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Title: Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum.
Authors: Kesinee Chotivanich
เกศินี โชติวานิช
Tripura, Rupam
Das, Debashish
Poravuth Yi,c
Day, Nicholas P. J.
Sasithon Pukrittayakamee
ศศิธร ผู้กฤตยาคามี
Chuor, Char Meng
Socheat, Duong
Dondorp, Arjen M.
White, Nicholas J.
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine.
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford University Tropical Medicine Research Unit.
White, Nicholas J.
Keywords: Artemisinin-Resistant;Plasmodium falciparum;Open Access article
Issue Date: Jun-2014
Citation: Chotivanich K, Tripura R, Das D, Yi P, Day NP, Pukrittayakamee S. et al. Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum. Antimicrob Agents Chemother. 2014 Jun;58(6):3157-61.
Abstract: Conventional 48-h in vitro susceptibility tests have low sensitivity in identifying artemisinin-resistant Plasmodium falciparum, defined phenotypically by low in vivo parasite clearance rates. We hypothesized originally that this discrepancy was explained by a loss of ring-stage susceptibility and so developed a simple field-adapted 24-h trophozoite maturation inhibition (TMI) assay focusing on the ring stage and compared it to the standard 48-h schizont maturation inhibition (WHO) test. In Pailin, western Cambodia, where artemisinin-resistant P. falciparum is prevalent, the TMI test mean (95% confidence interval) 50% inhibitory concentration (IC50) for artesunate was 6.8 (5.2 to 8.3) ng/ml compared with 1.5 (1.2 to 1.8) ng/ml for the standard 48-h WHO test (P = 0.001). TMI IC50s correlated significantly with the in vivo responses to artesunate (parasite clearance time [r = 0.44, P = 0.001] and parasite clearance half-life [r = 0.46, P = 0.001]), whereas the standard 48-h test values did not. On continuous culture of two resistant isolates, the artemisinin-resistant phenotype was lost after 6 weeks (IC50s fell from 10 and 12 ng/ml to 2.7 and 3 ng/ml, respectively). Slow parasite clearance in falciparum malaria in western Cambodia results from reduced ring-stage susceptibility.
ISSN: 0066-4804 (printed)
1098-6596 (electronic)
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