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Koch's postulates are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and refined and published by Koch in 1890. Koch applied the postulates to establish the etiology of anthrax and tuberculosis, but they have been generalized to other diseases.

Contents

The postulates

Koch's postulates are:

  1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals.
  2. The microorganism must be isolated from a diseased organism and grown in pure culture.
  3. The cultured microorganism should cause disease when introduced into a healthy organism.
  4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

However, Koch abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of cholera[1] and, later, of typhoid fever. Asymptomatic or subclinical infection carriers are now known to be a common feature of many infectious diseases, especially viruses such as polio, herpes simplex, HIV and hepatitis C. As a specific example, all doctors and virologists agree that poliovirus causes paralysis in just a few infected subjects, and the success of the polio vaccine in preventing disease supports the conviction that the poliovirus is the causative agent.

The third postulate specifies "should", not "must", because as Koch himself proved in regard to both tuberculosis and cholera,[2] not all organisms exposed to an infectious agent will acquire the infection. Noninfection may be due to such factors as general health and proper immune functioning; acquired immunity from previous exposure or vaccination; or genetic immunity, as with the resistance to malaria conferred by possessing at least one sickle cell allele.

The second postulate may also be suspended for certain microorganisms which we cannot (at the present time) grow in pure culture, such as some viruses. In summary, a body of evidence that satisfies Koch's postulates is sufficient but not necessary to establish causation.

History

Koch's postulates were developed in the 19th century as general guidelines to identify pathogens that could be isolated with the techniques of the day.[3] Even in Koch's time, it was recognized that some infectious agents were clearly responsible for disease even though they did not fulfill all of the postulates.[2][4] Attempts to rigidly apply Koch's postulates to the diagnosis of viral diseases in the late 19th century, at a time when viruses could not be seen or isolated in culture, may have impeded the early development of the field of virology.[5][6] Currently, a number of infectious agents are accepted as the cause of disease despite their not fulfilling all of Koch's postulates.[7] Therefore, while Koch's postulates retain historical importance and continue to inform the approach to microbiologic diagnosis, fulfillment of all four postulates is not required to demonstrate causality.

Koch's postulates have also influenced scientists who examine microbial pathogenesis from a molecular point of view. In the 1980s, a molecular version of Koch's postulates was developed to guide the identification of microbial genes encoding virulence factors.[8]

See also

References

  1. ^ Koch Robert (1893). "Über den augenblicklichen Stand der bakteriologischen Choleradiagnose" (in German). Zeitschrift für Hygiene und Infectionskrankheiten 14: 319–333. doi:10.1007/BF02284324.  
  2. ^ a b Koch Robert (1884). "2 Die Aetiologie der Tuberkulose". Mitt Kaiser Gesundh. pp. 1–88.  
  3. ^ Walker L, Levine H, Jucker M (2006). "Koch's postulates and infectious proteins.". Acta Neuropathol (Berl) 112 (1): 1–4. doi:10.1007/s00401-006-0072-x. PMID 16703338.  
  4. ^ Koch R (1893). "Ueber den augenblicklichen Stand der bakteriologischen Choleradiagnose". J. Hyg. Inf. 14: 319–33. doi:10.1007/BF02284324.  
  5. ^ Brock TD (1999). Robert Koch: a life in medicine and bacteriology. Washington DC: American Society of Microbiology Press. ISBN 1555811434.  
  6. ^ Evans AS (May 1976). "Causation and disease: the Henle-Koch postulates revisited". Yale J Biol Med 49 (2): 175–95. PMID 782050.  
  7. ^ Jacomo V, Kelly P, Raoult D (2002). "Natural history of Bartonella infections (an exception to Koch's postulate)". Clin Diagn Lab Immunol 9 (1): 8–18. doi:10.1128/CDLI.9.1.8-18.2002. PMID 11777823.  
  8. ^ Falkow S (1988). "Molecular Koch's postulates applied to microbial pathogenicity". Rev. Infect. Dis. 10 (Suppl 2): S274–6. PMID 3055197.  

Further reading

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Koch's postulates are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and refined and published by Koch in 1890. Koch applied the postulates to establish the etiology of anthrax and tuberculosis, but they have been generalized to other diseases.

Contents

The postulates

Koch's postulates are:

  1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals.
  2. The microorganism must be isolated from a diseased organism and grown in pure culture.
  3. The cultured microorganism should cause disease when introduced into a healthy organism.
  4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

However, Koch abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of cholera[1] and, later, of typhoid fever. Asymptomatic or subclinical infection carriers are now known to be a common feature of many infectious diseases, especially viruses such as polio, herpes simplex, HIV and hepatitis C. As a specific example, all doctors and virologists agree that poliovirus causes paralysis in just a few infected subjects, and the success of the polio vaccine in preventing disease supports the conviction that the poliovirus is the causative agent.

The third postulate specifies "should", not "must", because as Koch himself proved in regard to both tuberculosis and cholera,[2] not all organisms exposed to an infectious agent will acquire the infection. Noninfection may be due to such factors as general health and proper immune functioning; acquired immunity from previous exposure or vaccination; or genetic immunity, as with the resistance to malaria conferred by possessing at least one sickle cell allele.

The second postulate may also be suspended for certain microorganisms or entities that cannot (at the present time) be grown in pure culture, such as prions responsible for Creutzfeldt–Jakob disease.[3] In summary, a body of evidence that satisfies Koch's postulates is sufficient but not necessary to establish causation.

History

Koch's postulates were developed in the 19th century as general guidelines to identify pathogens that could be isolated with the techniques of the day.[4] Even in Koch's time, it was recognized that some infectious agents were clearly responsible for disease even though they did not fulfill all of the postulates.[2][5] Attempts to rigidly apply Koch's postulates to the diagnosis of viral diseases in the late 19th century, at a time when viruses could not be seen or isolated in culture, may have impeded the early development of the field of virology.[6][7] Currently, a number of infectious agents are accepted as the cause of disease despite their not fulfilling all of Koch's postulates.[8] Therefore, while Koch's postulates retain historical importance and continue to inform the approach to microbiologic diagnosis, fulfillment of all four postulates is not required to demonstrate causality.

Koch's postulates have also influenced scientists who examine microbial pathogenesis from a molecular point of view. In the 1980s, a molecular version of Koch's postulates was developed to guide the identification of microbial genes encoding virulence factors.[9]

See also

References

  1. ^ Koch Robert (1893). [Expression error: Unexpected < operator "Über den augenblicklichen Stand der bakteriologischen Choleradiagnose"] (in German). Zeitschrift für Hygiene und Infectionskrankheiten 14: 319–333. doi:10.1007/BF02284324. 
  2. ^ a b Koch Robert (1884). "2 Die Aetiologie der Tuberkulose". Mitt Kaiser Gesundh. pp. 1–88. 
  3. ^ Inglis TJ (November 2007). "Principia aetiologica: taking causality beyond Koch's postulates". J. Med. Microbiol. 56 (Pt 11): 1419–22. doi:10.1099/jmm.0.47179-0. PMID 17965339. http://jmm.sgmjournals.org/cgi/content/full/56/11/1419. 
  4. ^ Walker L, Levine H, Jucker M (2006). [Expression error: Unexpected < operator "Koch's postulates and infectious proteins."]. Acta Neuropathol (Berl) 112 (1): 1–4. doi:10.1007/s00401-006-0072-x. PMID 16703338. 
  5. ^ Koch R (1893). [Expression error: Unexpected < operator "Ueber den augenblicklichen Stand der bakteriologischen Choleradiagnose"]. J. Hyg. Inf. 14: 319–33. doi:10.1007/BF02284324. 
  6. ^ Brock TD (1999). Robert Koch: a life in medicine and bacteriology. Washington DC: American Society of Microbiology Press. ISBN 1555811434. 
  7. ^ Evans AS (May 1976). [Expression error: Unexpected < operator "Causation and disease: the Henle-Koch postulates revisited"]. Yale J Biol Med 49 (2): 175–95. PMID 782050. 
  8. ^ Jacomo V, Kelly P, Raoult D (2002). [Expression error: Unexpected < operator "Natural history of Bartonella infections (an exception to Koch's postulate)"]. Clin Diagn Lab Immunol 9 (1): 8–18. doi:10.1128/CDLI.9.1.8-18.2002. PMID 11777823. 
  9. ^ Falkow S (1988). [Expression error: Unexpected < operator "Molecular Koch's postulates applied to microbial pathogenicity"]. Rev. Infect. Dis. 10 (Suppl 2): S274–6. PMID 3055197. 

Further reading


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