Human resistance to Plasmodium falciparum increases during puberty and is predicted by dehydroepiandrosterone sulfate levels

Immunity to Plasmodium falciparum develops slowly in areas of endemicity, a nd this is often ascribed to poorly immunogenic or highly variant parasite antigens, However, among populations newly exposed to malaria, adults acqui re immunity more rapidly than children. We examined the relationship betwee n pubertal development and resistance to P. falciparum, During two transmis sion seasons in western Kenya, we treated the same cohort of young males to eradicate P. falciparum and then obtained blood smears each week for 4 mon ths. We determined pubertal development by Tanner staging and by levels of dehydroepiandrosterone sulfate (DHEAS) and testosterone in plasma. In multi variate and age-stratified analyses, we examined the effect of pubertal dev elopment on resistance to malaria. In both seasons (:n = 248 and 144 volunt eers, respectively), older males were less susceptible than younger males. Age-related decreases in the frequency and density of parasitemia were grea test during puberty (15- to 20-year-olds). DHEAS and testosterone were sign ificant independent predictors of resistance to P, falciparum parasitemia, even after accounting for the effect of age. Fifteen- to 20-year-old males with high DHEAS levels had a 72% lower mean parasite density (P < 0.01) tha n individuals with low DHEAS levels. Similarly, 21- to 35-year-old males wi th high DHEAS levels had a 92% lower mean parasite density (P < 0.001) and 48% lower frequency of parasitemia (P < 0.05) than individuals with low DHE AS levels. These data suggest that the long period needed to attain full im munity could be explained as a consequence of host development rather than as the requirement to recognize variant or poorly immunogenic parasite anti gens.