Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study

Abstract

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.

Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.

Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population.

Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.

Funding: The Bill & Melinda Gates Foundation.

Figure 1

Approaches for estimation of global RSV associated morbidity and mortality in children aged 0–4 years In this study, we report four different sets of estimates—number of episodes of (severe) RSV-ALRI at global and national levels, global RSV-ALRI hospital admissions, and global estimates of RSV-ALRI deaths in hospital and overall (in community). This figure summarises our approach for each of these categories and also shows how they relate to (and feed into each other). Global estimates of hospital admissions for RSV-ALRI have been estimated using two independent approaches and datasets (after ensuring all included studies satisfy the common case definition that hospital admission was based on a physician diagnosis of ALRI). Similarly, the in-hospital deaths due to RSV-ALRI are based on studies reporting in-hospital CFR for RSV and RSV-ALRI hospital admissions (again ensuring that all included studies satisfy the common case definition). RSV=respiratory syncytial virus. ALRI=acute lower respiratory infection. hCFR=in-hospital case fatality ratio. VA=verbal autopsy. DHS=demographic and health survey. *For details description of imputation see appendix p 7. †For detailed description of risk-factor based model see appendix pp 54–57.

Figure 2

Flow diagram for selection of studies RSV=respiratory synctical virus. Studies could have contributed data to more than one category.

Figure 3

Location of studies reporting incidence, hospital admission, and in-hospital case fatality in children with RSV-ALRI RSV-ALRI=RSV-associated acute lower respiratory infection.

Figure 4

Global burden of RSV-associated severe ALRI including burden on hospital services RSV=respiratory syncytial virus. ALRI=acute lower respiratory infection. Understanding the contribution of RSV to burden on hospital services and the proportion of “severe” cases not accessing hospital care or deaths outside of hospital is relevant for development of health policies to reduce global (RSV-associated) ALRI mortality. The orange boxes show the estimated number of “severe cases” and overall RSV-related deaths in LMICs that are based on relatively limited data. The green boxes show estimated burden on hospital inpatient services that are based on robust data. The blue boxes reflect the inferred (derived) burden estimates for severe cases and deaths that have no access to hospital care.