Influenza rates are higher in family contacts of a person with influenza, so preventing the spread of influenza within the household is an effective way to control the spread of influenza throughout the community. Amantadine and rimantadine have been used as postcontact prophylaxis; however, these drugs are associated with rapid development of resistance, lack of efficacy against influenza B and poor tolerance (associated with amantadine). Welliver and associates investigated the efficacy of oseltamivir in preventing the spread of influenza among household contacts.
A cluster-randomized, double-blind, placebo-controlled study was conducted at 76 participating centers in North America and Europe during a community outbreak of influenza during the winter of 1998-99. Investigators recruited participants as a primary case if they presented within 48 hours of onset of influenza symptoms (at a minimum, cough and coryza). Nasal and pharyngeal cultures and serum samples were collected from all primary cases during this initial time frame. Follow-up was conducted and an additional serum sample collected during a clinic visit between study days 17 and 25. Nasal and pharyngeal cultures, a serum sample, and blood and urine samples were obtained from the household contacts. A follow-up physical examination was conducted on day 8, and a serum sample was obtained and a clinic visit occurred between study days 17 and 25.
Randomization was by household cluster so that all members of the same family received the same therapy. Of the 955 household contacts (377 households), 493 were randomized by household cluster to receive 75 mg of oseltamivir and 462 were randomized to receive placebo once daily for seven days, with therapy initiated within 48 hours of the first reported symptoms. Primary contacts did not receive antiviral therapy. Influenza was defined as a temperature of at least 37.2° C (99.0° F), at least one respiratory symptom and at least one constitutional symptom during a single 24-hour period, along with laboratory confirmation.
Among household contacts of the 377 primary contacts with symptoms, oseltamivir reduced the incidence of clinical influenza with 89 percent protective efficacy. Of the 377 primary contacts, 163 (43 percent) had laboratory-confirmed influenza. Of these 163 primary contacts, the overall efficacy of oseltamivir against clinical influenza was 89 percent for individuals and 84 percent for households. Oseltamivir was well tolerated, with gastrointestinal tract effects reported in 9.3 percent of those receiving oseltamivir versus 7.2 percent of those receiving placebo. In addition, oseltamivir inhibited viral shedding.
The authors conclude that 75 mg of oseltamivir taken once daily for seven days effectively protects close contacts against influenza if it is started within 48 hours of exposure to a symptomatic case of influenza. Although the primary contacts did not take oseltamivir, doing so would likely reduce the transmission risk further by decreasing viral shedding.