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A Brief History of Viral Pathogenesis The Relationships among Microbes and the Diseases They Cause

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Long before any disease-causing microbes were identified, poisonous air (miasma) was generally presumed to cause epidemics of contagious diseases. The causative association of particular microorganisms, initially bacteria, with specific diseases can be attributed to the work of the German physician Robert Koch. With his colleague Friedrich Loeffler, Koch developed four criteria that, if met, would prove a causal relationship between a given microbe and a particular disease. These criteria, Koch’s postulates, were first published in 1884 and are still used today as a standard by which pathogens are identified. The postulates are as follows:

 the microorganism must be associated regularly with the disease and its characteristic lesions but should not be found in healthy individuals;

 the microorganism must be isolated from the diseased host and grown in culture;

 the disease should be reproduced when a pure preparation of the microorganism is introduced into a healthy, susceptible host; and

 the same microorganism must be reisolated from the experimentally infected host.

Guided by these postulates and the methods developed by Pasteur for the sterile culture and isolation of purified preparations of microorganisms, researchers identified and classified many pathogenic bacteria (as well as yeasts and fungi) during the latter part of the 19th century. Identifying a cause-and-effect relationship between a microbe and a pathogenic outcome set the stage for transformative therapeutic advances, including the development of antibiotics to treat bacterial infections.

However, during the last decade of the 19th century, it became clear that not all diseases could be attributed to bacterial or fungal agents. This apparent breakdown of the paradigm led to the identification of a new class of infectious agents: submicroscopic particles that came to be called viruses. Koch’s postulates can often be applied to viruses, but not all virus-disease relationships meet these criteria. While compliance with Koch’s principles will establish that a particular virus is the causative agent of a specific disease, failure to comply does not rule out a possible cause-and-effect relationship (Box 1.1).

Principles of Virology, Volume 2

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