Mahtab Sana, Madewell Zachary J, Baillie Vicky, Dangor Ziyaad, Lala Sanjay G, Assefa Nega, Berihun Mulu, Madrid Lola, Regassa Lemma Demissie, Scott J Anthony G, Ameh Soter, Bangura Joseph S, Ita Okokon, Kaluma Erick, Ogbuanu Ikechukwu Udo, Gaume Brigitte, Kotloff Karen L, Sow Samba O, Tapia Milagritos D, Ajanovic Sara, Garrine Marcelino, Mandomando Inacio, Varo Rosauro, Xerinda Elisio G, Alam Muntasir, El Arifeen Shams, Gurley Emily S, Hossain Mohammad Zahid, Rahman Afruna, Akelo Victor, Igunza Kitiezo Aggrey, Onyango Clayton, Onyango Dickens, Verani Jennifer R, Mutevedzi Portia, Whitney Cynthia G, Blau Dianna M, Madhi Shabir A, Bassat Quique
South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Global Health Center, Centers for Disease Control and Prevention, Atlanta, GA, USA.
J Infect. 2024 Dec;89(6):106341. doi: 10.1016/j.jinf.2024.106341. Epub 2024 Nov 8.
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.
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.
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.
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.
脑膜炎在导致死亡以及5岁以下儿童死亡方面的作用尚不清楚，尤其是在广泛使用疫苗预防常见脑膜炎病因之后。儿童健康与死亡率预防监测（CHAMPS）采用死后微创组织采样（MITS）和死前数据来探究死亡原因。我们旨在评估脑膜炎对死亡率的影响，并在CHAMPS网络站点内确定5岁以下儿童的致病病原体。
在这项观察性研究中，我们分析了2016年12月16日至2023年12月31日期间在撒哈拉以南非洲六个国家（埃塞俄比亚、肯尼亚、马里、莫桑比克、塞拉利昂、南非）和孟加拉国的CHAMPS流域发生的5岁以下活产儿童死亡情况。在死亡后24 - 72小时内进行MITS，包括血液和脑脊液（CSF）培养、对血液、脑脊液和肺组织进行多病原体靶向核酸扩增检测，以及对肺、肝和脑进行组织病理学检查。每个站点的专家小组审查数据，以根据国际疾病分类第十版（ICD - 10）标准确定死亡原因。
脑膜炎是7.0%（270/3857）死亡病例的病因路径；在4.8%（13/270）的病例中，脑膜炎被视为根本病因。新生儿占65.9%（178/270），婴儿或儿童占34.1%（92/270）。在新生儿脑膜炎死亡病例中，55.6%（99/178）发生在入院≥72小时后；常见病原体为鲍曼不动杆菌（49.5%，49/99；主要来自南非）和肺炎克雷伯菌（40.4%，40/99）。44%（79/178）的新生儿脑膜炎死亡病例与社区相关，主要原因是肺炎克雷伯菌（35.4%，28/79）和大肠杆菌（13.9%，11/79）。在婴儿和儿童脑膜炎死亡病例中，43.5%（40/92）发生在入院≥72小时后；常见病原体为肺炎克雷伯菌（42.5%，17/40）和鲍曼不动杆菌（17.5%，7/40）。在婴儿和儿童与社区相关的脑膜炎死亡病例中（56.5%，52/92），肺炎链球菌（34.6%，18/52）和肺炎克雷伯菌（19.2%，10/52）是常见病原体。病原体流行率因地区而异。
我们的研究强调脑膜炎是低收入和中等收入国家5岁以下儿童死亡率的重要促成因素。肺炎克雷伯菌和鲍曼不动杆菌的突出作用，特别是在医疗环境和特定地区，凸显了加强感染控制、针对性干预和更有效治疗策略的必要性。
