Global Respiratory Syncytial Virus-Related Infant Community Deaths

Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized.

Methods: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital.

Results: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001).

Conclusions: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.

Keywords: community death; lower respiratory tract infection; respiratory syncytial virus.

Figure 1.

Flowchart of children included in this study. Flowchart shows children excluded via both data quality and per definition of study population. For the primary analysis we analyzed 629 children dying under age 6 months (473 in-hospital deaths and 156 community deaths). For the secondary analysis we analyzed 661 children dying under age 12 months (611 in-hospital deaths and 50 community deaths). GOLD I: Pediatric deaths published as a retrospective case series from 1 November 2014 to 31 October 2015 [9]. GOLD II includes pediatric deaths collected after this publication. Abbreviations: m, months; BMGF, Bill & Melinda Gates Foundation; GOLD, Global Online Mortality Database; RSV, respiratory syncytial virus; ZPRIME, Zambia Pertussis RSV Infant Mortality Estimation Study.

Figure 2.

A, World map showing L(M)ICs and UMICs that shared RSV-confirmed community deaths under 12 months of age and number of RSV-confirmed community deaths shared to the registry. The color gradient of purple indicates number of deaths shared, with darker purple representing increased number of deaths shared. Numbers of deaths are visible on the map. B, World map showing L(M)ICs and UMICs that shared RSV-confirmed in-hospital deaths under 12 months of age and number of deaths of RSV-confirmed in-hospital deaths shared to the registry. The color gradient of green indicates number of deaths shared, with darker green representing increased number of deaths shared. Numbers of deaths are visible on the map. Abbreviations: L(M)ICs, lower-income-lower-middle-income country; RSV, respiratory syncytial virus; UMIC, upper-middle-income country.

Figure 3.

A, Histogram and density plot of age at death for children under 6 months who died with RSV in the community compared with in-hospital in L(M)ICs and UMICs. The histogram shows number of deaths (count, left y-axis) shared to the registry by age at death in months (rounded to the nearest integer) from age 0 up to 6 months for all infants under 6 months of age. Lines show the kernel density estimate of age at death in months (density, right y-axis). Deaths that occurred in the community are shown in purple, while deaths that occurred in the hospital are shown in green. B, Histogram and density plot of age at RSV-related death for children under 12 months who died in the community compared with in-hospital in L(M)ICs and UMICs. The histogram shows number of deaths shared (count, left y-axis) to the registry by age at death from age 0 up to 12 months for the 12m cohort. Lines show the kernel density estimate of age at death in months (density, right y-axis). Deaths that occurred in the community are shown in purple, while deaths that occurred in the hospital are shown in green. Abbreviations: L(M)ICs, lower income and lower middle income country; RSV, respiratory syncytial virus; UMIC, upper-middle-income country.