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

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.

Received June 8, 2006. Accepted for publication October 24, 2006.

Acknowledgments: The authors thank all the patients involved in this study and Drs. Maniphone Khanthavong, Vonthalom Thongpraseuth, and Siamphay Keola, Manisack Phommasansack, Bounpone Phimphalat, Pitta Sengkeomahavong, Bounmy Syphachanh, Ammala Phomsimone, Vilayphone, Chanthala Vilaihong, and all medical assistants and nurses in Phalanxay District Hospital for their technical help. We are very grateful to Dr. M. Makler for supplying the monoclonal antibody, to Dr. D. E. Kyle for supplying artesunate and DHA, to Drs. Pranom Phongmany and Odai Xaysitthideth and Phomma for their valuable advice and for the support of the Minister of Health, His Excellency Dr. Ponmek Dalaloy, the Directors of Hygiene and Preventive Medicine, Drs. Douangchanh Keo-Asa and Bounlay Phommasack, and the Director of Mahosot Hospital, Professor Chanpheng Thammavong. Special thanks to Dr. Francois Nosten for reviewing the manuscript.

Financial support: This study was supported by The Wellcome Trust of Great Britain. T.J.C.A., S.N., and .D.S are supported by NIH RO1 AI48071. The molecular work at the Southwest Foundation for Biomedical Research was conducted in facilities constructed with support from Research Facilities Improvement Program Grant C06 RR013556 from the National Center for Research Resources, National Institutes of Health.

^* Address correspondence to Paul N. Newton, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR. E-mail: paul{at}tropmedres.ac

Authors’ addresses: Mayfong Mayxay, Nicholas J. White, and Paul N. Newton, Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Mahosot Road, Vientiane, Lao PDR, Telephone: 85621-250752, Fax: 85621-242168, E-mail: paul{at}tropmedres.ac. Mayfong Mayxay, Department of Medicine, Faculty of Medical Science, National University of Laos, Lao PDR, Telephone: 85621-250752, Fax: 85621-242168, E-mail: mmayxay{at}yahoo.com. Marion Barends, Alan Brockman, and Anchalee Jaidee, Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand. Marion Barends, Nicholas J. White, and Paul N. Newton, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK. Marion Barends, Alan Brockman, and Nicholas J. White, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, 420/6 Rajvithi Road, Bangkok, 10400, Thailand, Telephone: +66 23549172; Fax: +66 23549169; E-mail: nickw{at}tropmedres.ac. Alan Brockman, Australian Centre of International Tropical Health and Nutrition, University of Queensland, Brisbane, Australia. Shalini Nair, Dan Sudimack, and Tim Anderson, Southwest Foundation for Biomedical Research. San Antonio, Texas, Telephone: +210-2589596. Tiengkham Pongvongsa, Savannakhet Provincial Malaria Station, Savannakhet Province, Lao PDR. Samlane Phompida, and Rattanaxay Phetsouvanh, Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR, Telephone: 85621-214040, Fax: 85621-218131.

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