List of Chronic Human Diseases Linked to Infectious Pathogens




Introduction

This article is about chronic human diseases that have been linked to infectious pathogens, and are thus suspected of being caused by those pathogens.

Many common chronic diseases have been found to be linked to infectious pathogens, such as viruses, bacteria, fungi or parasites. When we say a disease is linked to (or associated with) an infectious pathogen, we mean this pathogen is found much more frequently in patients with the disease than in healthy people. Researchers often suspect that pathogens which are associated with a disease in this way might be the actual cause of the disease, or at least might be playing a partial causal role. Some scientists believe that a substantial percentage of chronic human diseases with currently unknown etiology may in fact be caused by infectious agents.

For an infectious microbe that is found to frequently accompany a disease, there are several logical possibilities that can explain this observed association:

    An epithelial cell infected with Chlamydia pneumoniae bacteria
  • The pathogen is an "innocent bystander" that plays no causal role in the etiology of the disease, but for some reason is more prevalent in patients with the disease (perhaps because the disease compromises the immune response, for example).
  • The pathogen predisposes to disease development (increases the risk of getting the disease), but the pathogen does not cause the disease (for example, genital herpes increases the risk of acquiring HIV).
  • The pathogen is a necessary, but not sufficient, cause of the disease. In other words, the pathogen can cause the disease, but does so only in combination with one or more other causal factors (such as host genetic factors, or concurrent exposure to toxins).
  • The pathogen is a direct and singular cause of the disease, but this causality has yet to be proven.

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

  • The time between contracting an infectious pathogen and the appearance of the first disease symptoms can be lengthy.
  • An infectious pathogen may not cause its associated disease in every person.
  • An infection may be asymptomatic in its acute phase (when first contracted), and so go unnoticed; symptoms may only appear much later — in the form of a chronic disease.
  • Sometimes, only specific strains of a microbe are linked to a disease; other strains of the same microbe may be less pathogenic (for example, multiple sclerosis is strongly associated with certain genetic variants of the Epstein-Barr virus).
  • A given pathogen may not always cause the same disease — infection with it may lead to one of several different diseases.
  • 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 pathogen may only precipitate the disease when it infects specific tissue compartments (for example, temporal lobe epilepsy is linked to human herpesvirus 6 virus infection of certain cells in the brain).
  • There may be pathogens that are not readily detectable that play a causal role in a disease (intracellular infections for example can be difficult to detect).
  • For obvious ethical reasons, you cannot inoculate infectious pathogens into humans to see if these do cause the disease or not.
  • A pathogenic microbe may cause disease by relatively easy to observe direct means, such as infecting and destroying cells or causing cellular dysfunction; or may cause disease by more complex indirect means, such as through the damage or dysfunction resulting from inflammatory cytokines or autoimmune processes that may be induced by the microbial infection (for example, tuberculosis infection induces an inflammatory cytokine response that causes severe tissue damage; and in coxsackievirus B myocarditis, this virus triggers an autoimmune attack on the heart muscle mitochondria).
  • A pathogenic microbe may not necessarily be present in the diseased tissues or organs (bacterial toxins for example can travel to sites distant from the infection site; and inflammatory or autoimmune processes precipitated by infectious pathogens can also act at tissue sites far removed from the infection).

In spite of the difficulties in obtaining proof of causality, evolutionary biologist Paul W. Ewald and physicist Gregory M. Cochran are noted for their assertion that many common chronic diseases of currently unknown etiology are likely caused by chronic low-level microbial infection, countering the prevailing view that genes are predominantly responsible for the development of chronic disease. Ewald and Cochran support their thesis with the logic of evolutionary biology, with Ewald explaining that: "chronic diseases, if they are common and damaging, must be powerful eliminators of any genetic instruction that may cause them."

In other words, any disease-causing gene that reduces survival and reproduction will eliminate itself over a number of generations, just by evolutionary pressures; therefore such genetic diseases are self-extinguishing. Ewald says the only genetic diseases that will persist are those that provide a compensating benefit. For example, genes that encode for sickle cell anemia disease are maintained and persist down generations, as these genes also protect against malaria, which kills millions worldwide each year.

Infectious pathogens are one of several potential causes of disease; other causal factors include: environmental toxins, genetics, epigenetics, events during pregnancy, stress, diet and lifestyle factors.

Diseases may also be multifactorial, such that the disease only manifests when multiple causal factors occur in combination. For example: in mice, 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. Thus a pathogen's causal role in a disease may well be contingent upon several other causal factors.

Infectious pathogen-associated diseases include many of the most common and costly chronic illnesses. 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 (amounting to $1.7 trillion in 2009).




List of Diseases Associated With Infectious Pathogens

In the list of diseases associated with infectious pathogens given below, bear in mind that there is no definitive proof that the associated pathogens do play a causal role in the disease, just a possibility that they might. Further research is required to determine whether or not these pathogens participate causally in their associated diseases. Note that this list covers some of the most common human diseases associated with infectious pathogens, but it is not intended to be a comprehensive list.

Disease Pathogens Linked to the Disease
Alzheimer's disease Alzheimer's disease is associated with the bacteria Chlamydia pneumoniae and Helicobacter pylori, and with the protozoan parasite Toxoplasma gondii. 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). Fungal infections have been found in the brains of Alzheimer patients. HHV-6A and HHV-7 have been found more frequently in the brains of Alzheimer's patients than those of healthy controls.
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, and with retrovirus 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 species bacteria is associated with anorexia nervosa. In rare cases, anorexia nervosa may arise after infection with Streptococcus species bacteria. Anorexia (which is distinct from anorexia nervosa) is associated with the protozoan parasite Dientamoeba fragilis.
Anxiety disorder Anxiety is associated with cytomegalovirus, and the bacterium Helicobacter pylori. Anxiety is associated with Toxoplasma gondii, or at least associated with higher levels of IgG antibodies to this parasite. Anxiety as a personality trait is associated with higher antibody titers to Epstein-Barr virus.
Asthma Asthma is associated with rhinovirus, human respiratory syncytial virus, and the bacterium Chlamydia pneumoniae. Chlamydia pneumoniae is particularly associated with adult-onset asthma.
Atherosclerosis Atherosclerosis is associated with cytomegalovirus, and the bacteria Helicobacter pylori and Chlamydia pneumoniae.
Attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) and learning disorders are associated with the bacteria Borrelia burgdorferi and Streptococcus, and with HIV and enterovirus 71. Febrile seizures due to human herpesvirus 6 or influenza A are a risk factor for ADHD. Viral infections during pregnancy, at birth, and in early childhood are risk factors for ADHD.
Autism Autism is linked to congenital infection with rubella virus or cytomegalovirus. Clostridia bacterial species are associated with autism (these bacteria are present in greater numbers in the guts of autistic children).
Autoimmune diseases Autoimmune diseases are strongly associated with enteroviruses such as Coxsackie B virus. Autoimmune diseases are also associated with Epstein-Barr virus, cytomegalovirus, parvovirus B19, and HIV, and the bacterium Mycobacterium tuberculosis. Autoimmune thyroid disease is associated with Epstein-Barr virus and Helicobacter pylori.
Bipolar disorder Bipolar disorder is associated with bornavirus, and with Borrelia species bacteria. The level of cognitive impairment in bipolar disorder is associated with herpes simplex virus 1.
Cancer Some estimates currently attribute 15% to 20% of all cancers to infectious pathogen causes. 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. (Note: for the sake of completeness, some infectious pathogens known to cause cancers are included in the list, in addition to the infectious pathogens linked to cancers.)


Adrenal tumor is associated with BK virus and simian virus 40.
Anal cancer is associated with human papillomaviruses.
Bladder cancer can be caused by Schistosoma helminths.
Brain tumor. Glioblastoma multiforme is associated with cytomegalovirus, BK virus, JC virus, and simian virus 40.
Breast cancer is associated with bovine leukemia virus, mouse mammary tumor virus, Epstein-Barr virus, and human papillomaviruses.
Carcinoid tumors are associated with enterovirus infections.
Cervical cancer can be caused by human papillomaviruses.
Colorectal cancer is associated with the bacteria Helicobacter pylori, Streptococcus bovis and Fusobacterium nucleatum, with human papillomaviruses, and with the helminth Schistosoma japonicum. JC virus may be a risk factor for colorectal cancer.
Gallbladder cancer is associated with the bacterium Salmonella typhi.
Hodgkin's lymphoma is associated with Epstein-Barr virus, hepatitis C virus, and HIV.
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, and by the helminth Schistosoma japonicum.
Lung cancer is associated with the bacterium Chlamydia pneumoniae, with human papillomaviruses, and with Merkel cell polyomavirus.
Leukemia. Adult T-cell leukemia can be caused by human T-cell leukemia virus-1.
Mesothelioma is associated with simian virus 40, especially in conjunction with asbestos exposure.
Nasopharyngeal carcinoma can be caused by Epstein-Barr virus.
Non-Hodgkin lymphoma is associated with HIV and simian virus 40.
Oropharyngeal cancer can be caused by human papillomaviruses.
Ovarian cancer is associated with mumps virus.
Pancreatic cancer is associated with hepatitis B virus and the bacterium Helicobacter pylori.
Prostate cancer is associated with xenotropic murine leukemia virus-related virus and BK virus.
Skin neoplasm is associated with human papillomaviruses.
Squamous cell carcinoma is associated with human papillomaviruses.
Stomach cancer is associated with the bacterium Helicobacter pylori.
Thyroid cancer is associated with simian virus 40.

Chronic fatigue syndrome Chronic fatigue syndrome (also known as myalgic encephalomyelitis) is associated with enteroviruses (such as Coxsackie B virus), partial reactivation of Epstein-Barr virus, human herpesvirus 6 variant A, human herpesvirus 7, and parvovirus B19. The bacteria Coxiella burnetii and Chlamydia pneumoniae are known causes of chronic fatigue syndrome (antibiotics can treat these bacterial forms of chronic fatigue syndrome).
Chronic myocarditis Chronic myocarditis is associated with the enterovirus coxsackievirus B.
Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (which includes both chronic bronchitis and emphysema) is associated with Chlamydia pneumoniae and Epstein-Barr virus.
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 and Serratia marcescens. 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). Crohn's disease is associated with Mycobacterium avium subspecies paratuberculosis. In a murine model, Crohn's disease is precipitated by the norovirus CR6 strain, 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.
Dementia Dementia is associated with herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, West Nile virus, bornavirus, and HIV. Dementia is also associated with the helminth Taenia solium (pork tapeworm), and with Borrelia species bacteria.
Depression Depression is associated with cytomegalovirus and West Nile virus, and the protozoan parasite Toxoplasma gondii. 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.

Major depressive disorder is associated with bornavirus, as well as Bartonella and Borrelia species bacteria.
Seasonal affective disorder is associated with Epstein-Barr virus.

Diabetes mellitus type 1 Diabetes mellitus type 1 is associated with viral species from the enterovirus genus, specifically echovirus 4 and Coxsackie B virus (the latter it is thought may infect and destroy the insulin producing beta-cells in the pancreas and also damage these cells via indirect autoimmune mechanisms). One study found Coxsackie B1 virus associated with a higher risk of the beta cell autoimmunity that portends type 1 diabetes; though Coxsackie B3 and B6 viruses were found to be associated with a reduced risk of such autoimmunity (possibly due to immune cross-protection against Coxsackie B1 virus). Coxsackievirus B4 has also been linked to type 1 diabetes. In boys, human parechovirus infection has been linked to a subsequent appearance of diabetes-associated autoantibodies.
Diabetes mellitus type 2 Diabetes mellitus type 2 is associated with cytomegalovirus, hepatitis C virus, enteroviruses and Ljungan virus, 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.
Dilated cardiomyopathy Dilated cardiomyopathy is associated with enteroviruses such as Coxsackie B virus.
Epilepsy Mesial temporal lobe epilepsy is associated with infection by the B variant of human herpesvirus 6 virus (HHV-6B) of the astrocyte cells of the brain. Epilepsy is associated with human papillomavirus infection of the brain.
Guillain–Barré syndrome Guillain–Barré syndrome is associated with the bacterium Campylobacter jejuni, and with the viruses cytomegalovirus and enterovirus.
Hypertension Hypertension (high blood pressure) is associated with enteroviruses such as coxsackievirus B5 and echovirus.
Infertility Infertility is associated with an infection of the endometrium with the A variant of human herpesvirus 6 virus (HHV-6A ).
Interstitial cystitis Interstitial cystitis is associated with an infection of the bladder tissues with polyomavirus, and in particular BK virus.
Irritable bowel syndrome Irritable bowel syndrome (IBS) is associated with the bacteria enteroaggregative Escherichia coli and Mycobacterium avium subspecies paratuberculosis, the protozoan parasite Giardia lamblia, and pathogenic strains of the protozoan parasite Blastocystis hominis. Irritable bowel syndrome in those with HIV is associated with the protozoan Dientamoeba fragilis.
Low back pain Lower back pain is associated with a spinal disc infection with anaerobic bacteria, especially the bacterium Propionibacterium acnes.
Lupus Lupus is associated with the viruses parvovirus B19, Epstein-Barr virus, and cytomegalovirus.
Macular degeneration Neovascular (wet) macular degeneration is associated with high titers of cytomegalovirus.
Metabolic syndrome Metabolic syndrome is associated with the bacteria Chlamydia pneumoniae and Helicobacter pylori, as well as the viruses cytomegalovirus and herpes simplex virus 1.
Multiple sclerosis Multiple sclerosis, a demyelinating disease, is associated with Epstein-Barr virus (and strongly associated with certain genetic variants of this virus) which is found in the brain tissues of most ME patients, human herpesvirus 6, varicella zoster virus, and the bacterium Chlamydia pneumoniae.
Myocardial infarction Myocardial infarction (heart attack) is associated with Chlamydia pneumoniae, cytomegalovirus and Coxsackie B virus (an enterovirus). (Coxsackie B virus is also associated with sudden unexpected death due to myocarditis).
Myopia Myopia (short sightedness) is associated with childhood febrile illnesses of measles, rubella, pertussis and mumps.
Obesity Obesity is associated with adenovirus 36, which is found in 30% of obese people, but only in 11% of non-obese people. It has further been demonstrated that animals experimentally infected with adenovirus 36 (or adenovirus 5, or adenovirus 37) will develop increased obesity. Adenovirus 36 induces obesity by infecting fat cells (adipocytes), wherein the expression of the adenovirus E4orf1 gene turns on both the cell's fat producing enzymes and also instigates the generation of new fat cells. Evidence suggests that obesity can be a viral disease, and that the worldwide obesity epidemic that began in the 1980s may be in part due to viral infection.

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.

Obsessive–compulsive disorder Obsessive–compulsive disorder is associated with Streptococcus and Borrelia species bacteria.
Panic disorder Panic disorder is associated with Borrelia and Bartonella species bacteria.
Parkinson's disease Parkinson's disease is associated with enterovirus, influenza A virus, as well as the protozoan parasite Toxoplasma gondii.
Psoriasis Psoriasis is associated with a Helicobacter pylori trigger.
Rheumatoid arthritis Rheumatoid arthritis is linked to the bacterium Proteus mirabilis. Rheumatoid arthritis is associated with parvovirus B19. Antibodies to Borrelia outer surface protein A are associated with rheumatoid arthritis.
Sarcoidosis Sarcoidosis is associated with Mycobacteria species and the bacterium Helicobacter pylori
Schizophrenia Schizophrenia is associated with bornavirus, the bacterium Chlamydia trachomatis, as well as Borrelia species bacteria. Schizophrenia is also linked to neonatal infection with Coxsackie B virus (an enterovirus), which one study found carries an increased risk of adult onset schizophrenia. Prenatal exposure to influenza virus in the first trimester of pregnancy increases the risk of schizophrenia by 7-fold.
Sjögren's syndrome Primary Sjögren's syndrome is associated with the enterovirus Coxsackie B virus.
Stroke Stroke is associated with the bacteria Chlamydia pneumoniae, Helicobacter pylori, Mycobacterium tuberculosis, and Mycoplasma pneumoniae, as well as the virus varicella zoster virus and the fungus Histoplasma.
Tourette syndrome Tourette syndrome is associated with the bacterium Streptococcus. Aggravating or contributory microbes in Tourette's may include the bacteria Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis, and the protozoan parasite Toxoplasma gondii.
Vasculitis Vasculitis is associated with HIV, parvovirus B19, and hepatitis B virus. The hepatitis C virus is an established cause of vasculitis.




Cross Reference: Pathogens and Their Associated Diseases

For some selected pathogens, the set of their disease associations is shown in the bar graphs below. For each bar below, the pathogen in question has been found more frequently in patients with the listed diseases than it has in healthy controls — but it has not been proven that the pathogen plays any causal role in the listed diseases; though usually investigations to examine whether it might participate causally are ongoing. By contrast, the diseases below enclosed in brackets ( ) indicate that the pathogen is a proven cause of that disease.

Pathogen Diseases Linked to the Pathogen
Cytomegalovirus
Anxiety disorderAtherosclerosisAutismAutoimmune diseasesBrain tumorDementiaDepressionDiabetes mellitus type 2Guillain–Barré syndromeLupusMacular degenerationMetabolic syndromeMyocardial infarction
Enteroviruses Amyotrophic lateral sclerosisADHDAutoimmune diseasesCarcinoid tumorsChronic fatigue syndromeCrohn's diseaseDiabetes mellitus type 1Diabetes mellitus type 2Chronic myocarditisDilated cardiomyopathyGuillain–Barré syndromeHypertension Myocardial infarctionSchizophreniaParkinson's diseaseSjögren's syndrome

Note that persistent infections are due to an aberrant mutated form of enterovirus called non-cytolytic enterovirus.
Epstein-Barr virus
Autoimmune diseasesBreast cancerBurkitt's LymphomaEsophageal cancerHodgkin's lymphoma • (Nasopharyngeal carcinoma) • Chronic obstructive pulmonary diseaseSeasonal affective disorderLupusMultiple sclerosis
Hepatitis B virus
(Hepatocellular carcinoma) • Pancreatic cancerVasculitis
Hepatitis C virus
Hodgkin's lymphoma • (Hepatocellular carcinoma) • Diabetes mellitus type 2 • (Vasculitis)
Herpes simplex virus
Alzheimer's diseaseBipolar disorderCoronary heart diseaseDementiaMetabolic syndrome
HIV
ADHDAutoimmune diseasesHodgkin's lymphoma • (Kaposi's Sarcoma) • Non-Hodgkin lymphomaDementiaVasculitis
Human herpesvirus 6
ADHDAlzheimer's diseaseChronic fatigue syndromeEpilepsyInfertilityMultiple sclerosis
Influenza A
ADHDParkinson's disease
Parvovirus B19
Autoimmune diseasesChronic fatigue syndromeLupusRheumatoid arthritisVasculitis
Bartonella
Major depressive disorderPanic disorder
Borrelia
Anorexia nervosaADHDBipolar disorderDementiaDepressionObsessive–compulsive disorderRheumatoid arthritisSchizophrenia
Chlamydia pneumoniae
Alzheimer's diseaseAsthmaAtherosclerosisLung cancer • (Chronic fatigue syndrome) • Chronic obstructive pulmonary diseaseCoronary heart diseaseMetabolic syndromeMultiple sclerosisMyocardial infarctionStrokeTourette syndrome
Helicobacter pylori
Alzheimer's disease Anxiety disorderAtherosclerosisAutoimmune diseasesPancreatic cancerStomach cancer • (Stomach ulcers) • Metabolic syndromeObesityPsoriasisSarcoidosisStroke
Mycobacterium tuberculosis
Autoimmune diseasesStroke
Streptococcus
Anorexia nervosaADHDColorectal cancerObsessive–compulsive disorderTourette syndrome
Toxoplasma gondii
Alzheimer's diseaseDepressionParkinson's diseaseTourette syndrome



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