Copyright © 2013 Elsevier Ltd All rights reserved. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies The Lancet Infectious Diseases, Early Online Publication, 11 September 2013 Benoit Witkowski PhD a †, Chanaki Amaratunga PhD b †, Nimol Khim MSc a, Sokunthea Sreng c, Pheaktra Chim a, Saorin Kim a, Pharath Lim MD a b c, Sivanna Mao MD d, Chantha Sopha MD e, Baramey Sam MD f, Jennifer M Anderson PhD b, Prof Socheat Duong MD c, Char Meng Chuor MD c, Walter R J Taylor MD g, Seila Suon MD c, Odile Mercereau-Puijalon PhD h, Dr Rick M Fairhurst MD b , Dr Didier Menard PhD a Background Artemisinin resistance in Plasmodium falciparum lengthens parasite clearance half-life during artemisinin monotherapy or artemisinin-based combination therapy. Absence of in-vitro and ex-vivo correlates of artemisinin resistance hinders study of this phenotype. We aimed to assess whether an in-vitro ring-stage survival assay (RSA) can identify culture-adapted P falciparum isolates from patients with slow-clearing or fast-clearing infections, to investigate the stage-dependent susceptibility of parasites to dihydroartemisinin in the in-vitro RSA, and to assess whether an ex-vivo RSA can identify artemisinin-resistant P falciparum infections. Methods We culture-adapted parasites from patients with long and short parasite clearance half-lives from a study done in Pursat, Cambodia, in 2010 (registered with ClinicalTrials.gov, number NCT00341003) and used novel in-vitro survival assays to explore the stage-dependent susceptibility of slow-clearing and fast-clearing parasites to dihydroartemisinin. In 2012, we implemented the RSA in prospective parasite clearance studies in Pursat, Preah Vihear, and Ratanakiri, Cambodia (NCT01736319), to measure the ex-vivo responses of parasites from patients with malaria. Continuous variables were compared with the Mann-Whitney U test. Correlations were analysed with the Spearman correlation test. Findings In-vitro survival rates of culture-adapted parasites from 13 slow-clearing and 13 fast-clearing infections differed significantly when assays were done on 0—3 h ring-stage parasites (10·88% vs 0·23%; p=0·007). Ex-vivo survival rates significantly correlated with in-vivo parasite clearance half-lives (n=30, r=0·74, 95% CI 0·50—0·87; p
Posted on: Sun, 15 Sep 2013 07:15:12 +0000
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