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Original Contribution
February 14, 2001

Effectiveness of Oseltamivir in Preventing Influenza in Household Contacts: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Children's Hospital, Buffalo, NY (Dr Welliver); University of Michigan School of Public Health, Ann Arbor (Dr Monto); Comprehensive Clinical Research, Berlin, NJ (Dr Hassman); Kentucky Pediatric and Adult Research, Bardstown, Ky (Dr Hedrick); Roche Global Development, Welwyn, England (Drs Jackson, Huson, and Ward); and St Bartholomew's and Royal London Hospital School of Medicine and Dentistry, and Retroscreen Virology Ltd, London, England (Dr Oxford). Dr Carewicz is in private practice in Heidelberg, Germany, and Dr Schatteman is in private practice in Drogen, Ghent, Belgium.

JAMA. 2001;285(6):748-754. doi:10.1001/jama.285.6.748

Context Influenza virus is easily spread among the household contacts of an infected person, and prevention of influenza in household contacts can control spread of influenza in the community.

Objective To investigate the efficacy of oseltamivir in preventing spread of influenza to household contacts of influenza-infected index cases (ICs).

Design and Setting Randomized, double-blind, placebo-controlled study conducted at 76 centers in North America and Europe during the winter of 1998-1999.

Participants Three hundred seventy-seven ICs, 163 (43%) of whom had laboratory-confirmed influenza infection, and 955 household contacts (aged ≥12 years) of all ICs (415 contacts of influenza-positive ICs).

Interventions Household contacts were randomly assigned by household cluster to take 75 mg of oseltamivir (n = 493) or placebo (n = 462) once daily for 7 days within 48 hours of symptom onset in the IC. The ICs did not receive antiviral treatment.

Main Outcome Measure Clinical influenza in contacts of influenza-positive ICs, confirmed in a laboratory by detection of virus shedding in nose and throat swabs or a 4-fold or greater increase in influenza-specific serum antibody titer between baseline and convalescent serum samples.

Results In contacts of an influenza-positive IC, the overall protective efficacy of oseltamivir against clinical influenza was 89% for individuals (95% confidence interval [CI], 67%-97%; P<.001) and 84% for households (95% CI, 49%-95%; P<.001). In contacts of all ICs, oseltamivir also significantly reduced incidence of clinical influenza, with 89% protective efficacy (95% CI, 71%-96%; P<.001). Viral shedding was inhibited in contacts taking oseltamivir, with 84% protective efficacy (95% CI, 57%-95%; P<.001). All virus isolates from oseltamivir recipients retained sensitivity to the active metabolite. Oseltamivir was well tolerated; gastrointestinal tract effects were reported with similar frequency in oseltamivir (9.3%) and placebo (7.2%) recipients.

Conclusion In our sample, postexposure prophylaxis with oseltamivir, 75 mg once daily for 7 days, protected close contacts of influenza-infected persons against influenza illness, prevented outbreaks within households, and was well tolerated.