Talk:Epstein-Barr virus

Studies to add to this page:

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

//////////////////////// @Dr_M_Guthridge comments/info:

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.

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.

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.

Below is info and numbered (1-6) references that might be included on the EBV page:

EBV incidence and epidemiology 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

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

Cell Types Infected by EBV. 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

EBV and B-lymphocytes 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

Acute Infectious Mononucleosis (AIM or Glandular Fever) 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

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.

Diagnosis of EBV infection and EBV-induced diseases (squelae) Possible diagnostic tests2 used in the differential diagnosis of primary EBV infection and/or EBV-induced diseases are: •	Heterophile antibody test (also known as the Monospot test) •	Serology of EBV viral capsid antigen (VCA) IgM/IgG •	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) •	PCR measurement of EBV viral load (EBV-VL) in peripheral blood •	Reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of EBV expressed genes •	Peripheral blood counts including neutrophil/lymphocyte/monocyte counts •	Inflammatory markers including C-reactive protein (CRP) and/or Erythrocyte Sedimenation Rate (ESR)

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.

EBV in patients with immunodeficiency: 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

Chronic Active EBV (CA-EBV) disease 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

Treatment for EBV 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

1.	JI, C. EPSTEIN–BARR VIRUS INFECTION. NEJM 343, 481-492 (2000). 2.	Vouloumanou, E.K., Rafailidis, P.I. & Falagas, M.E. Current diagnosis and management of infectious mononucleosis. Curr. Opin. Hematol. 19, 14-20 (2012). 3.	Pender, M.P. & Burrows, S.R. Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clinical & translational immunology 3, e27 (2014). 4.	Gulley, M.L. & Tang, W. Laboratory assays for Epstein-Barr virus-related disease. The Journal of molecular diagnostics : JMD 10, 279-292 (2008). 5.	Rafailidis, P.I., Mavros, M.N., Kapaskelis, A. & Falagas, M.E. Antiviral treatment for severe EBV infections in apparently immunocompetent patients. J. Clin. Virol. 49, 151-157 (2010). 6.	Jeffrey I. Cohen, E.S.J., 2 Janet K. Dale,1 Stefania Pittaluga,2 Helen E. Heslop,3 Cliona M. Rooney,3, Stephen Gottschalk, C.M.B., 3 V. Koneti Rao,1 Adriana Marques,1 Peter D. Burbelo,4 Siu-Ping Turk,1, Rachael Fulton, A.S.W., 5 Richard F. Little,6 Mitchell S. Cairo,7 Nader K. El-Mallawany,7 Daniel Fowler,8 & Claude Sportes, M.R.B., 8 Wyndham Wilson,9 and *Stephen E. Straus1. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. 117, 5835-5849 (2011).