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,The Lancet

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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
The Lancet ( IF 168.9 ) Pub Date : 2022-05-19 , DOI: 10.1016/s0140-6736(22)00478-0
You Li ₁ , Xin Wang ₁ , Dianna M Blau ₂ , Mauricio T Caballero ₃ , Daniel R Feikin ₄ , Christopher J Gill ₅ , Shabir A Madhi ₆ , Saad B Omer ₇ , Eric A F Simões ₈ , Harry Campbell ₉ , Ana Bermejo Pariente ₉ , Darmaa Bardach ₁₀ , Quique Bassat ₁₁ , Jean-Sebastien Casalegno ₁₂ , Giorgi Chakhunashvili ₁₃ , Nigel Crawford ₁₄ , Daria Danilenko ₁₅ , Lien Anh Ha Do ₁₆ , Marcela Echavarria ₁₇ , Angela Gentile ₁₈ , Aubree Gordon ₁₉ , Terho Heikkinen ₂₀ , Q Sue Huang ₂₁ , Sophie Jullien ₂₂ , Anand Krishnan ₂₃ , Eduardo Luis Lopez ₂₄ , Joško Markić ₂₅ , Ainara Mira-Iglesias ₂₆ , Hannah C Moore ₂₇ , Jocelyn Moyes ₂₈ , Lawrence Mwananyanda ₅ , D James Nokes ₂₉ , Faseeha Noordeen ₃₀ , Evangeline Obodai ₃₁ , Nandhini Palani ₃₂ , Candice Romero ₃₃ , Vahid Salimi ₃₄ , Ashish Satav ₃₅ , Euri Seo ₃₆ , Zakhar Shchomak ₃₇ , Rosalyn Singleton ₃₈ , Kirill Stolyarov ₁₅ , Sonia K Stoszek ₃₉ , Anne von Gottberg ₄₀ , Danielle Wurzel ₄₁ , Lay-Myint Yoshida ₄₂ , Chee Fu Yung ₄₃ , Heather J Zar ₄₄ , , Harish Nair ₄₅ ,

Affiliation

School of Public Health, Nanjing Medical University, Nanjing, China; Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Fundacion INFANT, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Department of Immunizations, Vaccines, and Biologicals, WHO, Geneva, Switzerland.
Boston University School of Public Health, Department of Global Health, Boston, Massachusetts, USA.
South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; African Leadership Initiative in Vaccinology Expertise, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa.
Yale Institute for Global Health, New Haven, CT, USA.
Department of Pediatrics, Section of Infectious Diseases, University of Colorado, School of Medicine, Aurora, CO, USA; Department of Epidemiology and Center for Global Health, Colorado School of Public Health, Aurora, CO, USA.
Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
National Center for Communicable Diseases (Mongolia), Ulaanbaatar, Mongolia.
ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain; Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique; Catalan Institution for Research and Advanced Studies, Barcelona, Spain.
Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Centre de Biologie Nord, Institut des Agents Infectieux, Laboratoire de Virologie, Lyon, France.
National Center for Disease Control and Public Health, Tbilisi, Georgia.
The Royal Children's Hospital, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
Smorodintsev Research Institute of Influenza, Saint Petersburg, Russia.
Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
Clinical Virology Unit, Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina.
Ricardo Gutierrez Children Hospital, Buenos Aires, Argentina.
Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
WHO National Influenza Centre, Institute of Environmental Science and Research, Wellington, New Zealand.
ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain; Jigme Dorji Wangchuck National Referral Hospital, Gongphel Lam, Thimphu, Bhutan.
Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India.
Hospital de Niños Dr. Ricardo Gutiérrez, Department of Medicine, Pediatric Infectious Diseases Program, Universidad de Buenos Aires, Buenos Aires, Argentina.
Department of Pediatrics, University Hospital Split, Split, Croatia; University of Split, School of Medicine, Split, Croatia.
Área de Investigación en Vacunas, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Salud Pública, Valencia, Spain.
Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia.
National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya; School of Life Sciences, University of Warwick, Coventry, UK.
Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
Virology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana.
Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India.
Vysnova Partners, Lima, Perú.
Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
MAHAN Trust Mahatma Gandhi Tribal Hospital, Karmgram, Utavali, Tahsil, Dharni, India.
Department of Pediatrics, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, South Korea.
Department of Pediatrics, Hospital Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
Alaska Native Tribal Health Consortium, Anchorage, AK, USA.
GlaxoSmithKline, Rockville, Maryland, USA.
School of Pathology, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Murdoch Children's Research Institute, Melbourne, Australia; Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Infectious Diseases Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Duke-NUS Medical School, Singapore; Lee Kong Chian School of Medicine, Imperial College, Nanyang Technological University, Singapore.
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.
Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK; Respiratory Syncytial Virus Network Foundation, Zeist, Netherlands, on behalf of the Respiratory Virus Global Epidemiology Network, and the RESCEU investigators.

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).

中文翻译：

2019 年 5 岁以下儿童呼吸道合胞病毒引起的急性下呼吸道感染的全球、区域和国家疾病负担估计：一项系统分析

背景

呼吸道合胞病毒 (RSV) 是幼儿急性下呼吸道感染的最常见原因。我们之前估计，2015 年，0-60 个月大的儿童中发生了 33·100 万例 RSV 相关急性下呼吸道感染，导致全球共有 118200 人死亡。从那时起，已经进行了几项社区监测研究，以获得对 RSV 相关社区死亡的更精确估计。我们旨在更新 2019 年全球、区域和国家层面 0-60 个月儿童的 RSV 相关急性下呼吸道感染发病率和死亡率，重点关注总体死亡率和 RSV 预防药物开发中针对的更窄的婴儿年龄组.

方法

在这项系统分析中，我们通过更新搜索 2017 年 1 月 1 日至 2020 年 12 月 31 日期间发表的论文的新数据来扩展我们的全球 RSV 疾病负担数据集，这些论文来自 MEDLINE、Embase、Global Health、CINAHL、Web of Science、 LILACS、OpenGrey、CNKI、万方和重庆VIP。我们还包括来自 RSV GEN 合作者的未发表数据。符合条件的研究报告了 0-60 个月儿童的数据，这些儿童在社区环境中以 RSV 作为原发性感染并伴有急性下呼吸道感染，或需要住院的急性下呼吸道感染；报告至少连续 12 个月的数据，住院病死率 (CFR) 或 RSV 季节性明确定义的情况除外；以及报告的发病率、住院率、急性下呼吸道感染入院或院内病死率中RSV阳性比例。如果病例定义未明确定义或未始终如一地应用，RSV 感染未得到实验室证实或仅基于血清学，或者报告中包含的急性下呼吸道感染病例少于 50 例，则研究被排除在外。我们应用广义线性混合效应模型 (GLMM) 来估计 2019 年全球和区域（按国家发展状况和世界银行收入分类）的 RSV 相关急性下呼吸道感染发病率、住院率和住院死亡率。我们通过基于风险因素的模型估计了国家级 RSV 相关急性下呼吸道感染的发病率。我们开发了新模型（通过 GLMM），该模型结合了最新的 RSV 群落死亡率数据，用于估计总体 RSV 死亡率。该评论已在 PROSPERO (CRD42021252400) 中注册。

发现

除了我们之前审查中包含的 317 项研究外，我们还确定并纳入了 113 项新的符合条件的研究和来自 51 项研究的未发表数据，总共 481 项研究。我们估计，2019 年全球有 33·0 百万例 RSV 相关急性下呼吸道感染事件（不确定性范围 [UR] 25·4–44·6 百万），3·600 万例 RSV 相关急性下呼吸道感染住院(2·9–4·6 百万), 26 300 例 RSV 相关的急性下呼吸道感染院内死亡 (15 100–49 100), 以及 101 400 例 RSV 引起的总死亡 (84 500–125 200) 岁儿童0-60 个月。在 0-6 个月大的婴儿中，我们估计有 6·6 百万次 RSV 相关的急性下呼吸道感染事件（4·6-9·7 百万），1·400 万例 RSV 相关急性下呼吸道感染住院（1·0-2·0 百万），13300 例 RSV 相关急性下呼吸道感染院内死亡（6800-28100），以及 45700 例 RSV 归因总死亡人数（38 400–55 900）。2·0% 的 0–60 个月大儿童死亡 (UR 1·6–2·4) 和 3·6% 的 28 天至 6 个月大儿童死亡 (3·0–4·4) 归因于呼吸道合胞病毒。在所有年龄段中，超过 95% 的 RSV 相关急性下呼吸道感染事件和超过 97% 的 RSV 可归因死亡发生在低收入和中等收入国家 (LMIC)。2·0% 的 0–60 个月大儿童死亡 (UR 1·6–2·4) 和 3·6% 的 28 天至 6 个月大儿童死亡 (3·0–4·4) 归因于呼吸道合胞病毒。在所有年龄段中，超过 95% 的 RSV 相关急性下呼吸道感染事件和超过 97% 的 RSV 可归因死亡发生在低收入和中等收入国家 (LMIC)。2·0% 的 0–60 个月大儿童死亡 (UR 1·6–2·4) 和 3·6% 的 28 天至 6 个月大儿童死亡 (3·0–4·4) 归因于呼吸道合胞病毒。在所有年龄段中，超过 95% 的 RSV 相关急性下呼吸道感染事件和超过 97% 的 RSV 可归因死亡发生在低收入和中等收入国家 (LMIC)。

解释

RSV 在全球范围内大大增加了 0-60 个月大儿童的发病率和死亡率负担，尤其是在生命的前 6 个月和中低收入国家。我们强调了全球 RSV 疾病的惊人总体死亡率负担，在 0-60 个月大的儿童中，每 50 例死亡中就有 1 例，在 28 天到 6 个月大的儿童中，每 28 例死亡中就有 1 例死于 RSV。对于每例与 RSV 相关的急性下呼吸道感染院内死亡，我们估计社区中约有 3 例死亡归因于 RSV。以生命最初 6 个月期间的保护为目标的 RSV 被动免疫计划可能对减少 RSV 疾病负担产生实质性影响，尽管需要更多数据来了解实施这些计划时 RSV 负担峰值的潜在年龄转移对老年人的影响.