List of chronic diseases linked to infectious pathogens

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.

Links to chronic disease
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.

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.

Pathogens as a cause of chronic diseases
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 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%.

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.

Difficulties in determining if a pathogen causes the disease
Determining whether a pathogen plays a causal role in a given chronic disease is difficult for the following reasons: 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.
 * 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 a disease indirectly, such as via autoimmune processes induced by the pathogen.

Notable studies

 * 2004, The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary - Forum on Microbial Threats
 * 2004, Infectious Causes of Chronic Inflammatory Diseases and Cancer - Lilly Research Laboratories
 * 2006, Emerging Infectious Determinants of Chronic Diseases
 * 2006, The infection connection: Helicobacter pylori is more than just the cause of gastric ulcers: it offers an unprecedented opportunity to study changes in human micro ecology and the nature of chronic disease
 * 2008, Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1
 * 2010, Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioural, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 2
 * 2012, Evidence That Chronic Disease is Caused by Pathogens - Autoimmunity Research Foundation
 * 2013, Causal Inference Regarding Infectious Aetiology of Chronic Conditions: A Systematic Review
 * Toward a unified, evolutionary theory of cancer - Paul Ewald (presentation)

Articles and blogs

 * Can an Infection Suddenly Cause OCD? - Harvard Health Blog, 2012
 * Mechanisms of Viral Pathogenicity - Gerald Tritz (Lecture Notes)
 * Equations that Spell Disaster: Researchers are Pinpointing the Factors that Combine to Produce Complex Diseases - The Scientist
 * Challenging the Primacy of Genetics in Late-Onset Alzheimer Disease - Alzheimer Research Forum, 2005
 * Infection Eyed as Culprit In Chronic Disease - American Medical News, 2004

Learn more

 * Plague Time: The New Germ Theory of Disease - Paul W. Ewald, Anchor, 2002
 * Interview With Evolutionary Biologist Paul Ewald - Amy Proal, 2008
 * Stealth Germs in Your Body - Erno Daniel, Sterling Publishing Company, 2008
 * Infections can affect your IQ - Science Daily, 2015
 * A New Germ Theory: Part 1 - The Atlantic Monthly Magazine, 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   -Discover Magazine, 2009
 * The Infection Connection - Psychology Today, 1999
 * Can Infections Result in Mental Illness? - Psychology Today, 2012
 * Do Germs Cause Cancer? - Forbes, 1999
 * The Emerging Role Of Infection In Alzheimer's Disease - Science Daily, 2008
 * People Hospitalized For Infections Are 62% More Likely To Develop A Mood Disorder - Medical Daily, J2013
 * Chronic Infections Linked with Memory Problems Later in Life - Live Science, 2014