Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs

Abstract

BackgroundAs a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT) (which includes artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar.MethodsThe ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH) ELISA for the following drugs: chloroquine (CQ), quinine (QN), mefloquine (MQ), monodesethylamodiaquine (MDAQ), lumefantrine (LMF), dihydroartemisinin (DHA) and doxycycline (DOX).ResultsAfter transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50), the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P < 0.0001), LMF and QN (r = 0.511; P < 0.0001), LMF and DHA (r = 0.428; P = 0.0001), LMF and MQ (r = 0.413; P = 0.0002), QN and DHA (r = 0.402; P = 0.0003) and QN and MQ (r = 0.421; P = 0.0001).ConclusionsThe introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.

Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

“…Thus, after several years of extensive use of artesunate plus amodiaquine and of artemether plus lumefantrine as first-line treatments for P. falciparum malaria in Niger, there is no evidence of a decline in sensitivity to artemisinin. Our data are similar to those reported in Senegal and Congo and are consistent with findings of studies indicating a lack of decrease in sensitivity to artesunate in Gabon, Senegal, and Djibouti despite the extensive and growing use of ACT in these regions (12)(13)(14)(15)(16)(17)(18). A decrease in parasite susceptibility to artemisinin derivatives has been reported to date only in Southeast Asia along the border between Thailand and Cambodia.…”

High-Throughput Analysis of Antimalarial Susceptibility Data by the WorldWide Antimalarial Resistance Network (WWARN) In Vitro Analysis and Reporting Tool

“…Fourteen data sets from 11 laboratories fulfilled these criteria ( Table 1). The laboratory methodologies for many of these studies have been described previously (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). The primary growth outputs from assays were formatted as uniform 12-by-8 96-well plate layouts in spreadsheets to facilitate automated processing and analysis.…”

Absence of Association between Polymorphisms in the RING E3 Ubiquitin Protein Ligase Gene and Ex Vivo Susceptibility to Conventional Antimalarial Drugs in Plasmodium falciparum Isolates from Dakar, Senegal

“…We did not find in field isolates that P. falciparum parasites carrying the mutation D113N allele for this gene were less susceptible in vitro to CQ and DQ as previously shown in genetically modified parasites (8). The isolates were categorized as being susceptible or resistant or showing reduced susceptibility using the following cutoff values: 77 nM (CQ), 61 nM (DQ), 115 nM (LMF), 12 nM (DHA and AS), 611 nM (QN), 30 nM (MQ), 135 nM (PPQ), 60 nM (PND), and 37 M (DOX) (10,11). These cutoff values for reduced in vitro susceptibility to antimalarial drugs were previously estimated using the arithmetic mean plus two standard deviations of the IC 50 s (10, 11).…”