Table 1.

Koch’s postulates revisited.

Postulates	Caveats
The agent must be found in abundance in all individuals suffering from the disease but not in healthy individuals (Koch later abandoned the universal requirement for this postulate)	Healthy individuals may harbor cholera and typhoid and not be affected but become carriers; polio only causes paralysis in a small subset of cases; asymptomatic or subclinical infections occur for many viruses, such as HIV and hepatitis C as well as HSV For HSV, many variables influence disease (see Box 1)
The microorganism must be isolated from a diseased individual and grown in culture	Prions have never been grown in culture, and many other difficult- or impossible-to-culture infectious disease-causing organisms exist that are now identified by nucleic acid assays and confirmed by consensus as disease-causing For HSV, this postulate has been fulfilled for mucosal blisters and acute encephalitis. DNA has been found in the CNS in many studies
The cultured microorganism should cause disease when introduced into a healthy organism	Infection may depend on host factors as well, as in the resistance to malaria of individuals carrying the sickle-cell gene. Koch himself used the word 'should' instead of 'must' to indicate that this is not universal. This postulate cannot be ethically satisfied for fatal diseases with no animal model, such as sporadic Alzheimer's disease For HSV, this postulate has been fulfilled for cold sores, encephalitis and teratology
The microorganism must be re-isolated from the inoculated diseased individual	Re-isolation requires that the microorganism can be inoculated For HSV, this postulate has been fulfilled for cold sores, encephalitis and teratology