Background: During influenza epidemics, more than 40 percent of preschool children and 30 percent of school-aged children can be infected, and school-aged children are primarily responsible for bringing influenza into their households. Currently, about 30 percent of influenza A (H1N1) cases in the United Kingdom have occurred in children younger than 10 years. Although deaths from seasonal influenza are rare in children, complications such as acute otitis media and other respiratory tract infections are common.
Vaccination is the primary control strategy, but immunization rates vary and emerging strains may not be adequately covered. Consequently, antiviral medications are also used to treat and prevent the spread of influenza. The neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) are better tolerated and have wider effectiveness than amantadine (Symmetrel) and rimantadine (Flumadine). Oseltamivir is approved in the United Kingdom for treatment and postexposure prophylaxis of influenza in children one year and older. Zanamivir is approved in the United Kingdom for treatment and postexposure prophylaxis in children five and older. Shun-Shin and colleagues reviewed published and unpublished randomized controlled trials (RCTs) to assess the effectiveness, safety, and tolerability of neuraminidase inhibitors in children.
The Study: This meta-analysis updates a 2005 Cochrane review. The authors searched Medline and EMBASE articles through July 2009 and June 2009, respectively. They also searched clinical trial registries, the Cochrane central register of controlled trials, hand-searched reference lists and guidelines, and reviewed unpublished data from the two pharmaceutical manufacturers. The primary outcomes studied were time to resolution of illness in treatment trials and the rate of symptomatic influenza in children during the prophylaxis period in prevention trials. Secondary outcomes included time to resolution of individual symptoms; time to return to school, day care or usual activities; effect on respiratory function in children with asthma; and adverse events.
Results: Of the 4,917 articles identified, seven RCTs met inclusion criteria. The trials used different strategies to confirm clinical influenza signs and symptoms with virologic testing. Two treatment trials tested inhaled zanamivir and two tested oral oseltamivir. They enrolled a total of 1,766 children from one to 12 years of age, of whom 1,243 had confirmed influenza. Of the three treatment trials that reported influenza type, 55 to 69 percent had influenza A.
Three postexposure prophylaxis studies were included, with two zanamivir trials and one oseltamivir trial. Of the 863 children in these studies, 427 were in the intervention groups and 436 in the control groups. Only one of the treatment trials was considered high quality by the authors. The other six were designated of moderate quality because details about allocation concealment and adequate blinding were not reported.
Heterogeneity among the trials prevented pooling of data, but the treatment trials showed that either medication reduced symptom duration and time to return to usual activities by 0.5 to 1.5 days. Prophylaxis of family members with either medication was associated with an 8 percent reduction in the risk of developing clinical influenza after a confirmed case was introduced into the household. This results in a number needed to treat of 13.
In these studies, neuraminidase inhibitors had no significant effects on the rate of subsequent antibiotic use, the incidence of acute otitis media in children older than five years, or the rate of asthma exacerbations. One study of oseltamivir showed a significant reduction (from 31 to 15 percent) in the incidence of acute otitis media in children one to five years of age. Both drugs appeared to be well tolerated and safe in treatment and prophylaxis trials.
Conclusion: Compared with the 2005 Cochrane review, this more recent analysis shows that treating children with neuraminidase inhibitors decreases the duration of illness by about one day, and is effective in preventing influenza in household contacts. Of note, these data did not include any trials with emerging influenza strains including influenza A.
editor's note: This study does not mention the emergence of oseltamivir-resistant influenza A strains. Seasonal influenza A was resistant to oseltamivir in 2008–2009, whereas novel influenza A seemed to be sensitive to it (see accompanying table1,2). The Advisory Committee on Immunization Practices will publish updated guidelines in time for the 2009–2010 influenza season. In the meantime, the Centers for Disease Control and Prevention's interim guidelines recommend regular review of local or state virus surveillance to determine which influenza subtypes are likely circulating in the community.1—a.c.f
|Influenza type/subtype||Oseltamivir resistance?||Recommendation for treatment or Prophylaxis|
|Seasonal A (H1N1)||Yes||Zanamivir (Relenza) or oseltamivir (Tamiflu) plus rimantadine (Flumadine)|
|Seasonal A (H3N2)||No||Oseltamivir or zanamivir|
|Novel A (H1N1)||No||Oseltamivir or zanamivir|
|Seasonal B||No||Oseltamivir or zanamivir|