Many chronic diseases are linked or associated with infectious pathogens. 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 — 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:
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 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 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).
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 biologistPaul W. Ewald and physicistGregory 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, 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, 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. 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.
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).
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.
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 associated with cancers.)
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.
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).
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.
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.
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