Ex vivo drug sensitivity profiles of Plasmodium falciparum field isolates from Cambodia and Thailand, 2005 to 2010, determined by a histidine-rich protein-2 assay

Tyner, Lon Chanthap, Se Youry, Bethell Delia, Socheat Doung, Noedl Harald, Sea Darapiseth, Satimai Wichai, Schaecher Kurt, Rutvisuttinunt Wiriya, Fukuda, Chaorattanakawee Suwanna, Yingyuen Kritsanai, Sundrakes Siratchana, Chaichana Panjaporn, Saingam Piyaporn, Buathong Nillawan, Sriwichai Sabaithip, Chann Soklyda, Timmermans Ans, Saunders, Walsh

Description

In vitro drug susceptibility assay of Plasmodium falciparum field isolates processed “immediate ex vivo ” (IEV), without culture adaption, and tested using histidine-rich protein-2 (HRP-2) detection as an assay, is an expedient way to track drug resistance. Methods From 2005 to 2010, a HRP-2 in vitro assay assessed 451 P. falciparum field isolates obtained from subjects with malaria in western and northern Cambodia, and eastern Thailand, processed IEV, for 50% inhibitory concentrations (IC 50 ) against seven anti-malarial drugs, including artesunate (AS), dihydroartemisinin (DHA), and piperaquine. Results In western Cambodia, from 2006 to 2010, geometric mean (GM) IC 50 values for chloroquine, mefloquine, quinine, AS, DHA, and lumefantrine increased. In northern Cambodia, from 2009–2010, GM IC 50 values for most drugs approximated the highest western Cambodia GM IC 50 values in 2009 or 2010. Conclusions Western Cambodia is associated with sustained reductions in anti-malarial drug susceptibility, including the artemisinins, with possible emergence, or spread, to northern Cambodia. This potential public health crisis supports continued in vitro drug IC 50 monitoring of P. falciparum isolates at key locations in the region.

Sujets

• Cambodia
• Malaria
• Plasmodium falciparum
• HRP-2
• Drug resistance

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 15
• Langue: English

Extrait

Tyneret al. Malaria Journal2012,11:198 http://www.malariajournal.com/content/11/1/198

R E S E A R C HA R T I C L EOpen Access Ex vivodrug sensitivity profiles ofPlasmodium falciparumfield isolates from Cambodia and Thailand, 2005 to 2010, determined by a histidinerich protein2 assay 1†1*†2 321 1 Stuart D Tyner, Chanthap Lon, Youry Se , Delia Bethell , Doung Socheat , Harald Noedl , Darapiseth Sea , 4 11 11 Wichai Satimai , Kurt Schaecher , Wiriya Rutvisuttinunt , Mark M Fukuda , Suwanna Chaorattanakawee , 1 1 11 1 Kritsanai Yingyuen , Siratchana Sundrakes , Panjaporn Chaichana , Piyaporn Saingam , Nillawan Buathong , 1 11 11 Sabaithip Sriwichai , Soklyda Chann , Ans Timmermans , David L Saundersand Douglas S Walsh

Abstract Background:In vitrodrug susceptibility assay ofPlasmodium falciparumfield isolates processed“immediateex vivo” (IEV), without culture adaption, and tested using histidinerich protein2 (HRP2) detection as an assay, is an expedient way to track drug resistance. Methods:From 2005 to 2010, a HRP2in vitroassay assessed 451P. falciparumfield isolates obtained from subjects with malaria in western and northern Cambodia, and eastern Thailand, processed IEV, for 50% inhibitory concentrations (IC 50 ) against seven antimalarial drugs, including artesunate (AS), dihydroartemisinin (DHA), and piperaquine. Results:In western Cambodia, from 2006 to 2010, geometric mean (GM) IC 50 values for chloroquine, mefloquine, quinine, AS, DHA, and lumefantrine increased. In northern Cambodia, from 2009–2010, GM IC 50 values for most drugs approximated the highest western Cambodia GM IC 50 values in 2009 or 2010. Conclusions:Western Cambodia is associated with sustained reductions in antimalarial drug susceptibility, including the artemisinins, with possible emergence, or spread, to northern Cambodia. This potential public health crisis supports continuedin vitrodrug IC 50 monitoring ofP. falciparumisolates at key locations in the region. Keywords:Cambodia, malaria,Plasmodium falciparum, HRP2, Antimalarial drugs, Drug resistance

Background Since the 1980s, measuringin vitrodrug 50% inhibitory concentrations (IC 50 ) againstP. falciparumfield isolates has been useful in tracking clinical drug susceptibility patterns [13]. In Southeast Asia, especially along the ThailandCambodia border, changes in drug susceptibil ity often emerge first, with worldwide implications,

* Correspondence: [e-mail] † Equal contributors 1 Department of Immunology and Medicine, US Army Medical Corps, Armed Forces Research Institute of Medical Sciences (USAMCAFRIMS), Bangkok, Thailand Full list of author information is available at the end of the article

underscoring the region’s importance as a sentinel site for antimalarial drug resistance [3]. In 2003, artesunate (AS)+ mefloquine(MQ) was implemented as the firstline artemisinincombination therapy (ACT) for falciparum malaria in Cambodia. By 2005, subjects with falciparum malaria along ThaiCam bodia border treated with oral artesunate were showing longer parasite clearance times, suggesting the emer gence of reduced susceptibility to artemisinins, as well as to the partner drug [4]. The nonradioisotope histidinerich protein2 (HRP2) ELISA, a relatively sensitive assay, which reliably depicts drug IC 50 values forP. falciparumisolates, reduces obstacles for conducting assays in remote settings [5,6].

© 2012 Tyner et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.