Cytokine-Driven Immune Phenotypes at Delivery as Indicators of Malaria Infection Risk Among Primigravidae in Burkina Faso: An Exploratory Clustering Analysis

Introduction: In malaria-endemic regions, women remain vulnerable to malaria infection even at the time of delivery and shortly thereafter. However, the immunological mechanisms underlying this susceptibility remain poorly characterized. This exploratory study investigated whether cytokine-based immune profiles could help identify primigravid women at increased risk of malaria infection at delivery, potentially informing postpartum risk prediction. Methods: We assessed a cohort of 33 primigravid women from Nanoro, Burkina Faso (mean age 19 years; range 18–20.5), at the time of delivery. Immune profiles were developed by measuring antibody responses to Plasmodium falciparum antigens (PfCSP, PfAMA-1, and EBA-175) and levels of key cytokines (IL-4, IL-10, IL-6, TNF-α, and IFN-γ) using enzyme immunoassays. Multivariate analyses, including principal component analysis (PCA) and hierarchical clustering, were used to detect immune profile patterns. Results: Three distinct immune profiles were identified: (1) a low-inflammatory cluster with reduced IL-6 and TNF-α; (2) a TNF-α–dominant cluster; and (3) a highly pro-inflammatory cluster with elevated IL-6 and TNF-α. Bootstrapping confirmed the stability of these clusters (AU ≥ 92%). All women in the most inflammatory cluster were infected with Plasmodium falciparum at delivery (Fisher’s exact test, p = 0.04). Conclusions: Cytokine-driven immune profiles at delivery reflect biologically distinct inflammatory states among primigravidae. Elevated IL-6 and TNF-α levels were strongly associated with active malaria infection at delivery. These findings highlight the potential of cytokine-based profiling as a hypothesis-generating tool for identifying women at increased risk of malaria around childbirth.