Recent research has cast the spotlight on a viral disease – the respiratory syncytial virus (RSV) – that is killing more than 100,000 children a year worldwide.
RSV is the most common cause of acute lower respiratory tract infections in infants and children around the globe but the Respiratory Syncytial Virus Consortium in Europe says the burden of disease is disproportionately high in developing countries.
Writing in the Mail & Guardian, Sanjeet Bagcchi reports that the researchers analysed 481 studies and estimated that in 2019, among under-fives, there were 33m RSV-associated acute lower respiratory infection episodes, and 101,400 deaths attributable to RSV. For infants up to the age of six months, the estimated figures were 6.6m and 45 700, respectively.
Lower respiratory infections affect the airways below the larynx, including the trachea and tiny air sacs in the lungs. They include acute bronchitis, bronchiolitis and pneumonia.
Figures published in The Lancet show that more than 95% of incidents of acute lower respiratory infection associated with RSV and more than 97% of deaths attributable to RSV, among children under five, occur in low- and middle-income countries (LMICs).
“RSV is an important cause of death due to lower respiratory tract infections in children, especially infants,” says Anand Krishnan, an author of the study and professor at the Centre for Community Medicine at the New Delhi-based All India Institute of Medical Sciences.
“Yet there is little routine testing for RSV in clinical settings, even in tertiary (specialised health care) facilities, primarily as no specific treatment is available.”
The researchers from countries including India, South Africa, UK and USA point out that RSV plays a significant part in the suffering and death of young children across the world – particularly in the initial six months of life and in the low- and middle-income countries.
Internationally, RSV disease leads to one in every 50 deaths among children under five and one in every 28 deaths among those aged 28 days to six months, they found.
“The disproportionately high RSV burden in the younger age groups in LMICs warrants more extensive community case management and effective and affordable immunisation programmes,” the study suggests.
There is no specific RSV vaccine but the researchers urge the implementation of passive immunisation programmes to combat the disease. Instead of a vaccine, which provides active immunity, in passive immunisation, a person receives antibodies – proteins produced in the body in response to a foreign invader or antigen.
The researchers said passive immunisation programmes to provide protection against RSV in the first six months of life could significantly reduce the burden of RSV. But they say more data around this approach is needed.
They were also surprised to find that hospital admissions in babies aged up to six months were “consistently lower” in low- and middle-income countries than in high-income countries, “reflecting the fact that access and availability to hospital care is still limited in LMICs”, they said.
Experts say RSV cases are likely to increase, as masks and lockdowns have led to a reduction in natural immunity against this and other common viruses.
Development of a vaccine had been slow after an unsuccessful one in the 1960s resulted in lung inflammation during the first natural RSV infection after vaccination, proving fatal in two cases, according to the World Health Organisation.
But new understanding of the virus in recent years has led to multiple vaccine candidates undergoing development, some of which may receive regulatory approval in the near future, the WHO says.
“RSV-targeted interventions are likely to be an important component of infant mortality rate reduction strategies globally, especially for LMICs,” says Krishnan.
“It is important that the manufacturers and global health agencies bear that in mind as they make decisions on access and price of upcoming products.”
As newer biomedical interventions are in the pipeline, he added that it was important for governments to prepare to make appropriate evidence-based decisions for their use.
Sushmita Roy Chowdhury, director of pulmonology at the Fortis Hospital in Kolkata, India, says the study highlights “startling mortality risk from RSV”.
“In LMICs, the burden is likely to be even bigger, due to overcrowding and poverty, hence mandatory passive immunisation plays a major role in the prevention of severe RSV disease,” she said.
Study details
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 Blau, Mauricio Caballero, Daniel Feikin, Christopher Gill, et al.
Published in The Lancet on 19 May 2022
Summary
Background
Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that 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 an updated 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 data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the 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, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality.
Findings
In addition to 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 estimated that globally in 2019, there were 33·0 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-associated acute 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 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory 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 children aged 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 attributable to RSV.
More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-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 RSV disease 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-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented.
Mail & Guardian article – Respiratory virus kills 100 000 children worldwide (Open access)
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