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

Abstract

BackgroundIn 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).MethodsThe 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.ResultsThe 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%.ConclusionsThe 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.

Impact of Antimalarial Treatment and Chemoprevention on the Drug Sensitivity of Malaria Parasites Isolated from Ugandan Children

“…Recent changes suggest that we should reconsider the use of aminoquinolines to treat malaria, including AS-AQ, which showed inferior efficacy to AL in Tanzania (54) and Uganda (55,56) some years ago but excellent recent efficacy in West and Central Africa (57-61); DP, which has shown excellent efficacy (7,(62)(63)(64)(65)(66); and perhaps combinations that include chloroquine (52,67). Further, we should be cautious regarding the long-term antimalarial efficacy of AL, as although both the clinical efficacy of AL (57)(58)(59)(60)(61)(64)(65)(66) and ex vivo activity of DHA and lumefantrine (31,42,(68)(69)(70) ies, current results suggest that the antimalarial potency of lumefantrine is decreasing. Our data show that antimalarial treatment regimens rapidly select for parasites with decreased drug sensitivity.…”

Pfmdr1 gene polymorphism of Plasmodium falciparum isolates from asymptomatic individuals of Dienga, southeastern Gabon

“…A surveillance of molecular markers of drug resistance, in parasites from asymptomatic individuals, a hidden reservoir, is particularly important to improve malaria control strategies. In sub-Saharan African countries, the monitoring of malaria and anti-malarial drug resistance in rural areas is unusual, as most data are commonly reported from urban areas in Gabon [24,26], in Zanzibar [31], Cameroon [32], Senegal [33] and Mozambique [34].…”

Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda

“…However, with widespread discontinued use, numerous molecular-epidemiological studies showed that there was return of chloroquine susceptibility in P. falciparum field isolates [4]. This is supported by ex vivo [5][6][7][8][9][10][11][12][13][14][15][16] and in vivo drug-susceptibility studies [5,17,18]. Findings suggest that chloroquine might be re-used in the future as an option for the treatment and/or chemoprophylaxis on the condition that chloroquine sensitivity is maintained in the area.…”