Elevated adiponectin and altered metabolic signaling in asymptomatic malaria: a community-based study of Nigerian children

Asymptomatic Plasmodium falciparum infection is common among school-aged children in endemic settings, yet its metabolic consequences are poorly defined. We investigated whether subclinical malaria is associated with altered adipocytokine profiles in Nigerian children and whether effects vary with parasite density. In a community-based cross-sectional survey in Ibadan, Nigeria, we enrolled 317 primary-school children and ascertained malaria by rapid test and light microscopy. Plasma adiponectin, leptin, and resistin were quantified using validated enzyme immunoassays, and the leptin-to-adiponectin ratio was derived. Multivariable linear models with clustering by school evaluated associations between asymptomatic malaria and each biomarker, adjusting for age, sex, height-for-age and body-mass-index-for-age z-scores, socioeconomic status, and hemoglobin. Sensitivity analyses restricted exposure to microscopy-confirmed infection and to participants with C-reactive protein [≤]3 mg/L. Among malaria-positive children, we examined correlations between parasite density and adipocytokines with false discovery rate control. Of 317 children, 102 (32.2%) had asymptomatic parasitemia. Compared with uninfected peers, infected children had higher adiponectin (geometric mean 45.2 vs 32.1 g/mL) and a lower leptin-to-adiponectin ratio. In adjusted analyses, asymptomatic malaria was associated with +42% adiponectin (95% CI 18 to 71) and -31% leptin-to-adiponectin ratio (95% CI, -49 to -7); leptin and resistin were not independently associated with infection status. Among malaria-positive children, higher parasite density correlated with higher adiponectin (Spearman 0.31; 95% CI, 0.12 to 0.47), while correlations with other markers were not significant. Findings were consistent in sensitivity analyses, including after restricting to low C-reactive-protein samples. Asymptomatic malaria in childhood is characterized by elevated adiponectin and a reduced leptin-to-adiponectin ratio, indicating altered metabolic signaling during subclinical infection. The dose-response with parasite density suggests that ostensibly silent infections are metabolically active. These results suggest considering metabolic factors in child-focused malaria control strategies and motivate tests of whether treating asymptomatic infection normalizes metabolic signals and improves longer-term health.