Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trialsBMJ 2009; 339 doi: http://dx.doi.org/10.1136/bmj.b3172 (Published 10 August 2009) Cite this as: BMJ 2009;339:b3172
- Matthew Shun-Shin, academic foundation year 2 doctor1,
- Matthew Thompson, senior clinical scientist2,
- Carl Heneghan, clinical lecturer2,
- Rafael Perera, university lecturer in medical statistics2,
- Anthony Harnden, university lecturer in general practice2,
- David Mant, professor of general practice2
- 1Kadoorie Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU
- 2Oxford University Department of Primary Health Care, Rosemary Rue Building, Headington, Oxford OX3 7LF
- Correspondence to: M Thompson
- Accepted 3 August 2009
Objective To assess the effects of the neuraminidase inhibitors oseltamivir and zanamivir in treatment of children with seasonal influenza and prevention of transmission to children in households.
Design Systematic review and meta-analysis of data from published and unpublished randomised controlled trials.
Data sources Medline and Embase to June 2009, trial registries, and manufacturers and authors of relevant studies.
Review methods Eligible studies were randomised controlled trials of neuraminidase inhibitors in children aged ≤12 in the community (that is, not admitted to hospital) with confirmed or clinically suspected influenza. Primary outcome measures were time to resolution of illness and incidence of influenza in children living in households with index cases of influenza.
Results We identified four randomised trials of treatment of influenza (two with oseltamivir, two with zanamivir) involving 1766 children (1243 with confirmed influenza, of whom 55-69% had influenza A), and three randomised trials for postexposure prophylaxis (one with oseltamivir, two with zanamivir) involving 863 children; none of these trials tested efficacy with the current pandemic strain. Treatment trials showed reductions in median time to resolution of symptoms or return to normal activities, or both, of 0.5-1.5 days, which were significant in only two 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 one trial, oseltamivir did not reduce asthma exacerbations or improve peak flow in children with asthma. Treatment was not associated with reduction in overall use of antibiotics (risk difference −0.30, −0.13 to 0.01). Zanamivir was 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 and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.
The Department of Primary Health Care is a member of the NIHR funded School of Primary Care Research. Richard Mayon-White provided valuable advice on drafts of the manuscript. Nia Roberts provided assistance with literature searching and organisation. We also thank Nick Matheson, Mkael Symmonds-Abrahams, Sasha Shepherd, and Aziz Sheikh, who were involved in the previous Cochrane systematic review, and GlaxoSmithKline (Alison Webster) and Roche (James Smith) for providing data.
Contributors: MS-S and MT conducted the searches, collated and reviewed the studies, extracted the data, performed the initial analysis, and wrote the initial draft. CH and RP contributed to the analysis, revised and commented on various drafts, and provided methodological support. AH conceived the idea for and the design of the study and wrote the initial protocol. DM revised and commented on various drafts. All authors contributed to the final report. MT is guarantor.
Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The Department of Primary Health care is part of the NIHR School of Primary Care Research.
Competing interests: None declared.
Ethical approval: Not required.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.