Neuraminidase inhibitors beneficial for treatment and prevention of influenza in children
Article Outline
- Question
- Design
- Data Sources
- Studies Selection and Assessment
- Outcomes
- Main Results
- Conclusions
- Commentary
- References
- Copyright
Shun-Shin M, Thompson M, Heneghan C, Perera R, Harnden A, Mant D. Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials. BMJ 2009;339:b3172.
Question
Among children with seasonal influenza, how effective are the neuraminidase inhibitors oseltamivir and zanamivir in treatment and in the prevention of transmission to children in households?
Design
Systematic review and meta-analysis of data from published and unpublished randomized controlled trials.
Data Sources
Medline and Embase to June 2009, trial registries, manufacturers, and authors of relevant studies.
Studies Selection and Assessment
Randomized controlled trials of neuraminidase inhibitors in children (≤12 years) in the community (ie, not hospitalized) with confirmed or clinically suspected influenza. The authors identified 4 randomized trials of treatment of influenza (2 with oseltamivir, 2 with zanamivir) involving 1766 children (1243 with confirmed influenza, of whom 55% to 69% had influenza A) and 3 randomized trials for postexposure prophylaxis (1 with oseltamivir, 2 with zanamivir) involving 863 children; none of these trials tested efficacy with the current pandemic strain.
Outcomes
Time to resolution of illness and incidence of influenza in children living in households with index cases of influenza.
Main Results
Treatment trials showed reductions in median time to resolution of symptoms or return to normal activities, or both, of 0.5 to 1.5 days, which were significant in 2 trials. A 10-day course of postexposure prophylaxis with zanamivir or oseltamivir resulted in an 8% (95% confidence interval, 5% to 12%) decrease in the incidence of symptomatic influenza. Based on only 1 trial, oseltamivir did not reduce asthma exacerbations or improve peak flow in children with asthma. In a pooled analysis of 2 trials, treatment was not associated with a reduction in overall use of antibiotics (risk difference, −0.30, −0.13 to 0.01). Zanamivir and oseltamivir were well tolerated, but oseltamivir was associated with an increased risk of vomiting (0.05, 0.02 to 0.09; number needed to harm = 20).
Conclusions
Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza when used for treatment and reducing household transmission when used for prophylaxis. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain, remain to be determined.
Commentary
Children continue to bear the greatest burden of pandemic (H1N1) 2009 influenza, and the virus remains susceptible to the neuraminidase inhibitors. The publication of this review is therefore opportune, and generated considerable media attention in the United Kingdom. Revising a previous Cochrane review,1 data are added from 1 further treatment trial and 2 further prevention trials. For the treatment of seasonal influenza, the authors restate the conclusion that a 5-day course of oseltamivir or zanamivir reduced median illness duration by about 1 day. The efficacy of the drugs in preventing extrapulmonary complications of influenza may be expected to differ, however, because of the greater systemic bioavailability of oral oseltamivir, compared with inhaled zanamivir. Care should therefore be taken when interpreting pooled data for these and related end points. In the only double-blind, randomized, controlled trial on the use of oseltamivir for the treatment of influenza in previously healthy children, significant reductions were observed in both overall physician-diagnosed complications requiring antibiotic use (relative risk reduction, 40%) and, specifically, in the likelihood of developing otitis media (relative risk reduction, 44%).2 For the prevention of seasonal influenza, the authors reach the conclusion that a 10-day course of postexposure prophylaxis with oseltamivir or zanamivir decreased the incidence of symptomatic influenza in pediatric contacts by only 8%. This is an estimate of absolute risk reduction, however, corresponding to a relative risk reduction of approximately 70%—comparable with the efficacy of vaccination.3 Based on the available evidence, therefore, neuraminidase inhibitors should still be considered for the treatment of seasonal and pandemic influenza and for the postexposure prophylaxis of high risk pediatric contacts.
References
PII: S0022-3476(09)01205-0
doi:10.1016/j.jpeds.2009.11.070
© 2010 Mosby, Inc. All rights reserved.
