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TRANSMISSION-BLOCKING ACTIVITY OF TAFENOQUINE (WR-238605) AND ARTELINIC ACID AGAINST NATURALLY CIRCULATING STRAINS OF PLASMODIUM VIVAX IN THAILAND

The sporontocidal activity of tafenoquine (WR-238605) and artelinic acid was determined against naturally circulating isolates of Plasmodium vivax in western Thailand. Primaquine was used as a negative control and a dihydroacridine-dione (WR-250547) was used as a positive control. Laboratory-reared Anopheles dirus mosquitoes were infected with P. vivax by allowing mosquitoes to feed on blood (placed in an artificial-membrane feeding apparatus) collected from gametocytemic volunteers reporting to local malaria clinics in Tak province, Thailand. Four days post-infection, mosquitoes were refed on uninfected mice treated 90 minutes earlier with a given drug. Drug activity was determined by assessing oocyst and sporozoite development. Neither primaquine nor artelinic acid affected oocyst or sporozoite development at a dose of 100 mg of base drug/kg of mouse body weight. In contrast, tafenoquine and WR-250547 affected sporogonic development at doses as low as 25.0 and 0.39 mg/kg, respectively. The potential role of these compounds in the prevention of malaria transmission is discussed, as are alternative strategies for the use of transmission-blocking antimalarial drugs.

Received October 31, 2002. Accepted for publication January 20, 2003.

Acknowledgments: We are grateful to Drs. Gabby Zollner, James Jones, and R. Scott Miller for reviewing the manuscript and to the staff of the Mae Sod and Mae Kasa malaria clinics for their support of this study. The test compounds originated from the Chemical Synthesis Program of the Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research (Washington, DC).

Financial support: Funding for this project was provided by the Military Infectious Diseases Research Program of the U.S. Army Medical Research and Materiel Command, Fort Detrick (Frederick, MD).

Disclaimer: The opinions of assertions contained in this manuscript are the private ones of the authors and are not to be construed as the official or reflecting views of the Department of Defense or the Armed Forces Research Institute of Medical Sciences.

Authors’ addresses: Narong Ponsa and Pattamaporn Kittayapong, Center of Vectors and Vector-Borne Diseases and Department of Biology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand. Jetsumon Sattabongkot, Nantana Eikarat, and Russell E. Coleman, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok 10400, Thailand.

Reprint requests: Department of Entomology, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok 10400, Thailand.