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List of chronic diseases linked to infectious pathogens
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==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.<ref name="PlagueTime">{{Cite book | title = Plague Time: The New Germ Theory of Disease|isbn=978-0-385-72184-4|language=en | url = https://books.google.co.uk/books?id=nUApzQwoZ44C&q=%22Bad+genes+and+bad+environments+have+often+been+falsely+accused,+or,+at+least+they+have+taken+more+than+their+share+of+the+blame&redir_esc=y | date = 2002|publisher=Anchor Books | last = Ewald | first = Paul W.}}</ref><ref name="InfectiousCausation">{{Cite journal | last = Cochran | first = G.M. | last2 = Ewald | first2 = P.W. | last3 = Cochran | first3 = K.D. | date = 2000 | title = Infectious causation of disease: an evolutionary perspective|url=https://pubmed.ncbi.nlm.nih.gov/10893730/|journal=Perspectives in Biology and Medicine|volume=43|issue=3 | pages = 406–448|doi=10.1353/pbm.2000.0016|issn=0031-5982|pmid=10893730}}</ref> 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''".<ref name="PlagueTime" /> 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%.<ref name="Pafron2019">{{Cite journal | last = Patron | first = Jonas | last2 = Serra-Cayuela | first2 = Arnau | last3 = Han | first3 = Beomsoo | last4 = Li | first4 = Carin | last5 = Wishart | first5 = David Scott | date = 2019 | title = Assessing the performance of genome-wide association studies for predicting disease risk | url = https://pubmed.ncbi.nlm.nih.gov/31805043/|journal=PloS One|volume=14|issue=12| pages = e0220215|doi=10.1371/journal.pone.0220215|issn=1932-6203|pmc=6894795|pmid=31805043}}</ref> 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.<ref name=":0">{{Cite journal | last = Cadwell|first = Ken | last2 = Patel | first2 = Khushbu K. | last3 = Maloney | first3 = Nicole S. | last4 = Liu | first4 = Ta-Chiang | last5 = Ng | first5 = Aylwin C.Y. | last6 = Storer | first6 = Chad E. | last7 = Head | first7 = Richard D. | last8 = Xavier | first8 = Ramnik | last9 = Stappenbeck | first9 = Thaddeus S. | date = 2010-06-25 | title = Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine|url=https://pubmed.ncbi.nlm.nih.gov/20602997/|journal=Cell|volume=141|issue=7|pages=1135–1145|doi=10.1016/j.cell.2010.05.009|issn=1097-4172|pmc=2908380|pmid=20602997}}</ref> 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.<ref name="Kockaya2010">{{Cite journal | last = Kockaya | first = Guvenc | last2 = Wertheimer | first2 = Albert | date = 2010-10-26 | title = What are the top most costly diseases for USA? The alignment of burden of illness with prevention and screening expenditures|url=http://www.scirp.org/Journal/Paperabs.aspx?paperid=2817|journal=Health|language=en|volume=2|issue=10|pages=1174–1178|doi=10.4236/health.2010.210172}}</ref> 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.<ref>{{Cite web | date = 2009 | title = Almanac of Chronic Disease|url=http://www.fightchronicdisease.org/sites/default/files/docs/2009AlmanacofChronicDisease_updated81009.pdf | last = Carmona | first = Richard H. | authorlink = |website=|archive-url=|archive-date=|url-status=|access-date=|at=Forward|publisher=Partnership to Fight Chronic Disease}}</ref>
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