Abstract

BackgroundCurrent estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age.MethodsMITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10).ResultsAn underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished.ConclusionsMITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality.

Highlights

  • Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD)

  • Current estimates on causes of under-5 childhood deaths are largely premised on modeling using vital registration data

  • Community engagement studies have suggested that minimally invasive tissue sampling (MITS) would be theoretically culturally acceptable in African and South Asian countries [6]

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Summary

Objectives

We aimed to evaluate the acceptability and utility of MITS, as proof of concept, in ascertaining the causal pathway of death in children >1 month of age in an LMIC setting (Soweto, South Africa). We aimed to undertake MITS within 24 hours of death and excluded those cases in which the procedure could not be performed within 72 hours

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