Interleukin-8 Predicts Fatal Kala-Azar: A Case-Control Study

Abstract

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]; p < 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.

Keywords: cytokines; inflammation; mortality; prognosis; visceral leishmaniasis.

Figure 1

Distribution of pretreatment serum cytokine levels (pg/mL, Log Scale) in kala-azar patients stratified by outcome. This figure illustrates the distribution of serum cytokine levels measured prior to the initiation of specific anti-Leishmania treatment in patients with kala-azar, stratified into survivors and non-survivors. Values are expressed in pg/mL and were log₁₀-transformed to improve visualization of data variability.Colored dots indicate outliers beyond 1.5 times the interquartile range.

Figure 2

Receiver operating characteristic (ROC) curve analysis of interleukin-8 (IL-8) performance in predicting mortality in kala-azar patients, comparing continuous and dichotomized forms. This figure illustrates the predictive performance of IL-8 (in both its continuous and dichotomized forms) for mortality in patients with kala-azar. The comparison of their respective areas under the curve (AUCs) was performed using DeLong’s test.