title: Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia.
abstract: Decreased in vitro susceptibility to dihydroartemisinin (21.2 nM) and artesunate (16.3 nM) associated with decreased susceptibility or resistance to quinine (1131 nM), mefloquine (166 nM), lumefantrine (114 nM), pyronaridine (70.5 nM) and piperaquine (91.1 nM) is reported in a patient returning from South-East Asia after trekking along the Mekong from the south of Laos to the north of Thailand. Decreased in vitro susceptibility to artemisinin derivatives did not appear to be mediated by the number of copies of pfmdr1 or pfATPase6, pfcrt, pfmdr1 or pfmrp polymorphism. The high IC(50) to mefloquine of this Asian isolate was not associated with pfmdr1 copy number. Pfnhe-1 microsatellite ms4760 showed a profile 7 (ms4760-7) with three repeats of DNNND and one repeat of DDDNHNDNHNN, which is associated with high quinine reduced susceptibility. The patient recovered in three days without relapse after treatment with the association of quinine and doxycycline. Decreased in vitro susceptibility to quinine and the delayed effect of doxycycline may both have contributed to the delayed parasite clearance time, D4 (0.5%) and D7 (0.004%). The in vitro data, with IC(50) for dihydroartemisinin and artesunate were up to ten times those of the reference clone W2, which suggests that this isolate may be resistant to artemisinin derivatives, associated with a decreased susceptibility to quinine.
authors.affiliation: Unité de Recherche en Biologie et Epidémiologie Parasitaires-Unité de Recherche pour les Maladies Infectieuses et Tropicales Emergentes-UMR 6236, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France. bruno.pradines@free.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
authors.forename: Lionel
authors.initials: L
authors.lastname: Bertaux
authors.forename: Christelle
authors.initials: C
authors.lastname: Pomares
authors.forename: Pascal
authors.initials: P
authors.lastname: Delaunay
authors.forename: Pierre
authors.initials: P
authors.lastname: Marty
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D001210:Asia, Southeastern; D004318:Doxycycline / Q000008:administration & dosage; D004351:Drug Resistance; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000469:parasitology*; D008875:Middle Aged; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics; D011803:Quinine / Q000008:administration & dosage; D014195:Travel; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D015800:Protozoan Proteins; C031327:artemisinin; D011803:Quinine; D004318:Doxycycline