Plasmodium falciparum genotypes, low complexity of infection, and resistance to subsequent malaria in participants in the Asembo Bay cohort project

To assess the relationship between the within-host diversity of malaria inf ections and the susceptibility of the host to subsequent infection, we geno typed 60 children's successive infections from birth through 3 years of lif e. MSP-1 Block2 genotypes were used to estimate the complexity of infection (COI). Malaria transmission and age were positively associated with the nu mber of K1 and Mad20 alleles detected (COIKM) (P < 0.003). Controlling for previous parasitemia, transmission, drug treatment, parasite density, sickl e cell, and age, COIKM was negatively correlated with resistance to parasit emia of > 500/mul (P < 0.0001). Parasitemias with the RO-genotype were more resistant than those without this genotype (P < 0.0000). The resistance in low COIKM infections was not genotype specific. We discuss the impact of g enotype-transcending immunity to conserved antigenic determinants. We also propose a diversity-driven immunomodulation hypothesis that may explain the delayed development of natural immunity in the first few years of life and suggest that interventions that decrease the COIKM could facilitate the de velopment of protective immunity.