Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infections (bronchiolitis and pneumonia) in infants and young children worldwide.[1,2] RSV is also the leading cause of hospitalisations in infants.[3] RSV accounts for up to 80% of all hospitalisations for bronchiolitis in infants younger than 1 year at the peak of the viral season, and is the predominant cause of viral pneumonia requiring hospital admission in children younger than 5 years of age.[4,5] Most hospitalisations occur in infants with no underlying conditions and born at term.[6,7] The burden of disease from RSV is disproportionately high in developing countries: more than 90% of RSV-associated respiratory tract infections and 99% of RSV-related childhood mortality occur in these settings.[2] RSV is also the most significant cause of LRTI-related death in first year of life in developing countries.[1,2] Ms Mwanajuma Ngama, clinical officer in Kilifi, Kenya, and Dr Simon Drysdale, paediatric infectious diseases consultant in London, England, shared their knowledge and experiences on the differences in RSV care between high and low-middle income countries.
Availability of ICU beds
In contrast to England and the rest of Europe, paediatric intensive care units (PICUs) are scarce in low- and middle- income countries. Across Kenya, a country comprising an area of 580,367 square kilometres, there are only 10 public hospitals with a PICU. Ms Ngama told us: ‘Our hospital in Kilifi, Kenya, doesn’t have a PICU. Children who are in urgent need for oxygen supplementation are admitted to our high dependency unit, where we can offer high flow oxygen. The nearest hospital with a PICU is a one-hour drive away. To be able to transfer a child to the PICU, we have to make sure that there is a PICU bed available, and that the child is stable enough to be transported. Often, we prefer to keep the child at our hospital.’ Dr Drysdale said: ‘In hospitals in the UK that don’t have a PICU, babies with RSV often have to be transferred to another hospital with a PICU. Fortunately, in the UK there is a well-established network for this. Occasionally, in severe RSV seasons, PICUs have to create additional beds to cope with the increased demand or babies have to be transferred from hospitals with PICUs that are full to those with free beds. I have, thankfully, never experienced a complete lack of PICU beds as may happen in some developing countries.’
Treatment and prevention
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urrently there is no cure or protection from RSV for all infants. Pre-term and children with co-morbidities (like chronic lung disease and congenital heart disease) who are at high individual risk for RSV disease are recommended Palivizumab to prevent severe disease, but this requires monthly injections and is highly restricted to these populations. This immunisation is widely used in high income countries, and its use is much less or even completely non-existent in low- and middle-income countries. Ms Ngama said: ‘Unfortunately, Palivizumab is very expensive. Because many parents can’t afford it, it is not being offered at our hospital.’ But the differences are not only confined to prophylaxis: ‘A lot of children who were admitted to the hospital because of RSV will have complaints of wheezing for many years afterwards’, Dr Drysdale told us. ‘While children in the UK have wide access to follow-up, this is significantly reduced in low-income countries. Furthermore, the ability to test for RSV in these areas is also limited. While in the hospitals in the UK we often test for RSV when we suspect this diagnosis, doctors in developing countries will have to act on clinical symptoms only instead of obtaining a microbiology confirmed diagnosis.’
Development of preventive options
The WHO acknowledges that new RSV prevention strategies are needed, as current preventative solutions are limited to a few.[8] Currently, there are several candidate immunisations (vaccines and monoclonal antibodies) against RSV in development, which are relatively close to becoming available for widespread use. In January 2021, the WHO chief Tedros Adhanom Ghebreyesus expressed his worries about the inequitable access of low- and middle-inc
ome countries to vaccines against COVID-19.[9] Dr Drysdale: ‘This COVID era reflects the unbalanced global access to new preventive options. This will probably also be the case regarding immunisations against RSV. When an effective RSV immunisation does make it to the market, it will be the Western high-income countries that stake their claim first, despite needing it less. I’m sure any immunisation will eventually also become available in low- and middle-income countries but slower than it probably should. Another important question will be, if an immunisation that is mainly tested in high-income countries will have similar efficacy in low- and middle-income countries.’
Sometimes it is preferable to first launch an immunisation in mature markets, especially when the product is innovative, because of the need for reliable national regulatory authorities (stringent regulatory authorities, a concept developed by the WHO) and robust post-marketing evaluation programs. Furthermore, it is important to realise that licensing of new immunisations in low- and middle-income countries can take a lot of time because of regulatory hurdles and long evaluation timelines, and it is difficult to license an immunisation in a worldwide manner at the same time.
GAVI was created to improve access to new and under-used immunisations for millions of vulnerable children in low- and middle-income countries and undoubtedly will help provide them with any licensed and available RSV immunisation.[10] Although it is uncertain when we can expect an immunisation against RSV for all infants to become available, we hope that when it does, it will become globally available, because all infants and children’s lives have equal value.
Corline Parmentier, Sanne Truijen
On behalf of the RSV Patient Network
References
1: Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380: 2095-2128
2: Shi T, McAllister DA, O’Brien KL, Simoes EAF, Madhi SA, Gessner BD, et al. 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. Lancet. 2017 Sep 2;390(10098):946-958.
3: Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr. 2003 Nov;143(5 Suppl):S127-32.
4: Meissner HC. Viral Bronchiolitis in Children. N Engl J Med. 2016 Jan 7;374(1):62-72.
5: Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010 May 1;375(9725):1545-55.
6: Arriola CS, Kim L, Langley G, Anderson EJ, Openo K, Martin AM, et al. Estimated Burden of Community-Onset Respiratory Syncytial Virus-Associated Hospitalizations Among Children Aged <2 Years in the United States, 2014-15. J Pediatric Infect Dis Soc. 2020 Nov 10;9(5):587-595.
7: Rha B, Curns AT, Lively JY, Campbell AP, Englund JA, Boom JA, et al. Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015-2016. Pediatrics. 2020;146(1):e20193611
8: World Health Organization. Preferred product Characteristics for Respiratory Syncitial Virus (RSV) Vaccines. 2017
9: BBC News: Covid vaccine: WHO warns of ‘catastrophic moral failure’. [internet] Available from: https://www.bbc.com/news/world-55709428 [Accessed 2nd February 2021].
10: Gavi: the Vaccine Alliance. https://www.gavi.org/
Early career researchers involved in RESCEU were given the opportunity to present the progress that has been made in their respective work packages. Ting Shi and You Li (both research fellows at the Usher Institute, University of Edinburgh) presented a systematic literature review on RSV and the current estimates of burden of disease; Deniz Öner (Jannsen Pharmaceutica), Joseph McGinley and Gu-Lung Lin (University of Oxford ) disclosed their findings on presumed risk factors and biomarkers for RSV-related severe disease and related sequelae. As for Xiao Li (University of Antwerp), she focused on retrospective resource use analyses from existing databases and networks whilst Joanne Wildenbeest (University Medical Center Utrecht) offered a presentation on prospective data collection. In fact, assembling existing RSV data to inform policy‐making and regulatory decisions is one of RESCEU’s main objectives.
