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AMINO ACID MUTATIONS IN PLASMODIUM VIVAX DHFR AND DHPS FROM SEVERAL GEOGRAPHICAL REGIONS AND SUSCEPTIBILITY TO ANTIFOLATE DRUGS

The increasing use of sulfadoxine-pyrimethamine (SP) for the treatment of chloroquine-resistant Plasmodium falciparum has resulted in increased reports of SP resistance of P. falciparum worldwide. Selection of SP-resistant Plasmodium vivax in areas where P. falciparum and P. vivax co-exist is not entirely clear. We examined the prevalence and extent of point mutations in pvdhfr and pvdhps in 70 P. vivax isolates from China, East Timor, Papua New Guinea (PNG), Philippines, Vanuatu, and Vietnam. Mutations in seven codon positions were found in pvdhfr, with the majority of isolates having double mutations (S58R/S117N). The greatest range of mutations was observed in the PNG and Vanuatu isolates, ranging from single to quadruple mutations (F57L/S58R/T61M/S117T). Single mutations in pvdhps were observed only in parasites with mutations in corresponding pvdhfr. Parasites with the S58R/S117N dhfr allelic type showed an MIC level for pyrimethamine and cycloguanil comparable to that previously reported, but were susceptible to WR99210.

Received February 23, 2006. Accepted for publication June 12, 2006.

Acknowledgments: P. vivax isolates from Agusan Dal Sur, Mindanao, Philippines, were collected as part of a project funded by the National Health and Medical Research Council, Australia, and assisted by AusID through the Research Institute for Tropical Medicine, Philippines. We thank colleagues from the Malaria Study Group, Research Institute for Tropical Medicine, for collecting malaria-infected samples in the Philippines. P. vivax isolates from Vietnam were obtained as part of a Vietnam Australia Defence Malaria Project (VADMP), co-operative project between the Vietnam People’s Army and the Australian Defence Force. The VADMP is sponsored by the International Policy Division, Department of Defence, Australia.

Disclaimer: The opinions expressed herein are those of the authors and do not necessarily reflect those of the Defence Health Service or any extant policy of Department of Defence, Australia, or United States Army.

^* Address correspondence to Qin Cheng, Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Brisbane, Qld 4051, Australia. E-mail: qin.cheng{at}defence.gov.au

The DNA sequences of pvdhfr and pvdhps have been deposited in the GenBank database (accession numbers DQ244102-DQ244124 and DC379957-DC379962, respectively).

Authors’ addresses: Alyson M. Auliff, Nanhua Chen, Mike O’Neil, and Qin Cheng, Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Brisbane, Qld 4051, Australia, Telephone: +61-7-3332 4801, Fax: +61-7-3332 4800, E-mails: alyson.auliff{at}defence.gov.au, nanhua.chen{at}defence.gov.au, mike.oneil{at}defence.gov.au, and qin.cheng{at}defence.gov.au. Danny Wilson, Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Vic, Australia, E-mail: dwilson{at}wehi.edu.au. Bruce Russell, International Health Research, Menzies School of Health Research, Casuarina NT, Australia, Telephone: +61-8-8922 7918, E-mail: Bruce.Russell{at}menzies.edu.au. Qi Gao, Jiangsu Institute of Parasitic Diseases, Wuxi, China, E-mail: gaoqi54{at}hotmail.com. Le Ngoc Anh, Military Institute of Hygiene and Epidemiology, Department of Military Medicine, Vietnam, E-mail: Le_Anh2001{at}yahoo.com.au. Jason Maguire, Infectious Disease Division, Naval Medical Center, Portsmouth, VA, E-mail: maguirejason{at}yahoo.com. David Bell, Western Pacific Regional Office, World Health Organization, Manila, Philippines, E-mail: belld{at}wpro.who.int.

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