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Plasmodium falciparum susceptibility to anti-malarial drugs in Dakar, Senegal, in 2010: an ex vivo and drug resistance molecular markers study

Bécaye Fall1, Aurélie Pascual234, Fatoumata D Sarr5, Nathalie Wurtz23, Vincent Richard5, Eric Baret234, Yaya Diémé1, Sébastien Briolant23, Raymond Bercion1, Boubacar Wade6, Adama Tall5 and Bruno Pradines1234*

Author Affiliations

1 Laboratoire d’étude de la chimiosensibilité du paludisme, Fédération des laboratoires, Hôpital Principal de Dakar, Dakar, Sénégal

2 Unité de Parasitologie, Département d’Infectiologie de Terrain, Institut de Recherche Biomédicale des Armées, Marseille, France

3 Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Marseille, Inserm 1095, France

4 Centre National de référence du Paludisme, Marseille, France

5 Unité d’Epidémiologie des Maladies Infectieuses, Institut Pasteur de Dakar, Dakar, Sénégal

6 Chefferie, Hôpital Principal de Dakar, Dakar, Sénégal

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Malaria Journal 2013, 12:107  doi:10.1186/1475-2875-12-107

Published: 20 March 2013

Abstract

Background

In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. Since the introduction of ACT, there have been very few reports on the level of resistance of P. falciparum to anti-malarial drugs. To determine whether parasite susceptibility has been affected by the new anti-malarial policies, an ex vivo susceptibility and drug resistance molecular marker study was conducted on local isolates obtained from the Centre de santé Elizabeth Diouf (Médina, Dakar, Senegal).

Methods

The prevalence of genetic polymorphisms in genes associated with anti-malarial drug resistance, i.e., pfcrt, pfdhfr, pfdhps and pfmdr1, were evaluated for a panel of 165 isolates collected from patients recruited from 17 August 2010 to 6 January 2011. The malaria isolates were assessed for susceptibility to chloroquine (CQ); quinine (QN); monodesethylamodiaquine (MDAQ), the active metabolite of amodiaquine; mefloquine (MQ); lumefantrine (LMF); dihydroartemisinin (DHA), the active metabolite of artemisinin derivatives; and doxycycline (DOX) using the Plasmodium lactate dehydrogenase (pLDH) ELISA.

Results

The prevalence of the in vitro resistant isolates, or isolates with reduced susceptibility, was 62.1% for MQ, 24.2% for CQ, 10.3% for DOX, 11.8% MDAQ, 9.7% for QN, 2.9% for LMF and 0% for DHA. The Pfcrt 76T mutation was identified in 43.6% of the samples. The pfmdr1 86Y, 184F and 1246Y mutations were found in 16.2%, 50.0% and 1.6% of the samples, respectively. The pfdhfr 108N, 51I and 59R mutations were identified in 81.9%, 77.4% and 79.4% of the samples, respectively. The double mutant (108N and 51I) was detected in 75.5% of the isolates, and the triple mutant (108N, 51I and 59R) was detected in 73.6% of the isolates. The pfdhps 437G, 436A and 613S mutations were found in 54.4%, 38.6% and 1.2% of the samples, respectively. There was only one double mutant, 437G and 540E, and one quintuple mutant, pfdhfr 108N, 51I and 59R and pfdhps 437G and 540E. The prevalence of the quadruple mutant (pfdhfr 108N, 51I and 59R and pfdhps 437G) was 36.7%.

Conclusions

The results of this study indicate that an intensive surveillance of the in vitro P. falciparum susceptibility to anti-malarial drugs must be conducted in Senegal.

Keywords:
Malaria; Plasmodium falciparum; Anti-malarial; in vitro; Resistance; Molecular marker; Senegal