List of chronic diseases linked to infectious pathogens

Introduction

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). 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.

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.
• 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.

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).
• 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 disease by 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. 

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.

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". 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 that 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, which kills millions worldwide each year.

One large meta-analysis found that 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%.

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. 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. 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.

List of Diseases Associated With Infectious Pathogens

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
Alzheimer's disease	Alzheimer's disease is associated with the bacteria Porphyromonas gingivalis, 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. (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. 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 BK virus, and human papillomaviruses. 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 intracellular bacterium Chlamydia pneumoniae is also linked 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	Type 1 diabetes is associated with viral species from the enterovirus genus, such as echovirus 4, echovirus 16, and Coxsackie B4 virus. Coxsackie B virus can infect and destroy the insulin-producing beta cells in the pancreas, and also damage these cells via indirect autoimmune mechanisms). 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). In boys, human parechovirus infection has been linked to a subsequent appearance of diabetes-associated autoantibodies. Like enterovirus, parechovirus is a genus in the picornavirus family.
Diabetes mellitus type 2	Type 2 diabetes 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	The ulcerative form of interstitial cystitis is associated with an infection of the bladder tissues with polyomavirus, and in particular BK virus. Interstitial cystitis is associated with an infection of the bladder tissues with Epstein-Barr 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, human herpesvirus 6 variant A, 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 and enterovirus are also associated with sudden unexpected death due to myocarditis. 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.
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 (and likewise adenovirus 5 or adenovirus 37) will develop increased obesity. And it is known adenovirus 36 causes a proliferation of fat cells (adipocytes). 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. 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 Porphyromonas gingivalis, and 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 linked to an aberrant immune response to Epstein-Barr virus. 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	Persistent enterovirus infection (Coxsackie B virus or echovirus) is linked to the development of acute 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 and proven cause of vasculitis.

chronic disease a disease or condition that usually lasts for 3 months or longer and may get worse over time. Chronic diseases are long-term (typically incurable and requiring long-term management) but are not necessarily severe.

protozoa Protozoa are microscopic organisms. They usually exists as a single, independent cell. Examples include the parasites giardia lamblia, toxoplasma gondii and babesia.

chronic disease a disease or condition that usually lasts for 3 months or longer and may get worse over time. Chronic diseases are long-term (typically incurable and requiring long-term management) but are not necessarily severe.

muscle strain An injury involving a stretched or torn muscle or tendon (tendons are fibrous cords of tissue that connect muscle to bone).

etiology The cause of origin, especially of a disease.

mouse model The use of special strains of mice to study a human disease or condition, and how to prevent and treat it

chronic illness any long-term illness, regardless of the severity. Chronic illnesses are typically incurable, requiring long-term management.

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

endogenous Growing or originating from within an organism.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

cognition Thought processes, including attention, reasoning, and memory.

muscle strain An injury involving a stretched or torn muscle or tendon (tendons are fibrous cords of tissue that connect muscle to bone).

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

β β / Β. Greek letter beta (a symbol used in science), equivalent to "b".

autoantibody An antibody that works against the body's own antigens, a hallmark of autoimmune diseases. Autoantibodies are the opposite of an antibodies.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

National Academy of Medicine (NAM) - An American non-profit, non-governmental organization which provides expert advice to governmental agencies on issues relating to biomedical science, medicine and health. Formerly known as the Institute of Medicine (IOM).