Department of Pediatrics, University of California, San Francisco, California.
Institute of Global Health Sciences, University of California, San Francisco, California.
Am J Trop Med Hyg. 2019 Dec;101(6):1424-1433. doi: 10.4269/ajtmh.18-0635.
Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 β [IL-1β], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1β, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1β compared with the other subgroups. IL-1β best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.
目前，在疟疾流行地区，由于疟疾和非疟疾性脓毒症之间的临床和病理生理学重叠，很难准确诊断撒哈拉以南非洲地区常见的儿童死亡原因——脓毒症。宿主生物标志物可区分脓毒症与单纯发热，但在无脓毒症的情况下，在疟疾中通常异常。为了在疟疾流行地区确定预测脓毒症的生物标志物，我们回顾性分析了 2016 年 1 月至 8 月在布兰太尔社区卫生中心就诊的发热马拉维儿童（6-60 个月）的病例对照研究中的数据和血清，这些儿童患有或不患有疟疾且无脓毒症。我们对 29 名无并发症疟疾且无脓毒症的儿童、25 名无疟疾或脓毒症的儿童、17 名患有疟疾和脓毒症的儿童以及 16 名无疟疾但患有脓毒症的儿童进行了生物标志物特征分析。脓毒症的定义是根据全身炎症反应标准；采用多重磁珠检测法测定生物标志物（白细胞介素-6 [IL-6]、肿瘤坏死因子受体-1、白细胞介素-1β [IL-1β]、白细胞介素-10 [IL-10]、血管性血友病因子抗原-2、细胞间黏附分子-1 和血管生成素-2 [Ang-2]）。与非疟疾性发热儿童相比，患有疟疾的儿童中 IL-6、IL-1β 和 IL-10 升高，Ang-2 降低。与其他亚组相比，患有非疟疾性脓毒症的儿童的 IL-1β 大大增加。IL-1β 对脓毒症的预测最佳，其接受者操作特征（ROC）曲线下面积（AUROC）为 0.71（95%CI：0.57-0.85）；联合生物标志物-临床特征模型提高了预测能力（AUROC 为 0.77，95%CI：0.67-0.85）。我们确定了非疟疾性脓毒症的独特生物标志物谱，并开发了脓毒症预测模型。需要更多的临床和生物学数据来进一步探讨疟疾流行地区的脓毒症病理生理学。
