2016 年至 2022 年撒哈拉以南非洲和南亚 1-59 月龄儿童肺炎死亡的尸检调查：一项观察性研究。

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.

机构信息

South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Global Health Center, Centers for Disease Control and Prevention, Atlanta, GA, USA.

出版信息

Lancet Child Adolesc Health. 2024 Mar;8(3):201-213. doi: 10.1016/S2352-4642(23)00328-0. Epub 2024 Jan 25.

DOI:10.1016/S2352-4642(23)00328-0

PMID:38281495

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10864189/

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.

摘要

背景

儿童健康与死亡预防监测（CHAMPS）网络项目进行死后微创组织取样（MITS），同时收集生前临床信息，以调查多个国家儿童死亡的原因。我们旨在评估肺炎在死亡路径中的总体作用以及在 CHAMPS 网络中纳入的 1-59 月龄儿童中致命性肺炎的致病病原体。

方法

在这项观察性研究中，我们分析了 2016 年 12 月 16 日至 2022 年 12 月 31 日期间，在撒哈拉以南非洲的六个国家（埃塞俄比亚、肯尼亚、马里、莫桑比克、塞拉利昂和南非）和一个南亚国家（孟加拉国）的 CHAMPS 网络中发生的死亡事件。在死亡后 24-72 小时内对死者进行了标准的 MITS 方法。诊断测试包括血培养、血液和肺组织多生物体靶向核酸扩增检测（NAATs）以及各种器官组织样本的组织病理学检查。每个地点的一个跨学科专家小组根据世界卫生组织推荐的报告标准，审查病例数据，以确定死因和发病机制。

发现

在 1120 名死者中，有 455 名（40.6%）的死因被归因于肺炎，死亡时的中位年龄为 9 岁（IQR 4-19）。在 455 例肺炎死亡中，有 377 例（82.9%）确定了病原体，218 例（57.8%）死亡涉及多种病原体。306 例（67.3%）死亡发生在社区或入院后 72 小时内（假定为社区获得性肺炎），主要细菌病原体为肺炎链球菌（108 例[35.3%]）、肺炎克雷伯菌（78 例[25.5%]）和非典型流感嗜血杆菌（37 例[12.1%]）。149 例（32.7%）死亡发生在入院后 72 小时以上（假定为医院获得性肺炎），最常见的病原体是肺炎克雷伯菌（64 例[43.0%]）、鲍曼不动杆菌（19 例[12.8%]）、肺炎链球菌（15 例[10.1%]）和铜绿假单胞菌（15 例[10.1%]）。总体而言，病毒在 455 例肺炎相关死亡中占 145 例（31.9%），包括 54 例（11.9%）归因于巨细胞病毒和 29 例（6.4%）归因于呼吸道合胞病毒。

解释

在本分析中，肺炎导致了 40.6%的所有儿童死亡。死后 MITS 的使用使大多数（82.9%）归因于肺炎的儿童死亡的死因能够得到生物学确认，在同一病例中通常涉及不止一种病原体。肺炎克雷伯菌、非典型流感嗜血杆菌和肺炎链球菌的突出作用突显了有必要审查低收入和中等收入国家中非常严重肺炎的经验性治疗指南，以及需要研究针对这些病原体的新疫苗或改进疫苗。