title: Madagascan isolates of Plasmodium falciparum showing low sensitivity to artemether in vitro.
abstract: In Madagascar, although chloroquine (CQ) remains the first-line treatment of choice for malaria, the gradual spread of resistance to this antimalarial drug is of increasing concern. As part of a larger investigation of the effectiveness of the second- and third-line drugs used to treat malaria, the in-vitro susceptibilities of Plasmodium falciparum collected in Madagascar to CQ, mefloquine (MQ) and artemether (ART) were therefore investigated. Median inhibitory concentrations (IC(50)) were determined for isolates collected from residents of two villages in the foothills of the central highlands. The IC(50) for ART ranged from 0.23-17.50 nM [N = 51; geometric mean = 4.02 nM; 95% confidence interval (CI) = 2.99-5.05 nM], four isolates exhibiting IC(50) (> 12 nM) indicative of resistance to this drug. The artemether IC(50) were found to be correlated with those of CQ (N = 46; Spearman's r = 0.51; P = 0.0002), which varied widely (0.4-254.3 nM; mean = 23.4 nM; CI = 7.1-39.7 nM; N = 46). Five (11%) of the 46 isolates exposed to CQ in vitro were considered resistant to this drug (i.e. to have IC(50) > 100 nM), with IC(50) ranging from 109-245.3 nM (mean = 171.6 nM; CI = 110.4-232.8 nM). However, all the CQ-resistant isolates were considered sensitive to ART and vice versa. All the isolates tested also appeared sensitive to MQ (IC(50) = 2.21-43.1 nM; mean = 10.5 nM; CI = 7.95-13.07 nM; N = 46), the IC(50) for MQ being correlated with those for CQ (N = 46; Spearman's r =0.46; P = 0.001). There was no significant correlation between ART and MQ activities. Although the sample was fairly small, the present results indicate that P. falciparum in Madagascar is generally becoming less sensitive to CQ and ART. The observation of a correlation between the IC(50) for these two drugs perhaps indicates that artemisinin derivatives would be better used in combination with antimalarial drugs other than 4-aminoquinolines.
authors.affiliation: Laboratoire de Paludisme, Institut Pasteur de Madagascar, B.P. 1274, (101) Antananarivo, Madagascar.
authors.forename: M
authors.initials: M
authors.lastname: Randrianarivelojosia
authors.forename: L A
authors.initials: LA
authors.lastname: Raharimalala
authors.forename: L
authors.initials: L
authors.lastname: Randrianasolo
authors.forename: A
authors.initials: A
authors.lastname: Ratsimbasoa
authors.forename: M A
authors.initials: MA
authors.lastname: Rason
authors.forename: F
authors.initials: F
authors.lastname: Ariey
authors.forename: R
authors.initials: R
authors.lastname: Jambou
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D000077549:Artemether; D037621:Artemisinins; D002738:Chloroquine / Q000494:pharmacology*; D016001:Confidence Intervals; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006801:Humans; D015767:Mefloquine / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests / Q000379:methods; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*; D018709:Statistics, Nonparametric
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D002738:Chloroquine; D000077549:Artemether; D015767:Mefloquine