RESCEU’s RSV Global Disease Burden study reveals substantial RSV community morbidity and mortality burden in young children in low- and middle-income countries

RESCEU scientists publish latest global disease burden estimates of RSV in The Lancet revealing substantial RSV community morbidity and mortality burden in young children in low- and middle-income countries (LMICs).

Some of the most relevant findings are:

    • Globally, 33 million episodes of RSV acute lower respiratory infection (including pneumonia and bronchiolitis) occur annually, with 95% of episodes occurring in LMICs.
    • Annually, for every 1,000 young children, 52 episodes of RSV acute lower respiratory infection can be found in LMICs compared to 24 episodes in high-income countries. However, a smaller proportion of young children could reach hospitals for RSV illnesses in LMICs than in high-income countries.
    • Globally, RSV is responsible for 101,000 deaths in young children, with more than 99% from LMICs.
    • For every one RSV death in hospitals, there are three more RSV deaths in the community.
    • Children younger than six months are most prone to RSV related morbidity and mortality, accounting for 20% of RSV acute lower respiratory infection episodes and 46% of RSV deaths in children under five years.

“RSV immunisation programmes targeting protection in infants younger than six months are likely to be impactful, especially in LMICs that have substantial RSV disease burden in the community. Children in LMICs who had limited access to care could only be protected from RSV severe outcomes through the implementation of RSV immunisation programmes.”, says Prof. You Li from Nanjing Medical University, the leading author of paper.

Acces the full publication here.

Read BBC World’s report here

RSV Patient Advisory Board publishes paper about patient involvement in RSV Research

RSV is a major cause of morbidity and mortality among young children, and also causes a substantial disease burden among elderly and high-risk adults. Involving patients in scientific research on RSV is of great importance to improve its quality and relevance. The RSV Patient Advisory Board (PAB) has drawn attention for more patient participation in research in a scientific publication in “The Journal of Infectious Diseases”.

The article is written by Nicole Derksen-Lazet (former chair of the PAB) and Corline Parmentier (member of the PAB support team) in collaboration with pediatric infectious diseases specialists dr. Joanne Wildenbeest and prof. dr. Louis Bont. The story of the RSV PAB, which was established in 2013 as a local advisory group in Utrecht (the Netherlands) and officially became part of the governance structure of RESCEU in 2016, demonstrates the additional values, success factors, and barriers to involve patients in scientific research.

Involvement of the PAB in RSV research has resulted in the establishment of an independent and credible advisory group for researchers, and many activities to improve RSV awareness among professionals and the general public. Nevertheless, there is still room for improvement: patients and their representatives are increasingly reshaping the research agenda, but medical and scientific experts are still the ones who set it. Patients and their representatives are important stakeholders in research, and their involvement should become the rule instead of the exception – as concluded by the authors.

Read the full article here.

BronchStart study will help predict RSV epidemics

Non-pharmaceutical interventions to slow or eliminate the spread of COVID-19 have had dramatic consequences on the transmission of other respiratory viruses, in particular Respiratory Syncytial Virus (RSV) in children. Now, the BronchStart surveillance study funded by RESCEU, will contribute to identify and interpret the impact of delayed bronchiolitis epidemic in the UK and Ireland. The study is being led by UEDIN.

The BronchStart project is a surveillance platform study run by the PERUKI network (Paediatric Emergency Research UK and Ireland) across paediatric emergency departments throughout the UK. PERUKI provides an ability to access a wide network of paediatric emergency medicine doctors (current almost 50 UK sites for BronchStart) who actively support studies and data entry. This capability has enabled BronchStart through PERUKI to commence surveillance activities at speed and low cost.

This is of extremely relevance, as the impact of non-pharmaceutical interventions for COVID-19 has disrupted RSV transmission, and with it, our ability to predict timing of RSV epidemics. BronchStart using a RedCAP database to gather live information from emergency departments is now able to deliver information on RSV case frequency and distribution in populations across the UK. Importantly BronchStart can also provide information on age distribution of cases (as lack of seasonality may enhance susceptability for particular age groups) and disease severity. These functions are reported live (through the microreact website) and can alert clinicians to anticipate changes in workload and prepare for out of season RSV surges. To date over 11000 children have been recruited. We are also now engaging with sites through BronchStart to interrogate genomic aspects of RSV spread and severity, adding another layer of information to our understanding of RSV disease.

The PERUKI network is long established. RESCEU funding has enabled us to demonstrate the value of BronchStart and we are actively capitalising on that value to seek funding to continue these activities beyond September.

By Steve Cunningham, Professor Paediatric Respiratory Medicine at University of Edinburgh and Damian Roland, Honorary Professor of Paediatric Emergency Medicine, at Leicester University.


BronchStart  study is sponsored by University Hospitals of Leicester NHS Trust.

RSV care in Europe versus low- and middle-income countries

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
Currently 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-income 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/

Europe’s project RESCEU sheds new light on the fight against the Respiratory Syncytial Virus and its economic impact

RESCEU scientists publish supplement in Journal of Infectious Diseases revealing impact of RSV, the most common cause of severe respiratory illness in infants and children worldwide.

• Globally, an estimated 33 million young children are diagnosed with RSV each year, over 3 million cases require hospitalisation. Annually, the virus causes 118,000 deaths.
• RSV costs governments around the world nearly 5 billion euros every year. Two potential vaccines and a monoclonal antibody to protect against this virus are in Phase III of the clinical studies.
• The RSV Patient Network organises RSV Awareness Week from 9th – 14th November to educate the public, especially young parents, of RSV symptoms and associated risks such as wheezing and asthma.

Since 2017, a multidisciplinary team of researchers, national and international public health experts, policymakers, pharmaceutical industry and community representatives have been partnering under the umbrella of the Respiratory Syncytial Virus Consortium in Europe (RESCEU) to shed new light into RSV – its epidemiological aspects, diagnostic biomarkers and economic impact — to inform future public health strategies. Scientists involved in this project, funded by the Innovative Medicines Initiative(IMI), have produced a considerable number of scientific publications, compiled now in a supplement published in the Journal of Infectious Diseases.

RESCEU Press Release 201105

The Patient Advisory Board takes a great leap forward in raising awareness about RSV

A key aspect to prevent the infection caused by RSV (Respiratory Syncytial Virus) and its sequels amongst young babies is making parents more aware of its existence. This last year, RESCEU’s Patient Advisory Board (PAB) has made a great leap forward by designing and implementing a plan aimed at promoting awareness about this common and contagious virus which can become life-threatening for young infants and children and older adults.
Nicole Derksen, chair of the PAB, shared during RESCEU’s 4th the progress made by her team. Comprehensive and lay content has been created for the RSV Patient Network web section. This site is a first port of call, where parents can learn some important facts about RSV, read personal stories and get to know the professionals’ perspectives and their work to prevent infections caused by this virus. The launch of this website coincided with RSV Awareness Week which took place between the 5th and 9th of November last year and reached over 50,000 people. A video with the testimonial of Jade, who lost a baby to RSV kicked off this campaign and was viewed over 25,000 times as Nicole Derksen explained during her intervention.
The RSV Patient Network has also reinforced its presence in social media and regularly shares news and interesting updates in TwitterFacebookLinkedIn and Instagram @RSVPatientNetwork.
Besides raising awareness, the PAB also supports the RESCEU project by bringing in patients’ feedback and input and by disseminating results to the general public.

ISAG encourages RESCEU to export its framework to fight vaccine preventable diseases such as COVID-19

The International Scientific Advisory Group (ISAGs) played a primary role, at RESCEU 4th GAM. Precisely, one of the main responsibilities of this body of experts on scientific and technical matters relevant to the project is to provide advice to the General Assembly and the Steering Committee and support their decision making.

In this year’s General Assembly Meeting, the ISAG was represented by its Chair,  Larry Anderson (Emory University), Mark A. Miller (National Institutes of Health) and  Pasi Penttinen (European Centre for Disease Prevention and Control – ECDC). After attending all presentations and scientific debates that took place in the two-half day sessions, they offered their feedback on the annual progress made by the different work packages.

Besides commending the project’s leadership and its substantial achievements in an exceptional context, they referred to the new scenario created by the COVID-19 emergency. From their point of view, RESCEU is a shiny example of what can be done to address other vaccine preventable diseases, including COVID-19. In this sense, they considered that RESCEU’s activities have set the standard in terms of generating the data and literature review that is relevant mainly for the National Immunisation Technical Advisory Groups (NITAGs). In fact, NITAGs were identified as a key audience for the RESCEU project.

They also encouraged the RESCEU Consortium to face the next scientific challenges formulated by the project itself, explore ways to collaborate and share data with other groups and, finally contribute to find a response in COVID-19 related studies.

Harish Naïr, RESCEU project coordinator, confirmed that the Consortium plans to collaborate with ECDC and NIGA going forward. “We will work together with policy makers to shape the agenda for the introduction of RSV immunization and raise awareness about this disease” he stated.

Early career researchers take the floor at RESCEU’s virtual 4th GAM

RSV research has a bright future judging by the good work and implication shown by the early career researchers during RESCEU’s virtual 4th General Assembly Meeting (GAM). Indeed, this year’s edition wanted to bring into focus the contribution young scientists are making to the project which intends to build knowledge on RSV for the future development of effective RSV preventative options and therapeutics.

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.

“I was very pleased to present the updates for our WP” explained Xiao Li. “It also helped me to co-ordinate and communicate more with our WP and other WPs” she added. For Gu-Lung Lin this first virtual meeting was a success. “It gave us the chance to receive updates from each WP in the RESCEU consortium during the coronavirus pandemic”.
In this sense, Joseph McGinley also highlighted the fact that RESCEU virtual GAM “showed that science need not be constrained by the pandemic”. For McGinley, the event proved how the RESCEU consortium continues to push the boundaries of its understanding of RSV disease.
In similar terms summarized Ting Shi her experience: “The RESCEU virtual meeting provided the most updated and comprehensive research on RSV disease. It was a huge success, especially under the challenge of COVID-19 pandemic”.Although the meeting was initially planned to take place face to face in Edinburgh, it was moved online once the pandemic broke out. This new format did not prevent knowledge sharing and science debate. “Although it was a virtual meeting, I felt very engaged and the synergy was very positive” observed Li.

RESCEU’s GAM goes virtual to continue fostering scientific debate around RSV

RESCEU celebrated its 4th General Assembly Meeting last 17th and 18th of June in exceptional circumstances due to COVID-19.  

The plans to congregate RESCEU’s Consortium members in the historical city of Edinburg to celebrate the 4th General Assembly Meeting (GAM) in a three-day event were cut short by COVID-19. Given this year’s challenging circumstances, knowledge sharing, and scientific debate were taken online. Nearly 90 participants gathered virtually to assess the achievements made so far by the project, discuss key topics, and set the agenda for the upcoming months.

The sessions were hosted and moderated by Harish Nair (Usher Institute, University of Edinburgh) and Clarisse Demont (Sanofi Pasteur), coordinator and project leader respectively of the RESCEU project, who repeatedly gave the floor to early careers researchers. Indeed, young scientists had a prominent role during the two half-day online event celebrated on 17th and 18th of June. Ting Shi and You Li (both research fellows at the Usher Institute, University of Edinburgh), Deniz Öner (Jannsen Pharmaceutica), Joseph McGinley and Gu-Lung Lin (University of Oxford), Xiao Li (University of Antwerp), and Joanne Wildenbeest (University Medical Center Utrecht) presented the results of their respective work packages which focus largely in assembling existing RSV data with a view to inform policy‐making and regulatory decisions within the European Union.

Harry Campbell and You Li (from the Usher Institute, University of Edinburgh) together with Anne Tierlinck (National Institute for Public Health and the Environment in the Netherlands) shared their progress on consolidation of health care systems data which will eventually support widespread cooperation, data sharing and surveillance across Europe.

 

With regards to the development of effective RSV prevention and treatment, Michael Abram (AstraZeneca) referred to the promising results obtained from a primary analysis of the phase 2b study of nirsevimab (MEDI8897). This immunization to prevent RSV is being developed by AstraZeneca in collaboration with Sanofi Pasteur.

The GAM also addressed other topics such as the impact of COVID-19 in RSV research and reviewed the important task carried out by the Patient Advisory Board this last year. As exposed by Nicole Derksen (PAB Coordinator at RESCEU), a substantial effort has been put into raising awareness about RSV, disseminating lay summaries of publications, and incorporating patients’ views to the project and vaccine trial developments.

Experts of the International Scientific Advisory Group (ISAG) also attended this virtual GAM. Larry Anderson (Emory University), Mark Miller (National Institutes of Health) and Pasi Penttinen (European Centre for Disease Prevention and Control) agreed on the outstanding progress made by the project in this challenging times and referred to the impact of COVID-19 in respiratory virus surveillance in Europe.

Clarisse Demont and Harish Nair closed the meeting by thanking all participants and members of the Consortium for their contribution and commitment to the fight to prevent RSV.

Get to Know the RESCEU Team! This month we talk to Joanne Wildenbeest from UMCU

 

Joanne Wildenbeest is a paediatric infectious diseases specialist at the Wilhelmina Children’s Hospital, University Medical Center Utrecht.

Tell us about your professional career.
I am a paediatric infectious diseases specialist and researcher at the Wilhelmina Children’s Hospital, University Medical Center Utrecht. I studied medicine at Ghent University in Belgium. After graduating I started my training in Paediatrics at the Academic Medical Center Amsterdam and specialized in Paediatric Infectious Diseases while obtaining my PhD, which was about viral infections in neonates and infants. Meanwhile I developed a special interest in vaccinology and worked as specialist advisor for vaccinations in children at the Centre for Infectious Disease Control, National Institute for Public Health and the Environment, in the Netherlands. In 2016 I started to work at the Wilhelmina Children’s Hospital, combining my work as clinician with the RESCEU project.
Can you please explain a bit about your role at UMCU as part of the RESCEU project?

Together with Louis Bont I am leading the clinical cohort studies of Work-Package (WP) 4.  The primary objective of the cohort studies is to determine the burden of RSV disease in healthy infants (the birth cohort study), community dwelling older adults (the older adults cohort study) and COPD patients (COPD cohort study). I have been  involved in the development of the study protocols, including the questionnaires and the sample collection plan for which we have worked closely together with WP 3 and WP 5. The clinical studies started in 2017. During the conduct of the studies regular teleconferences were held with the participating centers of each study to discuss recruitment and study progress and any issues that might arise. The older adults study has been finished and results will be published in the coming months. The birth cohort study and the COPD study are still ongoing. I am also the local principal investigator of the infant case-control study. I co-supervise 3 PhD students who are working on the RESCEU project.

How do you foresee the future of RSV infection after RESCEU project?

I expect that in the coming years an effective vaccine or treatment against RSV will become available. With the results of the RESCEU study we will be able to provide key information about the burden of RSV disease in healthy infants, older adults and COPD patients in Europe. This information will be important for regulators, governments and other stakeholders responsible for policy decisions regarding the implementation of new vaccines and therapeutics. RESCEU will also provide information about health care utilization and costs and societal impact. Results from the biomarker studies might aid the understanding of the mechanism for severe disease and long-term sequelae. I also hope that in the near future RSV related mortality and morbidity will be substantially diminished because of effective vaccination strategies, not only in developed countries, but also in developing countries.