' and higher levels of [[aerobic bacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|last2=Venket Rao|first2=A|last3=Irani|first3=Dinaz|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=http://www.medical-hypotheses.com/article/S0306-9877(03)00096-3/abstract|journal=Medical Hypotheses|language=English|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|issn=0306-9877}}</ref> in particular ''[[Enterococcus]]'' and ''[[Streptococcus]]'' species.<ref>{{Cite journal|last=Sheedy|first=John R.|last2=Wettenhall|first2=Richard E. H.|last3=Scanlon|first3=Denis|last4=Gooley|first4=Paul R.|last5=Lewis|first5=Donald P.|last6=McGregor|first6=Neil|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|last9=DE Meirleir|first9=Kenny L.|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=http://www.ncbi.nlm.nih.gov/pubmed/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|issn=0258-851X|pmid=19567398}}</ref> The latter produce [[D-lactate]], a form of lactic acid only produced by non-human cells that is poorly metabolized in humans. [[D lactate]] is associated with a wide variety of cognitive and neurological symptoms, such as in patients who suffer from [[Lactic acidosis|D-lactic acidosis]]. A study found that higher levels of enterococcus bacteria in CFS patients were associated with more severe neurological and cognitive dysfunction.<ref>https://getinfo.de/en/search/id/BLCP%3ACN055885616/%60Bacterial-Colonosis-in-Patients-with-Persistent/</ref><br />
<br />
CFS patients may suffer from [[small intestinal bacterial overgrowth]] (SIBO).<ref name=":0">{{Cite journal|title=Small Intestinal Transit Time Is Delayed in Small Intestinal Bacterial Overgrowth|date=2015-08|url=https://pubmed.ncbi.nlm.nih.gov/25319735|journal=Journal of Clinical Gastroenterology|volume=49|issue=7|pages=571–576|last=Roland|first=Bani Chander|last2=Ciarleglio|first2=Maria M.|last3=Clarke|first3=John O.|last4=Semler|first4=John R.|last5=Tomakin|first5=Eric|last6=Mullin|first6=Gerard E.|last7=Pasricha|first7=Pankaj J.|doi=10.1097/MCG.0000000000000257|pmid=25319735|issn=1539-2031}}</ref><br />
<br />
One hypothesized consequence of dysobiosis is an overproduction of [[hydrogen sulfide]] (H2S) by pathogenic bacteria. H2S can inhibit [[Mitochondrion|mitochondria]]l respiration by blocking [[cytochrome c oxidase]].{{Citation needed}}<br />
<br />
A study of Norwegian and Belgian patients found significantly decreased proportions of [[Firmicutes]] genera ''[[Holdemania]]'' and increased proportions of [[Bacteroidetes]] genera ''[[Alistipes]]'' in the Norwegian but not the Belgian sample. Significantly increased proportions of [[Firmicutes]] genera ''[[Lactonifactor]]'' were found in both.<ref>{{Cite journal|date=2013-08-01|title=High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients|url=https://www.sciencedirect.com/science/article/pii/S1075996413000929|journal=Anaerobe|language=en|volume=22|pages=50–56|doi=10.1016/j.anaerobe.2013.06.002|issn=1075-9964}}</ref><br />
<br />
=== Intestinal permeability ===<br />
<br />
{{main|page_name =Intestinal permeability}}<br />
<br />
In a healthy digestive tract, the intestinal walls provide a tight, selective barrier to allow the absorption of nutrients prevent the entry of bacteria or pathogens. However, in CFS patients, there is evidence of increased [[intestinal permeability]] or "leaky gut." Intestinal permeability can allow for the [[translocation]] of bacteria across the mucosal lining and inside the blood stream. <br />
<br />
One study found higher levels of serum [[Immunoglobulin A|IgA]] and [[Immunoglobulin M|IgM]] against [[lipopolysaccharides]] (LPS), a major component of the outer membrane of [[gram-negative]] bacteria, indicating translocation.<ref>{{Cite journal|last=Maes|first=Michael|last2=Mihaylova|first2=Ivana|last3=Leunis|first3=Jean-Claude|date=Apr 2007|title=Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut–intestinal permeability|url=http://www.jad-journal.com/article/S0165-0327(06)00355-7/abstract|journal=Journal of Affective Disorders|language=English|volume=99|issue=1-3|pages=237–240|doi=10.1016/j.jad.2006.08.021|issn=0165-0327}}</ref> Serum IgA was significantly correlated to the severity of illness.<br />
<br />
=== Malabsorption ===<br />
CFS patients may have malabsorption of micronutrients. Lactic acid bacteria have therapeutic potential in malabsorption of micronutrients by supporting the intestinal epithelial barrier.<ref name=":0" /><br />
<br />
==Learn more==<br />
*[[Gastroparesis]]<br />
*[[Irritable bowel syndrome]]<br />
<br />
==See also==<br />
*[[Antibiotics]]<br />
*[[Fecal bacteriotherapy]]<br />
*[[Helminthic therapy]]<br />
*[[Hygiene hypothesis]]<br />
*[[Microbiome]]<br />
*[[Probiotics]]<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Body systems]]<br />
[[Category:Digestive system]]</div>Darlahttps://me-pedia.org/w/index.php?title=Primer_for_patients&diff=94181Primer for patients2021-11-11T12:02:00Z<p>Darla:Corrected a grammatical error and heading coding error</p>
<hr />
<div>{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}<br />
This '''Primer for patients''' will provide the information you need to better understand your personal diagnosis of [[chronic fatigue syndrome]] (CFS), [[myalgic encephalomyelitis]] (ME), or [[ME/CFS]], which can be very different with severity and symptoms from patient to patient. <br />
<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo><br />
<br />
The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=[[Centers for Disease Control]]|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9-10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|access-date=}}</ref><ref name=":2">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation<br />
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers <br />
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain<br />
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir<br />
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson<br />
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas<br />
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner<br />
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested<br />
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry <br />
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi<br />
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles<br />
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey<br />
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande<br />
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols<br />
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115<br />
| date = 2003<br />
| pmid = <br />
| doi = 10.1300/J092v11n01_02<br />
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf<br />
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/genitourinary impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> <br />
<br />
Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda19942">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":0232">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=|last=}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=}}</ref> There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes;<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref name=":10">{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|language=en|issn=0140-0460|quote=|author-link=}}</ref> these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].{{Citation needed}} Some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref name=":11" /> <br />
<br />
CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.<br />
<br />
The acronym ME/CFS is widely used in research, by research and patient organizations, and patients. <br />
<br />
"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=41|issue=4|pages=612|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref> <br />
<br />
Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":4">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-11-08|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-22}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":3">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-22}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-04-12}}</ref><br />
<br />
Take time when you are able to review this Primer. Because you are not well, this can be overwhelming at times, so only do what you are mentally and physically able. <br />
<br />
[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]<br />
<br />
== Disease onset and course of illness==<br />
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu2">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergy|allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":04">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":14">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref><br />
<br />
The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref><br />
<br />
The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting body chemistry, changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=[[Centers for Disease Control]]|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":4" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or heart rate regulation.<ref name=":4" /> <br />
===Not a mental health disorder===<br />
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":4" /> <br />
<br />
===No clear evidence that ME/CFS is contagious===<br />
[[:Category:Infectious agents|Infectious episodes]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|access-date=}}</ref> Nowadays, the vast majority of ME/CFS cases are sporadic rather than epidemic, and there is no clear evidence that sporadic ME/CFS cases are contagious.<ref name="pediatricprimer">{{Cite journal|last=Rowe|first=Katherine S.|last2=Vallings|first2=Rosamund|last3=Stewart|first3=Julian M.|last4=Speight|first4=Nigel|last5=Schwartz|first5=Malcolm S.|last6=Medow|first6=Marvin S.|last7=Gurwitt|first7=Alan|last8=Friedman|first8=Kenneth J.|last9=Underhill|first9=Rosemary A.|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref><br />
<br />
Families, partners, and friends do not report contracting ME/CFS from someone with the disease nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Underhill and O'Gorman (2006) researched 219 patients with ME/CFS, and concluded that close household contact and genetics were both risk factors for CFS, finding 3.2% of spouses/partners of those with CFS also had the illness.<ref name="UnderhillInfectious">{{Cite journal|last=Underhill|first=Rosemary A.|last2=O'gorman|first2=Ruth|date=2006-01-01|title=Prevalence of Chronic Fatigue Syndrome and Chronic Fatigue Within Families of CFS Patients|url=https://doi.org/10.1300/J092v13n01_02|journal=Journal of Chronic Fatigue Syndrome|volume=13|issue=1|pages=3–13|doi=10.1300/J092v13n01_02|issn=1057-3321}}</ref> This was a higher prevalence than all genetic relatives except children of patients. Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a line of research recommended by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-02-13}}</ref><br /><br />
<br />
[[Michael Sikora]] and collaborators at the [[Open Medicine Foundation]] hope that their research on the role of [[T cell]]s and immune-related [[Genetics of chronic fatigue syndrome|genes]] will help address "whether ME/CFS is an autoimmune or infectious disease, or simply an activation of the immune system".<ref>https://www.omf.ngo/2018/06/04/omf-funded-research/</ref><br />
<br />
====Blood donation and organ transplant====<br />
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Blood and transport matters|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|url-status=dead|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref><br />
<br />
== Mini-Docs ==<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo><br />
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED<br />
<br />
Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=}}</ref><br />
<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo><br />
<br />
[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online<br />
<br />
This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=Palo Alto Online}}</ref><br />
<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo><br />
<br />
''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]<br />
<br />
This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=Unrest Film}}</ref><br />
<br />
==Epidemiology ==<br />
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":2" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref> <br />
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]<br />
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=[[Centers for Disease Control]]|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=[[Centers for Disease Control]]|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref><br />
*[[Female predominant diseases]]<br />
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=[[Centers for Disease Control]]|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref><br />
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]<br />
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2017-10-10|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":0">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-11-08|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-31}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":2" /><ref name="Carruthers, 20032" /> <ref name=":5" /><br />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]<br />
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness"|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-31}}</ref><br />
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]<br />
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":1">{{Cite journal|last=Cairns|first=R.|author-link=|last2=Hotopf|first2=M.|author-link2=|author-link3=|author-link4=|author-link5=|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087|quote=|via=}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":1" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref><br />
<br />
== Symptoms ==<br />
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-02-01}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.<br />
<br />
[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The <u title="Neurally mediated hypotension">onset of PEM can be delayed 24-72 hours</u> and depending on ME/CFS severity can last days, weeks, or even months]]<br />
<br />
[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]<br />
<br />
[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]<br />
<br />
[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]<br />
<br />
[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]<br />
<br />
[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]<br />
<br />
*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":02">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":03">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1" /> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":152">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":132">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":02" /><ref name=":03" /><ref name=":0" /><ref name=":1" /> Regarding PEM the [[CFIDS Association of America]] states:<br />
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote><br />
*[[chronic fatigue]]<br />
*[[cognitive dysfunction]]<br />
<br />
*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)<br />
*[[unrefreshing sleep]] See also: [[sleep disturbance]] <ref name=":6" /><ref name=":2" /> <br />
==== Other possible symptoms ====<br />
*[[chronic pain]] <br />
*[[immune system]]<br />
*<span class="plainlinks">[[:Category:Neurological signs and symptoms|neurological signs and symptoms]]</span> See also: [[neuroinflammation]].<br />
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]<br />
<br />
=== Comorbids ===<br />
*[[fibromyalgia]] (FMS)<br />
*[[irritable bowel syndrome]] (IBS)<br />
*[[multiple chemical sensitivity]] (MCS)<br />
*[[temporomandibular joint disorder]] (TMJ)<ref>{{Cite web|url=https://solvecfs.org/what-is-mecfs/|title=Get the Facts about ME/CFS|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-09-10}}</ref><br />
<br />
=== Government guides on symptoms ===<br />
'''US Government guides on symptoms'''<br />
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]] <br />
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]<br />
<br />
'''Canada guides on symptoms'''<br />
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]<br />
<br />
== Tests to discuss with your doctor ==<br />
* [[Natural killer cell]] (NKC) Blood Test<br />
<br />
*Sleep study for [[sleep apnea]], [[restless leg syndrome]], and other sleep disturbances. <br />
*[[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].<br />
<br />
==Drugs and treatments==<br />
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [[:Category:Potential_treatments|potential treatments]], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.<br />
<br />
===Drugs===<br />
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]<br />
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}} <br />
<br />
Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref name="experimental">{{Cite web|url=https://ammes.org/experimental-treatments/|title=Experimental treatments |last=|first=|date=|website=[[American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society]]|language=en-US|archive-url=|archive-date=|access-date=2021-03-18}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Hemispherx Biopharma, Inc.|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|access-date=2019-02-10}}</ref><br />
<br />
[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref><br />
<br />
[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref><br />
<br />
=== Treating other conditions ===<br />
Different forms of [[Orthostatic intolerance|OI]] are treated with beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=[[Centers for Disease Control]]|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" /><br />
<br />
===Controversy===<br />
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]<br />
Psychiatry has taken an inappropriate lead and treatment path for a biological disease. In the UK, [[GET]] and [[CBT]] are employed by ME Clinics. [[Exercise]] exacerbates symptoms and can further injure patients.<ref>[http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS - Slightly Alive - By: Mary Schweitzer]</ref><ref>[https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients GET and CBT are dangerous treatments for ME patients - Petition - 38 Degrees - By Michael Evison]</ref> [[Depression]] and [[anxiety]] drugs are utilized usually with poor and even damaging results.<ref name="myhill" /><br />
<br />
Treating a biological disease as a mental illness is cost effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance having clauses excluding a mental health illness/disease kick in stopping any payment or shortening the payout time-frame.<ref>[http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/ Trial by error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really? - By David Tuller Virology Blog]</ref><ref>[https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders Physical Illnesses May Soon Be Labeled “Mental Disorders” - Psychology Today - Toni Bernhard, J.D.]</ref><ref>[http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth People with mental illness face widespread discrimination - The Guardian - David Batty]</ref><ref>[http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/ Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits - Thoughts About ME]</ref> <br />
<br />
==== Graded exercise therapy & Cognitive behavioral therapy ====<br />
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]<br />
[[Graded exercise therapy]] (GET) and [[Cognitive behavioral therapy]] (CBT) are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.<br />
<br />
[[Exercise]], especially GET, can injure an ME/CFS patient further. <br />
<br />
*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.<br />
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter]. <br />
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.<br />
*[[Doctor Speedy]] was also seriously injured by GET.<br />
<br />
===Claims of curative treatments===<br />
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=[[Centers for Disease Control]]|language=en-us|archive-url=|archive-date=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-07-10|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-07-10|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-07-12|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-09-07}}</ref><br />
<br />
Additionally, there have been media reports of some athletes diagnosed with CFS that recovered in a relatively short period of time,<ref name=":7" /><ref name=":8" /><ref name=":9" /><ref name=":10" /> may have had [[overtraining syndrome]], a condition they sometimes acquire,{{Citation needed}} while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref name=":11">{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=}}</ref><br />
=== Working with government to move forward ===<br />
<br />
Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[National Institutes of Health]] (NIH), the [[Centers for Disease Control and Prevention]] (CDC) reinstating and increasing funding and education based on [[Institute of Medicine report]] recommendations and the [[U.S. Department of Health and Human Services|Health and Human Services]] (HHS) funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> #[[MEAction]] reports on this ongoing process.<br />
<br />
===CDC Website updates===<br />
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref><br />
<br />
*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref><br />
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=Medscape and CDC}}</ref><br />
<br />
'''MEAction input'''<br />
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.<br />
<br />
== Recommended viewing ==<br />
<br />
==== Documentary ====<br />
'''Films'''<br />
*[[Forgotten Plague]] is a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD purchase]. (2015)<br />
[[File:Forgotten Plague.jpeg|200px|thumb|center]]<br />
*[[Unrest|Unrest]] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)<br />
[[File:Unrest.jpg|400px|thumb|center]]<br />
<br />
==== Short film ====<br />
<br />
*[[The Last Great Medical Cover Up]] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)<br />
<br />
==== News media ====<br />
*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)<br />
<br />
==== Talks and interviews ====<br />
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Canary in a Coal Mine]] (now titled [[Unrest]]) at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20.] (2016)<br />
<br />
== Recommended reading ==<br />
====Government health organizations====<br />
:'''US'''<br />
<br />
:[[Centers for Disease Control]] (CDC)<br />
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html ME/CFS in Children Fact Sheets] (2017) Fact Sheets for Healthcare Professionals, Parents/Guardians, Education Professionals<br />
<br />
:[[National Institutes of Health]] (NIH)<br />
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]<br />
<br />
:[[Institute of Medicine]] (IOM)<br />
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts] From the [[Institute of Medicine report]]. (2015)<br />
<br />
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness] Report Brief on the Institute of Medicine report. (2015)<br />
<br />
==== ME/CFS research foundations ====<br />
:'''UK'''<br />
<br />
:[[Invest in ME]]<br />
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]<br />
<br />
:'''US'''<br />
<br />
:[[Open Medicine Foundation]] (OMF)<br />
:*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]<br />
<br />
==== ME/CFS organizations ====<br />
:'''Australia'''<br />
<br />
:[[Emerge Australia]]<br />
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]<br />
<br />
:'''UK'''<br />
<br />
:[[ME Association]]<br />
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]<br />
<br />
:[[Tymes Trust]] (Pediatric)<br />
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs] (2016)<br />
<br />
:'''US'''<br />
:[[Massachusetts CFIDS/ME & FM Association]]<br />
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]<br />
<br />
:[[Solve ME/CFS]]<br />
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?] (2017)<br />
<br />
:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS] (2016)<br />
<br />
:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?] (2013)<br />
<br />
:'''International''' <br />
:[[MEAction]] <br />
:*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers<br />
<br />
:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)] (2015)<br />
<br />
:*[http://www.meaction.net/reports-and-fact-sheets/? Reports and Fact Sheets] (2015)<br />
<br />
==== Other organizations ====<br />
:[https://rarediseases.org/ National Organization for Rare Disorders] (NORD) <br />
:*[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]<br />
<br />
==== Other reading====<br />
:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?] By: Suzan Jackson<br />
<br />
==History==<br />
*[[Osler's Web]] is a book by [[Hillary Johnson]] on the early history of CFS.<br />
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.<br />
<br />
=== Deaths of ME/CFS patients ===<br />
*[[Causes of death]]<br />
*[[Suicide]]<br />
<br />
'''Death certificates with ME or CFS'''<br />
*[[Merryn Crofts]]' death is attributed to ME. <br />
*[[Sophia Mirza]]'s death is attributed to CFS.<br />
<br />
In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref><br />
<br />
==Notable studies==<br />
*2014, Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Zeineh|first=Michael M.|author-link=Michael Zeineh|last2=Kang|first2=James|author-link2=|last3=Atlas|first3=Scott W.|author-link3=|last4=Raman|first4=Mira M.|author-link4=|last5=Reiss|first5=Allan L.|author-link5=|last6=Norris|first6=Jane L.|author-link6=|last7=Valencia|first7=Ian|author-link7=Ian Valencia|last8=Montoya|first8=Jose G.|author-link8=Jose Montoya|date=Feb 2015|title=Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome|url=http://pubs.rsna.org/doi/10.1148/radiol.14141079|journal=Radiology|language=en|volume=274|issue=2|pages=517–526|doi=10.1148/radiol.14141079|issn=0033-8419|pmc=|pmid=|access-date=|quote=|via=}}</ref><br />
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote><br />
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]<br />
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]<br />
<br />
*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]<br />
*[[List of enterovirus infection studies]]]<br />
*2016, [[Metabolic features of chronic fatigue syndrome]]<br />
<br />
*2019, [[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref><br />
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study]<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|url-status=|publisher=SolveCFS}}</ref> (TALK)<br />
<gallery widths="200" heights="100" class="center" caption="Images from talk: &quot;ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study&quot;"><br />
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]<br />
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]<br />
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]<br />
</gallery><br />
<br />
== Connect with organizations and other persons with ME/CFS ==<br />
*For information and support, you may want to review materials offered by a patient group in your area. <br />
<br />
:See: [[Patient groups by country]] <br />
<br />
*:[[Science for ME]], [[Phoenix Rising]], r/cfs [https://www.reddit.com/r/cfs/], and [[Health Rising]] are forums where you can ask questions, get support, and read about the latest research.<br />
<br />
*There are many research initiatives around the world working on ME/CFS. <br />
<br />
:See: [[Research initiatives by country]] <br />
<br />
*:[[Solve ME/CFS]] produces printed, online, and e-mail newsletters. Take their [http://solvecfs.org/do-i-have-mecfs-quiz/ Do I have ME/CFS? QUIZ]<br />
<br />
== See also ==<br />
*[[Primer for family, friends and care providers]]<br />
==Learn more==<br />
'''[[Patient mental health]]'''<br />
<br />
:Patients who had been deemed as suffering from mental health and not a biological illness:<br />
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.<br />
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.<br />
:*[[Ean Proctor]] was taken from his parents as a young boy, and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in a pool to make him swim and put on a scary theme park ride to scare him into moving.<br />
<br />
*ME/CFS is not [[depression]]. It causes a lack of energy, not a lack desire to do activities.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref></ref><ref name="myhill">{{Cite web |url =http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title = CFS or depression - what are the differences|last=Myhill |first =Sarah |author-link =Sarah Myhill|website = DrMyhill|access-date = 2021-03-22}}</ref><br />
<br />
'''Outbreaks'''<br />
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]<br />
<br />
* [[List of outbreaks]]<br />
<br />
'''Other resources'''<br />
*[[Phoenix Rising]] Citizen Scientists debate the latest ME/CFS science.<br />
*[[Science for ME]] Friendly forum on ME/CFS, FMS, and comorbid illnesses. <br />
*[https://twitter.com/search?f=tweets&vertical=default&q=%23mecfs&src=tyah Twitter #mecfs] Connect with patients, caregivers, and ME/CFS organizations for support, articles, and research.<br />
*[[Verywell FMS/CFS]] Well written articles with simply stated facts about ME/CFS and Fibromyalgia.<br />
<br />
== References ==<br />
{{Reflist}}<br />
<br />
[[Category:Primers]]</div>Darlahttps://me-pedia.org/w/index.php?title=Primer_for_patients&diff=94180Primer for patients2021-11-11T11:58:28Z<p>Darla:Added link for r/cfs</p>
<hr />
<div>{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}<br />
This '''Primer for patients''' will provide the information you need to better understand your personal diagnosis of [[chronic fatigue syndrome]] (CFS), [[myalgic encephalomyelitis]] (ME), or [[ME/CFS]], which can be very different with severity and symptoms from patient to patient. <br />
<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo><br />
<br />
The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=[[Centers for Disease Control]]|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9-10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|access-date=}}</ref><ref name=":2">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation<br />
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers <br />
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain<br />
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir<br />
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson<br />
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas<br />
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner<br />
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested<br />
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry <br />
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi<br />
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles<br />
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey<br />
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande<br />
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols<br />
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115<br />
| date = 2003<br />
| pmid = <br />
| doi = 10.1300/J092v11n01_02<br />
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf<br />
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/genitourinary impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> <br />
<br />
Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda19942">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":0232">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=|last=}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=}}</ref> There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes;<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref name=":10">{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|language=en|issn=0140-0460|quote=|author-link=}}</ref> these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].{{Citation needed}} Some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref name=":11" /> <br />
<br />
CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.<br />
<br />
The acronym ME/CFS is widely used in research, by research and patient organizations, and patients. <br />
<br />
"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=41|issue=4|pages=612|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref> <br />
<br />
Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":4">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-11-08|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-22}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":3">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-22}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-04-12}}</ref><br />
<br />
Take time when you are able to review this Primer. Because you are not well, this can be overwhelming at times, so only do what you are mentally and physically able. <br />
<br />
[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]<br />
<br />
== Disease onset and course of illness==<br />
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu2">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergy|allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":04">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":14">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref><br />
<br />
The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref><br />
<br />
The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting body chemistry, changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=[[Centers for Disease Control]]|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":4" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or heart rate regulation.<ref name=":4" /> <br />
===Not a mental health disorder===<br />
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":4" /> <br />
<br />
===No clear evidence that ME/CFS is contagious===<br />
[[:Category:Infectious agents|Infectious episodes]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|access-date=}}</ref> Nowadays, the vast majority of ME/CFS cases are sporadic rather than epidemic, and there is no clear evidence that sporadic ME/CFS cases are contagious.<ref name="pediatricprimer">{{Cite journal|last=Rowe|first=Katherine S.|last2=Vallings|first2=Rosamund|last3=Stewart|first3=Julian M.|last4=Speight|first4=Nigel|last5=Schwartz|first5=Malcolm S.|last6=Medow|first6=Marvin S.|last7=Gurwitt|first7=Alan|last8=Friedman|first8=Kenneth J.|last9=Underhill|first9=Rosemary A.|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref><br />
<br />
Families, partners, and friends do not report contracting ME/CFS from someone with the disease nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Underhill and O'Gorman (2006) researched 219 patients with ME/CFS, and concluded that close household contact and genetics were both risk factors for CFS, finding 3.2% of spouses/partners of those with CFS also had the illness.<ref name="UnderhillInfectious">{{Cite journal|last=Underhill|first=Rosemary A.|last2=O'gorman|first2=Ruth|date=2006-01-01|title=Prevalence of Chronic Fatigue Syndrome and Chronic Fatigue Within Families of CFS Patients|url=https://doi.org/10.1300/J092v13n01_02|journal=Journal of Chronic Fatigue Syndrome|volume=13|issue=1|pages=3–13|doi=10.1300/J092v13n01_02|issn=1057-3321}}</ref> This was a higher prevalence than all genetic relatives except children of patients. Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a line of research recommended by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-02-13}}</ref><br /><br />
<br />
[[Michael Sikora]] and collaborators at the [[Open Medicine Foundation]] hope that their research on the role of [[T cell]]s and immune-related [[Genetics of chronic fatigue syndrome|genes]] will help address "whether ME/CFS is an autoimmune or infectious disease, or simply an activation of the immune system".<ref>https://www.omf.ngo/2018/06/04/omf-funded-research/</ref><br />
<br />
====Blood donation and organ transplant====<br />
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Blood and transport matters|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|url-status=dead|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref><br />
<br />
== Mini-Docs ==<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo><br />
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED<br />
<br />
Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=}}</ref><br />
<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo><br />
<br />
[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online<br />
<br />
This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=Palo Alto Online}}</ref><br />
<br />
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo><br />
<br />
''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]<br />
<br />
This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=Unrest Film}}</ref><br />
<br />
==Epidemiology ==<br />
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":2" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref> <br />
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]<br />
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=[[Centers for Disease Control]]|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=[[Centers for Disease Control]]|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref><br />
*[[Female predominant diseases]]<br />
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=[[Centers for Disease Control]]|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref><br />
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]<br />
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2017-10-10|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":0">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-11-08|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-31}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":2" /><ref name="Carruthers, 20032" /> <ref name=":5" /><br />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]<br />
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness"|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-01-31}}</ref><br />
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]<br />
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":1">{{Cite journal|last=Cairns|first=R.|author-link=|last2=Hotopf|first2=M.|author-link2=|author-link3=|author-link4=|author-link5=|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087|quote=|via=}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":1" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref><br />
<br />
== Symptoms ==<br />
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2019-01-18|website=[[Centers for Disease Control]]|language=en-us|access-date=2019-02-01}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.<br />
<br />
[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The <u title="Neurally mediated hypotension">onset of PEM can be delayed 24-72 hours</u> and depending on ME/CFS severity can last days, weeks, or even months]]<br />
<br />
[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]<br />
<br />
[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]<br />
<br />
[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]<br />
<br />
[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]<br />
<br />
[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]<br />
<br />
*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":02">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":03">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1" /> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":152">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":132">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":02" /><ref name=":03" /><ref name=":0" /><ref name=":1" /> Regarding PEM the [[CFIDS Association of America]] states:<br />
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote><br />
*[[chronic fatigue]]<br />
*[[cognitive dysfunction]]<br />
<br />
*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)<br />
*[[unrefreshing sleep]] See also: [[sleep disturbance]] <ref name=":6" /><ref name=":2" /> <br />
==== Other possible symptoms ====<br />
*[[chronic pain]] <br />
*[[immune system]]<br />
*<span class="plainlinks">[[:Category:Neurological signs and symptoms|neurological signs and symptoms]]</span> See also: [[neuroinflammation]].<br />
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]<br />
<br />
=== Comorbids ===<br />
*[[fibromyalgia]] (FMS)<br />
*[[irritable bowel syndrome]] (IBS)<br />
*[[multiple chemical sensitivity]] (MCS)<br />
*[[temporomandibular joint disorder]] (TMJ)<ref>{{Cite web|url=https://solvecfs.org/what-is-mecfs/|title=Get the Facts about ME/CFS|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-09-10}}</ref><br />
<br />
=== Government guides on symptoms ===<br />
'''US Government guides on symptoms'''<br />
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]] <br />
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]<br />
<br />
'''Canada guides on symptoms'''<br />
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]<br />
<br />
== Tests to discuss with your doctor ==<br />
* [[Natural killer cell]] (NKC) Blood Test<br />
<br />
*Sleep study for [[sleep apnea]], [[restless leg syndrome]], and other sleep disturbances. <br />
*[[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].<br />
<br />
==Drugs and treatments==<br />
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [[:Category:Potential_treatments|potential treatments]], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.<br />
<br />
===Drugs===<br />
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]<br />
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}} <br />
<br />
Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref name="experimental">{{Cite web|url=https://ammes.org/experimental-treatments/|title=Experimental treatments |last=|first=|date=|website=[[American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society]]|language=en-US|archive-url=|archive-date=|access-date=2021-03-18}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Hemispherx Biopharma, Inc.|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|access-date=2019-02-10}}</ref><br />
<br />
[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref><br />
<br />
[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref><br />
<br />
=== Treating other conditions ===<br />
Different forms of [[Orthostatic intolerance|OI]] are treated with beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=[[Centers for Disease Control]]|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" /><br />
<br />
===Controversy===<br />
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]<br />
Psychiatry has taken an inappropriate lead and treatment path for a biological disease. In the UK, [[GET]] and [[CBT]] are employed by ME Clinics. [[Exercise]] exacerbates symptoms and can further injure patients.<ref>[http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS - Slightly Alive - By: Mary Schweitzer]</ref><ref>[https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients GET and CBT are dangerous treatments for ME patients - Petition - 38 Degrees - By Michael Evison]</ref> [[Depression]] and [[anxiety]] drugs are utilized usually with poor and even damaging results.<ref name="myhill" /><br />
<br />
Treating a biological disease as a mental illness is cost effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance having clauses excluding a mental health illness/disease kick in stopping any payment or shortening the payout time-frame.<ref>[http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/ Trial by error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really? - By David Tuller Virology Blog]</ref><ref>[https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders Physical Illnesses May Soon Be Labeled “Mental Disorders” - Psychology Today - Toni Bernhard, J.D.]</ref><ref>[http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth People with mental illness face widespread discrimination - The Guardian - David Batty]</ref><ref>[http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/ Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits - Thoughts About ME]</ref> <br />
<br />
==== Graded exercise therapy & Cognitive behavioral therapy ====<br />
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]<br />
[[Graded exercise therapy]] (GET) and [[Cognitive behavioral therapy]] (CBT) are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.<br />
<br />
[[Exercise]], especially GET, can injure an ME/CFS patient further. <br />
<br />
*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.<br />
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter]. <br />
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.<br />
*[[Doctor Speedy]] was also seriously injured by GET.<br />
<br />
===Claims of curative treatments===<br />
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=[[Centers for Disease Control]]|language=en-us|archive-url=|archive-date=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-07-10|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-07-10|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|date=2018-07-12|website=[[Centers for Disease Control]]|language=en-us|access-date=2018-09-07}}</ref><br />
<br />
Additionally, there have been media reports of some athletes diagnosed with CFS that recovered in a relatively short period of time,<ref name=":7" /><ref name=":8" /><ref name=":9" /><ref name=":10" /> may have had [[overtraining syndrome]], a condition they sometimes acquire,{{Citation needed}} while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref name=":11">{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=}}</ref><br />
=== Working with government to move forward ===<br />
<br />
Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[National Institutes of Health]] (NIH), the [[Centers for Disease Control and Prevention]] (CDC) reinstating and increasing funding and education based on [[Institute of Medicine report]] recommendations and the [[U.S. Department of Health and Human Services|Health and Human Services]] (HHS) funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> #[[MEAction]] reports on this ongoing process.<br />
<br />
===CDC Website updates===<br />
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref><br />
<br />
*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref><br />
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|publisher=Medscape and CDC}}</ref><br />
<br />
'''MEAction input'''<br />
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.<br />
<br />
== Recommended viewing ==<br />
<br />
==== Documentary ====<br />
'''Films'''<br />
*[[Forgotten Plague]] is a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD purchase]. (2015)<br />
[[File:Forgotten Plague.jpeg|200px|thumb|center]]<br />
*[[Unrest|Unrest]] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)<br />
[[File:Unrest.jpg|400px|thumb|center]]<br />
<br />
==== Short film ====<br />
<br />
*[[The Last Great Medical Cover Up]] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)<br />
<br />
==== News media ====<br />
*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)<br />
<br />
==== Talks and interviews ====<br />
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Canary in a Coal Mine]] (now titled [[Unrest]]) at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20.] (2016)<br />
<br />
== Recommended reading ==<br />
====Government health organizations====<br />
:'''US'''<br />
<br />
:[[Centers for Disease Control]] (CDC)<br />
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html ME/CFS in Children Fact Sheets] (2017) Fact Sheets for Healthcare Professionals, Parents/Guardians, Education Professionals<br />
<br />
:[[National Institutes of Health]] (NIH)<br />
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]<br />
<br />
:[[Institute of Medicine]] (IOM)<br />
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts] From the [[Institute of Medicine report]]. (2015)<br />
<br />
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness] Report Brief on the Institute of Medicine report. (2015)<br />
<br />
==== ME/CFS research foundations ====<br />
:'''UK'''<br />
<br />
:[[Invest in ME]]<br />
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]<br />
<br />
:'''US'''<br />
<br />
:[[Open Medicine Foundation]] (OMF)<br />
:*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]<br />
<br />
==== ME/CFS organizations ====<br />
:'''Australia'''<br />
<br />
:[[Emerge Australia]]<br />
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]<br />
<br />
:'''UK'''<br />
<br />
:[[ME Association]]<br />
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]<br />
<br />
:[[Tymes Trust]] (Pediatric)<br />
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs] (2016)<br />
<br />
:'''US'''<br />
:[[Massachusetts CFIDS/ME & FM Association]]<br />
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]<br />
<br />
:[[Solve ME/CFS]]<br />
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?] (2017)<br />
<br />
:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS] (2016)<br />
<br />
:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?] (2013)<br />
<br />
:'''International''' <br />
:[[MEAction]] <br />
:*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers<br />
<br />
:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)] (2015)<br />
<br />
:*[http://www.meaction.net/reports-and-fact-sheets/? Reports and Fact Sheets] (2015)<br />
<br />
==== Other organizations ====<br />
:[https://rarediseases.org/ National Organization for Rare Disorders] (NORD) <br />
:*[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]<br />
<br />
==== Other reading====<br />
:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?] By: Suzan Jackson<br />
<br />
==History==<br />
*[[Osler's Web]] is a book by [[Hillary Johnson]] on the early history of CFS.<br />
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.<br />
<br />
=== Deaths of ME/CFS patients ===<br />
*[[Causes of death]]<br />
*[[Suicide]]<br />
<br />
'''Death certificates with ME or CFS'''<br />
*[[Merryn Crofts]]' death is attributed to ME. <br />
*[[Sophia Mirza]]'s death is attributed to CFS.<br />
<br />
In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref><br />
<br />
==Notable studies==<br />
*2014, Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome<ref>{{Cite journal|last=Zeineh|first=Michael M.|author-link=Michael Zeineh|last2=Kang|first2=James|author-link2=|last3=Atlas|first3=Scott W.|author-link3=|last4=Raman|first4=Mira M.|author-link4=|last5=Reiss|first5=Allan L.|author-link5=|last6=Norris|first6=Jane L.|author-link6=|last7=Valencia|first7=Ian|author-link7=Ian Valencia|last8=Montoya|first8=Jose G.|author-link8=Jose Montoya|date=Feb 2015|title=Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome|url=http://pubs.rsna.org/doi/10.1148/radiol.14141079|journal=Radiology|language=en|volume=274|issue=2|pages=517–526|doi=10.1148/radiol.14141079|issn=0033-8419|pmc=|pmid=|access-date=|quote=|via=}}</ref><br />
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote><br />
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]<br />
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]<br />
<br />
*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]<br />
*[[List of enterovirus infection studies]]]<br />
*2016, [[Metabolic features of chronic fatigue syndrome]]<br />
<br />
*2019, [[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref><br />
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study]<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|url-status=|publisher=SolveCFS}}</ref> (TALK)<br />
<gallery widths="200" heights="100" class="center" caption="Images from talk: &quot;ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study&quot;"><br />
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]<br />
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]<br />
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]<br />
</gallery><br />
<br />
== Connect with organizations and other persons with ME/CFS ==<br />
*For information and support, you may want to review materials offered by a patient group in your area. <br />
<br />
:See: [[Patient groups by country]] <br />
<br />
*:[[Science for ME]], [[Phoenix Rising]], r/cfs [https://www.reddit.com/r/cfs/], and [[Health Rising]] are forums where you can ask questions, get support, and read about the latest research.<br />
<br />
*There are many research initiatives around the world working on ME/CFS. <br />
<br />
:See: [[Research initiatives by country]] <br />
<br />
*:[[Solve ME/CFS]] produces printed, online, and e-mail newsletters. Take their [http://solvecfs.org/do-i-have-mecfs-quiz/ Do I have ME/CFS? QUIZ]<br />
<br />
== See also ==<br />
*[[Primer for family, friends and care providers]]<br />
==Learn more==<br />
'''[[Patient mental health]]'''<br />
<br />
:Patients that had been deemed as suffering from mental health and not a biological illness.<br />
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.<br />
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.<br />
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.<br />
<br />
*ME/CFS is not [[depression]]. It causes a lack of energy, not a lack desire to do activities.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref></ref><ref name="myhill">{{Cite web |url =http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title = CFS or depression - what are the differences|last=Myhill |first =Sarah |author-link =Sarah Myhill|website = DrMyhill|access-date = 2021-03-22}}</ref><br />
<br />
'''Outbreaks'''<br />
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]<br />
<br />
* [[List of outbreaks]]<br />
<br />
===Other resources===<br />
*[[Phoenix Rising]] Citizen Scientists debate the latest ME/CFS science.<br />
*[[Science for ME]] Friendly forum on ME/CFS, FMS, and comorbid illnesses. <br />
*[https://twitter.com/search?f=tweets&vertical=default&q=%23mecfs&src=tyah Twitter #mecfs] Connect with patients, caregivers, and ME/CFS organizations for support, articles, and research.<br />
*[[Verywell FMS/CFS]] Well written articles with simply stated facts about ME/CFS and Fibromyalgia.<br />
<br />
== References ==<br />
{{Reflist}}<br />
<br />
[[Category:Primers]]</div>Darlahttps://me-pedia.org/w/index.php?title=Karl_Tronstad&diff=92902Karl Tronstad2021-08-27T11:01:25Z<p>Darla:/* Notable studies */</p>
<hr />
<div>[[File:Karl Tronstad.png|200px|thumb|right]]<br />
'''Karl Johan Tronstad''', PhD, is a professor in the Department of Biomedicine, University of Bergen, Bergen, Norway, where he heads the Tronstad Lab which studies cell metabolism and mitochondrial involvement in cancer and [[Myalgic Encephalomyelitis]]/[[Chronic Fatigue Syndrome]] ([[ME/CFS]]). In 2017, his research group received a grant of 9.5 million for the development of new [[ME/CFS]] treatment methods and biomarkers. Dr. Tronstad collaborates with Professor [[Olav Mella]] and [[Øystein Fluge]] at the Department of Oncology and Medical Physics at Haukeland University Hospital on [[ME/CFS]] research.<ref>{{Cite web|url=https://www.uib.no/biomedisin/108972/finding-cause-chronic-fatigue-syndromeme|title=Finding the cause of Chronic Fatigue Syndrome/ME|website=University of Bergen|language=en|access-date=2021-03-07}}</ref><br />
<br />
==Notable studies==<br />
*2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome<ref name="Fluge, 2016">{{Citation<br />
| last1 = Fluge | first1 = Øystein | authorlink1 = Øystein Fluge<br />
| last2 = Mella | first2 = Olav | authorlink2 = Olav Mella<br />
| last3 = Bruland | first3 = Ove | authorlink3 = <br />
| last4 = Risa | first4 = Kristin | authorlink4 = <br />
| last5 = Dyrstad | first5 = Sissel E. | authorlink5 = <br />
| last6 = Alme | first6 = Kine | authorlink6 = <br />
| last7 = Rekeland | first7 = Ingrid G. | authorlink7 = <br />
| last8 = Sapkota | first8 = Dipak | authorlink8 = <br />
| last9 = Røsland | first9 = Gro V. | authorlink9 = <br />
| last10 = Fosså | first10 = Alexander | authorlink10 =<br />
| last11 = Ktoridou-Valen | first11 = Irini | authorlink11 =<br />
| last12 = Lunde | first12 = Sigrid | authorlink12 =<br />
| last13 = Sørland | first13 = Kari | authorlink13 =<br />
| last14 = Lien | first14 = Katarina | authorlink14 =<br />
| last15 = Herder | first15 = Ingrid | authorlink15 =<br />
| last16 = Thürmer | first16 = Hanne | authorlink16 =<br />
| last17 = Gotaas | first17 = Merete E. | authorlink17 =<br />
| last18 = Baranowska | first18 = Katarzyna A. | authorlink18 =<br />
| last19 = Bohnen | first19 = Louis M.L.J. | authorlink19 =<br />
| last20 = Schäfer | first20 = Christoph | authorlink20 =<br />
| last21 = McCann | first21 = Adrian | authorlink21 =<br />
| last22 = Sommerfelt | first22 = Kristian | authorlink22 =<br />
| last23 = Helgeland | first23 = Lars | authorlink23 =<br />
| last24 = Ueland | first24 = Per M. | authorlink24 =<br />
| last25 = Dahl | first25 = Olav | authorlink25 =<br />
| last26 = Tronstad | first26 = Karl J. | authorlink26 = Karl Tronstad<br />
| title = Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome<br />
| journal = JCI Insight | volume = 1 | issue = 21 | page = <br />
| date = 2016<br />
| pmid = <br />
| doi = 10.1172/jci.insight.89376<br />
|url=https://doi.org/10.1172/jci.insight.89376|pages=|chapter=|edition=|isbn=}}<br />
</ref> [https://insight.jci.org/articles/view/89376 (Full Text)]<br />
* 2020, Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study<ref name="Rekeland2020">{{Cite journal|last=Rekeland|first=Ingrid G.|author-link=|last2=Fosså|first2=Alexander|author-link2=|last3=Lande|first3=Asgeir|author-link3=|last4=Ktoridou-Valen|first4=Irini|author-link4=|last5=Sørland|first5=Kari|author-link5=|last6=Holsen|first6=Mari|author-link6=|last7=Tronstad|first7=Karl J.|author-link7=Karl Tronstad|last8=Risa|first8=Kristin|author-link8=|last9=Alme|first9=Kine|author-link9=|date=2020|title=Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study|url=https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full|journal=Frontiers in Medicine|language=English|volume=7|issue=162|pages=|doi=10.3389/fmed.2020.00162|issn=2296-858X|pmc=|pmid=|access-date=|quote=|via=|last10=Viken|first10=Marte K.|author-link10=|last11=Lie|first11=Benedicte K.|author-link11=|last12=Dahl|first12=Olav|author-link12=|last13=Mella|first13=Olav|author-link13=Olav Mella|first14=Øystein|last14=Fluge|author-link14=Øystein Fluge}}</ref> - [https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full? (Full text)]<br />
* 2021, A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome<ref>{{Cite journal|last=Hoel|first=Fredrik|last2=Hoel|first2=August|last3=Pettersen|first3=Ina K.N.|last4=Rekeland|first4=Ingrid G.|last5=Risa|first5=Kristin|last6=Alme|first6=Kine|last7=Sørland|first7=Kari|last8=Fosså|first8=Alexander|last9=Tronstad|first9=Karl J.|date=2021-08-23|title=A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://insight.jci.org/articles/view/149217|journal=JCI Insight|language=en|volume=6|issue=16|pages=e149217|doi=10.1172/jci.insight.149217|issn=2379-3708|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> - [https://insight.jci.org/articles/view/149217 (Full text)]<br />
<br />
= Talks and interviews =<br />
* 2019, Speaker at the 14th Invest in ME International ME Conference; Speech title: ''Metabolic profiling and associations to clinical data in ME -'' [https://www.youtube.com/watch?v=Vk0vTFiCfDs (Video)]<br />
<br />
==Online presence==<br />
*[https://www.researchgate.net/profile/Karl_Johan_Tronstad ResearchGate]<br />
<br />
==Learn more==<br />
*[http://www.uib.no/en/biomedisin/108972/finding-cause-chronic-fatigue-syndromeme Finding the cause of Chronic Fatigue Syndrome/ME] (2017)<br />
*[http://www.uib.no/en/rg/tronstad/103206/biography Tronstad Lab bio page]<br />
<br />
==See also==<br />
*[[Olav Mella]]<br />
*[[Øystein Fluge]]<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Researchers]]<br />
[[Category:Norway researchers]]</div>Darlahttps://me-pedia.org/w/index.php?title=Karl_Tronstad&diff=92901Karl Tronstad2021-08-27T10:58:05Z<p>Darla:/* Notable studies */</p>
<hr />
<div>[[File:Karl Tronstad.png|200px|thumb|right]]<br />
'''Karl Johan Tronstad''', PhD, is a professor in the Department of Biomedicine, University of Bergen, Bergen, Norway, where he heads the Tronstad Lab which studies cell metabolism and mitochondrial involvement in cancer and [[Myalgic Encephalomyelitis]]/[[Chronic Fatigue Syndrome]] ([[ME/CFS]]). In 2017, his research group received a grant of 9.5 million for the development of new [[ME/CFS]] treatment methods and biomarkers. Dr. Tronstad collaborates with Professor [[Olav Mella]] and [[Øystein Fluge]] at the Department of Oncology and Medical Physics at Haukeland University Hospital on [[ME/CFS]] research.<ref>{{Cite web|url=https://www.uib.no/biomedisin/108972/finding-cause-chronic-fatigue-syndromeme|title=Finding the cause of Chronic Fatigue Syndrome/ME|website=University of Bergen|language=en|access-date=2021-03-07}}</ref><br />
<br />
==Notable studies==<br />
*2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome<ref name="Fluge, 2016">{{Citation<br />
| last1 = Fluge | first1 = Øystein | authorlink1 = Øystein Fluge<br />
| last2 = Mella | first2 = Olav | authorlink2 = Olav Mella<br />
| last3 = Bruland | first3 = Ove | authorlink3 = <br />
| last4 = Risa | first4 = Kristin | authorlink4 = <br />
| last5 = Dyrstad | first5 = Sissel E. | authorlink5 = <br />
| last6 = Alme | first6 = Kine | authorlink6 = <br />
| last7 = Rekeland | first7 = Ingrid G. | authorlink7 = <br />
| last8 = Sapkota | first8 = Dipak | authorlink8 = <br />
| last9 = Røsland | first9 = Gro V. | authorlink9 = <br />
| last10 = Fosså | first10 = Alexander | authorlink10 =<br />
| last11 = Ktoridou-Valen | first11 = Irini | authorlink11 =<br />
| last12 = Lunde | first12 = Sigrid | authorlink12 =<br />
| last13 = Sørland | first13 = Kari | authorlink13 =<br />
| last14 = Lien | first14 = Katarina | authorlink14 =<br />
| last15 = Herder | first15 = Ingrid | authorlink15 =<br />
| last16 = Thürmer | first16 = Hanne | authorlink16 =<br />
| last17 = Gotaas | first17 = Merete E. | authorlink17 =<br />
| last18 = Baranowska | first18 = Katarzyna A. | authorlink18 =<br />
| last19 = Bohnen | first19 = Louis M.L.J. | authorlink19 =<br />
| last20 = Schäfer | first20 = Christoph | authorlink20 =<br />
| last21 = McCann | first21 = Adrian | authorlink21 =<br />
| last22 = Sommerfelt | first22 = Kristian | authorlink22 =<br />
| last23 = Helgeland | first23 = Lars | authorlink23 =<br />
| last24 = Ueland | first24 = Per M. | authorlink24 =<br />
| last25 = Dahl | first25 = Olav | authorlink25 =<br />
| last26 = Tronstad | first26 = Karl J. | authorlink26 = Karl Tronstad<br />
| title = Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome<br />
| journal = JCI Insight | volume = 1 | issue = 21 | page = <br />
| date = 2016<br />
| pmid = <br />
| doi = 10.1172/jci.insight.89376<br />
|url=https://doi.org/10.1172/jci.insight.89376|pages=|chapter=|edition=|isbn=}}<br />
</ref> [https://insight.jci.org/articles/view/89376 (Full Text)]<br />
* 2020, Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study<ref name="Rekeland2020">{{Cite journal|last=Rekeland|first=Ingrid G.|author-link=|last2=Fosså|first2=Alexander|author-link2=|last3=Lande|first3=Asgeir|author-link3=|last4=Ktoridou-Valen|first4=Irini|author-link4=|last5=Sørland|first5=Kari|author-link5=|last6=Holsen|first6=Mari|author-link6=|last7=Tronstad|first7=Karl J.|author-link7=Karl Tronstad|last8=Risa|first8=Kristin|author-link8=|last9=Alme|first9=Kine|author-link9=|date=2020|title=Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study|url=https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full|journal=Frontiers in Medicine|language=English|volume=7|issue=162|pages=|doi=10.3389/fmed.2020.00162|issn=2296-858X|pmc=|pmid=|access-date=|quote=|via=|last10=Viken|first10=Marte K.|author-link10=|last11=Lie|first11=Benedicte K.|author-link11=|last12=Dahl|first12=Olav|author-link12=|last13=Mella|first13=Olav|author-link13=Olav Mella|first14=Øystein|last14=Fluge|author-link14=Øystein Fluge}}</ref> - [https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full? (Full text)]<br />
* 2021, A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome<ref>{{Cite journal|last=Hoel|first=Fredrik|last2=Hoel|first2=August|last3=Pettersen|first3=Ina K.N.|last4=Rekeland|first4=Ingrid G.|last5=Risa|first5=Kristin|last6=Alme|first6=Kine|last7=Sørland|first7=Kari|last8=Fosså|first8=Alexander|last9=Lien|first9=Katarina|date=2021-08-23|title=A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://insight.jci.org/articles/view/149217|journal=JCI Insight|language=en|volume=6|issue=16|pages=e149217|doi=10.1172/jci.insight.149217|issn=2379-3708}}</ref> - [https://insight.jci.org/articles/view/149217 (Full text)]<br />
<br />
= Talks and interviews =<br />
* 2019, Speaker at the 14th Invest in ME International ME Conference; Speech title: ''Metabolic profiling and associations to clinical data in ME -'' [https://www.youtube.com/watch?v=Vk0vTFiCfDs (Video)]<br />
<br />
==Online presence==<br />
*[https://www.researchgate.net/profile/Karl_Johan_Tronstad ResearchGate]<br />
<br />
==Learn more==<br />
*[http://www.uib.no/en/biomedisin/108972/finding-cause-chronic-fatigue-syndromeme Finding the cause of Chronic Fatigue Syndrome/ME] (2017)<br />
*[http://www.uib.no/en/rg/tronstad/103206/biography Tronstad Lab bio page]<br />
<br />
==See also==<br />
*[[Olav Mella]]<br />
*[[Øystein Fluge]]<br />
<br />
==References==<br />
{{Reflist}}<br />
<br />
[[Category:Researchers]]<br />
[[Category:Norway researchers]]</div>Darlahttps://me-pedia.org/w/index.php?title=Lightening_the_Shadow&diff=92281Lightening the Shadow2021-04-28T10:47:53Z<p>Darla:Added "ebook" and capitalized "cover"</p>
<hr />
<div><i>'''Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness'''</i> is a memoir by Darla Nagel about her experiences and lessons learned from getting a diagnosis of and learning to live with ME/CFS. It was published in 2018.<br />
<br />
{{Infobox book<br />
| name = Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness<br />
| image = File:Lightening the Shadow.png<br />
| caption = Cover of Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness<br />
| author = Darla Nagel<br />
| cover_artist = Michael Brady<br />
| country = United States<br />
| language = English<br />
| subject = Chronic illness <br />
| genre = Memoir <br />
| publisher = IngramSpark <br />
| pub_date = 2018 <br />
| media_type = ePub and print <br />
| pages = 156<br />
| isbn = 978-0-692-14949-2 (print); 978-0-692-14950-8 (ebook)<br />
| website = http://www.darlanagel.com/book.html <br />
}}<br />
<br />
==Publisher's synopsis==<br />
''(This synopsis was provided by the publisher for promotional purposes. For book reviews, please see Links section below.)''<br />
<br />
"An active, overachieving nineteen-year-old’s college education was diverted by a crash course in investigating diagnoses and scaling back life plans after crushing exhaustion, cognitive difficulties, and other symptoms developed following a cold. Crash she nearly did because of disbelieving doctors and treatments that harmed more than helped and the near failure of her family and faith to offset the damage.<br />
<br />
What didn’t fail was her determination to have a meaningful life despite her invisible illness. She continued her studies and career preparation for two years even as symptoms multiplied and worsened, plunging her into depression and guilt for depending on others. Once she received a tentative and later certain diagnosis of an incurable condition, she rebuilt a life that gave her what she valued: the ability to help others and financial security.<br />
<br />
This memoir doesn’t end with a heartwarming recovery. However, the crash course taught seven lessons that everyone with a chronic illness or invisible disability should know. Among all the noise about how to start living a healthy lifestyle, here is a distinct voice on how to start living a chronically ill lifestyle."<ref name=":0">{{Cite web|url=https://www.amazon.com/Lightening-Shadow-Diagnosing-Invisible-Chronic/dp/069214949X|title=Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness Paperback|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=amazon.com|archive-url=|archive-date=|url-status=|access-date=2021-04-27}}</ref><br />
<br />
==Reception==<br />
“Filled with wisdom, practical advice, and a detailed illustration of what patients experience.” [[Leonard Jason|Leonard A. Jason]], PhD, Professor of Psychology, DePaul University<ref name=":0" /><br />
<br />
“Her voice is relatable, honest, and unflinching; she doesn’t shy away from discussing difficulties.” Amazon review<br />
<br />
“I appreciate the clear picture she creates opening my eyes to unique and often overlooked challenges of people suffering silently with an invisible illness.” Amazon review<br />
<br />
<br />
==Online presence==<br />
* https://www.darlanagel.com/<br />
<br />
* https://twitter.com/DarlaNagel3<br />
<br />
==Learn more==<br />
* [https://beonthetown.com/living-in-the-shadow-of-me/2018-sept-oct/ Article "Living in the Shadow of ME"] by Darla Nagel<ref>{{Cite web|url=https://beonthetown.com/living-in-the-shadow-of-me/2018-sept-oct/|title=Living in the Shadow of Me|date=2018-10-19|website=On The Town Magazine|language=en-US|access-date=2021-04-27}}</ref><br />
<br />
* [https://wels.net/light-in-the-darkness-of-doubt/ Article "Light in the Darkness of Doubt"] by Darla Nagel<ref>{{Cite web|url=https://wels.net/light-in-the-darkness-of-doubt/|title=Light in the darkness of doubt|website=WELS|language=en-US|access-date=2021-04-27}}</ref><br />
<br />
==References==<br />
{{reflist}}<br />
[[Category:Books]]<br />
[[Category:English books]]<br />
[[Category:Memoir books]]</div>Darlahttps://me-pedia.org/w/index.php?title=File:Lightening_the_Shadow.png&diff=92280File:Lightening the Shadow.png2021-04-28T10:43:01Z<p>Darla:Provided by Darla Nagel</p>
<hr />
<div>== Summary ==<br />
==== Title: (or description) ====<br />
Lightening the Shadow cover<br />
<br />
==== Author: (or citation) ====<br />
Darla Nagel<br />
<br />
==== Source: (e.g. internet address) ====<br />
www.me-pedia.org<br />
<br />
==== Other information: ====<br />
Provided by Darla Nagel<br />
<br />
== Licensing ==<br />
{{FAL}}</div>Darlahttps://me-pedia.org/w/index.php?title=File:Lightening_the_Shadow.png&diff=92279File:Lightening the Shadow.png2021-04-28T10:42:23Z<p>Darla:www.me-pedia.org</p>
<hr />
<div>== Summary ==<br />
==== Title: (or description) ====<br />
Lightening the Shadow cover<br />
<br />
==== Author: (or citation) ====<br />
Darla Nagel<br />
<br />
==== Source: (e.g. internet address) ====<br />
www.me-pedia.org<br />
<br />
==== Other information: ====<br />
== Licensing ==<br />
{{FAL}}</div>Darlahttps://me-pedia.org/w/index.php?title=File:Lightening_the_Shadow.png&diff=92278File:Lightening the Shadow.png2021-04-28T10:41:40Z<p>Darla:Darla Nagel</p>
<hr />
<div>== Summary ==<br />
==== Title: (or description) ====<br />
Lightening the Shadow cover<br />
<br />
==== Author: (or citation) ====<br />
Darla Nagel<br />
<br />
==== Source: (e.g. internet address) ====<br />
<br />
==== Other information: ====<br />
== Licensing ==<br />
{{FAL}}</div>Darlahttps://me-pedia.org/w/index.php?title=File:Lightening_the_Shadow.png&diff=92277File:Lightening the Shadow.png2021-04-28T10:41:12Z<p>Darla:Lightening the Shadow cover</p>
<hr />
<div>== Summary ==<br />
==== Title: (or description) ====<br />
Lightening the Shadow cover<br />
<br />
==== Author: (or citation) ====<br />
<br />
==== Source: (e.g. internet address) ====<br />
<br />
==== Other information: ====<br />
== Licensing ==<br />
{{FAL}}</div>Darlahttps://me-pedia.org/w/index.php?title=Lightening_the_Shadow&diff=92251Lightening the Shadow2021-04-27T11:13:43Z<p>Darla:<i>Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness</i> is a memoir by Darla Nagel about her experiences and lessons learned from getting a diagnosis of and learning to live with ME/CFS. It was published in 2018.</p>
<hr />
<div><i>Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness</i> is a memoir by Darla Nagel about her experiences and lessons learned from getting a diagnosis of and learning to live with ME/CFS. It was published in 2018.<br />
<br />
{{Infobox book<br />
| name = Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness<br />
| image = [[File:Lightening_the_Shadow_cover_for NA]]<br />
| caption = cover of Lightening the Shadow: Diagnosing and Living with an Invisible Chronic Illness<br />
| author = Darla Nagel<br />
| cover_artist = Michael Brady<br />
| country = United States<br />
| language = English<br />
| subject = Chronic illness <br />
| genre = Memoir <br />
| publisher = IngramSpark <br />
| pub_date = 2018 <br />
| media_type = ePub and print <br />
| pages = 156<br />
| isbn = 978-0-692-14949-2 (print); 978-0-692-14950-8<br />
| website = http://www.darlanagel.com/book.html <br />
}}<br />
<br />
<br />
==Synopsis==<br />
An active, overachieving nineteen-year-old’s college education was diverted by a crash course in investigating diagnoses and scaling back life plans after crushing exhaustion, cognitive difficulties, and other symptoms developed following a cold. Crash she nearly did because of disbelieving doctors and treatments that harmed more than helped and the near failure of her family and faith to offset the damage.<br />
<br />
What didn’t fail was her determination to have a meaningful life despite her invisible illness. She continued her studies and career preparation for two years even as symptoms multiplied and worsened, plunging her into depression and guilt for depending on others. Once she received a tentative and later certain diagnosis of an incurable condition, she rebuilt a life that gave her what she valued: the ability to help others and financial security.<br />
<br />
This memoir doesn’t end with a heartwarming recovery. However, the crash course taught seven lessons that everyone with a chronic illness or invisible disability should know. Among all the noise about how to start living a healthy lifestyle, here is a distinct voice on how to start living a chronically ill lifestyle.<br />
<br />
==Reception==<br />
“Filled with wisdom, practical advice, and a detailed illustration of what patients experience.” Leonard A. Jason, PhD, Professor of Psychology, DePaul University<br />
<br />
“Her voice is relatable, honest, and unflinching; she doesn’t shy away from discussing difficulties.” Amazon review<br />
<br />
“I appreciate the clear picture she creates opening my eyes to unique and often overlooked challenges of people suffering silently with an invisible illness.” Amazon review<br />
<br />
<br />
==Online presence==<br />
https://www.darlanagel.com/<br />
<br />
https://twitter.com/DarlaNagel3<br />
<br />
==Learn more==<br />
Article "Living in the Shadow of ME" by Darla Nagel: https://beonthetown.com/living-in-the-shadow-of-me/2018-sept-oct/<br />
<br />
Article "Light in the Darkness of Doubt" by Darla Nagel: https://wels.net/light-in-the-darkness-of-doubt/<br />
<br />
[[Category:Books]]<br />
[[Category:English books]]<br />
[[Category:Memoirs]]</div>Darla