Etiologies and comorbidities of meningitis deaths in children under 5 years in high-mortality settings: Insights from the CHAMPS Network in the post-pneumococcal vaccine era

Sana Mahtab; Zachary J Madewell; Vicky Baillie; Ziyaad Dangor; Sanjay G Lala; Nega Assefa; Mulu Berihun; Lola Madrid; Lemma Demissie Regassa; J Anthony G Scott; Soter Ameh; Joseph S Bangura; Okokon Ita; Erick Kaluma; Ikechukwu Udo Ogbuanu; Brigitte Gaume; Karen L Kotloff; Samba O Sow; Milagritos D Tapia; Sara Ajanovic; Marcelino Garrine; Inacio Mandomando; Rosauro Varo; Elisio G Xerinda; Muntasir Alam; Shams El Arifeen; Emily S Gurley; Mohammad Zahid Hossain; Afruna Rahman; Victor Akelo; Kitiezo Aggrey Igunza; Clayton Onyango; Dickens Onyango; Jennifer R Verani; Portia Mutevedzi; Cynthia G Whitney; Dianna M Blau; Shabir A Madhi; Quique Bassat; CHAMPSconsortium

doi:10.1016/j.jinf.2024.106341

Etiologies and comorbidities of meningitis deaths in children under 5 years in high-mortality settings: Insights from the CHAMPS Network in the post-pneumococcal vaccine era

J Infect. 2024 Nov 8;89(6):106341. doi: 10.1016/j.jinf.2024.106341. Online ahead of print.

Authors

Sana Mahtab¹, Zachary J Madewell², Vicky Baillie³, Ziyaad Dangor³, Sanjay G Lala⁴, Nega Assefa⁵, Mulu Berihun⁶, Lola Madrid⁵, Lemma Demissie Regassa⁶, J Anthony G Scott⁷, Soter Ameh⁸, Joseph S Bangura⁹, Okokon Ita¹⁰, Erick Kaluma⁸, Ikechukwu Udo Ogbuanu⁸, Brigitte Gaume¹¹, Karen L Kotloff¹¹, Samba O Sow¹², Milagritos D Tapia¹¹, Sara Ajanovic¹³, Marcelino Garrine¹⁴, Inacio Mandomando¹⁵, Rosauro Varo¹³, Elisio G Xerinda¹⁴, Muntasir Alam¹⁶, Shams El Arifeen¹⁶, Emily S Gurley¹⁷, Mohammad Zahid Hossain¹⁶, Afruna Rahman¹⁶, Victor Akelo¹⁸, Kitiezo Aggrey Igunza¹⁹, Clayton Onyango²⁰, Dickens Onyango²¹, Jennifer R Verani²², Portia Mutevedzi²³, Cynthia G Whitney²³, Dianna M Blau², Shabir A Madhi²⁴, Quique Bassat²⁵; CHAMPSconsortium

Affiliations

¹ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: sana.mahtab@wits-vida.org.
² Global Health Center, Centers for Disease Control and Prevention, Atlanta, GA, USA.
³ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Department of Paediatrics & Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
⁵ College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
⁶ College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.
⁷ Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
⁸ CHAMPS Sierra Leone, Freetown, Sierra Leone.
⁹ Ministry of Health and Sanitation, Freetown, Sierra Leone.
¹⁰ University of Calabar Teaching Hospital, Nigeria.
¹¹ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
¹² Centre pour le Développement des Vaccins, Ministère de la Santé, Bamako, Mali.
¹³ Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique; ISGlobal, Barcelona, Spain, Facultat de Medicina i Ciències de la Salut, Unviersitat de Barcelona (UB), Barcelona, Spain.
¹⁴ Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.
¹⁵ Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique; ISGlobal, Barcelona, Spain, Facultat de Medicina i Ciències de la Salut, Unviersitat de Barcelona (UB), Barcelona, Spain; Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique.
¹⁶ International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh.
¹⁷ International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁸ Centers for Disease Control and Prevention-Kenya, Kisumu, Kenya.
¹⁹ Kenya Medical Research Institute, Center for Global Health Research, Kisumu, Kenya.
²⁰ Center for Global Health, US Centers for Disease Control and Prevention, Nairobi, Kenya.
²¹ Kisumu County Department of Health, Kisumu, Kenya.
²² National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
²³ Emory Global Health Institute, Emory University, Atlanta, GA, USA.
²⁴ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Wits Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²⁵ Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique; ISGlobal, Barcelona, Spain, Facultat de Medicina i Ciències de la Salut, Unviersitat de Barcelona (UB), Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain; Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública-CIBERESP, Madrid, Spain.

PMID: 39521254
DOI: 10.1016/j.jinf.2024.106341

Abstract

Background: The role of meningitis in causing deaths and in children under 5 is unclear, especially since widespread use of vaccines to prevent common causes of meningitis. Child Health and Mortality Prevention Surveillance (CHAMPS) uses post-mortem minimally invasive tissue sampling (MITS) and ante-mortem data to explore death causes. We aimed to assess meningitis's contribution to mortality and identify causative pathogens in children under 5 within CHAMPS Network sites.

Method: In this observational study, we analyzed deaths in live-born children <5 years of age that occurred between December 16, 2016, and December 31, 2023, in CHAMPS catchments in six sub-Saharan African countries (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, South Africa) and Bangladesh. MITS was conducted within 24-72 h of death, including blood and cerebrospinal fluid (CSF) culture, multi-organism targeted nucleic acid amplification tests on blood, CSF and lung tissue, and histopathology of lung, liver and brain. Expert panels at each site reviewed data to attribute causes of death following ICD-10 standards.

Result: Meningitis was in the causal pathway for 7.0% (270/3857) of deaths; in 4.8% (13/270) meningitis was considered the underlying condition. Neonates accounted for 65.9% (178/270) and infants or children 34.1% (92/270). Among neonatal meningitis deaths, 55.6% (99/178) occurred ≥72 h post-hospital admission; and common pathogens were Acinetobacter baumannii (49.5%, 49/99; mainly from South Africa) and Klebsiella pneumoniae (40.4%, 40/99). Forty-four percent (79/178) of neonatal meningitis deaths were community-associated, primarily due to K. pneumoniae (35.4%, 28/79) and Escherichia coli (13.9%, 11/79). Among infant and child meningitis deaths, 43.5% (40/92) occurred ≥72 h post-admission; and common pathogens were K. pneumoniae (42.5%,17/40) and A. baumannii (17.5%, 7/40). Among community-associated meningitis deaths in infants and children (56.5%, 52/92), Streptococcus pneumoniae (34.6%, 18/52) and K. pneumoniae (19.2%, 10/52) were common pathogens. Pathogen prevalence varied by region.

Conclusion: Our study highlights meningitis as a significant contributor to under-5 mortality in low-middle-income countries. The prominent role of K. pneumoniae and A. baumannii, particularly in healthcare settings and specific regions, highlights the need for better infection control, targeted interventions, and more effective treatment strategies.

Keywords: Community associated meningitis; Meningitis; Minimally invasive tissue sampling; Occurred ≥72 h post-hospital admission; Pathogens.