Elsevier

The Lancet

Volume 375, Issue 9725, 1–7 May 2010, Pages 1545-1555
The Lancet

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

https://doi.org/10.1016/S0140-6736(10)60206-1Get rights and content

Summary

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by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies.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mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality.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.

Introduction

Acute lower respiratory infection (ALRI) is the leading cause of global child mortality.1, 2 Respiratory syncytial virus (RSV) is believed to be the most important viral pathogen causing ALRI in young children, although its contribution to ALRI deaths is uncertain.3, 4, 5 Many data for incidence of and mortality from RSV-associated ALRI in developing countries remain unpublished. Therefore, we formed an RSV study group to supplement a systematic literature review with unpublished data. No global or regional estimates have been made previously of the burden of RSV-associated ALRI in children. Previous reviews have focused either on developing countries4, 6 or industrialised countries.7 We aimed to estimate the burden of disease worldwide due to RSV-associated ALRI in children younger than 5 years for 2005. We estimated only the ALRI component of the burden due to RSV infection because the main costs of RSV disease relate to health-service use for ALRI, and first-generation RSV vaccines are likely to protect against ALRI.3 This report is especially timely in view of the development of candidate vaccines that are sufficiently attenuated yet immunogenic in infants,8, 9, 10 and the increased funding for development and implementation of novel vaccines in developing countries that is available through the Global Alliance for Vaccines and Immunisation. We also aimed to emphasise important gaps in knowledge and to provide information about potential sites for vaccine trials.

Section snippets

Search strategy and selection criteria

We did a systematic literature review using a combination of search terms (webappendix pp 3–4), hand searching of online journals, and scanning of reference lists of identified citations. The search was limited to Medline (Ovid), Embase, CINAHL, Global Health, Web of Science, WHOLIS, LILACS, IndMed, and the grey literature (SIGLE) databases and to studies published between January, 1995, and June, 2009. Panel 1 shows eligibility criteria. No language or publication restrictions were applied. We

Results

We identified 36 studies with suitable data (figure 2): 19 published population-based studies reporting incidence of RSV-associated severe or non-severe ALRI in populations under surveillance; seven published studies estimating incidence on the basis of hospital discharge records or laboratory diagnosis reports and a census-based denominator of children at risk; and unpublished data from ten population-based studies, again reporting a clear denominator of children at risk (figure 3, table 1).18

Discussion

We estimated that in 2005, at least 33·8 (95% CI 19·3–46·2) million episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years, with incidence in developing countries more than twice that of industrialised countries. This estimate represents roughly 22% of all episodes of ALRI in young children. By comparison, 13·8 (10·8–17·2) million episodes of pneumococcal pneumonia and 7·9 (7·2–12·9) million episodes of Haemophilus influenzae type b pneumonia occurred in the same

References (56)

  • MW Weber et al.

    Respiratory syncytial virus infection in tropical and developing countries

    Trop Med Int Health

    (1998)
  • DJ Nokes
  • RA Karron et al.

    Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants

    J Infect Dis

    (2005)
  • JH Schickli et al.

    Challenges in developing a pediatric RSV vaccine

    Hum Vaccin

    (2009)
  • M Gomez et al.

    Phase-I study Medi-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children

    Pediatr Infect Dis J

    (2009)
  • Technical bases for the WHO recommendations on the management of pneumonia in children at first-level health facilities

    (1991)
  • GG Burton et al.

    Respiratory care. A guide to clinical practice

    (1997)
  • JA Mullins et al.

    Substantial variability in community respiratory syncytial virus season timing

    Pediatr Infect Dis J

    (2003)
  • State of the World's Children 2007

    (2007)
  • I Rudan et al.

    Global estimate of clinical pneumonia among children under 5 years of age

    Bull World Health Organ

    (2004)
  • IG Djelantik et al.

    Case fatality proportions and predictive factors for mortality among children hospitalised with severe pneumonia in a rural developing country setting

    J Trop Pediatr

    (2003)
  • FE Onyango et al.

    Hypoxaemia in young Kenyan children with acute lower respiratory infection

    BMJ

    (1993)
  • D Vicente et al.

    Hospitalization for respiratory syncytial virus in the paediatric population in Spain

    Epidemiol Infect

    (2003)
  • JA Weigl et al.

    Burden of disease in hospitalized RSV-positive children in Germany

    Klin Padiatr

    (2002)
  • MK Iwane et al.

    Population-based surveillance for hospitalizations associated with respiratory syncytial virus, influenza virus, and parainfluenza viruses among young children

    Pediatrics

    (2004)
  • KL Yorita et al.

    Severe bronchiolitis and respiratory syncytial virus among young children in Hawaii

    Pediatr Infect Dis J

    (2007)
  • SE Robertson et al.

    Respiratory syncytial virus infection: denominator-based studies in Indonesia, Mozambique, Nigeria and South Africa

    Bull World Health Organ

    (2004)
  • J Forster et al.

    Prospective population-based study of viral lower respiratory tract infections in children under 3 years of age (the PRI.DE study)

    Eur J Pediatr

    (2004)
  • Cited by (2149)

    • Respiratory syncytial virus infection in adults: Differences with influenza

      2024, Enfermedades Infecciosas y Microbiologia Clinica
    View all citing articles on Scopus
    View full text