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Background  Resistance of the malaria parasite  Plasmodium falciparum  to sulfadoxine-pyrimethamine (SP) has evolved worldwide. In the archipelago of São Tomé and Principe (STP), West Africa, although SP resistance is highly prevalent the drug is still in use in particular circumstances. To address the evolutionary origins of SP resistance in these islands, we genotyped point mutations at  P. falciparum dhfr  and  dhps  genes and analysed microsatellites flanking those genes.    Methods  Blood samples were collected in July and December 2004 in three localities of São Tomé Island and one in Principe Island. Species-specific nested-PCR was used to identify  P. falciparum  infected samples. Subsequently, SNPs at the  dhfr  and  dhps  genes were identified through PCR-RFLP. Isolates were also analysed for three microsatellite loci flanking the  dhfr  gene, three loci flanking  dhps  and four loci located at putative neutral genomic regions.    Results  An increase of resistance-associated mutations at  dhfr  and  dhps  was observed, in particular for the  dhfr / dhps  quintuple mutant, associated with clinical SP failure. Analysis of flanking microsatellites suggests multiple independent introductions for  dhfr  and  dhps  mutant haplotypes, possibly from West Africa. A reduced genetic diversity and increased differentiation at flanking microsatellites when compared to neutral loci is consistent with a selective sweep for resistant alleles at both loci.    Conclusions  This study provides additional evidence for the crucial role of gene flow and drug selective pressures in the rapid spread of SP resistance in  P. falciparum  populations, from only a few mutation events giving rise to resistance-associated mutants. It also highlights the importance of human migration in the spread of drug resistant malaria parasites, as the distance between the islands and mainland is not consistent with mosquito-mediated parasite dispersal.

Tracing the origins and signatures of selection of antifolate resistance in island populations of Plasmodium falciparum