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

In malaria-endemic regions, women remain vulnerable to <i>Plasmodium falciparum</i> infection at the time of delivery. However, the immunological mechanisms underlying infection-associated inflammation in primigravid women remain poorly characterized. This exploratory study investigated cytokine-based immune profiles reflecting malaria infection status at delivery. We assessed 33 primigravid women from Nanoro, Burkina Faso (mean age 19 years; range 18-20.5) at childbirth. Antibody responses to <i>P. falciparum</i> antigens (<i>Pf</i>CSP, <i>Pf</i>AMA-1, and EBA-175) and plasma levels of cytokines (IL-4, IL-10, IL-6, TNF-α, and IFN-γ) were quantified using enzyme immunoassays. Multivariate analyses, including principal component analysis (PCA) and hierarchical clustering, identified three distinct immune profiles: (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. Cluster stability was supported by bootstrap analysis (AU ≥ 92%). All women in the most inflammatory cluster were <i>P. falciparum</i>-positive at delivery (Fisher's exact test, <i>p</i> = 0.04; exploratory association). These cytokine-driven profiles reflect biologically distinct inflammatory states associated with concurrent infection at delivery rather than predictive immune predispositions. The findings underscore the potential of cytokine profiling as a hypothesis-generating tool to guide future longitudinal studies on immune regulation and the postpartum period.