%0 Journal Article %T Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. %+ Laboratoire d'épidémiologie moléculaire %+ Laboratory of Malaria and Vector Research %+ National Centre for Parasitology %+ Sampov Meas Referral Hospital %+ Makara 16 Referral Hospital %+ Ratanakiri Referral Hospital %+ Service de Médecine Internationale et Humanitaire %+ Immunologie moléculaire des parasites %A Witkowski, Benoit %A Amaratunga, Chanaki %A Khim, Nimol %A Sreng, Sokunthea %A Chim, Pheaktra %A Kim, Saorin %A Lim, Pharath %A Mao, Sivanna %A Sopha, Chantha %A Sam, Baramey %A Anderson, Jennifer M %A Duong, Socheat %A Chuor, Char Meng %A Taylor, Walter R J %A Suon, Seila %A Mercereau-Puijalon, Odile %A Fairhurst, Rick M %A Menard, Didier %< avec comité de lecture %@ 1473-3099 %J The Lancet Infectious Diseases %I New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001- %P epub ahead of print %8 2013-09-11 %D 2013 %R 10.1016/S1473-3099(13)70252-4 %M 24035558 %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology %Z Life Sciences [q-bio]/Human health and pathology/Infectious diseasesJournal articles %X 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<0*0001). INTERPRETATION: The in-vitro RSA of 0-3 h ring-stage parasites provides a platform for the molecular characterisation of artemisinin resistance. The ex-vivo RSA can be easily implemented where surveillance for artemisinin resistance is needed. FUNDING: Institut Pasteur du Cambodge and the Intramural Research Program, NIAID, NIH. %G English %2 https://riip.hal.science/pasteur-00863935/document %2 https://riip.hal.science/pasteur-00863935/file/Lancet_ID_RSA_v2.pdf %L pasteur-00863935 %U https://riip.hal.science/pasteur-00863935 %~ PASTEUR %~ RIIP %~ CNRS %~ RIIP_PARIS %~ RIIP_CAMBODGE %~ TEST3-HALCNRS