Background
Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in young children. Previously, we estimated that 33.1 million episodes of RSV-associated acute lower respiratory tract infection occurred in children aged 0 to 60 months in 2015, resulting in a total of 118,200 deaths worldwide. Since then, several community surveillance studies have been conducted to obtain a more accurate estimate of RSV-associated community deaths.
Our objective was to update morbidity and mortality from RSV-associated acute lower respiratory tract infections at global, regional and national levels in children 0 to 60 months of age for 2019, focusing on overall mortality and older age groups. of infants targeted by RSV prophylactics in development.
Methods
In this systematic analysis, we expand our RSV global disease burden dataset by obtaining new data from an updated search for articles published between January 1, 2017 and December 31, 2020, from MEDLINE, Embase, Global Health , CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang and ChongqingVIP. We also included unpublished data from VSR GEN collaborators.
Eligible studies reported data for children aged 0 to 60 months with RSV as a primary infection with acute lower respiratory tract infection in community settings, or acute lower respiratory tract infection requiring hospital admission; data reported for at least 12 consecutive months, except for hospital case fatality rate (CFR) or when RSV seasonality is well defined; and the reported incidence rate, hospital admission rate, proportion of RSV positive in hospital admission for acute lower respiratory tract infection or in-hospital CFR.
Studies were excluded if the case definition was not clearly defined or consistently applied, if RSV infection was not laboratory confirmed or based solely on serology, or if the report included fewer than 50 cases of Acute lower respiratory tract infection.
We applied a generalized linear mixed-effects model (GLMM) to estimate the incidence of RSV-associated acute lower respiratory tract infection, hospital admissions, and in-hospital mortality both globally and regionally (by state). of the country’s development and by World Bank income classification) in 2019.
We estimated the incidence of RSV-associated acute lower respiratory tract infection at the country level through a risk factor-based model. We developed new models (via GLMM) that incorporated the latest RSV community mortality data to estimate overall RSV mortality. This review was registered in PROSPERO (CRD42021252400).
Results
In addition to the 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies.
We estimate that globally in 2019, there were 33.0 million episodes of acute lower respiratory tract infection associated with RSV (uncertainty range [UR] 25.4–44.6 million), 3.6 million admissions hospital deaths from RSV-associated acute lower respiratory tract infection (2·9–4·6 million), 26,300 hospital deaths from RSV-associated acute lower respiratory tract infections (15,100–49,100), and 101,400 total deaths attributable to RSV (84,500–125,200) in children 0–60 months.
In infants aged 0 to 6 months, we estimate that there were 6.6 million episodes of RSV-associated acute lower respiratory tract infection (4.6 to 9.7 million), 1.4 million hospital admissions for acute respiratory tract infection, RSV-associated lower respiratory tract infection (1.0–2.0 million), 13,300 in-hospital deaths from RSV-associated acute lower respiratory tract infection (6,800–28,100), and 45,700 RSV-attributable deaths total deaths (38,400 –55 900). 2·0% of deaths in children 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children 28 days to 6 months (3·0–4·4 ) were attributable to VSR.
More than 95% of RSV-associated acute lower respiratory tract infection episodes and more than 97% of RSV-attributable deaths across all age ranges occurred in low- and middle-income countries (LMICs). 2·0% of deaths in children 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children 28 days to 6 months (3·0–4·4 ) were attributable to VSR.
Interpretation
RSV contributes substantially to the global burden of morbidity and mortality in children 0–60 months of age, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in 50 deaths in children aged 0 to 60 months and one in 28 deaths in children aged 28 days to 6 months attributable to RSV.
For every hospital death from RSV-associated acute lower respiratory tract infection, we estimated approximately three more RSV-attributable deaths in the community.
Passive immunization programs against RSV that focus on protection during the first 6 months of life could have a substantial effect on reducing the burden of RSV disease, although more data are needed to understand the implications of potential age changes in VRS peak load to an older age when implemented.
Money
EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
Comments
Acute lower respiratory tract infection caused by respiratory syncytial virus (RSV) contributes substantially to the global mortality burden in children, with RSV estimated to cause one in 50 deaths among children under five years of age and one in 28 deaths among children under six months.
More than 100,000 deaths in children under five years of age were attributable to RSV in 2019, and almost half of these (more than 45,000) occurred in children under six months of age. VSR is responsible for approximately 3.6 million hospital admissions each year.
97% of childhood deaths caused by RSV occurred in low- and middle-income countries. The authors say these findings highlight the urgent need to develop effective RSV vaccines and strategies that prioritize the most vulnerable groups, such as children under six months of age through passive immunization (i.e., vaccination during pregnancy )
A new study published in The Lancet estimates that acute lower respiratory tract infection attributable to RSV was responsible for more than 100,000 deaths in children under five years of age worldwide in 2019. There were more than 45,000 deaths in infants under six months in 2019, and one in five of the world’s total RSV cases occurred in this age group.
“RSV is the predominant cause of acute lower respiratory tract infection in young children and our updated estimates reveal that children six months and younger are particularly vulnerable, especially with cases increasing as COVID-19 restrictions ease. are relaxing around the world and most young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity to this virus).
With numerous RSV vaccine candidates in the pipeline, our estimates by narrower age ranges help identify groups that should be prioritized, including pregnant people, so that children in younger age groups can be similarly protected. to current strategies that offer vaccines for whooping cough, typhoid and tetanus in pregnant women,” says Harish Nair, co-author of the paper, University of Edinburgh, UK.
The findings of this new study are broadly consistent with previous estimates from a 2015 study, which put the number of annual RSV cases in children up to five years old at 33.1 million, resulting in a total of 118,200. deaths in general.
However, these updated estimates of global, regional, and national RSV mortality for 2019 include modeling data from more than 100 new studies, allowing researchers to provide estimates for smaller age groups, including 28 days to six months of age, which is known to be the age range with the highest RSV mortality rate and community mortality rates (i.e., deaths that did not occur in a hospital).
Worldwide in 2019, there were 33 million episodes of acute lower respiratory tract infection associated with RSV in children under five years of age, resulting in 3.6 million hospital admissions, 26,300 hospital deaths and 101,400 deaths attributable to RSV in general (including deaths in the community). This represents one in 50, or 2%, of annual deaths from any cause in this age range.
For children under six months, there were 6.6 million episodes of RSV-associated acute lower respiratory tract infections worldwide in 2019. There were 1.4 million hospital admissions, 13,300 hospital deaths, and 45,700 deaths. generally attributable to RSV in this age range, representing one in 50, or 2.1%, of annual deaths from any cause.
Based on estimates of in-hospital versus overall RSV mortality rates, globally only 26%, or approximately one in four RSV-associated deaths, occur in a hospital. This is particularly evident in low- and middle-income countries, where the hospital mortality rate for children under five is 1.4%, compared to 0.1% in high-income countries. Overall, 97% of RSV deaths in children under five years of age occurred in low- and middle-income countries.
Our study estimates that three-quarters of RSV deaths occur outside of a hospital setting. This gap is even greater in LMICs, especially in children under six months of age, where more than 80% of deaths occur in the community. This reflects the fact that access and availability of hospital care is still limited in these regions.
“Early identification of cases in the community and referral for hospital admission of sick children (particularly those with low peripheral blood oxygen saturation) and effective and affordable universal immunization programs will be vital in the future,” he says. Xin Wang, co-author of the study. study, Nanjing Medical University, China and University of Edinburgh, United Kingdom.
The authors acknowledge some limitations with this study. Variations in factors such as study setting, exact case definition for acute lower respiratory tract infection (ARRI), healthcare access and seeking behavior, and eligibility for RSV testing could affect the estimates of the mortality figures produced in the model. The breakdown by age bracket was also limited by the data available for the study. Additionally, all data were collected before the COVID-19 pandemic; It is unknown how the COVID-19 pandemic might affect the long-term burden of RSV disease.
Writing in a linked comment, Tina Hartert of Vanderbilt Medical School, US, who was not involved in the research, said: “The influence of these data cannot be underestimated. There is a substantial burden of ALRI RSV during the neonatal period in low- and middle-income countries, highlighting the potential for passive immunization strategies to significantly impact child health... Policymakers will compare the benefits of RSV prevention with other priority public health interventions. “Accurate estimates of the impact of prevention are critical to demonstrating the investment case for RSV prevention.”
Implications of all available evidence
By incorporating the latest RSV community mortality data, we provide robust estimates of the global and regional burden of RSV-related mortality. Our findings, together with other existing estimates of RSV disease burden, provide a comprehensive overview of the burden of RSV morbidity and mortality in infants and young children.
With many RSV prophylactic products in development, our narrower age range estimates provide important baseline information for the introduction, prioritization, and evaluation of these products. More evidence is warranted to understand the implications of potential age changes in peak RSV burden at an older age following administration of RSV prophylactics to infants younger than 6 months.
