American Journal of Epidemiology Advance Access originally published online on November 6, 2006
American Journal of Epidemiology 2007 165(2):212-221; doi:10.1093/aje/kwj362
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ORIGINAL CONTRIBUTIONS |
Antiviral Effects on Influenza Viral Transmission and Pathogenicity: Observations from Household-based Trials
1 Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, WA
2 Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA
3 Department of Internal Medicine, University of Virginia, Charlottesville, VA
4 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI
Reprint requests to Dr. M. Elizabeth Halloran, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, LE-400, Seattle, WA 98109-1024 (e-mail: halloran{at}fhcrc.org).
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.
antiviral agents; disease transmission; family characteristics; influenza, human; randomized controlled trials; treatment outcome
Abbreviations: AVEI, antiviral efficacy for infectiousness; AVEId, antiviral efficacy for infectiousness as measured by clinical disease outcome in the exposed contact; AVEIi, antiviral efficacy for infectiousness as measured by infection outcome in the exposed contact; AVEP, antiviral efficacy for pathogenicity; AVES, antiviral efficacy for susceptibility; AVESd, antiviral efficacy for susceptibility as measured by clinical disease outcome in the exposed contact; AVESi, antiviral efficacy for susceptibility as measured by infection outcome in the exposed contact; AVET, total antiviral efficacy; AVETd, total antiviral efficacy as measured by clinical disease outcome in the exposed contact; AVETi, total antiviral efficacy as measured by infection outcome in the exposed contact; Osel I, clinical trial of oseltamivir conducted by Hayden et al. (3); Osel II, clinical trial of oseltamivir conducted by Welliver et al. (4); SAR, secondary attack rate; Zan I, clinical trial of zanamivir conducted by Hayden et al. (1); Zan II, clinical trial of zanamivir conducted by Monto et al. (2)
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