Lima Simone Soares, Braz Débora Cavalcante, Silva Vladimir Costa, de Jesus Cardoso Farias Pereira Teresinha, da Costa Araújo Alves Carvalho Líndia Kalliana, Costa Dorcas Lamounier, Costa Carlos Henrique Nery
Department of Maternal and Child Health, Federal University of Piauí, Teresina 64049-550, Piauí, Brazil.
Postgraduate Program in Biotechnology, Northeast Network of Biotechnology (RENORBIO), Federal University of Piauí, Teresina 64049-550, Piauí, Brazil.
Trop Med Infect Dis. 2025 Sep 1;10(9):250. doi: 10.3390/tropicalmed10090250.
Kala-azar is associated with case-fatality rates as high as 10% in certain regions. Early identification of mortality biomarkers can significantly reduce this risk. This study, strengthened by a relatively high number of kala-azar-related deaths, aimed to identify serum cytokines as predictive biomarkers of fatal kala-azar. We compared 48 deceased patients with kala-azar to 42 survivors. The concentrations of IL-1β, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) were measured by flow cytometry. Cytokine levels were compared between groups using the Wilcoxon rank-sum test. Receiver operating characteristic (ROC) analysis, coupled with Youden's index, defined the optimal diagnostic threshold. Upon admission, IL-8 concentrations were substantially higher in deceased kala-azar patients (median 76.5 pg/mL [IQR 35.2-242.4 pg/mL]) than in survivors (median 26.4 pg/mL [IQR 15.1-47.7 pg/mL]; < 0.0001). ROC analysis identified 49.3 pg/mL as the optimal cutoff. When rounded to the clinically convenient value of 50 pg/mL, IL-8 predicted a fatal outcome with an area under the curve of 0.75, sensitivity of 70.8%, and specificity of 76.2%. In contrast, IL-1β, IL-6, IL-10, IL-12, and TNF-α showed no significant prognostic utility. Our findings suggest that IL-8 levels equal to or greater than 50 pg/mL are a reliable predictor of fatal kala-azar.
在某些地区，黑热病的病死率高达10%。早期识别死亡生物标志物可显著降低这种风险。这项研究因有相对较多的与黑热病相关的死亡病例而得到加强，旨在确定血清细胞因子作为致命性黑热病的预测生物标志物。我们将48例死于黑热病的患者与42例幸存者进行了比较。通过流式细胞术测量白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-12和肿瘤坏死因子-α（TNF-α）的浓度。使用Wilcoxon秩和检验比较组间细胞因子水平。通过受试者工作特征（ROC）分析并结合约登指数确定最佳诊断阈值。入院时，死于黑热病的患者IL-8浓度（中位数76.5 pg/mL[四分位间距35.2 - 242.4 pg/mL]）显著高于幸存者（中位数26.4 pg/mL[四分位间距15.1 - 47.7 pg/mL]；<0.0001）。ROC分析确定49.3 pg/mL为最佳截断值。当四舍五入到临床方便使用的值50 pg/mL时，IL-8预测致命结局的曲线下面积为0.75，敏感性为70.8%，特异性为76.2%。相比之下，IL-1β、IL-6、IL-10、IL-12和TNF-α没有显著的预后价值。我们的研究结果表明，IL-8水平等于或高于50 pg/mL是致命性黑热病的可靠预测指标。
