SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, Canada.
Public Health Ontario, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.
EBioMedicine. 2023 Aug;94:104721. doi: 10.1016/j.ebiom.2023.104721. Epub 2023 Jul 17.
Children in Africa carry a disproportionate burden of malnutrition and infectious disease. Together, malnutrition and infection are major contributors to global child mortality; however, their collective impact on immune activation are not well described.
This was a secondary analysis of a prospective cohort study of children hospitalized with acute febrile illness at a single centre in Uganda. We investigated the association between malnutrition (determined using the mid-upper arm circumference, MUAC), immune activation (as measured by inflammatory markers IL-6, IL-8, CXCL10, CHI3L1, sTNFR1, Cystatin C, granzyme B, and sTREM-1), and mortality.
Of the 1850 children eligible for this secondary analysis, 71 (3.8%) and 145 (11.7%) presented with severe acute malnutrition (SAM, MUAC <115 mm) and moderate malnutrition (MUAC 115 to < 125 mm), respectively. SAM was associated with increased concentrations of CHI3L1, sTNFR1, Cystatin C, and sTREM-1, and decreased concentrations of CXCL10 and granzyme B, even after controlling for age, sex, and disease severity at presentation. There were 77 deaths (4.2%). SAM was associated with a 9.2-fold (95% CI 4.8-46), 17-fold (95% CI 3.9-74), and 13-fold (95% CI 3.5-52) increased odds of death in children with pneumonia, malaria, and diarrheal illness, respectively. Mediation analysis implicated sTREM-1 and CHI3L1 in the effect of SAM on mortality, suggesting that enhanced activation of these inflammatory pathways is associated with the increased mortality in undernourished children with pneumonia and malaria.
Collectively, these data highlight systemic inflammation as a common pathway associated with malnutrition and infection that could be targeted to mitigate the burden of acute febrile illness in LMICs.
This work was supported in part by the Canadian Institutes of Health Research, and by kind donations from The Tesari Foundation and Kim Kertland. The funders had no role in design, analysis, or reporting of these studies.
非洲儿童营养不良和传染病负担过重。营养不良和感染共同导致了全球儿童死亡的主要原因；然而，它们对免疫激活的综合影响尚未得到很好的描述。
这是对乌干达单一中心因急性发热性疾病住院的儿童进行的前瞻性队列研究的二次分析。我们研究了营养不良（用中上臂围 MUAC 确定）、免疫激活（用炎症标志物 IL-6、IL-8、CXCL10、CHI3L1、sTNFR1、Cystatin C、颗粒酶 B 和 sTREM-1 测量）与死亡率之间的关联。
在符合二次分析条件的 1850 名儿童中，71 名（3.8%）和 145 名（11.7%）分别患有严重急性营养不良（SAM，MUAC<115mm）和中度营养不良（MUAC 115-<125mm）。SAM 与 CHI3L1、sTNFR1、Cystatin C 和 sTREM-1 的浓度增加以及 CXCL10 和颗粒酶 B 的浓度降低相关，即使在控制了发病时的年龄、性别和疾病严重程度后也是如此。共有 77 例死亡（4.2%）。SAM 与肺炎、疟疾和腹泻病患儿死亡的风险分别增加 9.2 倍（95%CI 4.8-46）、17 倍（95%CI 3.9-74）和 13 倍（95%CI 3.5-52）相关。中介分析表明，sTREM-1 和 CHI3L1 介导了 SAM 对死亡率的影响，这表明这些炎症途径的增强激活与营养不足的肺炎和疟疾患儿的死亡率增加有关。
总的来说，这些数据强调了系统性炎症是与营养不良和感染相关的共同途径，这可能成为减轻中低收入国家急性发热性疾病负担的目标。
这项工作部分得到了加拿大卫生研究院的支持，并得到了 Tesari 基金会和 Kim Kertland 的慷慨捐赠。这些资助者在这些研究的设计、分析或报告中没有任何作用。
