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

• Main Authors: Bertaux Lionel, Pradines Bruno, Pomares Christelle, Delaunay Pascal, Marty Pierre
• Format: Article
• Language: English
• Published: BMC 2011-09-01
• Series: Malaria Journal
• Online Access: http://www.malariajournal.com/content/10/1/268

<p>Abstract</p> <p>Decreased <it>in vitro </it>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 <it>in vitro </it>susceptibility to artemisinin derivatives did not appear to be mediated by the number of copies of <it>pfmdr1 </it>or <it>pfATPase6, pfcrt, pfmdr1 </it>or <it>pfmrp </it>polymorphism. The high IC₅₀to mefloquine of this Asian isolate was not associated with <it>pfmdr1 </it>copy number. <it>Pfnhe-1 </it>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 <it>in vitro </it>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 <it>in vitro </it>data, with IC₅₀for 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.</p>