Table 1.

Criteria for disease causation: a unified concept appropriate for viruses as causative agents of disease, based on the Henle–Koch postulates, and modified by A. S. Evans

1. Prevalence of the disease is significantly higher in subjects exposed to the putative virus than in those not so exposed.

2. Incidence of the disease is significantly higher in subjects exposed to the putative virus than in those not so exposed (prospective studies).

3. Evidence of exposure to the putative virus is present more commonly in subjects with the disease than in those without the disease.

4. Temporally, the onset of disease follows exposure to the putative virus, always following an incubation period.

5. A regular pattern of clinical signs follows exposure to the putative virus, presenting a graded response, often from mild to severe.

6. A measurable host-immune response, such as an antibody response and/or a cell-mediated response, follows exposure to the putative virus. In those individuals lacking prior experience, the response appears regularly, and in those individuals with prior experience, the response is anamnestic.

7. Experimental reproduction of the disease follows deliberate exposure of animals to the putative virus, but nonexposed control animals remain disease free. Deliberate exposure may be in the laboratory or in the field, as with sentinel animals.

8. Elimination of the putative virus and/or its vector decreases the incidence of the disease.

9. Prevention or modification of infection, via immunization or drugs, decreases the incidence of the disease.

10. “The whole thing should make biologic and epidemiologic-sense.”