Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia

Malaria Journal

Case Report

Lionel Bertaux¹  Pascal Delaunay²  Christelle Pomares²  Pierre Marty²  Bruno Pradines³ 

[1] Centre National de Référence du Paludisme, Marseille, France;Unité de Recherche en Physiologie et Pharmacocinétique Parasitaires - UMR-MD3 Relations Hôte-Parasites - Pharmacologie et Thérapeutique, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France;Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire l'Archet, Nice, France;Inserm U 895, Equipe 6, Université de Nice Sophia Antipolis, Nice, France;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;Centre National de Référence du Paludisme, Marseille, France;

关键词: Malaria;    Doxycycline;    Quinine;    Mefloquine;    Artesunate;   

DOI  :  10.1186/1475-2875-10-268

 received in 2011-07-20, accepted in 2011-09-18,  发布年份 2011

来源: Springer

【 摘 要 】

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 IC50 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 IC50 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.

【 授权许可】

CC BY   
© Pradines et al; licensee BioMed Central Ltd. 2011