Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Harish Nair, D James Nokes, Bradford D Gessner, Mukesh Dherani, Shabir A Madhi, Rosalyn J Singleton, Katherine L O'Brien, Anna Roca, Peter F Wright, Nigel Bruce, Aruna Chandran, Evropi Theodoratou, Agustinus Sutanto, Endang R Sedyaningsih, Mwanajuma Ngama, Patrick K Munywoki, Cissy Kartasasmita, Eric A F Simões, Igor Rudan, Martin W Weber, Harry Campbell, Harish Nair, D James Nokes, Bradford D Gessner, Mukesh Dherani, Shabir A Madhi, Rosalyn J Singleton, Katherine L O'Brien, Anna Roca, Peter F Wright, Nigel Bruce, Aruna Chandran, Evropi Theodoratou, Agustinus Sutanto, Endang R Sedyaningsih, Mwanajuma Ngama, Patrick K Munywoki, Cissy Kartasasmita, Eric A F Simões, Igor Rudan, Martin W Weber, Harry Campbell

Abstract

Background: The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005.

Methods: We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality.

Findings: In 2005, an estimated 33.8 (95% CI 19.3-46.2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3.4 (2.8-4.3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000-199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting.

Interpretation: Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority.

Funding: WHO; Bill & Melinda Gates Foundation.

Copyright 2010 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Approaches for estimation of global RSV incidence and mortality in children aged 0–5 years RSV=respiratory syncytial virus. ALRI=acute lower respiratory infection. CFR=case fatality ratio. *Approach justified by large difference in reported incidence between studies using active and passive case ascertainment; studies with passive ascertainment reported much lower estimates than did those with active ascertainment. †Approach justified by the decision that hospital-based data would be most useful for population-based projections, since all severe episodes are likely to need hospital treatment; also, we noted no difference in reported incidence of RSV-associated severe ALRI between studies with active and passive case ascertainment. †Approach based on assumptions that: i) baseline proportional mortality of RSV-associated ALRI in all ALRI would be similar to proportional incidence of severe ALRI in all severe ALRI, and ii) there is no overall effect from seasonality of other respiratory pathogens; then, if all excess ALRI mortality during RSV seasonal peaks is assigned to RSV as the only cause (in a setting with many seasonal peaks) and this mortality is added to baseline mortality estimates, this approach is likely to overestimate the contribution of RSV to mortality from all ALRI. §Approach deemed to yield a lower bound for RSV-associated ALRI mortality because patients with severe RSV-associated ALRI treated in hospital might have higher CFRs than do all severe cases of RSV (treated and untreated), but a substantial (but unknown) proportion of severe cases will not present to health services for treatment, thereby increasing overall CFR.
Figure 2
Figure 2
Flow diagram for selection of studies
Figure 3
Figure 3
Location of the 36 studies by Global Burden of Diseases, Injuries and Risk Factors regions
Figure 4
Figure 4
ALRI-associated mortality pattern in children younger than 2 years in Lombok, Indonesia RSV=respiratory syncytial virus. ALRI=acute lower respiratory infection.

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