Elsevier

The Lancet

Volume 378, Issue 9807, 3–9 December 2011, Pages 1917-1930
The Lancet

Articles
Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis

https://doi.org/10.1016/S0140-6736(11)61051-9Get rights and content

Summary

Background

The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years.

Methods

We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality.

Findings

We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49–162 million) new cases of influenza (data from nine studies), 20 million (13–32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1–2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28 000–111 500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting.

Interpretation

Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available.

Funding

WHO; Bill & Melinda Gates Foundation.

Introduction

Acute lower respiratory infections (ALRI) such as pneumonia and bronchiolitis are a leading cause of morbidity and mortality in young children.1 Around 156 million new episodes of ALRI occur worldwide every year and about 1·56 million young children died as a result of such infections in 2008.2, 3 Respiratory viruses are commonly associated with ALRI episodes in young children.4, 5, 6, 7, 8, 9, 10 We previously estimated that respiratory syncytial virus (RSV) is present in 22% of such episodes, making it the most prevalent pathogen in children with ALRI.11 Influenza has long been regarded as an important disease in the elderly because of its high incidence and concomitant high rate of hospital admissions and mortality in individuals older than 65 years.12 However, studies in the past decade suggested that the burden of disease due to hospital admissions for influenza-associated ALRI in young and very young children is also substantial.13, 14, 15, 16

Previously, no estimates of the global burden of disease from seasonal influenza virus-associated ALRI in young children have been made. We identified only two systematic reviews of the incidence of influenza-associated pneumonia,17, 18 neither of which provided summary incidence rates. Recent estimates of global ALRI incidence and mortality associated with Streptococcus pneumoniae, Haemophilus influenzae type b, and RSV11, 19, 20 do not fully explain the paediatric ALRI burden, and so the role of other pathogens needs to be explored. Influenza is associated with a large but unknown number of hospital admissions in young children globally and is vaccine preventable. Globally, there is an increasing capacity for laboratory-confirmed diagnosis of influenza infection which led to increased recognition (especially) of severe influenza-related illness in children and adults in developing countries during the influenza A H1N1 pandemic in 2009. Additionally, studies from developing countries have provided population-based estimates of burden of influenza in children that have added to the evidence of the health effects of the disease worldwide. Moreover, the influenza A H1N1 (2009) pandemic raised questions about the baseline incidence and mortality from seasonal influenza in young children so as to better assess the need for and structure of vaccination programmes.

Many data for incidence and mortality from influenza-associated ALRI in developing countries remain unpublished. Therefore, we formed an international Influenza Study Group to supplement our systematic literature review with unpublished data. We aimed to estimate the burden of disease due to influenza-associated ALRI in children younger than 5 years for 2008 globally and for six WHO regions.

Section snippets

Search strategy and selection criteria

We undertook a systematic literature review with various search terms (webappendix pp 3–4) and hand searched online journals and scanned reference lists of identified citations. We restricted the search to Medline (Ovid), Embase, CINAHL, Global Health, Web of Science, WHOLIS, LILACS, IndMed, grey literature (SIGLE), and Chinese language databases and to studies published between Jan 1, 1995, and Oct 31, 2010. Panel 1 shows study eligibility criteria. No language or publication restrictions were

Results

We identified 43 studies15, 16, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 with suitable data (table 1, figure 2): 18 were population-based studies reporting incidence of influenza-associated severe or non-severe ALRI in populations under surveillance; 10 were studies estimating incidence on the basis of hospital-discharge records or laboratory reports and a census-based denominator of children at risk; and 15 were population-based studies

Discussion

Our study is the first to estimate global incidence of influenza-associated ALRI and resultant mortality in children younger than 5 years. We estimated that, in 2008, there were about 90 million (95% CI 49–162 million) new cases of influenza episodes, 20 million (13–32 million) cases of influenza-associated ALRI, and 1 million (1–2 million) cases of influenza-associated severe ALRI in this group, causing 28 000–111 500 deaths. Estimates are very variable within countries or regions and between

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