Global Molecular Epidemiology of Respiratory Syncytial Virus from the 2017−2018 INFORM-RSV Study

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Abstract

ABSTRACT

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. INFORM-RSV is a multiyear clinical study designed to describe the global molecular epidemiology of RSV in children under 5 years of age by monitoring temporal and geographical evolution of current circulating RSV strains, F protein antigenic sites, and their relationships with clinical features of RSV disease. During the pilot season (2017–2018), 410 RSV G-F gene sequences were obtained from 476 RSV-positive nasal samples collected from 8 countries (United Kingdom, Spain, The Netherlands, Finland, Japan, Brazil, South Africa, and Australia). RSV B (all BA9 genotype) predominated over RSV A (all ON1 genotype) globally (69.0% versus 31.0%) and in all countries except South Africa. Geographic clustering patterns highlighted wide transmission and continued evolution with viral spread. Most RSV strains were from infants of <1 year of age (81.2%), males (56.3%), and patients hospitalized for >24 h (70.5%), with no differences in subtype distribution. Compared to 2013 reference sequences, variations at F protein antigenic sites were observed for both RSV A and B strains, with high-frequency polymorphisms at antigenic site Ø (I206M/Q209R) and site V (L172Q/S173L/K191R) in RSV B strains. The INFORM-RSV 2017–2018 pilot season establishes an important molecular baseline of RSV strain distribution and sequence variability with which to track the emergence of new strains and provide an early warning system of neutralization escape variants that may impact transmission or the effectiveness of vaccines and MAbs under development.

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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

Ting Shi, David McAllister, Katherine L O'Brien … (2017)

Summary 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.

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Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Harish Nair, D Nokes, Bradford Gessner … (2010)

Summary Background The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. Methods We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Interpretation Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. Funding WHO; Bill & Melinda Gates Foundation.

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The burden of respiratory syncytial virus infection in young children.

Caroline Hall, Geoffrey A Weinberg, Marika K. Iwane … (2009)

The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004. RSV was detected by culture and reverse-transcriptase polymerase chain reaction. Clinical information was obtained from parents and medical records. We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits. Among 5067 children enrolled in the study, 919 (18%) had RSV infections. Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most of the children had no coexisting illnesses. Only prematurity and a young age were independent risk factors for hospitalization. Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments. Outpatients had moderately severe RSV-associated illness, but few of the illnesses (3%) were diagnosed as being caused by RSV. RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection. 2009 Massachusetts Medical Society

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Author and article information

Contributors

Yi-Wei Tang: Role: Editor

Journal

Journal ID (nlm-ta): J Clin Microbiol

Journal ID (iso-abbrev): J Clin Microbiol

Journal ID (hwp): jcm

Journal ID (pmc): jcm

Journal ID (publisher-id): JCM

Title: Journal of Clinical Microbiology

Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )

ISSN (Print): 0095-1137

ISSN (Electronic): 1098-660X

Publication date (Electronic preprint): 21 October 2020

Publication date (Electronic): 17 December 2020

Publication date Collection: January 2021

Volume: 59

Issue: 1

Electronic Location Identifier: e01828-20

Affiliations

(University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands);

(ReSViNET Foundation, Zeist, The Netherlands and King’s College London, London, United Kingdom);

(ReSViNET Foundation, Zeist, The Netherlands and University of Turku and Turku University Hospital, Turku, Finland);

(Pontificia Universidade Catolica de Rio Grande do Sul, Porto Alegre, Brazil);

(The University of Western Australia, Perth, Australia);

(Hospital Clínico Universitario de Santiago, Galicia, Spain);

(ReSViNET Foundation, Zeist, The Netherlands and University of the Witwatersrand, Johannesburg, South Africa);

(Fukushima Medical University School of Medicine, Fukushima, Japan);

(University Hospital Giessen and Marburg, Marburg, Germany);

(Université Paris XII, Créteil, France);

(McGill University Health Centre, Montreal, Canada);

(McMaster University, Hamilton, Canada).

[a ]Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA

[b ]Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, San Francisco, California, USA

[c ]Department of Paediatrics, Division of Paediatric Infectious Diseases, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands

[d ]Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands

[e ]Data Sciences & Artificial Intelligence, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA

[f ]ReSViNET Foundation, Zeist, The Netherlands

[g ]Julius Clinical, Zeist, The Netherlands

Cepheid

Author notes

Address correspondence to Michael E. Abram, Michael.Abram@ 123456astrazeneca.com .

David E. Tabor, Fiona Fernandes, and Annefleur C. Langedijk contributed equally to this work. Author order was determined on the basis of seniority.

Citation Tabor DE, Fernandes F, Langedijk AC, Wilkins D, Lebbink RJ, Tovchigrechko A, Ruzin A, Kragten-Tabatabaie L, Jin H, Esser MT, Bont LJ, Abram ME, the INFORM-RSV Study Group. 2021. Global molecular epidemiology of respiratory syncytial virus from the 2017−2018 INFORM-RSV study. J Clin Microbiol 59:e01828-20. https://doi.org/10.1128/JCM.01828-20.

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Michael E. Abram https://orcid.org/0000-0002-6505-7281

Article

Publisher ID: 01828-20

DOI: 10.1128/JCM.01828-20

PMC ID: 7771447

PubMed ID: 33087438

SO-VID: 2fdcd86c-5ec9-43ab-af28-badba38fa84d

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This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

History

Date received : 14 July 2020

Date revision requested : 22 August 2020

Date accepted : 15 October 2020

Page count

Figures: 4, Tables: 2, Equations: 0, References: 43, Pages: 13, Words: 8172

Funding

Funded by: AstraZeneca (AstraZeneca PLC), https://doi.org/10.13039/100004325;

Award Recipient : Michael E. Abram Award Recipient : Louis Bont Award Recipient : Robert Jan Lebbink Award Recipient : Andrey Tovchigrechko Award Recipient : Fiona Fernandes Award Recipient : David E. Tabor Award Recipient : Annefleur C. Langedijk Award Recipient : Deidre Wilkins Award Recipient : Alexey Ruzin Award Recipient : Leyla Kragten-Tabatabaie Award Recipient : Hong Jin Award Recipient : Mark T. Esser Award Recipient : INFORM-RSV Study Group

Funded by: Sanofi US | Sanofi Pasteur, https://doi.org/10.13039/100014588;

Funded by: Julius Clinical (Julius Clinical B.V.), https://doi.org/10.13039/501100017027;

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cover-date January 2021

ScienceOpen disciplines: Microbiology & Virology

Keywords: evolution,genetic variation,molecular epidemiology,resistance,respiratory syncytial virus,surveillance

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ScienceOpen disciplines: Microbiology & Virology

Keywords: evolution, genetic variation, molecular epidemiology, resistance, respiratory syncytial virus, surveillance

Global Molecular Epidemiology of Respiratory Syncytial Virus from the 2017−2018 INFORM-RSV Study

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Most cited references 40

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

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

The burden of respiratory syncytial virus infection in young children.

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