Characterization of Plasmodium falciparum isolated from the Amazon region of Brazil: evidence for quinine resistance.
Am J Trop Med Hyg
; 58(5): 630-7, 1998 May.
Article
em En
| MEDLINE
| ID: mdl-9598453
The prevalence and severity of drug-resistant malaria is emerging rapidly in the Amazon basin of Brazil. In support of clinical trials using the new antimalarial drug combination of atovaquone and proguanil, we performed in vitro drug sensitivities, molecular characterization of parasite populations using the circumsporozoite protein, merozoite surface antigen-1 (MSA-1), and MSA-2 markers, and an analysis of the Plasmodium falciparum multidrug resistance (pfmdr1) gene sequence and copy number in 26 isolates of P. falciparum obtained in a gold-mining endemic area in Peixoto de Azevedo, Mato Grosso State. All 26 isolates were found to be resistant to chloroquine (50% inhibitory concentration [IC50] = 100-620 nM) and sensitive to mefloquine (IC50 < 23 nM) and halofantrine (IC50 < 6 nM). The isolates also show reduced susceptibility to quinine (IC50 = 48-280 nM). Sequence analysis of the pfmdr1 gene revealed Asn, Phe, Cys, Asp, and Tyr in positions 86, 184, 1034, 1042, and 1246, respectively. These point mutations were similar to that previously described in other Brazilian isolates. Southern blot analysis revealed no amplification of the pfmdr1 gene. These results suggest that three different mechanisms for drug resistance exist for chloroquine, mefloquine, and quinine.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Proteínas de Protozoários
/
DNA de Protozoário
/
Transportadores de Cassetes de Ligação de ATP
/
Antimaláricos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
País/Região como assunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Am J Trop Med Hyg
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos