Candida, Epstein Barr Virus, Hepatitus C, - infectious microbial causes

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This article is about diseases with possible (but as yet unconfirmed) infectious microbial causes. For a list of diseases with proven infectious causes, see List of infectious diseases.

This article provides a list of diseases with possible (but unconfirmed) infectious etiologies.
Many chronic diseases are linked or associated with infectious pathogens.^[1][2] A disease is said to be linked or associated with an infectious pathogen when that pathogen is found more frequently in patients with the disease than in healthy controls. Often, infectious pathogens associated with a disease may be suspected of playing a causal role in that disease — and some scientists believe a substantial portion of chronic diseases may in part be caused by infectious agents^[3] — though association alone does not automatically prove causality (because correlation does not imply causation).
Indeed, the terms linked and associated are used here in a strict technical sense: they mean there is a frequent co-occurrence of certain pathogens in certain diseases; but it should not be read that linked and associated imply there is a proven causal relationship between pathogen and disease. An observed association only flags up the possibility that there might be a causal relation.
For an infectious pathogenic microbe that has been noted 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).^[4]
• 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 toxin exposure).
• 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^[5] for the following reasons:

• The time between contracting an infectious pathogen and the appearance of the first disease symptoms can be lengthy, sometimes decades.
• An infectious pathogen may not cause 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 pathogen are linked to a disease; other strains of the same microbe may be harmless.
• A pathogen may precipitate the disease only in combination with one or more other causal factors.
• There may be more than one pathogen that can precipitate a given disease.
• A given pathogen may not always cause the same disease — infection with it may lead to one of several different diseases.
• There may be pathogens that are not readily detectable that play a causal role in a disease.
• 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 track direct means, such as by infecting and destroying cells; or may cause disease via more complex and convoluted indirect means, such as through the damage created by inflammatory cytokines or autoimmune processes that are induced by the microbial infection (for example, tuberculosis infection induces an inflammatory cytokine that then itself causes severe tissue damage).^[6][7]
• A pathogenic microbe may not necessarily be present in the diseased tissues or organs (bacterial toxins for example can travel and damage tissues at 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,^[8][9] 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."^[10]
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.^[10]
Infectious pathogens are one of several potential causes of disease; other causal factors include: environmental toxins, certain types of radiation exposure, diet and lifestyle factors, stress, genetics, and epigenetics. All these factors are generally explored as potential causes of a disease.
Diseases may also be multifactorial,^[11] such that the disease only manifests when multiple causal factors occur in combination. For example: in a murine 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.^[12] 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^[13] chronic illnesses. About 70% of all deaths in the United States result from chronic diseases,^[5] with the treatment of chronic diseases accounting for 75% of all US healthcare costs (amounting to $1.7 trillion in 2009).^[14]

List of diseases associated with infectious Bacteria [edit]

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.

Alzheimer's disease	Alzheimer's disease is associated with the bacteria Chlamydia pneumoniae[15] and Helicobacter pylori,[16] and with the protozoan parasite Toxoplasma gondii.[17] 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).[18]
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,[19] and with retrovirus[20] 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[21] species bacteria is associated with anorexia nervosa. In rare cases, anorexia nervosa may arise after infection with Streptococcus[22] species bacteria. Anorexia (which is distinct from anorexia nervosa) is associated with the protozoan parasite Dientamoeba fragilis.[23]
Anxiety disorder	Anxiety is associated with cytomegalovirus,[24] and the bacterium Helicobacter pylori.[25]
Asthma	Asthma is associated with rhinovirus, human respiratory syncytial virus,[26] and the bacterium Chlamydia pneumoniae.[27] Chlamydia pneumoniae is particularly associated with adult-onset asthma.[28]
Atherosclerosis	Atherosclerosis is associated with the bacterium Chlamydia pneumoniae.[29][30]
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.[31]
Autism	Autism is associated with prenatal maternal infection with rubella virus or cytomegalovirus.[32][33] Clostridia bacteria species are associated with autism (these bacteria are present in greater numbers in the guts of autistic children).[34]
Autoimmune diseases	Autoimmune diseases are strongly associated with enteroviruses such as Coxsackie B virus.[35] Autoimmune diseases are also associated with Epstein-Barr virus,[36] cytomegalovirus,[37] parvovirus B19,[38] and HIV,[39] and the bacterium Mycobacterium tuberculosis.[40] Autoimmune thyroid disease is associated with Epstein-Barr virus[41] and Helicobacter pylori.[42]
Bipolar disorder	Bipolar disorder is associated with bornavirus,[43] and with Borrelia[21] species bacteria. The level of cognitive impairment in bipolar disorder is associated with herpes simplex virus 1.[44]
Cancer	Some estimates currently attribute 15% to 20% of all cancers to infectious pathogen causes.[45][46] 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 associated with cancers.) Adrenal tumor is associated with BK virus and simian virus 40.[47] Anal cancer is associated with human papillomaviruses.[48] Bladder cancer can be caused by Schistosoma helminths.[49] Brain tumor. Glioblastoma multiforme is associated with cytomegalovirus,[50] BK virus, JC virus, and simian virus 40.[51] Breast cancer is associated with mouse mammary tumor virus, Epstein-Barr virus, and human papillomaviruses.[52] Carcinoid tumors are associated with enterovirus infections.[53] Cervical cancer can be caused by human papillomaviruses.[54] Colorectal cancer is associated with the bacteria Helicobacter pylori, Streptococcus bovis and Fusobacterium nucleatum,[55] with human papillomaviruses,[56] and with the helminth Schistosoma japonicum.[57] JC virus may be a risk factor for colorectal cancer.[58] Gallbladder cancer is associated with the bacterium Salmonella typhi.[59] Hodgkin's lymphoma is associated with Epstein-Barr virus,[60] hepatitis C virus,[61] and HIV.[62] 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,[63] and by the helminth Schistosoma japonicum.[64] Lung cancer is associated with the bacterium Chlamydia pneumoniae,[65] with human papillomaviruses, and with Merkel cell polyomavirus.[66] Leukemia. Adult T-cell leukemia can be caused by human T-cell leukemia virus-1. Mesothelioma is associated with simian virus 40,[67] 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.[68] 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),[69][70] human herpesvirus 6 variant A,[71] human herpesvirus 7,[72] and parvovirus B19.[73][74] The bacteria Coxiella burnetii[75] and Chlamydia pneumoniae[76] are known causes of chronic fatigue syndrome (antibiotics can cure these bacterial forms of chronic fatigue syndrome).
Chronic obstructive pulmonary disease	Chronic obstructive pulmonary disease (which includes both chronic bronchitis and emphysema) is associated with Chlamydia pneumoniae[77] and Epstein-Barr virus.[78]
Crohn's disease	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).[79] Crohn's disease is associated with Mycobacterium avium subspecies paratuberculosis.[80] In a murine model, Crohn's disease is precipitated by the norovirus CR6 strain,[12][81] 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.[82]
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[21] species bacteria.
Depression	Depression is associated with cytomegalovirus[24] and West Nile virus,[83] and the protozoan parasite Toxoplasma gondii.[84] 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.[85][86] Major depressive disorder is associated with bornavirus,[43] as well as Bartonella[87] and Borrelia[21] species bacteria. Seasonal affective disorder is associated with Epstein-Barr virus.[88]
Diabetes mellitus type 1	Diabetes mellitus type 1 is associated with viral species from the enterovirus genus,[89][90] specifically echovirus 4[91] 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).[92][93]
Diabetes mellitus type 2	Diabetes mellitus type 2 is associated with cytomegalovirus,[94] hepatitis C virus,[95] enteroviruses,[90] and Ljungan virus.[96]
Dilated cardiomyopathy	Dilated cardiomyopathy is associated with enteroviruses such as Coxsackie B virus.[97]
Epilepsy	Epilepsy is associated with human herpesvirus 6.[98]
Guillain–Barré syndrome	Guillain–Barré syndrome is associated with the bacterium Campylobacter jejuni, and with the viruses cytomegalovirus[99] and enterovirus.[100]
Irritable bowel syndrome	Irritable bowel syndrome (IBS) is associated with the protozoan parasite Giardia lamblia,[101] and pathogenic strains of the protozoan parasite Blastocystis hominis.[102] Irritable bowel syndrome in those with HIV is associated with the protozoan Dientamoeba fragilis.[23] IBS is also associated with the bacterium Mycobacterium avium subspecies paratuberculosis.[103]
Low back pain	Lower back pain is associated with a spinal disc infection with anaerobic bacteria, especially the bacterium Propionibacterium acnes.[104][105]
Lupus	Lupus is associated with the viruses parvovirus B19,[106] Epstein-Barr virus,[107] and cytomegalovirus.[108]
Metabolic syndrome	Metabolic syndrome is associated with the bacteria Chlamydia pneumoniae[109] and Helicobacter pylori, as well as the viruses cytomegalovirus and herpes simplex virus 1.[110]
Multiple sclerosis	Multiple sclerosis, a demyelinating disease, is associated with Epstein-Barr virus,[111] human herpesvirus 6,[112] varicella zoster virus,[113] and the bacterium Chlamydia pneumoniae.[114]
Myocardial infarction	Myocardial infarction (heart attack) is associated with Chlamydia pneumoniae,[115] cytomegalovirus[116] and Coxsackie B virus (an enterovirus).[117] (Coxsackie B virus is also associated with sudden unexpected death due to myocarditis).[118]
Obesity	Obesity is associated with adenovirus 36, which is found in 30% of obese people, but only in 11% of non-obese people.[119][120] It has further been demonstrated that animals experimentally infected with adenovirus 36 (or adenovirus 5, or adenovirus 37) will develop increased obesity.[121] 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.[122] 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.[123][124] 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.[125]
Obsessive–compulsive disorder	Obsessive–compulsive disorder is associated with Streptococcus[126] and Borrelia[21] species bacteria.
Panic disorder	Panic disorder is associated with Borrelia[21] and Bartonella[87] species bacteria.[87]
Parkinson's disease	Parkinson's disease is associated with influenza A virus,[127] as well as the protozoan parasite Toxoplasma gondii.[128]
Psoriasis	Psoriasis is associated with a Helicobacter pylori trigger.[129]
Rheumatoid arthritis	Rheumatoid arthritis is associated with parvovirus B19.[106] Antibodies to Borrelia outer surface protein A are associated with rheumatoid arthritis.[130]
Sarcoidosis	Sarcoidosis is associated with Mycobacteria[131] species, and the bacteria Helicobacter pylori[132] and Borrelia burgdorferi.[133]
Schizophrenia	Schizophrenia is associated with bornavirus,[43] the bacterium Chlamydia trachomatis,[134] as well as Borrelia species bacteria.[21] 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.[135] Prenatal exposure to influenza virus in the first trimester of pregnancy increases the risk of schizophrenia by 7-fold.[136]
Stroke	Stroke is associated with the bacteria Chlamydia pneumoniae,[137] Helicobacter pylori,[138] Mycobacterium tuberculosis,[139] and Mycoplasma pneumoniae,[140] as well as the virus varicella zoster virus[141] and the fungus Histoplasma.[142]
Thromboangiitis obliterans	Thromboangiitis obliterans is associated with Rickettsia species bacteria.[143]
Tourette syndrome	Tourette syndrome is associated with the bacterium Streptococcus.[126] Aggravating or contributory microbes in Tourette's may include the bacteria Mycoplasma pneumoniae,[144] Chlamydia pneumoniae, Chlamydia trachomatis, and the protozoan parasite Toxoplasma gondii.[145]
Vasculitis	Vasculitis is associated with HIV, parvovirus B19,[106] and hepatitis B virus. The hepatitis C virus is an established cause of vasculitis.

Cross reference: Pathogens and their associated diseases [edit]

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.

Cytomegalovirus	Anxiety disorder Autism Autoimmune diseases Brain tumor Dementia Depression Diabetes mellitus type 2 Guillain–Barré syndrome Lupus Metabolic syndrome Myocardial infarction

Enteroviruses	Amyotrophic lateral sclerosis ADHD Autoimmune diseases Carcinoid tumors Chronic fatigue syndrome Crohn's disease Diabetes mellitus type 1 Diabetes mellitus type 2 Dilated cardiomyopathy Guillain–Barré syndrome Myocardial infarction Schizophrenia

Epstein-Barr virus	Autoimmune diseases Breast cancer Esophageal cancer Hodgkin's lymphoma (Nasopharyngeal carcinoma) Chronic obstructive pulmonary disease Seasonal affective disorder Lupus Multiple sclerosis

Hepatitis B virus	(Hepatocellular carcinoma) Pancreatic cancer Vasculitis

Hepatitis C virus	Hodgkin's lymphoma (Hepatocellular carcinoma) Diabetes mellitus type 2 (Vasculitis)

Herpes simplex virus	Alzheimer's disease Bipolar disorder Coronary heart disease Dementia Metabolic syndrome

HIV	ADHD Autoimmune diseases Hodgkin's lymphoma (Kaposi's Sarcoma) Non-Hodgkin lymphoma Dementia Vasculitis

Human herpesvirus 6	ADHD Chronic fatigue syndrome Epilepsy Multiple sclerosis

Influenza A	ADHD Parkinson's disease

Parvovirus B19	Autoimmune diseases Chronic fatigue syndrome Lupus Rheumatoid arthritis Vasculitis

Bartonella	Major depressive disorder Panic disorder

Borrelia	Anorexia nervosa ADHD Bipolar disorder Dementia Depression Obsessive–compulsive disorder Rheumatoid arthritis Sarcoidosis Schizophrenia

Chlamydia pneumoniae	Alzheimer's disease Asthma Atherosclerosis Lung cancer (Chronic fatigue syndrome) Chronic obstructive pulmonary disease Coronary heart disease Metabolic syndrome Multiple sclerosis Myocardial infarction Stroke Tourette syndrome

Helicobacter pylori	Anxiety disorder Alzheimer's disease Autoimmune diseases Pancreatic cancer Stomach cancer (Stomach ulcers) Metabolic syndrome Obesity Psoriasis Sarcoidosis Stroke

Mycobacterium tuberculosis	Autoimmune diseases Stroke

Streptococcus	Anorexia nervosa ADHD Colorectal cancer Obsessive–compulsive disorder Tourette syndrome

Toxoplasma gondii	Alzheimer's disease Depression Parkinson's disease Tourette syndrome

See also [edit]

• List of infectious diseases
• Infectious disease
• Virus diseases
• Fungal diseases
• Infectious causes of cancer
• Cancer bacteria
• Oncovirus
• List of clinically important bacteria
• List of parasites of humans
• Human Microbiome Project
• Human pathogen
• Medical microbiology
• Koch's postulates

Further reading [edit]

Popular science articles and books [edit]

• Plague Time: The New Germ Theory of Disease by Paul W. Ewald, Anchor, 2002
• Interview With Evolutionary Biologist Paul Ewald by Amy Proal, Feb 2008
• A New Germ Theory: Part 1 by Judith Hooper, The Atlantic Monthly Magazine, Feb 1999
• A New Germ Theory: Part 2: Antibiotics Against Heart Disease?
• A New Germ Theory: Part 3: The Great Synthesizer
• The Big Idea That Might Beat Cancer and Cut Health-Care Costs by 80 Percent by Andrew Grant, Discover Magazine, Sept 2009
• The Infection Connection by Harriet Washington, Psychology Today, July 1999
• Can Infections Result in Mental Illness? by Dr Jeff Szymanski, Psychology Today, Feb 2012
• Can You Catch a Heart Attack? by Becky McCall, Cosmos Magazine, Dec 2009
• Do Germs Cause Cancer? by Philip E. Ross, Forbes, Nov 1999
• Catching a Cancer: Viral Culprits May Explain a Host of Tumors With as Yet Unknown Triggers by Laura Beil, Science News Magazine, July 2012
• People Hospitalized For Infections Are 62% More Likely To Develop A Mood Disorder by Anoopa Singh, Medical Daily, June 2013

Academic articles [edit]

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