The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection
Introduction
Lower respiratory tract infection (LRTI) with respiratory syncytial virus (RSV) is a leading cause of hospitalization for severe bronchiolitis and pneumonia among infants and young children worldwide.1 Infants born preterm, or those diagnosed in infancy with bronchopulmonary dysplasia (BPD; or chronic lung disease of prematurity) or congenital heart disease (CHD) are at particularly high risk;2 they have longer hospital stays 3, 4 and are at higher risk of long-term RSV LRTI sequelae such as childhood asthma.5
In addition to increased morbidity, severe LRTIs, including due to RSV, are an important cause of childhood mortality worldwide, 6 although estimates of the magnitude of the risk of fatality vary. Among infants with underlying risk factors within the national Pediatric Investigators Collaborative Network on Infections in Canada RSV database, fatality rates in some subgroups were as high as 5.3%,4 while in a large population-based study in the United Kingdom, fatality rates were as low as 0.2%. 7 More recently, a study used data from a systematic review, supplemented with unpublished data, to project that 33 million episodes of RSV LRTI occur annually among children ≤5 years of age worldwide, 3.4 million of these requiring hospitalization.6 The global case fatality rate due to severe RSV LRTI was estimated between 1.9% and 5.9%. 6 The impact of underlying risk factors on RSV-specific mortality was not considered within that review, although another recent review estimated global fatality rates among children ≤18 years of age hospitalized for RSV LRTI from <1.0% (among those without underlying risk factors), to as high as 37% (among those with CHD). 8 Variability in the estimates between the two systematic reviews may be due to the inclusion of individuals at varying underlying RSV LRTI risk, but also due to differences in the age restrictions of the included studies, as younger age is a strong predictor of mortality due to RSV.9 Other sources of variability include the underlying epidemiology and distribution of RSV, and the availability of testing and treatment facilities (including access to intensive care units [ICUs]).
Understanding the risk of fatality due to severe RSV LRTI is critical not only to increase awareness of severe RSV-related effects, but also for researchers estimating the economic impact of future treatments or preventive measures. 8 Fatality risk may be particularly important for vulnerable populations at higher risk of severe RSV LRTI and its aftereffects2, 8 and younger patients at risk of more severe outcomes.8 The objective of this systematic review was to synthesize estimates of case fatality among young children (≤24 months of age) hospitalized for severe RSV LRTI according to underlying risk.
Section snippets
Study selection
A systematic review of the published literature was conducted in July 2011, using a customized search strategy consisting of RSV-, hospitalization-, and mortality-specific terms (Table 1). Articles published after January 1975 appearing in the Medline, EMBASE, and Cochrane Library databases, using randomized or observational designs, and reporting on the case fatality among young children hospitalized for severe RSV LRTI, were identified.
Two independent reviewers appraised the abstracts of all
Results
The search identified 1,187 potentially relevant abstracts; from those 1,187 abstracts, 58 articles were identified for full-text review. Of those 58 articles, 12 were excluded because they did not present risk group-specific estimates, and 12 were excluded because they included mixed groups of high-risk and non-high-risk children which could not be allocated to a specific risk group (Figure 2). The final review of 34 articles included two studies providing estimates for children not at high
Discussion
Severe LRTIs are known contributors to global pediatric mortality; 2, 6, 8 however, estimates of the magnitude of the fatality risk due to severe LRTIs, including due to RSV, vary. Two recent reviews estimated RSV-related fatality among hospitalized children; however, one did not stratify results by underlying risk factors, and the other included children ≤18 years of age.6, 8 We extended upon the results of other published reviews by synthesizing estimates of case fatality specifically among
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Financial disclosure: This review was sponsored by Abbott.
Conflict of interest statement: SMS and MMB are employees of Oxford Outcomes. KLG and PGV are employees of Abbott. PB is the president of Adzoe Inc. IM is a professor in the department of Paediatrics at the University of Calgary. ARL is a consultant to Oxford Outcomes.
Contributors' roles: All authors contributed to the conception and design of the study. SMS and MMB were responsible for acquisition of data. All authors participated in analysis and interpretation. SMS, MMB, and KLG drafted the article; PGV, ARL, IM and PB critically revised it. All authors provided final approval of the version to be published.