Mortality Among US Infants and Children Under 5 Years of Age with Respiratory Syncytial Virus and Bronchiolitis: A Systematic Literature Review

Abstract

Background A systematic literature review was conducted to summarize the mortality (overall and by disease severity factors) of US infants and children aged <5 years with respiratory syncytial virus (RSV) or all-cause bronchiolitis (ACB). Methods Comprehensive, systematic literature searches were conducted; articles were screened using prespecified eligibility criteria. A standard risk of bias tool was used to evaluate studies. Mortality was extracted as the rate per 100 000 or the case fatality ratio (CFR; proportion of deaths among RSV/ACB cases). Results Among 42 included studies, 36 evaluated inpatient deaths; 10 used nationally representative populations updated through 2013, and only 2 included late-preterm/full-term otherwise healthy infants and children. The RSV/ACB definition varied across studies (multiple International Classification of Diseases [ICD] codes; laboratory confirmation); no study reported systematic testing for RSV. No studies reported RSV mortality rates, while 3 studies provided ACB mortality rates (0.57–9.4 per 100 000). CFRs ranged from 0% to 1.7% for RSV (n = 15) and from 0% to 0.17% for ACB (n = 6); higher CFRs were reported among premature, intensive care unit-admitted, and publicly insured infants and children. Conclusions RSV mortality reported among US infants and children is variable. Current, nationally representative estimates are needed for otherwise healthy, late-preterm to full-term infants and children.

All Infants Are at Risk of Developing Medically Attended Respiratory Syncytial Virus Lower Respiratory Tract Infection and Deserve Protection

“…Prill et al [ 30 ] indicate that fundamental improvements, such as this, are needed to better define the magnitude of the problem, populations at risk, and impact of future interventions. In their systematic literature review, Bylsma et al [ 31 ] detail that most US studies of RSV infant mortality rates capture IP deaths only, lacking data for out-of-hospital deaths. These studies also report that limited data exist for mortality by subgroup such as chronological age, gestational age, comorbid conditions, race/ethnicity, and insurance payer type, all of which have been associated with high risk of disease.…”

The Burden of Respiratory Syncytial Virus Lower Respiratory Tract Disease in Infants in the United States: A Synthesis

“…Although globally RSV is the most important cause of mortality from LRTI in the pneumococcal vaccine era that is often underrecognized, most of these deaths occur in developing countries [ 16 ]. Although the case-fatality ratios from RSV vary between 0.5% and 7% in developing countries [ 16 ], these ratios vary from 0.04% to 0.90% in the United States based on large-scale or nationwide data [ 36 ]. A systematic review of studies reporting estimates of RSV mortality estimated that RSV deaths occurred at a rate of 8.4/million live births and bronchiolitis deaths varied between 20 and 94/million live births [ 36 ].…”

“…Although the case-fatality ratios from RSV vary between 0.5% and 7% in developing countries [ 16 ], these ratios vary from 0.04% to 0.90% in the United States based on large-scale or nationwide data [ 36 ]. A systematic review of studies reporting estimates of RSV mortality estimated that RSV deaths occurred at a rate of 8.4/million live births and bronchiolitis deaths varied between 20 and 94/million live births [ 36 ]. These estimates come from data extrapolated from a single nationwide study examining RSV deaths between 2004 and 2007 [ 37 ].…”

Mortality Associated With Respiratory Syncytial Virus, Bronchiolitis, and Influenza Among Infants in the United States: A Birth Cohort Study From 1999 to 2018

“…Because routine laboratory testing for RSV is not recommended [ 23 ], bronchiolitis was included as a potential upper estimate of RSV mortality, which is consistent with the methodology used in other RSV studies [ 1 , 12 , 17 ]. RSV is typically in circulation at the same time as influenza and prior RSV mortality studies have also assessed influenza mortality [ 7 , 20 , 24 ]; thus, influenza mortality was also evaluated.…”

“…RSV mortality varies by sociodemographic and clinical characteristics, including prematurity, comorbid conditions, and insurance payer status [ 1 , 10–17 ], although contemporary, nationally representative estimates of RSV mortality among US infants stratified by infant birth characteristics other than sex and race have yet to be published [ 17 ]. A few recent studies have examined the total number of infant deaths due to RSV in the United States.…”