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Koch's postulates ([ˈkɔx]) 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 cholera and tuberculosis, but they have been generalized to other diseases.
Koch's postulates are the following:
However, Koch abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of cholera 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 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.
The third postulate specifies "should", not "must", because as Koch himself proved in regard to both tuberculosis and cholera, 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.
In summary, a body of evidence that satisfies Koch's postulates is sufficient but not necessary to establish causation.
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. 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. 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. Currently, a number of infectious agents are accepted as the cause of disease despite their not fulfilling all of Koch's postulates. 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.
Koch’s postulates have played an important role in microbiology, yet they have major limitations. For example, Koch was well aware that in the case of cholera, the causal agent, Vibrio cholerae, could be found in both sick and healthy people, invalidating his first postulate. Furthermore, viral diseases were not yet discovered when Koch formulated his postulates, and there are many viruses that do not cause illness in all infected individuals, a requirement of the first postulate. Additionally, it was known through experimentation that H. pylori caused mild inflammation of the gastric lining when ingested. As evident as the inflammation was, it still did not immediately convince skeptics that H. pylori was associated with ulcers. Eventually, skeptics were silenced when a newly developed antibiotic treatment eliminated the bacteria and ultimately cured the disease. Contradictions and occurrences such as these have led many to believe that a fifth postulate may be required. If enacted, this postulate would state that sufficient microbial data should allow scientists to treat, cure, or prevent the particular disease.
More recently, modern nucleic acid-based microbial detection methods have made Koch’s original postulates even less relevant. These nucleic acid-based methods make it possible to identify microbes that are associated with a disease, but in many cases the microbes are uncultivable. Also, nucleic acid-based detection methods are very sensitive, and they can often detect the very low levels of viruses that are found in healthy people without disease.
The use of these new methods has led to revised versions of Koch’s postulates: Fredricks and Relman have suggested the following set of Koch’s postulates for the 21st century: