Four household-based, randomized clinical trials, two each of
zanamivir and
oseltamivir, were designed primarily to estimate the effect of postexposure prophylaxis on preventing
influenza illness in household contacts. However, the effect of
influenza antivirals on infectiousness as well as on the ability of the virus to cause disease--the pathogenicity--have important public health consequences. The authors show how such studies can provide estimates of pathogenicity,
antiviral efficacy for pathogenicity, and the
antiviral effect on infectiousness. Analysis of the four studies confirmed the high prophylactic efficacy against illness of both
zanamivir (75%, 95% confidence interval (CI): 54, 86) and
oseltamivir (81%, 95% CI: 35, 94). The effect on reducing infectiousness was 19% (95% CI: -160, 75) for
zanamivir and 80% (95% CI: 43, 93) for
oseltamivir. Pathogenicity in controls ranged from 44% (95% CI: 33, 55) to 66% (95% CI: 48, 72). Efficacy in reducing pathogenicity for
zanamivir was 52% (95% CI: 19, 72) and 56% (95% CI: 14, 77) in the two studies; for
oseltamivir, it was 56% (95% CI: 10, 73) and 79% (95% CI: 45, 92). Studies of
influenza antivirals in transmission units would be improved if randomization schemes were used that allow estimation of the
antiviral effect on infectiousness from individual studies.