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Meta-Analysis
. 2014 Dec 9;9(12):e113633.
doi: 10.1371/journal.pone.0113633. eCollection 2014.

Use of neuraminidase inhibitors for rapid containment of influenza: a systematic review and meta-analysis of individual and household transmission studies

George N Okoli  1 , Harmony E Otete  1 , Charles R Beck  1 , Jonathan S Nguyen-Van-Tam  1
Affiliations
Meta-Analysis

Use of neuraminidase inhibitors for rapid containment of influenza: a systematic review and meta-analysis of individual and household transmission studies

George N Okoli et al. PLoS One. .

Abstract

Objectives: To assess the effectiveness of neuraminidase inhibitors for use in rapid containment of influenza.

Method: We conducted a systematic review and meta-analysis in accordance with the PRISMA statement. Healthcare databases and sources of grey literature were searched up to 2012 and records screened against protocol eligibility criteria. Data extraction and risk of bias assessments were performed using a piloted form. Results were synthesised narratively and we undertook meta-analyses to calculate pooled estimates of effect, statistical heterogeneity and assessed publication bias.

Findings: Nine randomised controlled trials (RCTs) and eight observational studies met the inclusion criteria. Neuraminidase inhibitors provided 67 to 89% protection for individuals following prophylaxis. Meta-analysis of individual protection showed a significantly lower pooled odds of laboratory confirmed seasonal or influenza A(H1N1)pdm09 infection following oseltamivir usage compared to placebo or no therapy (n = 8 studies; odds ratio (OR) = 0.11; 95% confidence interval (CI) = 0.06 to 0.20; p<0.001; I2 = 58.7%). This result was comparable to the pooled odds ratio for individual protection with zanamivir (OR = 0.23; 95% CI 0.16 to 0.35). Similar point estimates were obtained with widely overlapping 95% CIs for household protection with oseltamivir or zanamivir. We found no studies of neuraminidase inhibitors to prevent population-wide community transmission of influenza.

Conclusion: Oseltamivir and zanamivir are effective for prophylaxis of individuals and households irrespective of treatment of the index case. There are no data which directly support an effect on wider community transmission.

Protocol registry: PROSPERO registration number: CRD42013003880.

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Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following competing interests: The University of Nottingham Health Protection and Influenza Research Group is currently in receipt of research funds from GlaxoSmithKline (GSK) and unrestricted educational grants for influenza research from F. Hoffmann-La Roche and Astra Zeneca. The aforementioned funding received from GSK, F. Hoffmann-La Roche and Astra Zeneca did not support any aspect of this study. Professor Van-Tam has received funding to attend influenza related meetings, lecture and consultancy fees and research funding, from several influenza antiviral drug and vaccine manufacturers. All forms of personal remuneration ceased in September 2010, but influenza-related research funding from GSK and F. Hoffmann-La Roche remains current, as stated above. He is a former employee of SmithKline Beecham plc. (now GlaxoSmithKline), Roche Products Ltd, and Aventis-Pasteur MSD (now Sanofi-Pasteur MSD), all prior to 2005, with no outstanding pecuniary interests by way of shareholdings, share options or accrued pension rights. Dr George N. Okoli, Miss Harmony E. Otete and Dr Charles R. Beck have no potential conflicts of interest to declare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Summary of the literature search and sifting process (PRISMA flow diagram).
CENTRAL = Cochrane Central Register of Controlled Trials; CDSR = Cochrane Database of Systematic Reviews; DARE = Database of Abstracts of Reviews; NHS = National Health Services; HTA = Health Technology Assessment; WHO Global Medical Index = World Health Organization Global Medical Index; OpenSIGLE = System for information on Grey Literature in Europe; CDC = Centers for Diseases Control and Prevention; IFPMA = International Federation of Pharmaceutical Manufacturers Associations.
Figure 2
Figure 2. Risk of bias assessment using the Cochrane Collaboration tool.
Upper panel: RCTs and prospective cohort studies (n = 14); Lower panel: RCTs only (n = 9).
Figure 3
Figure 3. Meta-analysis of pre- and post-exposure prophylaxis with oseltamivir against seasonal and influenza A(H1N1)pdm09 (Individual protection).
Horizontal axis represent odds ratio; Columns represent study authors and year of publication, effect size including pooled estimate of effect, and 95% CI, and the weighting of each study in the meta-analysis.
Figure 4
Figure 4. Meta-analysis of prophylaxis for households with oseltamivir against seasonal influenza.
Horizontal axis represent odds ratio; Columns represent study authors and year of publication, effect size including pooled estimate of effect, and 95% CI, and the weighting of each study in the meta-analysis.
Figure 5
Figure 5. Meta-analysis of pre- and post-exposure prophylaxis with zanamivir against seasonal influenza (individual protection).
Horizontal axis represent odds ratio; Columns represent study authors and year of publication, effect size including pooled estimate of effect, and 95% CI, and the weighting of each study in the meta-analysis.
Figure 6
Figure 6. Meta-analysis of prophylaxis for households with zanamivir against seasonal influenza.
Horizontal axis represent odds ratio; Columns represent study authors and year of publication, effect size including pooled estimate of effect, and 95% CI, and the weighting of each study in the meta-analysis.
See this image and copyright information in PMC

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