List of chronic diseases linked to infectious pathogens

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

Many chronic diseases are linked to infectious pathogens (meaning the pathogens are found in patients with the disease much more frequently than in healthy controls).[1][2] When a pathogen such as a virus, bacterium, fungus or protozoan is linked to a disease, researchers will start to investigate whether the pathogen might be the cause the disease, or might be playing a causal role.

Links to chronic disease[edit | edit source]

There are several explanations for why a pathogen is found associated with a disease:

  • The pathogen is an "innocent bystander" that plays no causal role in the disease, but is more prevalent in patients with the disease (for example because the disease compromises the immune response).
  • The pathogen increases the risk of getting the disease, but does not actually cause the disease. For example, genital herpes increases the risk of catching HIV, but does not cause AIDS.[3]
  • The pathogen causes the disease, but only combined with other causal factors (such as host genetic factors, or toxic exposure).
  • The pathogen is a singular cause of the disease.

Diseases associated with infectious pathogens[edit | edit source]

In the following list of diseases linked to infectious pathogens, there is a good possibility that the pathogens might cause the disease, but further research is need to work out whether these pathogens do play a causal role. 

This list covers some of the most common human diseases linked to infectious pathogens, but it is not intended to be a comprehensive list of pathogen-associated diseases.

Disease Pathogens Linked to the Disease
Acute flaccid myelitis Acute flaccid myelitis, a serious but rare neurological disease, is believed to be associated with the EV-D68 enterovirus[4] EV-D68 is a non-polio enterovirus.[4]
Alzheimer's disease Alzheimer's disease is associated with the bacteria porphyromonas gingivalis,[5] chlamydia pneumoniae[6] and helicobacter pylori,[7] and with the protozoan parasite toxoplasma gondii.[8]

Herpes simplex virus 1 is associated with Alzheimer's disease in individuals who possess the APOE-4 form of the APOE gene (APOE-4 enables the herpes virus to enter the brain).[9]

Fungal infections have been found in the brains of Alzheimer patients.[10]HHV-6A and HHV-7 have been found more frequently in the brains of Alzheimer's patients than those of healthy controls.[11]

Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis, the most common of five forms of motor neuron disease, is associated with echovirus, an enterovirus infection of the central nervous system,[12] and with retrovirus[13] activity (it is not known whether this retrovirus activity arises from a human endogenous retrovirus, or from an exogenous retrovirus).
Anorexia nervosa Infection with borrelia[14] species bacteria is associated with anorexia nervosa. In rare cases, anorexia nervosa may arise after infection with streptococcus[15] species bacteria. Anorexia (the symptom of appetite loss, which is distinct from anorexia nervosa) is associated with the protozoan parasite dientamoeba fragilis.[16]
Anxiety disorder Anxiety is associated with cytomegalovirus,[17][18] and the bacterium helicobacter pylori.[19] Anxiety is associated with toxoplasma gondii,[20] or at least associated with higher levels of IgG antibodies to this parasite.[21] Anxiety as a personality trait is associated with higher antibody titers to Epstein-Barr virus.[22]
Asthma Asthma is associated with rhinovirus, human respiratory syncytial virus,[23] and the bacterium chlamydia pneumoniae.[24] Chlamydia pneumoniae is particularly associated with adult-onset asthma.[25]
Atherosclerosis Atherosclerosis is associated with cytomegalovirus,[26] and the bacteria helicobacter pylori[27] and chlamydia pneumoniae.[28]
Attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) and learning disabilities are associated with the bacteria borrelia burgdorferi and streptococcus, and with HIV and enterovirus 71.

Febrile seizures due to human herpesvirus 6 or subtype A are a risk factor for ADHD. Viral infections during pregnancy, at birth, and in early childhood are risk factors for ADHD.[29]

Autism Autism is linked to congenital infection with rubella virus or cytomegalovirus.[30][31] Clostridia bacterial species are associated with autism (these bacteria are present in greater numbers in the guts of autistic children).[32]
Autoimmune diseases Autoimmune diseases are strongly associated with enteroviruses such as Coxsackie B virus.[33] Autoimmune diseases are also associated with Epstein-Barr virus,[34] cytomegalovirus,[35] parvovirus B19,[36] and HIV,[37] and the bacterium mycobacterium tuberculosis.[38] Autoimmune thyroid disease is associated with Epstein-Barr virus,[39] and helicobacter pylori.[40]
Bipolar disorder Bipolar disorder is associated with Borna disease virus,[41] and with Borrelia species bacteria.[14] The level of cognitive impairment in bipolar disorder is associated with herpes simplex virus 1.[42]

Some estimates currently attribute 15% to 20% of all cancers to infectious pathogen causes.[43][44] In future, this percentage may be revised upwards if the pathogens currently associated with cancers (such as those listed below) are proven to actually cause those cancers. (For the sake of completeness, some pathogens proven to cause cancers are included in the list, in addition to pathogens that have been linked to cancers, but are not yet proven to cause the cancer.)

Adrenal tumor is associated with BK virus and simian virus 40.[45]
Anal cancer is associated with human papillomaviruses (HPV).[46]
Bladder cancer can be caused by schistosoma helminths.[47]
Brain tumor. Glioblastoma multiforme is associated with cytomegalovirus,[48] BK virus, JC virus, and simian virus 40.[49]
Breast cancer is associated with bovine leukemia virus,[50] mouse mammary tumor virus, Epstein-Barr virus, and human papillomaviruses (HPV).[51]
Carcinoid tumors are associated with enterovirus infections.[52]
Cervical cancer can be caused by HPV.[53]
Colorectal cancer is associated with the bacteria helicobacter pylori, streptococcus bovis and fusobacterium nucleatum,[54] with HPV,[55] and with the helminth schistosoma japonicum.[56] JC virus may be a risk factor for colorectal cancer.[57]
Gallbladder cancer is associated with the bacterium salmonella typhi.[58]
Hodgkin's lymphoma is associated with Epstein-Barr virus,[59] hepatitis C virus,[60] and HIV.[61]
Kaposi's Sarcoma can be caused by Kaposi's sarcoma herpesvirus and HIV.
Liver cancer. Hepatocellular carcinoma can be caused by hepatitis B virus, hepatitis C virus,[62] and by the helminth schistosoma japonicum.[63]
Lung cancer is associated with the bacterium clamydia pneumoniae,[64] with HPV, and with Merkel cell polyomavirus.[65]
Leukemia. Adult T-cell leukemia can be caused by human T-cell leukemia virus-1.
Mesothelioma is associated with simian virus 40,[66] especially in conjunction with asbestos exposure.

Multiple myeloma is associated with hepatitis B virus[67] and hepatitis C virus.[68]
Nasopharyngeal carcinoma can be caused by Epstein-Barr virus.
Non-Hodgkin lymphoma is associated with HIV and simian virus 40.[69]
Oropharyngeal cancer can be caused by HPV.
Ovarian cancer is associated with mumps virus.[70]
Pancreatic cancer is associated with hepatitis B virus,[71] and the bacterium helicobacter pylori.[72]
Prostate cancer is associated with BK virus,[73] and HPV.[74]
Skin neoplasm (skin tumor or cancer) is associated with HPV.[75]
Squamous cell carcinoma is associated with HPV.[76]
Stomach cancer is associated with the bacterium helicobacter pylori.[77]
Thyroid cancer is associated with simian virus 40.[78]

Chronic fatigue syndrome ME/CFS is associated with enteroviruses (such as coxsackie B virus),[79][80] partial reactivation of Epstein-Barr virus,[81] human herpesvirus 6A,[82] human herpesvirus 7,[83] and parvovirus B19.[84][85] The intracellular bacterium chlamydia pneumoniae[86] is also linked chronic fatigue syndrome.
Chronic myocarditis Chronic myocarditis is associated with the enterovirus coxsackie B virus.[87]
Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD), which includes both chronic bronchitis and emphysema, is associated with chlamydia pneumoniae[88] and Epstein-Barr virus.[89]
Crohn's disease Crohn's disease is linked to a thin layer of infection on the intestinal lining with the fungus candida tropicalis, in tandem with the bacteria escherichia coli (e-coli) and serratia marcescens.[90]

One study found ileocecal Crohn's disease is associated with viral species from the enterovirus genus (but note that all the study cohort with ileocecal Crohn's disease had disease-associated mutations in either their NOD2 or ATG16L1 genes).[91]

Crohn's disease is associated with mycobacterium avium subspecies paratuberculosis.[92]

In a mouse model, Crohn's disease is precipitated by the norovirus CR6 strain,[93] but only in combination with a variant of the Crohn's susceptibility gene ATG16L1, and chemical toxic damage to the gut. In other words, in this mouse model, Crohn's is precipitated only when these three causal factors (virus, gene, and toxin) act in combination.
Coronary heart disease Coronary heart disease is associated with herpes simplex virus 1 and the bacterium chlamydia pneumoniae.[94] Coronary heart disease is linked to cytomegalovirus.[95]
Dementia Dementia is associated with herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, West Nile virus, Borna disease virus, and HIV. Dementia is also associated with the helminth taenia solium (pork tapeworm), and with borrelia[14] species bacteria.

Depression is associated with cytomegalovirus[17] and West Nile virus,[96] and the protozoan parasite toxoplasma gondii.[97] It is thought that depression may be precipitated by the effect of immune signals (such as pro-inflammatory cytokines) reaching the brain from infections located in the peripheries of the body.[98][99]

Major depressive disorder is associated with Borna disease virus,[41] as well as bartonella[100] and borrelia[14] species bacteria.
Seasonal affective disorder is associated with Epstein-Barr virus.[101]

Diabetes mellitus type 1 Type 1 diabetes is associated with viral species from the enterovirus genus,[102][103] such as echovirus 4,[104] echovirus 16,[105] and coxsackie B4 virus.[106][107] coxsackie B virus can infect and destroy the insulin-producing beta cells in the pancreas, and also damage these cells via indirect autoimmune mechanisms).[108]

Coxsackie B1 virus is associated with a higher risk of the beta cell autoimmunity that portends type 1 diabetes, whereas Coxsackie B3 and B6 viruses is associated with a reduced risk of such autoimmunity (possibly due to immune cross-protection against Coxsackie B1 virus).[109]

In boys, human parechovirus infection has been linked to a subsequent appearance of diabetes-associated autoantibodies.[110] Like enterovirus, parechovirus is a genus in the picornavirus family.

Diabetes mellitus type 2 Type 2 diabetes is associated with cytomegalovirus,[111] hepatitis C virus,[112] enteroviruses[103] and ljungan virus,[113] In rabbits, exposure to toxic shock syndrome toxin-1 from a staphylococcus aureus infection leads to impaired glucose tolerance, the hallmark of type 2 diabetes in humans.[114]
Dilated cardiomyopathy Dilated cardiomyopathy is associated with enteroviruses such as coxsackie B virus.[115]
Epilepsy Mesial temporal lobe epilepsy is associated with infection by human herpesvirus 6 virus variant B (HHV-6B) of the astrocyte cells of the brain.[116][117] Epilepsy is associated with HPV infection of the brain.[118]
Guillain-Barré syndrome Guillain-Barré syndrome is associated with the bacterium campylobacter jejuni,[119] and with the viruses cytomegalovirus[120] and enterovirus.[121]
Hypertension Hypertension (high blood pressure) is associated with enteroviruses such as coxsackievirus B5 and echovirus.[122]
Infertility Infertility is associated with an infection of the endometrium with the A variant of human herpesvirus 6 virus (HHV-6A ).[123]
Interstitial cystitis The ulcerative form of interstitial cystitis is associated with an infection of the bladder tissues with polyomavirus, and in particular BK virus.[124] Interstitial cystitis is associated with an infection of the bladder tissues with Epstein-Barr virus.[125]
Irritable bowel syndrome Irritable bowel syndrome (IBS) is associated with the bacteria Escherichia coli[126] and Mycobacterium avium subspecies paratuberculosis,[127] the protozoan parasite Giardia lamblia,[128] and pathogenic strains of the protozoan parasite blastocystis hominis.[129] Irritable bowel syndrome in those with HIV is associated with the protozoan Dientamoeba fragilis.[16]
Lower back pain Lower back pain is associated with a spinal disc infection with anaerobic bacteria, especially the bacterium Propionibacterium acnes.[130][131]
Lupus Lupus is associated with the viruses parvovirus B19,[132] Epstein-Barr virus,[133] cytomegalovirus[134] and torque teno virus.[135]
Macular degeneration Neovascular (wet) macular degeneration is associated with high titers of cytomegalovirus.[136][137]
Metabolic syndrome Metabolic syndrome is associated with the bacteria chlamydia pneumoniae[138] and helicobacter pylori, as well as the viruses cytomegalovirus] and herpes simplex virus 1.[139]
Multiple sclerosis Multiple sclerosis, a demyelinating disease, is associated with Epstein-Barr virus[140] (and strongly associated with certain genetic variants of this virus[141] which is found in the brain tissues of most ME patients,[142] human herpesvirus 6,[143] human herpesvirus 6 variant A,[144] varicella zoster virus,[145] and the bacterium chlamydia pneumoniae.[146] Epsilon toxin from the bacterium Clostridium perfringen may be a triggering factor for MS.[147]
Myocardial infarction Myocardial infarction (heart attack) is associated with chlamydia pneumoniae,[148] cytomegalovirus[149] and Coxsackie B virus (an enterovirus).[150]

Coxsackie B virus and enterovirus are also associated with sudden unexpected death due to myocarditis.[151] An autopsy study found 40% of those who died of sudden heart attack had enterovirus markers in their endomyocardial tissues, compared to 8% in controls.[150]

Myopia Myopia (short-sightedness) is associated with childhood febrile illnesses of measles, rubella, pertussis and mumps.[152]

Obesity is associated with adenovirus 36, which is found in 30% of obese people, but only in 11% of non-obese people.[153][154] It has further been demonstrated that animals experimentally infected with adenovirus 36 (and likewise adenovirus 5 or adenovirus 37) will develop increased obesity.[155] And it is known adenovirus 36 causes a proliferation of fat cells (adipocytes).[156]

Evidence suggests that obesity may be a viral disease, and that the worldwide obesity epidemic that began in the 1980s may be in part due to viral infection.[157][158] Obesity is also associated with higher gut levels of certain Firmicutes bacteria in relation to bacteroidetes bacteria. Overweight individuals tend have more Firmicutes bacteria (such as clostridium, staphylococcus, streptococcus, and helicobacter pylori) in their gut, whereas normal weight individuals tend have more bacteroidetes bacteria.[159]

Obsessive-compulsive disorder Obsessive-compulsive disorder is associated with streptococcus[17] and borrelia[14] species bacteria.
Panic disorder Panic disorder is associated with borrelia[14] and bartonella species bacteria.[100]
Parkinson's disease Parkinson's disease is associated with enterovirus/picornavirus[160][161] influenza A virus,[162] as well as the protozoan parasite toxoplasma gondii.[163]
Psoriasis Psoriasis is associated with a helicobacter pylori trigger.[164]
Rheumatoid arthritis Rheumatoid arthritis is linked to the bacterium porphyromonas gingivalis,[165] and the bacterium proteus mirabilis.[166] Rheumatoid arthritis is associated with parvovirus B19.[132] Antibodies to borrelia outer surface protein A are associated with rheumatoid arthritis.[167]
Sarcoidosis Sarcoidosis is associated with mycobacteria[168] species and the bacterium helicobacter pylori.[169]
Schizophrenia Schizophrenia is associated with Borna disease virus,[41] the bacterium chlamydia trachomatis,[170] borrelia species bacteria (Lyme disease),[14] and Bartonella henselae bacteria (cat scratch disease).[171] One study found a central nervous system infection as a child (particularly with coxsackievirus B5) increases the risk of developing schizophrenia as an adult by nearly 5-fold.[172] A large study found influenza virus infection during the first trimester of pregnancy increases the risk the baby will get schizophrenia later in life by 7-fold; there was no increased risk if the mother caught influenza during the second or third trimesters.[173] Schizophrenia is linked to an aberrant immune response to Epstein-Barr virus.[174]
Sjögren's syndrome Primary Sjögren's syndrome is associated with the enterovirus coxsackie B virus.[175]
Stroke Persistent enterovirus infection (Coxsackie B virus or echovirus) is linked to the development of acute stroke.[176] Stroke is associated with the bacteria chlamydia pneumoniae,[177] helicobacter pylori,[178] mycobacterium tuberculosis,[179] and mycoplasma_pneumoniae,[180] as well as the virus varicella zoster virus[181] and the fungus histoplasma.[182]
Tourette syndrome Tourette's is associated with the bacterium streptococcus.[183] Aggravating or contributory microbes in Tourette's may include the bacteria mycoplasma pneumoniae,[184] chlamydia pneumoniae, chlamydia trachomatis, and the protozoan parasite toxoplasma gondii.[185]
Valvular heart disease Heart valve disease is linked to enterovirus[186] and coxsackievirus B[187] infection of the heart valve tissue.
Vasculitis Vasculitis is associated with HIV, parvovirus B19,[132] and hepatitis B virus. The hepatitis C virus is an established and proven cause of vasculitis.

Pathogens as a cause of chronic diseases[edit | edit source]

One champion of the theory that pathogens are the likely cause of many chronic diseases is evolutionary biologist Professor Paul W. Ewald, who is one of an increasing number of researchers who believe that many chronic diseases of presently unknown etiology will probably turn out to be caused by persistent low-level microbial infections.[188][189]

Professor Ewald supports his thesis with an argument from evolutionary biology, explaining that "chronic diseases, if they are common and damaging, must be powerful eliminators of any genetic instruction that may cause them".[188] In other words, a disease-causing gene which reduces an animal's survival and its creation of offspring will tend to eliminate itself over a number of generations. Therefore such genetic diseases are self-extinguishing.

Professor Ewald explains that the only genetic diseases which are likely to persist are those which provide a compensating benefit. For example, genes that encode for sickle cell anemia disease are maintained and persist down the generations, as these genes also protect against malaria.

One large meta-analysis found the vast majority of diseases have a very small genetic contribution of only 5% to 10% at most. Though notable exceptions include Crohn's disease, celiac disease and macular degeneration, which have a genetic contribution of about 40% to 50%.[190]

Infectious pathogens are one of several potential causes of disease; other causal factors include environmental toxins (naturally-occurring and man-made), radiation, genetics, epigenetics, events during pregnancy, stress, diet and lifestyle factors.

More than one causal factor may be involved in the development of a disease, and an illness may only manifest when several causal factors are present at the same time. For example, in a mouse model, Crohn's disease can be precipitated by a norovirus, but only when both a specific gene variant is present and a certain toxin has damaged the gut.[93] Thus a pathogen's ability to cause a disease may be contingent upon several other causal factors.

Pathogen-associated diseases include many of the most common and costly chronic illnesses.[191] About 70% of all deaths in the United States result from chronic diseases, with the treatment of chronic diseases accounting for 75% of all US healthcare costs.[192]

Difficulties in determining if a pathogen causes the disease[edit | edit source]

Determining whether a pathogen plays a causal role in a given chronic disease is difficult for the following reasons:

  • The time between contracting the infectious pathogen and the appearance of the first chronic disease symptoms can be lengthy, sometimes decades.
  • An infection may be asymptomatic when first contracted and go unnoticed.
  • An infectious pathogen may not cause its associated disease in every person.
  • Only specific strains of a pathogen may be linked to a disease; other strains may not be so harmful (for example, multiple sclerosis is strongly associated with certain genetic variants of Epstein-Barr virus).[193]
  • A given disease may be precipitated by more than one pathogen.
  • A pathogen may precipitate the disease only in combination with one or more other causal factors.
  • A pathogenic microbe may only precipitate the disease when it breaches into and infects specific organs. When it infects different organs, a different disease (or no disease) may be precipitated.
  • Some pathogens are not easily detectable, and it is difficult to link hard-to-detect pathogens to a disease.
  • For obvious ethical reasons, you cannot inoculate pathogenic microbes into humans to see if they do cause the disease.
  • A pathogen may cause a disease indirectly, such as via autoimmune processes induced by the pathogen.

In spite of the difficulties in obtaining proof of causality, investigation into the link between pathogenic microbes and chronic disease is ongoing, and there is a large volume of published studies which demonstrate these associations.

Notable studies[edit | edit source]

Articles and blogs[edit | edit source]

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. Institute of Medicine (US) Forum on Microbial Threats; Knobler, Stacey L.; O'Connor, Siobhán; Lemon, Stanley M.; Najafi, Marjan (2004). Preface. National Academies Press (US).
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  4. 4.0 4.1 Centers for Disease Control (August 12, 2020). "Non-Polio Enterovirus | About EV-D68 | Enterovirus D68". Centers for Disease Control and Prevention. Retrieved August 18, 2020.
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  12. Corcia, P.; Giraud, P.; Guennoc, A.-M.; de Toffol, B.; Autret, A. (January 2003). "[Acute motor axonal neuropathy, enterovirus and Amyotrophic lateral sclerosis: can there be a link?]". Revue Neurologique. 159 (1): 80–82. ISSN 0035-3787. PMID 12618659.
  13. McCormick, A.L.; Brown, R.H.; Cudkowicz, M.E.; Al-Chalabi, A.; Garson, J.A. (January 22, 2008). "Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate". Neurology. 70 (4): 278–283. doi:10.1212/01.wnl.0000297552.13219.b4. ISSN 1526-632X. PMID 18209202.
  14. 14.0 14.1 14.2 14.3 14.4 14.5 14.6 Fallon, B.A.; Nields, J.A. (November 1994). "Lyme disease: a neuropsychiatric illness". The American Journal of Psychiatry. 151 (11): 1571–1583. doi:10.1176/ajp.151.11.1571. ISSN 0002-953X. PMID 7943444.
  15. Sokol, M.S. (2000). "Infection-triggered anorexia nervosa in children: clinical description of four cases". Journal of Child and Adolescent Psychopharmacology. 10 (2): 133–145. doi:10.1089/cap.2000.10.133. ISSN 1044-5463. PMID 10933123.
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