Simple jQuery Dropdowns
Please use this identifier to cite or link to this item:
Title: Ex vivo piperaquine resistance developed rapidly in Plasmodium falciparum isolates in northern Cambodia compared to Thailand
Authors: Suwanna Chaorattanakawee
Chanthap Lon
Krisada Jongsakul
Jariyanart Gawee
Somethy Sok
Siratchana Sundrakes
Nareth Kong
Chatchadaporn Thamnurak
Soklyda Chann
Sorayut Chattrakarn
Chantida Praditpol
Nillawan Buathong
Nichapat Uthaimongkol
Philip Smith
Narongrid Sirisopana
Rekol Huy
Satharath Prom
Mark M. Fukuda
Delia Bethell
Douglas S. Walsh
Charlotte Lanteri
David Saunders
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Royal Thai Army
Royal Cambodian Armed Forces
National Center for Parasitology, Entomology and Malaria Control
Brooke Army Medical Center
Keywords: Immunology and Microbiology;Medicine
Issue Date: 21-Oct-2016
Citation: Malaria Journal. Vol.15, No.1 (2016)
Abstract: © 2016 The Author(s). Background: The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. Methods: Ex vivo parasite susceptibilities were tracked to determine the rate of progression of DHA, PPQ and mefloquine (MQ) resistance from sentinel sites on the Thai-Cambodian and Thai-Myanmar borders from 2010 to 2015. Immediate ex vivo (IEV) histidine-rich protein 2 (HRP-2) assays were used on fresh patient Plasmodium falciparum isolates to determine drug susceptibility profiles. Results: IEV HRP-2 assays detected the precipitous emergence of PPQ resistance in Cambodia beginning in 2013 when 40 % of isolates had an IC90 greater than the upper limit of prior years, and this rate doubled to 80 % by 2015. In contrast, Thai-Myanmar isolates from 2013 to 14 remained PPQ-sensitive, while northeastern Thai isolates appeared to have an intermediate resistance profile. The opposite trend was observed for MQ where Cambodian isolates appeared to have a modest increase in overall sensitivity during the same period, with IC50 declining to median levels comparable to those found in Thailand. A significant association between increased PPQ IC50 and IC90 among Cambodian isolates with DHA-PPQ treatment failure was observed. Nearly all Cambodian and Thai isolates were deemed artemisinin resistant with a >1 % survival rate for DHA in the ring-stage assay (RSA), though there was no correlation among isolates to indicate cross-resistance between PPQ and artemisinins. Conclusions: Clinical DHA-PPQ failures appear to be associated with declines in the long-acting partner drug PPQ, though sensitivity appears to remain largely intact for now in western Thailand. Rapid progression of PPQ resistance associated with DHA-PPQ treatment failures in northern Cambodia limits drugs of choice in this region, and urgently requires alternative therapy. The temporary re-introduction of artesunate AS-MQ is the current response to PPQ resistance in this area, due to inverse MQ and PPQ resistance patterns. This will require careful monitoring for re-emergence of MQ resistance, and possible simultaneous resistance to all three drugs (AS, MQ and PPQ).
ISSN: 14752875
Appears in Collections:Scopus 2016-2017

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.