| The purpose of this study was to identify environmental and host factors that distinguish children who remain persistently uninfected from those with persistent Plasmodium falciparum infection in the village of Bancoumana, Mali (West Africa). Previous studies have shown that sickle trait (Hb AS) protects against severe disease (but not infection) due to P. falciparum. Within a village-wide cohort of 2,000 children aged 0 to 9 years, we identified and followed 181 who were persistently smear negative, 476 who persistently smear positive, and 194 who were intermittently smear positive. In addition, 2 nested case-controls studies were conducted during the 1996 and 1997 transmission seasons (June to October) to identify risk/protective factors for parasitemia. During the 2 year study period from June 1996 to June 1998, 2 children remained persistently smear negative and 26 remained persistently smear positive. However, these 2 children had high titres (≥1:160) of antibodies against asexual P. falciparum, suggesting a previous parasitemia with this parasite. Sickle cell trait (Hb AS) was associated with protection against persistent parasitemia as manifested by a prolonged time to infection (HR = 0.56; 95% CI [0.33--0.96]; p = 0.036) after controlling for antimalarial treatment, spleen size and age. In contrast, neither Hb C nor ABO blood group protected against persistent parasitemia. The relationship between MN blood group and persistent parasitemia was suggestive, but inconclusive.;Older children (5--9 years) were infected at a rate that was twice that of younger children (0--4 years), after controlling for antimalarial therapy, spleen size, and hemoglobin (HR = 1.98; 95% CI [1.28--3.08]; p = 0.002). Persistently negative children were of higher socioeconomic status than persistently positive children. These results suggest that children in Bancoumana are universally susceptible to P. falciparum infection. The existence of an absolute resistance to P. falciparum cannot be ruled out from this study. However, if refractoriness to P. falciparum exists in this region of Africa, its frequency must be less than 1 in 2,000 children. Further research on the biological factors associated with a delayed time to infection among sickle trait children may increase our understanding of P. falciparum interactions with human red blood cells. |
