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Molecular surveillance of the antifolate-resistant mutation I164L in imported african isolates of Plasmodium falciparum in Europe: sentinel data from TropNetEurop

DOI: 10.1186/1475-2875-2-17

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TropNetEurop is a network for the surveillance of travel-associated diseases and seems to cover approximately 12% of all malaria cases imported into Europe. Within this network we screened 277 imported African isolates of P. falciparum with the help of PCR- and enzyme-digestion-methods for the antifolate-resistant mutation I164L.The I164L mutation was not detected in any of the isolates tested.Continuous molecular surveillance of mutations in P. falciparum, as it is practised within TropNetEurop, is an essential tool for the understanding and early detection of the spread of antimalarial drug resistance in Africa.Drug resistant malaria is a major problem in malaria control. At the present, there are few antimalarial drugs available in endemic areas which are both cheap and save. Since resistance to chloroquine has spread across sub-Saharan Africa, several countries have switched their first-line drug to the antifolate sulfadoxine-pyrimethamine [1].Soon after sulfadoxine-pyrimethamine was introduced to malaria-control programs in the late 1960s, resistance to this drug was noted [2]. The efficacy of sulfadoxine-pyrimethamine primarily depends on the sensitivity of the parasite to pyrimethamine [3]. The dihydrofolate reductase domain of Plasmodium falciparum (pfDHFR) is the target of this drug. DHFR catalyzes the reduction of dihydrofolate to regenerate tetrahydrofolate which is required for one-carbon transfer reactions and deoxythymidylate synthesis of the parasites.The discovery of changes in codons of the pfDHFR-gene strongly indicated that single amino acid changes lead to observed resistance. Mutations at amino acid position 51, 59, 108 and 164 have been shown to be linked with resistance of P. falciparum to antifolate antimalarials. A scheme for evolution of resistance could be derived as a result of stepwise mutations starting with the S108N mutation, which was shown to be the optimal mutation in leading to both the decreased binding affinity for inhibitors an


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