RESUMO
The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria.
Assuntos
Antimaláricos/uso terapêutico , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Plasmodium falciparum/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Proteínas de Protozoários/genética , Alelos , Amodiaquina/uso terapêutico , Artemisininas/uso terapêutico , Brasil/epidemiologia , Variações do Número de Cópias de DNA , Combinação de Medicamentos , Genótipo , Haplótipos , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Família Multigênica , Mutação , Nigéria/epidemiologia , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Reação em Cadeia da Polimerase , Proteínas de Protozoários/metabolismo , Análise de Sequência de DNARESUMO
Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical application of the reversal phenomenon.
Assuntos
Amodiaquina/administração & dosagem , Antimaláricos/administração & dosagem , Cloroquina/administração & dosagem , Clorfeniramina/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Malária Falciparum/tratamento farmacológico , Adolescente , Animais , Criança , Pré-Escolar , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Lactente , Malária Falciparum/parasitologia , Proteínas de Membrana Transportadoras/genética , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Proteínas de Protozoários/genéticaRESUMO
Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical appliation of the reversal phenomenon.