TABLE 2-3.

Criteria for Causation: A Unified Concept Appropriate for Viruses as Causative Agents, Based on the Henle–Koch Postulates^a

1. Prevalence of the disease should be significantly higher in those exposed to the putative cause than in controls not so exposed 2. Exposure to the putative cause should be present more commonly in those with the disease than in controls without the disease when all other risk factors are held constant 3. Incidence of the disease should be significantly higher in those exposed to the putative cause than in those not so exposed as shown in prospective studies 4. Temporally, the disease should follow exposure to the putative agent with a distribution of incubation periods on a bell-shaped curve 5. A spectrum of host responses should follow exposure to the putative agent along a logical biological gradient from mild to severe 6. A measurable host response following exposure to the putative cause should regularly appear in those lacking this before exposure (i.e., antibody, cancer cells) or should increase in magnitude if present before exposure; this pattern should not occur in those not so exposed 7. Experimental reproduction of the disease should occur in higher incidence in animals or man appropriately exposed to the putative cause than in those not so exposed; this exposure may be experimentally induced in the laboratory, or demonstrated in a controlled natural exposure (as with sentinel animals) 8. Elimination or modification of the putative cause or of the vector carrying it should decrease the incidence of the disease 9. Prevention or modification of the host's response on exposure to the putative cause should decrease or eliminate the disease (immunization, drugs) 10.The whole thing should make biological and epidemiological sense

^aFrom A. S. Evans, Yale J. Biol. Med.49, 175 (1976).