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In resource-limited settings where vital registration and medical death certificates are unavailable or incomplete, verbal autopsy (VA) is often used to attribute causes of death (CoD) and prioritize resource allocation and interventions. We aimed to determine the CoD concordance between InterVA and CHAMPS's method. The causes of death (CoDs) of children <5 were determined by two methods using data from seven low- and middle-income countries (LMICs) enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. The first CoD method was from the DeCoDe panel using data from Minimally Invasive Tissue Sampling (MITS), whereas the second method used Verbal Autopsy (VA), which utilizes the InterVA software. This analysis evaluated the agreement between the two using Lin's concordance correlation coefficient. The overall concordance of InterVA4 and DeCoDe in assigning causes of death across surveillance sites, age groups, and causes of death was poor (0.75 with 95% CI: 0.73-0.76) and lacked precision. We found substantial differences in agreement by surveillance site, with Mali showing the lowest and Mozambique and Ethiopia the highest concordance. The InterVA4 assigned CoD agrees poorly in assigning causes of death for U5s and stillbirths. Because VA methods are relatively easy to implement, such systems could be more useful if algorithms were improved to more accurately reflect causes of death, for example, by calibrating algorithms to information from programs that used detailed diagnostic testing to improve the accuracy of COD determination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

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., Competing Interests: Declaration of interests CGW received honoraria from the University of St Andrews for speaking to alumni about CHAMPS and global health work. SAM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Merck, Providence, Gritstone, and ImmunityBio. SAM has received honoraria from GSK for lecturing. GR has received grants from Fleming Fund Kenya Country, Deutsche Forschungsgemeinschaft, and bioMerieux. SA and JAGS have received support for attending meetings or travels, or both, for WHO, Bill & Melinda Gates Foundation (SA) and the International Society of Pneumonia & Pneumococcal Diseases (JAGS). CGW, JAGS, and SAM report serving on data safety monitoring boards for Safety Platform for Emergency VACcines (SPEAC; CGW), PATH (SAM), Centre for the AIDS Programme of Research in South Africa (CAPRISA; SAM), MRC The Gambia (JAGS) and ILiAD Biotechnologies (JAGS). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CGW received honoraria from the University of St. Andrews for speaking to alumni about CHAMPS and global health work. JAGS reports receiving funding from the Wellcome Trust, UK FCDO, European Union, and the National Institute for Health Research. SM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Providence, Gritstone, and ImmunityBio. SM has received honoraria from GSK for lecturing. CGW and SM report serving on data safety monitoring boards for SPEAC (CGW) and PATH and CAPRISA (SM). DT-F reports having received the support of a fellowship from “La Caixa” Foundation (ID 100010434, “LCF/BQ/DR21/11880018”). All other investigators declare no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)