Abstract
Background The use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in Southeast Asia. Monitoring of artemisinin combination therapy (ACT) is critical in order to detect and prevent the spread of resistance in endemic areas. Ex vivo studies and genotyping of molecular markers of resistance can be used as part of this routine monitoring strategy. One gene that has been associated in some ACT partner drug resistance is the Plasmodium falciparum multidrug resistance protein 1 (pfmdr1) gene. The purpose of this study was to assess the drug susceptibility of P. falciparum populations from Thiès, Senegal by ex vivo assay and typing molecular markers of resistance to drug components of ACT currently used for treatment.Methods The ex vivo susceptibility of 170 P. falciparum isolates to chloroquine, amodiaquine, lumefantrine, artesunate, and artemether was determined using the DAPI ex vivo assay. The high resolution melting technique was used to genotype the pfmdr1 gene at codons 86, 184 and 1246.ResultsA significant decrease in IC50 values was observed between 2012 and 2013: from 13.84 to 6.484 for amodiaquine, 173.4 to 113.2 for lumefantrine, and 39.72 to 18.29 for chloroquine, respectively. Increase of the wild haplotype NYD and the decrease of the mutant haplotype NFD (79 and 62.26 %) was also observed. A correlation was observed between the wild type allele Y184 in pfmdr1 and higher IC50 for all drugs, except amodiaquine.ConclusionThis study has shown an increase in sensitivity over the span of two transmission seasons, marked by an increase in the WT alleles at pfmdr1. Continuous the monitoring of the ACT used for treatment of uncomplicated malaria will be helpful.
Highlights
The use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in Southeast Asia
Since April 2001, the World Health Organization (WHO) has recommended the use of artemisinin-based combination therapy (ACT) in countries where P. falciparum is resistant to CQ, SP, and amodiaquine (AMQ), to avoid early emergence of resistance to these molecules [6]
This work aims to study the consequences of use of artemisinin combination therapy (ACT) (ASAQ and artemether– lumefantrine combination (AL)) for uncomplicated malaria treatment in Senegal by using the ex vivo sensitivity to ARS, AMQ, artemether (AMT) and lumefantrine (LUM) of P. falciparum isolates from Thiès collected during the transmission period of malaria combined to the pfmdr1 gene polymorphism at codon N86 86Y MIXTE (N86Y), N184F and D1246Y
Summary
The use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in Southeast Asia. Since April 2001, the World Health Organization (WHO) has recommended the use of artemisinin-based combination therapy (ACT) in countries where P. falciparum is resistant to CQ, SP, and amodiaquine (AMQ), to avoid early emergence of resistance to these molecules [6]. Despite these efforts, cases of resistance to artemisinin (ART) have emerged in Cambodia and in other regions of Southeast Asia [7]. The haplotype N86F184D1246 is selected by a high drug pressure of AL [15, 16], while 1034C, 1042D and 1246Y mutations have been reported to confer resistance against quinine (QN) and increased susceptibility to MQ, halofantrine (HF) and ART [17, 18]
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