title: Plasmodium falciparum susceptibility to anti-malarial drugs in Dakar, Senegal, in 2010: an ex vivo and drug resistance molecular markers study.
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.
authors.affiliation: Laboratoire d'étude de la chimiosensibilité du paludisme, Fédération des laboratoires, Hôpital Principal de Dakar, Dakar, Sénégal.
authors.forename: Bécaye
authors.initials: B
authors.lastname: Fall
authors.forename: Aurélie
authors.initials: A
authors.lastname: Pascual
authors.forename: Fatoumata D
authors.initials: FD
authors.lastname: Sarr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wurtz
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Eric
authors.initials: E
authors.lastname: Baret
authors.forename: Yaya
authors.initials: Y
authors.lastname: Diémé
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briolant
authors.forename: Raymond
authors.initials: R
authors.lastname: Bercion
authors.forename: Boubacar
authors.initials: B
authors.lastname: Wade
authors.forename: Adama
authors.initials: A
authors.lastname: Tall
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000494:pharmacology*; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics; D012675:Senegal; D055815:Young Adult
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D007770:L-Lactate Dehydrogenase