IMBALANCED DISTRIBUTION OF PLASMODIUM-FALCIPARUM MSP-1 GENOTYPES RELATED TO SICKLE-CELL TRAIT

Background: The sickle-cell trait protects against severe Plasmodium f alciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by vir tue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and A A subjects. Materials and Methods: Blood was collected from asymptomat ic individuals living in two different regions of Africa. The polymorp hic MSP-1 and MSP-2 lod were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specifi c probes. Multivariate logistic regression was used to analyze allele distribution. Results: In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families a nd had an impact on distinct individual alleles, whereas the distribut ion of MSP-2 alleles was marginally affected. There was no influence o f other genetic traits, including the HLA Bw53 genotype, or factors su ch as place of residence within the village. In a cohort of Gabonese s choolchildren in which the influence of age was abrogated, a similar i mbalance in the MSP-1 allelic distribution but not of MSP-2 allelic di stribution by hemoglobin type was observed. Conclusions: The influence of the host's hemoglobin type on P. falciparum genotypes suggests tha t parasite fitness for a specific host is strain-dependent, which is c onsistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle- cell traits.