RESUMO

The global emergence and spread of malaria parasites resistant to antimalarial drugs is the major problem in malaria control. The genetic basis of the parasite's resistance to the antimalarial drug chloroquine (CQ) is well-documented, allowing for the analysis of field isolates of malaria parasites to address evolutionary questions concerning the origin and spread of CQ-resistance. Here, we present DNA sequence analyses of both the second exon of the Plasmodium falciparum CQ-resistance transporter (pfcrt) gene and the 5' end of the P. falciparum multidrug-resistance 1 (pfmdr-1) gene in 40 P. falciparum field isolates collected from eight different localities of Odisha, India. First, we genotyped the samples for the pfcrt K76T and pfmdr-1 N86Y mutations in these two genes, which are the mutations primarily implicated in CQ-resistance. We further analyzed amino acid changes in codons 72-76 of the pfcrt haplotypes. Interestingly, both the K76T and N86Y mutations were found to co-exist in 32 out of the total 40 isolates, which were of either the CVIET or SVMNT haplotype, while the remaining eight isolates were of the CVMNK haplotype. In total, eight nonsynonymous single nucleotide polymorphisms (SNPs) were observed, six in the pfcrt gene and two in the pfmdr-1 gene. One poorly studied SNP in the pfcrt gene (A97T) was found at a high frequency in many P. falciparum samples. Using population genetics to analyze these two gene fragments, we revealed comparatively higher nucleotide diversity in the pfcrt gene than in the pfmdr-1 gene. Furthermore, linkage disequilibrium was found to be tight between closely spaced SNPs of the pfcrt gene. Finally, both the pfcrt and the pfmdr-1 genes were found to evolve under the standard neutral model of molecular evolution.

Assuntos

RESUMO

Se realizó una evaluación in vivo de la eficacia de la cloroquina para el tratamiento de la malaria por Plasmodium vivax, en elsitio centinela de Palmar Chico, Municipio de Yacuiba, Provincia Gran Chaco, Departamento de Tarija al Sur de Bolivia. Fueronincluidos en el estudio 61 pacientes entre 5 y 59 años de edad que presentaban monoinfección por P. vivax. Todos los pacientesrecibieron una dosis total de cloroquina de 25 mg/Kg en 3 días (10mg/Kg el primer día; 7,5 mg/Kg el segundo y tercer días).De acuerdo al protocolo estandarizado de la OPS/OMS, todos los pacientes fueron seguidos por 28 días (controles clínicos yparasitológicos). Se completó el seguimiento de 60 pacientes, ninguno de los pacientes tuvo recurrencias de la parasitemia opresentó manifestaciones clínicas después del tercer día de tratamiento. Este estudio mostró 100% de sensibilidad de P. vivaxa la cloroquina, lo que justifica su permanencia en la política de medicamentos antimaláricos como la droga más adecuada parael tratamiento de las infecciones por P. vivax en el Sur de Bolivia.

We carried out an evaluation in vivoof the chloroquine efficacy for the treatment of malaria by Plasmodium vivax, in the sentinelsite of Palmar Chico, Municipality of Yacuiba, Province Gran Chaco, Department of Tarija to the South of Bolivia. Sixty one patientsaged between 5 and 59 years that presented monoinfection by P. vivaxwere included in the study. All patient received undersupervision a total dose of chloroquine 25mg/kg over three days (10mg/kg on the first day; 7.5 mg/kg on the second and thirddays). According the standardized protocol of the PAHO/WHO, all patients were followed-up for 28 days (clinical and parasitologicalcontrols). Sixty patients completed the follow-up, none of the patients had recurrences of parasitemia or presented clinicalmanifestations after third day of treatment. This study showed 100% of sensibility from P. vivax to chloroquine, what justifies theirpermanency in the antimalarial drug policy as the most adequate drug for the treatment of the P. vivax infections in the South of Bolivia.

Assuntos