Prevalence of mutations in dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum: analysis of imported cases of malaria in Italy

Excerpt

The human malaria parasite Plasmodium falciparum is the main cause of mortality and morbility in tropical and subtropical regions, particularly in Africa. In an increasing number of countries the effectiveness of routinely administered antimalarial drugs like chloroquine and pyrimethamine/sulfadoxine (PM/SX) has been severely reduced by the development of multidrug resistance in P. falciparum [1‐3]. This is particularly evident in sub-Saharan regions where malaria is endemic. Resistance of P. falciparum to antifolate has been correlated with point mutations in the dhfr gene encoding the enzyme dihydrofolate reductase, which is selectively inhibited by PM and cycloguanil, and in the dhps gene encoding the enzyme dihydropteroate synthetase, which is selectively inhibited by SX [2‐4]. These gene mutations have been validated as markers of antifolate resistance in epidemiological analyses of the dhfr and dhps P. falciparum genes conducted in several regions endemic for malaria where the levels of PM/SX sensitivity differ. They have also been demonstrated in molecular surveillance studies of drug resistance performed on imported isolates of P. falciparum in Europe [4‐6]. Following these approaches, our study was aimed at investigating the prevalence of point mutations in dhps and dhfr genes of P. falciparum in isolates obtained from Italian travellers and immigrants who had returned to Italy from sub-Saharan countries. …