RESUMO
In 2000 we used a sensitive technique to examine 9 isolates from malaria patients in Muheza, Tanzania who had failed treatment with sulfadoxine-pyrimethamine (SP). Three isolates carried, at low levels, the leucine to isoleucine change at amino acid 164 that is associated with clinical failure of SP. Numerous other highly resistant alleles were also observed.
Assuntos
Antimaláricos/uso terapêutico , Resistência a Medicamentos/genética , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Pirimetamina/uso terapêutico , Tetra-Hidrofolato Desidrogenase/genética , Animais , Criança , Amplificação de Genes , Humanos , Plasmodium falciparum/enzimologia , Mutação Puntual/genética , Reação em Cadeia da Polimerase/métodos , TanzâniaRESUMO
We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya. We assessed the presence of mutations at codons 436, 437, 540, 581, and 613 of dhps. The results showed that the dhps genotype had a strong influence on the sensitivity to sulfadoxine and dapsone, but that the correlation was far from perfect. Eleven isolates carried a wild-type dhps allele, but were resistant to sulfadoxine (IC(50) values >10 microg/ml), and 4/28 isolates were classed as sensitive to sulfadoxine (IC(50) values <10 microg/ml), but carried a triple mutant (436/437/613) allele of dhps. These data show that in low folate medium in vitro, the dhps genotype alone did not account completely for sulfadoxine or dapsone resistance; other factors such as the utilisation of exogenous folate must also be considered.