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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

      research-article

      , PhD a , , MD b , , Prof, MD c , , Prof, MD d , , Prof, PhD e , f , , MD g , , Prof, MD h , , MPH a , , MD i , * , , MD j , * , , MD k , * , , MD l , * , , Prof, PhD m , * , , Prof, MD n , * , , MBBCh o , * , , MD p , q , * , , MD r , s , * , , PhD e , * , , MD t , , MD u , * , , PhD v , * , w , , Prof, MD i , x , y , * , , MD z , * , , MPH aa , * , , Prof, MD ab , * , , Prof, MD ac , * , , MD c , p , * , , Prof, MD ad , * , , Prof, PhD ae , * , , MS af , * , , PhD ag , ah , * , , MBChB a , * , , MS ai , * , , MD aj , * , , PhD ak , * , , PhD al , * , , MSc am , * , , PhD an , ao , * , , MD ap , * , , Prof, PhD aq , * , , MD ar , * , , PhD c , * , , PhD ae , * , , MD as , * , , MD m , * , , PhD at , * , , RN au , * , , BSc av , * , , MD q , * , , MD aw , * , , Prof, MD ax , * , , PhD ay , * , , MBBS c , p , * , , PhD ag , * , , PhD e , f , * , , MD az , * , , PhD ba , * , , PhD p , bb , * , , PhD m , bc , bd , * , , MD be , * , , MD x , bf , * , , Prof, PhD bg , * , , Prof, MD bh , * , , Prof, MD bi , * , , Prof, MD ad , * , , MD h , az , bj , * , , MD bk , * , , MD bl , * , , MD ax , * , , MD bm , * , , PhD at , * , , ScD be , * , , MD bn , * , , PhD g , * , , PhD bo , * , , FCPaeds e , f , * , , MD x , * , , MBBCh an , ao , * , , PhD o , bp , * , , MD bg , * , , Prof, PhD bq , * , , Prof, PhD o , br , * , , MD bs , * , , MD au , * , , MD bt , * , , MD n , * , , PhD bu , * , , MD bv , * , , DVM bu , * , , PhD p , * , , MD bw , * , , MD by , * , , Prof, PhD by , * , , Prof, MD bz , * , , MD ca , * , , Prof, PhD cb , * , , PhD cc , * , , MSc r , * , , MD ab , * , , PhD cd , * , , Prof, FRCP o , ce , * , , MD cf , * , , Prof, MD cg , * , , MD af , ch , * , , MPH j , * , , Prof, PhD v , ci , * , , MD cj , * , , Prof, MD ck , * , , MD bi , * , , MD r , * , , MPH by , * , , PhD cl , * , , PhD cm , * , , Prof, PhD cn , * , , MSc co , * , , Prof, PhD cp , * , , MSc cm , * , , Prof, MD cq , * , , MD aw , * , , Prof, PhD cr , * , , Prof, MD a , , Prof, PhD a , cs , , * , RSV Global Epidemiology Network

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          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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          Most cited references 35

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          Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015

          Summary Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography–year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4–61·9) in 1980 to 71·8 years (71·5–72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7–17·4), to 62·6 years (56·5–70·2). Total deaths increased by 4·1% (2·6–5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8–18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6–16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9–14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1–44·6), malaria (43·1%, 34·7–51·8), neonatal preterm birth complications (29·8%, 24·8–34·9), and maternal disorders (29·1%, 19·3–37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000–183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000–532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Funding Bill & Melinda Gates Foundation.
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            Meta-analysis in clinical trials.

            This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
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              Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals

              Summary Background Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal (MDG) 4 target of a two-thirds reduction of under-5 mortality rate (U5MR) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000–15 to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival. Methods We increased the estimation input data for causes of deaths by 43% among neonates and 23% among 1–59-month-olds, respectively. We used adequate vital registration (VR) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate VR for low U5MR countries and verbal autopsy data for high U5MR countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of modelled estimates for China; and to consider the effects of pneumococcal conjugate vaccine and rotavirus vaccine in the estimation. Findings In 2015, among the 5·9 million under-5 deaths, 2·7 million occurred in the neonatal period. The leading under-5 causes were preterm birth complications (1·055 million [95% uncertainty range (UR) 0·935–1·179]), pneumonia (0·921 million [0·812 −1·117]), and intrapartum-related events (0·691 million [0·598 −0·778]). In the two MDG regions with the most under-5 deaths, the leading cause was pneumonia in sub-Saharan Africa and preterm birth complications in southern Asia. Reductions in mortality rates for pneumonia, diarrhoea, neonatal intrapartum-related events, malaria, and measles were responsible for 61% of the total reduction of 35 per 1000 livebirths in U5MR in 2000–15. Stratified by U5MR, pneumonia was the leading cause in countries with very high U5MR. Preterm birth complications and pneumonia were both important in high, medium high, and medium child mortality countries; whereas congenital abnormalities was the most important cause in countries with low and very low U5MR. Interpretation In the SDG era, countries are advised to prioritise child survival policy and programmes based on their child cause-of-death composition. Continued and enhanced efforts to scale up proven life-saving interventions are needed to achieve the SDG child survival target. Funding Bill & Melinda Gates Foundation, WHO.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier
                0140-6736
                1474-547X
                02 September 2017
                02 September 2017
                : 390
                : 10098
                : 946-958
                Affiliations
                [a ]Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK
                [b ]Institute of Health and Wellbeing, University of Glasgow, Scotland, UK
                [c ]Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MS, USA
                [d ]University of Colorado, Aurora, CO, USA
                [e ]Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa
                [f ]Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa
                [g ]Agence de Medecine Preventive, Paris, France
                [h ]Fundacion INFANT, Buenos Aires, Argentina
                [i ]Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
                [j ]Epidemiology Department, Ministry of Health, Chile
                [k ]Ministry of Health, Togo
                [l ]Department of Pediatrics and Child Health, Aga Khan University, Pakistan
                [m ]Medical Research Council Unit The Gambia, Basse, The Gambia
                [n ]Department of Pediatrics, King George's Medical University, Lucknow (UP), India
                [o ]Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
                [p ]International Centre for Diarrhoeal Disease Research, Bangladesh
                [q ]Centers for Disease Control and Prevention, Atlanta, GA, USA
                [r ]Global Disease Detection Center, Thailand Ministry of Public Health—US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand
                [s ]Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, GA, USA
                [t ]Ministry of Health, Nicaragua
                [u ]Hospital Materno Infantil Jose Domingo de Obaldia, Ciudad De David, Chiriqui, Panama
                [v ]Center for International Health, University of Bergen, Norway
                [w ]Department of Child Health, Tribhuvan University Institute of Medicine, Nepal
                [x ]ISGlobal, Barcelona Ctr Int Health Res (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
                [y ]ICREA, Pg Lluís Companys 23, 08010 Barcelona, Spain
                [z ]Hospital General Pediátrico Niños de Acosta Ñu, Ministerio de Salud Pública y Bienestar Social, San Lorenzo, Paraguay
                [aa ]Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya
                [ab ]Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands
                [ac ]Emory Global Health Institute, Emory University, AT, USA
                [ad ]All India Institute of Medical Sciences, New Delhi, India
                [ae ]Department of Public Health and Policy, University of Liverpool, Liverpool, UK
                [af ]Arctic Investigations Program, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centres for Disease Control and Prevention, Anchorage, AK, USA
                [ag ]Institute Pasteur Cambodia, Children's Hospital Colorado, Aurora, CO, USA
                [ah ]GSK Vaccines Singapore, Children's Hospital Colorado, Aurora, CO, USA
                [ai ]Department of Pediatric Infectious Diseases, Children's Hospital Colorado, Aurora, CO, USA
                [aj ]National Institute of Virology, Pune, India
                [ak ]University Teaching Hospital, Lusaka, Zambia
                [al ]Rodolphe Merieux Laboratory, Faculty of Pharmacy, University of Health Sciences, Phnom Penh, Cambodia
                [am ]Centers for Disease Control and Prevention, Central American Region, Guatemala City, Guatemala
                [an ]Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa
                [ao ]School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
                [ap ]Hospital San Juan de Dios, Santa Ana, Ministry of Health, El Salvador
                [aq ]National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
                [ar ]Bayanzurkh District General Hospital, Ulaanbaatar, Mongolia
                [as ]Department of Pneumology, National Pediatric Hospital, Phnom Penh, Cambodia
                [at ]Centro de Educación Médica envestigaciones Clínicas “CEMIC”, Argentina
                [au ]Health Secretariat of the City of Belo Horizonte, Brazil
                [av ]Public Health Institute, Chile
                [aw ]Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China
                [ax ]Epidemiology Department, Austral University and Ricardo Gutiérrez Children Hospital, Argentina
                [ay ]Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
                [az ]Vanderbilt University, Nashville, TN, USA
                [ba ]KEM Hospital Research Center, Pune, India
                [bb ]School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, NSW, Australia
                [bc ]Department of Paediatrics, University of Auckland, Auckland, New Zealand
                [bd ]Centre for International Health, University of Otago, Dunedin, New Zealand
                [be ]Center for Health Studies, Universidad del Valle de Guatemala, Guatemala
                [bf ]Unit of Training and Research in Public Health, School of Medicine and Pharmacy of Rabat, University Mohamed V, Rabat, Morocco
                [bg ]University of Padjdjaran, Bandung, Indonesia
                [bh ]University of Jordan, Amman, Jordan
                [bi ]Department of Pediatrics and Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA
                [bj ]National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
                [bk ]Hospital Dr Ernesto Torres Galdames, Iquique, Chile
                [bl ]Research Institute for Tropical Medicine, Muntinlupa, Philippines
                [bm ]Research Institute for Tropical Medicine-Department of Health, Philippines
                [bn ]Ministry of Public Health and Social Welfare, Guatemala
                [bo ]Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Nairobi, Kenya
                [bp ]Pwani University, Kilifi, Kenya
                [bq ]Division of Medical Microbiology, University of Cape Town and National Health Laboratory Services, South Africa
                [br ]School of Life Sciences, University of Warwick, Coventry, UK
                [bs ]Mongolian Academy of Medical Sciences, Ulaanbaatar, Mongolia
                [bt ]Tohoku University Graduate School of Medicine, Department of Virology, Miyagi Prefecture, Japan
                [bu ]Emerging Pathofens Laboratory, Fondation Mérieux, Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France
                [bv ]Emory University, Rollins School of Public Health, AT, USA
                [bw ]Centre d'Infectiologie Charles Mérieux (CICM), Antananarivo, Madagascar
                [by ]Fogarty International Center Division of International Epidemiology and Population Studies, NIH, Bethesda, MD, USA
                [by ]Department of Pediatrics, Charité University Medical Center, Berlin, Germany
                [bz ]Hôpital Femme-Mère-Enfant, Antananarivo, Madagascar
                [ca ]United States Naval Medical Research Unit No. 6, Callao, Peru
                [cb ]Departamento de Biología Molecular y Genética, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion, Paraguay
                [cc ]School of Public Health, Virology Department, Tehran University of Medical Sciences, Iran
                [cd ]Robert Koch Institute (RKI), Berlin, Germany
                [ce ]London School of Hygiene & Tropical Medicine, London, UK
                [cf ]Department of Emergency Medicine, University of New Mexico, Albuquerque, New Mexico, USA
                [cg ]Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Beijing, China
                [ch ]Alaska Native Tribal Health Consortium, Anchorage, AK, USA
                [ci ]Department of Research, Innlandet Hospital Trust, Lillehammer, Norway
                [cj ]Ministry of Health, Indonesia
                [ck ]CHU Gabriel Touré, Bamako, Mali
                [cl ]Centre for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, USA
                [cm ]Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
                [cn ]Centre for Viral Zoonosis, Department of Medical Virology, University of Pretoria, Pretoria, South Africa
                [co ]National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Thailand
                [cp ]MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China
                [cq ]Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
                [cr ]Department of Paediatrics and Child Heath, Red Cross War Memorial Children's Hospital and MRC Unit on Child & Adolescent Health, University of Cape Town, South Africa
                [cs ]Public Health Foundation of India, New Delhi, India
                Author notes
                [* ]Correspondence to: Prof Harish Nair, Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, Edinburgh Medical School, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UKCorrespondence to: Prof Harish Nair, Centre for Global Health ResearchUsher Institute of Population Health Sciences and InformaticsEdinburgh Medical SchoolUniversity of EdinburghTeviot PlaceEdinburghEH8 9AGUK harish.nair@ 123456ed.ac.uk
                [*]

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                [†]

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                Article
                S0140-6736(17)30938-8
                10.1016/S0140-6736(17)30938-8
                5592248
                28689664
                © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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