Post-mortem investigation of deaths due to pneumonia in children aged 1-59 months in sub-Saharan Africa and South Asia from 2016 to 2022: an observational study

Abstract

Background: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network.

Methods: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards.

Findings: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus.

Interpretation: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens.

Funding: Bill & Melinda Gates Foundation.

Figure 1

Common conditions other than pneumonia that were in the causal pathway, based on CHAMPS Network data for Dec 16, 2016, to Dec 31, 2022 Most common conditions other than pneumonia that were in the causal pathway leading to death for pneumonia, by age group and by whether the death from pneumonia occurred in the community or in less than 72 h of hospital admission or whether it occurred at least 72 h after hospital admission. The left panels include other conditions anywhere in the causal pathway (including as the underlying condition; presumed community-acquired: N=306; presumed hospital-acquired: N=149). The right panels show underlying causes of death when pneumonia was either an immediate or antecedent cause of death (presumed community-acquired pneumonia: N=226; presumed hospital-acquired pneumonia: N=135). CHAMPS=Child Health and Mortality Prevention Surveillance.

Figure 2

Pathogens attributed to deaths from pneumonia, based on CHAMPS Network data for Dec 16, 2016, to Dec 31, 2022 Pathogens attributed to deaths from pneumonia in children aged 1–59 months enrolled in the CHAMPS Network, by CHAMPS site and by whether the pneumonia death occurred in the community or less than 72 h of hospital admission or whether it occurred 72 h or more after hospital admission. Pathogens implicated in at least three deaths were included. CHAMPS=Child Health and Mortality Prevention Surveillance.