Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis

YOU LI; XIN WANG; DIANNA M BLAU; MAURICIO T CABALLERO; DANIEL R FEIKIN; CHRISTOPHER J GILL; SAAD B OMER; MARCELA ECHAVARRÍA; HARISH NAIR

LANCET

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2022

0140-6736

SummaryBackground Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in youngchildren. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infectionoccurred in children aged 0?60 months, resulting in a total of 118 200 deaths worldwide. Since then, several communitysurveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. Weaimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, andnational levels in children aged 0?60 months for 2019, with focus on overall mortality and narrower infant age groupsthat are targeted by RSV prophylactics in development.Methods In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from anupdated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health,CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished datafrom RSV GEN collaborators. Eligible studies reported data for children aged 0?60 months with RSV as primaryinfection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitatinghospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or forwhere RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion inacute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was notclearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or ifthe report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, andin-hospital mortality both globally and regionally (by country development status and by World Bank IncomeClassification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through arisk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV communitymortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400).Findings In addition to 317 studies included in our previous review, we identified and included 113 new eligible studiesand unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4?44·6 million),3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9?4·6 million), 26 300 RSV-associatedacute lower respiratory infection in-hospital deaths (15 100?49 100), and 101 400 RSV-attributable overall deaths(84 500?125 200) in children aged 0?60 months. In infants aged 0?6 months, we estimated that there were 6·6 millionRSV-associated acute lower respiratory infection episodes (4·6?9·7 million), 1·4 million RSV-associated acute lowerrespiratory infection hospital admissions (1·0?2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800?28 100), and 45 700 RSV-attributable overall deaths (38 400?55 900). 2·0% of deaths in childrenaged 0?60 months (UR 1·6?2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0?4·4) were attributableto RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% ofRSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs).Interpretation RSV contributes substantially to morbidity and mortality burden globally in children aged 0?60 months,especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSVdisease worldwide, with one in every 50 deaths in children aged 0?60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospitaldeath, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisationprogrammes targeting protection during the first 6 months of life could have a substantial effect on reducing RSVdisease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSVburden to older age when these are implemented