Epidemiology of human metapneumovirus among children with severe or very severe pneumonia in high pneumonia burden settings: the Pneumonia Etiology Research for Child Health (PERCH) study experience

Ryo Miyakawa; Haijun Zhang; W Abdullah Brooks; Christine Prosperi; Henry C Baggett; Daniel R Feikin; Laura L Hammitt; Stephen R C Howie; Karen L Kotloff; Orin S Levine; Shabir A Madhi; David R Murdoch; Katherine L O'Brien; J Anthony G Scott; Donald M Thea; Martin Antonio; Juliet O Awori; Charatdao Bunthi; Amanda J Driscoll; Bernard Ebruke; Nicholas S Fancourt; Melissa M Higdon; Ruth A Karron; David P Moore; Susan C Morpeth; Justin M Mulindwa; Daniel E Park; Mohammed Ziaur Rahman; Mustafizur Rahman; Rasheed A Salaudeen; Pongpun Sawatwong; Phil Seidenberg; Samba O Sow; Milagritos D Tapia; Maria Deloria Knoll

doi:10.1016/j.cmi.2024.10.023

Epidemiology of human metapneumovirus among children with severe or very severe pneumonia in high pneumonia burden settings: the Pneumonia Etiology Research for Child Health (PERCH) study experience

Clin Microbiol Infect. 2024 Nov 1:S1198-743X(24)00505-6. doi: 10.1016/j.cmi.2024.10.023. Online ahead of print.

Authors

Ryo Miyakawa¹, Haijun Zhang², W Abdullah Brooks³, Christine Prosperi⁴, Henry C Baggett⁵, Daniel R Feikin⁶, Laura L Hammitt⁷, Stephen R C Howie⁸, Karen L Kotloff⁹, Orin S Levine⁴, Shabir A Madhi¹⁰, David R Murdoch¹¹, Katherine L O'Brien⁴, J Anthony G Scott¹², Donald M Thea¹³, Martin Antonio¹⁴, Juliet O Awori¹⁵, Charatdao Bunthi¹⁶, Amanda J Driscoll¹⁷, Bernard Ebruke¹⁸, Nicholas S Fancourt¹⁹, Melissa M Higdon⁴, Ruth A Karron²⁰, David P Moore²¹, Susan C Morpeth²², Justin M Mulindwa²³, Daniel E Park²⁴, Mohammed Ziaur Rahman²⁵, Mustafizur Rahman²⁵, Rasheed A Salaudeen²⁶, Pongpun Sawatwong¹⁶, Phil Seidenberg²⁷, Samba O Sow²⁸, Milagritos D Tapia⁹, Maria Deloria Knoll⁴

Affiliations

¹ Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA.
² International Vaccine Access Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Health Policy and Management, School of Public Health, Peking University, Beijing, China. Electronic address: zhanghj966@gmail.com.
³ Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b), Dhaka and Matlab, Bangladesh.
⁴ International Vaccine Access Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
⁵ Division of Global Health Protection, Thailand Ministry of Public Health-U.S. Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand; Division of Global Health Protection, Global Health Center, Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁶ International Vaccine Access Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Division of Viral Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁷ International Vaccine Access Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
⁸ Medical Research Council Unit at the London School of Hygiene and Tropical Medicine, Basse, The Gambia; Department of Paediatrics: Child & Youth Health, University of Auckland, Auckland, New Zealand; College of Medicine, Nursing and Health Sciences, Fiji National University, Suva, Fiji.
⁹ Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁰ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Wits Infectious Diseases and Oncology Research Institute, University of the Witwatersrand, Johannesburg, South Africa.
¹¹ Department of Pathology and Biomedical Sciences, University of Otago, Christchurch, New Zealand; Microbiology Unit, Canterbury Health Laboratories, Christchurch, New Zealand.
¹² Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
¹³ Department of Global Health, Boston University School of Public Health, Boston, MA, USA.
¹⁴ Medical Research Council Unit at the London School of Hygiene and Tropical Medicine, Basse, The Gambia; Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, Microbiology and Infection Unit, Warwick Medical School, University of Warwick, Coventry, UK.
¹⁵ Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
¹⁶ Division of Global Health Protection, Thailand Ministry of Public Health-U.S. Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand.
¹⁷ International Vaccine Access Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁸ Medical Research Council Unit at the London School of Hygiene and Tropical Medicine, Basse, The Gambia.
¹⁹ Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Microbiology Laboratory, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.
²⁰ Department of International Health, Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
²¹ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Wits Infectious Diseases and Oncology Research Institute, University of the Witwatersrand, Johannesburg, South Africa; Department of Paediatrics & Child Health, Chris Hani Baragwanath Academic Hospital and University of the Witwatersrand, Johannesburg, South Africa.
²² Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
²³ Department of Paediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia.
²⁴ International Vaccine Access Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
²⁵ International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b), Dhaka and Matlab, Bangladesh.
²⁶ Medical Research Council Unit at the London School of Hygiene and Tropical Medicine, Basse, The Gambia; Medical Microbiology Department, Lagos University Teaching Hospital, Lagos, Nigeria.
²⁷ Department of Global Health, Boston University School of Public Health, Boston, MA, USA; Department of Emergency Medicine, University of New Mexico, Albuquerque, NM, USA.
²⁸ Centre pour le Développement des Vaccins (CVD-Mali), Bamako, Mali.

PMID: 39489292
DOI: 10.1016/j.cmi.2024.10.023

Abstract

Objectives: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases.

Methods: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics.

Results: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%).

Discussion: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

Keywords: Africa; Asia; Human metapneumovirus (hMPV); Paediatric; Severe pneumonia.