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

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.

Fig. 1

Flowchart of enrolled under-five deaths from CHAMPS sites between December 2016 – December 2023, that had minimally invasive tissue samples (MITS).

Fig. 2

Most common comorbidities for meningitis deaths, by age group and by whether the meningitis death 1) occurred in the community or with fewer than 72 h in the hospital (N = 131 or 2) was determined to be hospital-associated or occurred 72 or more hours after hospital admission (N = 139), CHAMPS, December 2016 – December 2023.

Fig. 3

Pathogens attributed to meningitis deaths in children 1–59 months of age enrolled in CHAMPS, by CHAMPS site and by whether the death 1) occurred in the community or with fewer than 72 h in the hospital (N = 131) or 2) was determined to be hospital-associated or occurred 72 or more hours after hospital admission (N = 139), CHAMPS, December 2016 – December 2023. Pathogens implicated in at least three deaths were included.