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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 Publisher Pubmed



Li Y1, 2 ; Wang X1, 2 ; Blau DM3 ; Caballero MT4, 5 ; Feikin DR6 ; Gill CJ7 ; Madhi SA8, 9 ; Omer SB11 ; Simoes EAF12, 13 ; Campbell H2 ; Pariente AB2 ; Bardach D14 ; Bassat Q15, 16, 17 ; Casalegno JS18 Show All Authors
Authors
  1. Li Y1, 2
  2. Wang X1, 2
  3. Blau DM3
  4. Caballero MT4, 5
  5. Feikin DR6
  6. Gill CJ7
  7. Madhi SA8, 9
  8. Omer SB11
  9. Simoes EAF12, 13
  10. Campbell H2
  11. Pariente AB2
  12. Bardach D14
  13. Bassat Q15, 16, 17
  14. Casalegno JS18
  15. Chakhunashvili G19
  16. Crawford N20, 21, 22
  17. Danilenko D24
  18. Do LAH21, 22
  19. Echavarria M25
  20. Gentile A26
  21. Gordon A27
  22. Heikkinen T28
  23. Huang QS29
  24. Jullien S15, 30
  25. Krishnan A31
  26. Lopez EL32
  27. Markic J33, 34
  28. Miraiglesias A35
  29. Moore HC36
  30. Moyes J37
  31. Mwananyanda L7
  32. Nokes DJ38, 39
  33. Noordeen F40
  34. Obodai E41
  35. Palani N42
  36. Romero C43
  37. Salimi V44
  38. Satav A45
  39. Seo E46
  40. Shchomak Z47
  41. Singleton R48
  42. Stolyarov K24
  43. Stoszek SK49
  44. Von Gottberg A10, 37, 50
  45. Wurzel D21, 23
  46. Yoshida LM51
  47. Yung CF52, 53, 54
  48. Zar HJ55
  49. Nair H2, 56
Show Affiliations
Authors Affiliations
  1. 1. School of Public Health, Nanjing Medical University, Nanjing, China
  2. 2. Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
  3. 3. Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States
  4. 4. Fundacion INFANT, Buenos Aires, Argentina
  5. 5. Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires, Argentina
  6. 6. Department of Immunizations, Vaccines, and Biologicals, WHO, Geneva, Switzerland
  7. 7. Boston University School of Public Health, Department of Global Health, Boston, MA, United States
  8. 8. South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa
  9. 9. African Leadership Initiative in Vaccinology Expertise, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa
  10. 10. School of Pathology, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa
  11. 11. Yale Institute for Global Health, New Haven, CT, United States
  12. 12. Department of Pediatrics, Section of Infectious Diseases, University of Colorado, School of Medicine, Aurora, CO, United States
  13. 13. Department of Epidemiology and Center for Global Health, Colorado School of Public Health, Aurora, CO, United States
  14. 14. National Center for Communicable Diseases (Mongolia), Ulaanbaatar, Mongolia
  15. 15. ISGlobal, Hospital Clinic – Universitat de Barcelona, Barcelona, Spain
  16. 16. Centro de Investigacao em Saude de Manhica, Maputo, Mozambique
  17. 17. Catalan Institution for Research and Advanced Studies, Barcelona, Spain
  18. 18. Hospices Civils de Lyon, Hopital de la Croix-Rousse, Centre de Biologie Nord, Institut des Agents Infectieux, Laboratoire de Virologie, Lyon, France
  19. 19. National Center for Disease Control and Public Health, Tbilisi, Georgia
  20. 20. The Royal Children's Hospital, Melbourne, Australia
  21. 21. Murdoch Children's Research Institute, Melbourne, Australia
  22. 22. Department of Paediatrics, The University of Melbourne, Melbourne, Australia
  23. 23. Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
  24. 24. Smorodintsev Research Institute of Influenza, Saint Petersburg, Russian Federation
  25. 25. Clinical Virology Unit, Centro de Educacion Medica e Investigaciones Clinicas, Buenos Aires, Argentina
  26. 26. Ricardo Gutierrez Children Hospital, Buenos Aires, Argentina
  27. 27. Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States
  28. 28. Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
  29. 29. WHO National Influenza Centre, Institute of Environmental Science and Research, Wellington, New Zealand
  30. 30. Jigme Dorji Wangchuck National Referral Hospital, Gongphel Lam, Thimphu, Bhutan
  31. 31. Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India
  32. 32. Hospital de Ninos Dr. Ricardo Gutierrez, Department of Medicine, Pediatric Infectious Diseases Program, Universidad de Buenos Aires, Buenos Aires, Argentina
  33. 33. Department of Pediatrics, University Hospital Split, Split, Croatia
  34. 34. University of Split, School of Medicine, Split, Croatia
  35. 35. Area de Investigacion en Vacunas, Fundacion para el Fomento de la Investigacion Sanitaria y Biomedica de la Comunitat Valenciana, Salud Publica, Valencia, Spain
  36. 36. Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia
  37. 37. National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa
  38. 38. Kenya Medical Research Institute—Wellcome Trust Research Programme, Kilifi, Kenya
  39. 39. School of Life Sciences, University of Warwick, Coventry, United Kingdom
  40. 40. Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
  41. 41. Virology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana
  42. 42. Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
  43. 43. Vysnova Partners, Lima, Peru
  44. 44. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  45. 45. MAHAN Trust Mahatma Gandhi Tribal Hospital, Karmgram, Utavali, Tahsil, Dharni, India
  46. 46. Department of Pediatrics, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, South Korea
  47. 47. Department of Pediatrics, Hospital Santa Maria, Centro Hospitalar Universitario Lisboa Norte, Lisbon, Portugal
  48. 48. Alaska Native Tribal Health Consortium, Anchorage, AK, United States
  49. 49. GlaxoSmithKline, Rockville, Maryland, United States
  50. 50. Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
  51. 51. Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
  52. 52. Infectious Diseases Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore
  53. 53. Duke-NUS Medical School, Singapore
  54. 54. Lee Kong Chian School of Medicine, Imperial College, Nanyang Technological University, Singapore
  55. 55. Department of Paediatrics and Child Health, and South African Medical Research Council Unit on Child & Adolescent Health, University of Cape Town and Red Cross War Memorial Children's Hospital, Cape Town, South Africa
  56. 56. Respiratory Syncytial Virus Network Foundation, on behalf of the Respiratory Virus Global Epidemiology Network, and the RESCEU investigators, Zeist, Netherlands

Source: The Lancet Published:2022


Abstract

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. This review was registered in PROSPERO (CRD42021252400). 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. Funding: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU). © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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