Factors associated with decreased Plasmodium falciparum infection risk in Malian children.

Malaria control efforts remain suboptimal for many reasons including knowledge gaps in malaria epidemiology and immunology. To better understand the epidemiologic and immunologic factors associated with risk of P. falciparum infection and clinical malaria, we conducted a longitudinal cohort study of 695 individuals aged 3 months to 25 years in the rural village of Kalifabougou, Mali. We did bi-weekly active surveillance for P. falciparum infection by PCR and weekly active clinical surveillance for clinical malaria. Nearly all adults and children over four years of age became infected during the malaria season at a rate that was independent of age (log-rank test, p =.37), indicating that sterile immunity to P. falciparum infection is not acquired through natural exposure; and as expected, the risk of clinical malaria decreased with increasing age (logrank test, p =.0038). Surprisingly, we observed that children under 4 years of age were less likely to be infected with P. falciparum compared to older subjects (p <0.0001), and indeed, 24% of children under 4 years of age remained PCR negative throughout the intense 6-month malaria season. Exposure was measured by antibody response to gSG6, an Anopheles gambiae specific salivary protein, and results indicate that uninfected children were less likely to have serologic evidence of exposure to the mosquito vector over the course of the malaria season. Self-reported bed net use was not different between infected and uninfected children. Because evidence of decreased exposure did not fully explain decreased infection risk in young children, we are taking several approaches to test the hypothesis that uninfected children have enhanced pre-erythrocytic immunity and/or that developmental differences render young children less permissive to P. falciparum infection. Findings from this study may help inform strategies to prevent P. falciparum infection in malaria endemic areas.