Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.


Journal

The Lancet. Microbe
ISSN: 2666-5247
Titre abrégé: Lancet Microbe
Pays: England
ID NLM: 101769019

Informations de publication

Date de publication:
10 Jan 2024
Historique:
received: 16 12 2022
revised: 25 07 2023
accepted: 30 08 2023
medline: 14 1 2024
pubmed: 14 1 2024
entrez: 13 1 2024
Statut: aheadofprint

Résumé

Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. Bill & Melinda Gates Foundation.

Sections du résumé

BACKGROUND BACKGROUND
Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings.
METHODS METHODS
We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin).
FINDINGS RESULTS
Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin.
INTERPRETATION CONCLUSIONS
K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally.
FUNDING BACKGROUND
Bill & Melinda Gates Foundation.

Identifiants

pubmed: 38218193
pii: S2666-5247(23)00290-2
doi: 10.1016/S2666-5247(23)00290-2
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of interests SEA, KLK, and MT report receiving funding from Emory University. JAGS reports receiving funding from Emory University, the Bill & Melinda Gates Foundation, Wellcome Trust, UK Foreign Commonwealth & Development Office, European Union, and National Institute for Health Research. SMad reports receiving funds from the Bill & Melinda Gates Foundation, Pfizer, Minervax, GSK, South African Medical Research Council, Merck, PATH, and Center for the AIDS Programme of Research in South Africa. All other authors declare no competing interests.

Auteurs

Jennifer R Verani (JR)

Center for Global Health, US Centers for Disease Control and Prevention, Nairobi, Kenya. Electronic address: jverani@cdc.gov.

Dianna M Blau (DM)

Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, GA, USA.

Emily S Gurley (ES)

Maternal and Child Health Division, International Center for Diarrhoeal Diseases Research (icddr,b), Dhaka, Bangladesh; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Victor Akelo (V)

Center for Global Health, US Centers for Disease Control and Prevention Kenya, Kisumu, Kenya.

Nega Assefa (N)

College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.

Vicky Baillie (V)

South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa.

Quique Bassat (Q)

ISGlobal - Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique; Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain; Hospital Sant Joan de Déu, Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.

Mussie Berhane (M)

College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.

James Bunn (J)

World Health Organization, Sierra Leone, Freetown, Sierra Leone.

Anelsio C A Cossa (ACA)

Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.

Shams El Arifeen (S)

Maternal and Child Health Division, International Center for Diarrhoeal Diseases Research (icddr,b), Dhaka, Bangladesh.

Revathi Gunturu (R)

Aga Khan University Hospital, Nairobi, Kenya.

Martin Hale (M)

National Health Laboratory Service, Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Aggrey Igunza (A)

Kenya Medical Research Institute (KEMRI), Kisumu, Kenya.

Adama M Keita (AM)

Centre pour le Développement des Vaccins (CVD-Mali), Ministère de la Santé, Bamako, Mali.

Sartie Kenneh (S)

Ministry of Health and Sanitation, Freetown, Sierra Leone.

Karen L Kotloff (KL)

Department of Pediatrics and Department of Medicine, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Dickens Kowuor (D)

Crown Agents, Freetown, Sierra Leone.

Rita Mabunda (R)

ISGlobal - Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Zachary J Madewell (ZJ)

Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, GA, USA.

Shabir Madhi (S)

South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa.

Lola Madrid (L)

College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

Sana Mahtab (S)

South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa.

Judice Miguel (J)

Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.

Florence V Murila (FV)

University of Nairobi, Nairobi, Kenya.

Ikechukwu U Ogbuanu (IU)

Crown Agents, Freetown, Sierra Leone.

Julius Ojulong (J)

ICAP - Columbia University, Makeni, Sierra Leone.

Dickens Onyango (D)

Kisumu County Department of Health, Kisumu, Kenya.

Joe O Oundo (JO)

College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

J Anthony G Scott (JAG)

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

Samba Sow (S)

Centre pour le Développement des Vaccins (CVD-Mali), Ministère de la Santé, Bamako, Mali.

Milagritos Tapia (M)

Department of Pediatrics and Department of Medicine, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Cheick B Traore (CB)

Department of Pathological Anatomy and Cytology, University Hospital of Point G, Bamako, Mali.

Sithembiso Velaphi (S)

Department of Pediatrics, Chris Hani Baragwanath Academic Hospital, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Cynthia G Whitney (CG)

Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Inacio Mandomando (I)

Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique; Instituto Nacional de Saúde (INS), Maputo, Mozambique.

Robert F Breiman (RF)

Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Infectious Diseases and Oncology Research Institute, University of the Witwatersrand, Johannesburg, South Africa.

Classifications MeSH