The influenza viruses are highly contagious, which partially explains the observation that 25 to 50 percent of all household contacts of an index patient will contract the “flu” during an outbreak. Postexposure prophylaxis with amantadine or rimantadine is often used and has proved effective in several studies. However, at least two studies found no protection from this therapy, partially because of the rapid emergence of viral resistance to these medications. Zanamivir is a member of a new class of influenza therapies known as neuraminidase inhibitors. Inhaled zanamivir is effective for the acute treatment of influenza and has been found to confer seasonal protection when administered as daily prophylaxis. Hayden and colleagues performed a randomized, double-blind, placebo-controlled, parallel group study of zanamivir for the treatment and prevention of influenza in families.
Families eligible for the study had to include at least one adult and one child who was five to 17 years of age. Excluded were persons younger than five years and those with hypersensitivity to zanamivir or any immunocompromised state, and those who were pregnant or breast-feeding. Influenza-like illness had to include at least two of the following symptoms: fever higher than 37.8°C (100°F), cough, headache, sore throat and myalgias. A diagnosis of influenza was confirmed by rapid viral isolation and serologic testing. Family members who were index cases of influenza were randomly assigned to receive 10 mg of inhaled zanamivir or placebo twice daily for five days. Healthy household members were given 10 mg of zanamivir or placebo once daily for 10 days. Treatments were started within 36 hours of the onset of symptoms. All participants recorded the presence or absence of influenza symptoms twice daily for 14 days. The index case patients were seen on days 1 and 5, and household contacts were seen on days 11 and 28, and were also screened by telephone on days 5 and 14. The primary end point of the study was the proportion of families with at least one initially healthy member in whom symptomatic, laboratory-confirmed influenza was diagnosed.
Of the 337 families that participated in the study, 163 index cases were randomly assigned to the zanamivir arm and 158 index cases were randomly assigned to the placebo arm. The comparable number of household contacts for each group was 414 and 423, respectively. The proportion of families with one or more household contacts in whom laboratory-confirmed influenza developed was 19 percent in the group receiving placebo and 4 percent in the group receiving zanamivir. In families where the index case was laboratory-confirmed, influenza developed in 29 percent of patients in the placebo group and 8 percent of patients in the zanamivir group. The proportion of families with at least one family member who had confirmed symptomatic influenza was 15 percent of patients in the placebo group and 2 percent of patients in the zanamivir group, which translates to an 84 percent rate of protection with the influenza therapy. In all patients who had laboratoryconfirmed influenza, the duration of symptoms was 2.5 days shorter for those receiving zanamivir compared with those receiving placebo. The frequency of adverse events was low and similar in both groups.
The authors conclude that administration of inhaled zanamivir to the index case and healthy family members significantly decreases the incidence of infection in household contacts. Although not a substitute for vaccination, clinical benefits of zanamivir include a rapid onset of action, a high degree of protection and good tolerability.