Molecular analysis of Plasmodium falciparum infections in man]

Plasmodium falciparum diversity has been analysed in two Senegalese villages with different transmission conditions and distinct kinetics of immunity acquisition. A very large allelic polymorphism was observed in both villages, with a similar number of alleles but quite distinct allelic frequencies, indicating a substantial micro-geographical heterogeneity of malaria parasite populations. In addition, the molecular characteristics of the infections differed in both villages. As in most endemic areas, many infected subjects carry multiple parasite clones. In Dielmo, the number of distinct clones hosted decreases at the age of acquisition of an efficient immunity. There was no influence of age on the number of clones hosted in Ndiop where adults experience clinical attacks. This indicates that complexity reflects acquired immunity. The precise longitudinal follow-up of parasitaemia, clinical signs and parasite genetic characteristics showed a rapid turn over of parasite populations in the peripheral blood during the transmission season, suggesting that immunity does not prevent infection but restricts multiplication of numerous genotypes at the erythrocytic stage. Clinical malaria occurs after a rapid, apparently unrestricted growth of recently inoculated parasites. The successive clinical attacks experienced by children are associated with genotypes different for each attack and different from those that the child carried during preceding asymptomatic phases. These data indicate that parasite diversity contributes to the pathology of infection and that control of parasite density, which is at least in part strain-specific, is an essential element of protection against malaria clinical attacks.