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Malaria Journal

, 15:347

First Online: 07 July 2016Received: 19 March 2016Accepted: 08 June 2016DOI: 10.1186-s12936-016-1379-2

Cite this article as: Boussaroque, A., Fall, B., Madamet, M. et al. Malar J 2016 15: 347. doi:10.1186-s12936-016-1379-2

Abstract

BackgroundTo determine the impact of the introduction of artemisinin-based combination therapy ACT on parasite susceptibility, a molecular surveillance for antimalarial drug resistance was conducted on local isolates from the Hôpital Principal de Dakar between November 2013 and January 2014 and between August 2014 and December 2014.

MethodsThe prevalence of genetic polymorphisms in antimalarial resistance genes pfcrt, pfmdr1, pfdhfr and pfdhps was evaluated in 103 isolates.

ResultsThe chloroquine-resistant haplotypes CVIET and CVMET were identified in 31.4 and 3.9 % of the isolates, respectively. The frequency of the pfcrt K76T mutation was increased from 29.3 % in 2013–2014 to 43.2 % in 2014. The pfmdr1 N86Y and Y184F mutations were identified in 6.1 and 53.5 % of the isolates, respectively. The pfdhfr triple mutant S108N, N51I and C59R was detected in the majority of the isolates 82.3 %. The prevalence of quadruple mutants pfdhfr S108N, N51I, C59R and pfdhps A437G was 40.4 %. One isolate 1.1 % harboured the pfdhps mutations A437G and K540E and the pfdhfr mutations S108N, N51I and C59R.

ConclusionsDespite a decline in the prevalence of chloroquine resistance due to the official withdrawal of the drug and to the introduction of ACT, the spread of resistance to chloroquine has continued. Furthermore, susceptibility to amodiaquine may be decreased as a result of cross-resistance. The frequency of the pfmdr1 mutation N86Y declined while the Y184F mutation increased in prevalence, suggesting that selective pressure is acting on pfmdr1, leading to a high prevalence of mutations in these isolates and the lack of specific mutations. The 50.5 % prevalence of the pfmdr1 polymorphisms N86Y and Y184F suggests a decrease in lumefantrine susceptibility. Based on these results, intensive surveillance of ACT partner drugs must be conducted regularly in Senegal.

KeywordsMalaria Plasmodium falciparum Anti-malarial In vitro Resistance Senegal Molecular marker AbbreviationsACTartemisinin-based combination therapy

pfcrtPlasmodium falciparum chloroquine resistance transporter gene

pfmdr1Plasmodium falciparum multidrug resistance 1 gene

pfdhfrPlasmodium falciparum dihydrofolate reductase gene

pfdhpsPlasmodium falciparum dihydropteroate synthase

IPTintermittent preventive treatment

WHOWorld Health Organization

SNPssingle-nucleotide polymorphisms

DNAdeoxyribonucleic acid

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Autor: Agathe Boussaroque - Bécaye Fall - Marylin Madamet - Khalifa Ababacar Wade - Mansour Fall - Aminata Nakoulima - Khadidiato

Fuente: https://link.springer.com/







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