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Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.
Lancet Glob Health. 2021 08; 9(8):e1077-e1087.LG

Abstract

BACKGROUND

Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age.

METHODS

We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570).

FINDINGS

203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome.

INTERPRETATION

We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions.

FUNDING

Bill & Melinda Gates Foundation.

Authors+Show Affiliations

Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK.Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK.Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.South African Medical Research Council, Vaccines and Infectious Diseases Analytical Research Unit, Soweto, South Africa; Department of Science and Technology, National Research Foundation, Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Research Institute for Tropical Medicine, Muntinlupa, Metro Manila, Philippines.Department of Child Health, Tribhuvan University, Katmandu, Nepal; the Centre for International Health, University of Bergen, Bergen, Norway.Barcelona Global Health Institute, Hospital Clínic-University of Barcelona, Barcelona, Spain; Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain; Paediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain.Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.Clinical Virology Unit, Centro de Educación Médica e Investigaciones Clínicas, Argentina.Public Health Institute of Chile, Región Metropolitana, Chile.Ricardo Gutierrez Children Hospital, Buenos Aires, Argentina.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh; Discipline of Paediatrics, School of Women's and Children's Health, The University of New South Wales, Sydney, NSW, Australia.Medical Research Council Unit, The Gambia at London School of Hygiene & Tropical Medicine, London, UK; Department of Paediatrics, Child & Youth Health, University of Auckland, Auckland, New Zealand.Department of Pediatrics and Department of Medicine, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Department of Pediatrics, University of Jordan, School of Medicine, Amman, Jordan.Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India.Research Institute for Tropical Medicine, Muntinlupa, Philippines.Research Institute for Tropical Medicine, Muntinlupa, Philippines.Department of Medical Microbiology, Vestre Viken Hospital Trust, Drammen, Norway.Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK.Área de Investigación en Vacunas, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Salud Pública, Valencia, Spain.Barcelona Global Health Institute, Hospital Clínic-University of Barcelona, Barcelona, Spain; Infectious Pediatric Diseases Section, Hospital Universitario de Octubre, Universidad Complutense, Research Institute Hospital de Octubre, Madrid, Spain.Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.Department of Virology, Tohoku University Graduate School of Medicine, Sendai, Japan.Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.Vienna Vaccine Safety Initiative, Berlin, Germany; Université Bourgogne-Franche Comté, Besançon, France.Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.Division of Global Health Protection, Thailand Ministry of Public Health and US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand.KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Kilifi, Kenya; Nuffield Department of Tropical Medicine, Oxford University, Oxford, UK; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.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.Epidemiology Department, Ministry of Health, Santiago, Chile.Department of Global Health and Development, Boston University School of Public Health, Boston, MA, USA.Department of Medical Virology, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.Department of Paediatrics & Child Health, Medical Research Council Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK.Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK. Electronic address: harish.nair@ed.ac.uk.No affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

34166626

Citation

Wang, Xin, et al. "Global Burden of Acute Lower Respiratory Infection Associated With Human Parainfluenza Virus in Children Younger Than 5 Years for 2018: a Systematic Review and Meta-analysis." The Lancet. Global Health, vol. 9, no. 8, 2021, pp. e1077-e1087.
Wang X, Li Y, Deloria-Knoll M, et al. Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis. Lancet Glob Health. 2021;9(8):e1077-e1087.
Wang, X., Li, Y., Deloria-Knoll, M., Madhi, S. A., Cohen, C., Arguelles, V. L., Basnet, S., Bassat, Q., Brooks, W. A., Echavarria, M., Fasce, R. A., Gentile, A., Goswami, D., Homaira, N., Howie, S. R. C., Kotloff, K. L., Khuri-Bulos, N., Krishnan, A., Lucero, M. G., ... Nair, H. (2021). Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis. The Lancet. Global Health, 9(8), e1077-e1087. https://doi.org/10.1016/S2214-109X(21)00218-7
Wang X, et al. Global Burden of Acute Lower Respiratory Infection Associated With Human Parainfluenza Virus in Children Younger Than 5 Years for 2018: a Systematic Review and Meta-analysis. Lancet Glob Health. 2021;9(8):e1077-e1087. PubMed PMID: 34166626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis. AU - Wang,Xin, AU - Li,You, AU - Deloria-Knoll,Maria, AU - Madhi,Shabir A, AU - Cohen,Cheryl, AU - Arguelles,Vina Lea, AU - Basnet,Sudha, AU - Bassat,Quique, AU - Brooks,W Abdullah, AU - Echavarria,Marcela, AU - Fasce,Rodrigo A, AU - Gentile,Angela, AU - Goswami,Doli, AU - Homaira,Nusrat, AU - Howie,Stephen R C, AU - Kotloff,Karen L, AU - Khuri-Bulos,Najwa, AU - Krishnan,Anand, AU - Lucero,Marilla G, AU - Lupisan,Socorro, AU - Mathisen,Maria, AU - McLean,Kenneth A, AU - Mira-Iglesias,Ainara, AU - Moraleda,Cinta, AU - Okamoto,Michiko, AU - Oshitani,Histoshi, AU - O'Brien,Katherine L, AU - Owor,Betty E, AU - Rasmussen,Zeba A, AU - Rath,Barbara A, AU - Salimi,Vahid, AU - Sawatwong,Pongpun, AU - Scott,J Anthony G, AU - Simões,Eric A F, AU - Sotomayor,Viviana, AU - Thea,Donald M, AU - Treurnicht,Florette K, AU - Yoshida,Lay-Myint, AU - Zar,Heather J, AU - Campbell,Harry, AU - Nair,Harish, AU - ,, Y1 - 2021/06/21/ PY - 2020/10/28/received PY - 2021/04/16/revised PY - 2021/04/22/accepted PY - 2021/6/25/pubmed PY - 2021/8/24/medline PY - 2021/6/24/entrez SP - e1077 EP - e1087 JF - The Lancet. Global health JO - Lancet Glob Health VL - 9 IS - 8 N2 - BACKGROUND: Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age. METHODS: We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570). FINDINGS: 203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome. INTERPRETATION: We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions. FUNDING: Bill & Melinda Gates Foundation. SN - 2214-109X UR - https://www.unboundmedicine.com/medline/citation/34166626/Global_burden_of_acute_lower_respiratory_infection_associated_with_human_parainfluenza_virus_in_children_younger_than_5_years_for_2018:_a_systematic_review_and_meta_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2214-109X(21)00218-7 DB - PRIME DP - Unbound Medicine ER -