IN VITRO ANTIMALARIAL DRUG SUSCEPTIBILITY AND PFCRT MUTATION AMONG FRESH PLASMODIUM FALCIPARUM ISOLATES FROM THE LAO PDR (LAOS)

MAYFONG MAYXAY Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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MARION BARENDS Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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ALAN BROCKMAN Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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ANCHALEE JAIDEE Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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SHALINI NAIR Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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DAN SUDIMACK Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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TIENGKHAM PONGVONGSA Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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SAMLANE PHOMPIDA Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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RATTANAXAY PHETSOUVANH Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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TIM ANDERSON Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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NICHOLAS J. WHITE Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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PAUL N. NEWTON Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR; Department of Post Graduate and Research, Faculty of Medical Science, National University of Laos, Lao PDR; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Australian Centre for International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia; Southwest Foundation for Biomedical Research, San Antonio, Texas; Savannakhet Malaria Station, Savannakhet Province, Lao PDR; Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom.

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Recent drug trials in Laos have shown high levels of Plasmodium falciparum resistance to chloroquine, but there are no published data on in vitro antimalarial drug susceptibility. We used the double-site enzyme-linked pLDH immunodetection (DELI) assay to estimate the in vitro antimalarial drug susceptibility of 108 fresh P. falciparum isolates from southern Laos. The geometric mean (95% confidence interval) 50% inhibitory concentration values (nmol/L) were 152.4 (123.8–187.6) for chloroquine, 679.8 (533.8–863.0) for quinine, 45.9 (37.9–55.7) for mefloquine, 5.0 (4.4–6.4) for artesunate, 6.3 (4.5–8.9) for dihydroartemisinin, and 59.1 (46.4–75.3) for lumefantrine. The proportion of isolates defined as resistant were 65%, 40%, and 8% for chloroquine, quinine, and mefloquine, respectively. Of 53 isolates genotyped for the pfcrt T76K chloroquine-resistance mutation, 48 (91%) were mutants. P. falciparum in Laos is multi-drug resistant; antimalarial immunity resulting from the use of ineffective chloroquine before 2005 probably contributes significantly to the therapeutic responses in clinical trials.

Author Notes

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