Distinct systemic cytokine signatures define symptomatic malaria in children: insights from a longitudinal study in Togo

Malaria remains a significant public health challenge in sub-Saharan Africa (SSA), particularly among children, where immune responses and clinical manifestations to Plasmodium falciparum infection vary widely. Understanding the interplay between parasitemia, immune responses, and clinical outcomes is essential to improving case management. This study aimed to identify systemic cytokine signatures that define symptomatic malaria in children, by analyzing cytokine dynamics over time and their association with parasite burden and clinical status in children aged 6–10 years in Togo. A longitudinal cohort study was conducted in the Prefecture d’Agoè, Togo, from November 2023 to February 2024. Sixty children were enrolled and treated with artemether-lumefantrine and albendazole. Weekly monitoring was performed over 12 weeks using microscopy and qPCR for P. falciparum detection. Systemic cytokines, including IL-1β, IL-6, IFN-γ, IL-17 A, IL-5, and IL-10, were measured by Sandwich ELISA. Associations between cytokine concentrations, parasite densities, and cycle threshold (Ct) values were assessed using Spearman’s correlation. Of the 60 children, 25% (n = 15) tested positive for P. falciparum by qPCR, while 15% (n = 9) had microscopy-confirmed infections. Overall, 33.3% (n = 5) progressed to symptomatic malaria; the remainder were asymptomatic carriers. Symptomatic cases exhibited significantly elevated IL-6 (vs. non-infected, p = 0.0004; vs. asymptomatic, p = 0.0003; vs. recovered, p = 0.0037), IFN-γ (vs. non-infected, p < 0.0001; vs. asymptomatic, p = 0.0048), and IL-10 levels (vs. non-infected, p < 0.0001; vs. recovered, p = 0.0004). IL-10 levels were also higher in asymptomatic children compared to non-infected (p = 0.0013), while IFN-γ was elevated in recovered cases (vs. non-infected, p = 0.0309). In symptomatic children, IL-10 levels showed a strong negative correlation with Ct values (r = -0.973, p = 0.001) and a strong positive correlation with parasite density (r = 0.911, p = 0.001). IFN-γ exhibited moderate correlations with both, Ct values (r = -0.442, p = 0.037) and parasite density (r = 0.518, p = 0.027). This study identifies distinct cytokine signatures, particularly elevated IL-10 and IFN-γ, that characterize symptomatic malaria in children and correlate with parasite burden. These cytokines may serve as prognostic biomarkers and offer insights for targeted interventions in paediatric malaria.