3643. Resistance to Artemisinin-Based Malaria Treatment Regimens: Does it Exist?
Session: Symposium: Emerging and Reemerging Infections
Monday, October 27, 2008: 12:00 AM
Room: Room 202B
Background. Artemisinin and its derivatives are plant-derived antimalarials with a rapid, broad stage specific action against Plasmodium falciparum and an excellent safety profile. Artemisinin based combination treatments (ACTs) are now recommended by the World Health Organization as first line treatment of uncomplicated falciparum malaria in all malaria endemic areas. Parenteral artesunate is recommended for the treatment of severe malaria in adults. However, there are recent concerns that artemisinin efficacy may have declined on the Thai-Cambodian border, historically the epicentre of antimalarial resistance. To address this problem, the World Health Organization and the Cambodian National Malaria Control Programme established a multipartite task-force.
Methods. A trial was organized comparing responses to artesunate in patiets with uncomplicated falciparum malaria in Pailin, Western Cambodia, an area where artemisinin derivatives have been used for over thirty years, and the NorthWestern Thai-Burmese border, where ACTs were first deployed at scale in 1994, and remain highly effective. Detailed in-vitro and in-vivo parasite susceptibility were assessed, as well as artesunate pharmacokinetics, and molecular markers for resistance.
Results. An doubling in parasite clearance times and a high proportion of early treatment failures was found in Western Cambodia but not in Western Thailand. Reduced artesunate efficacy could not be explained by differences in artesunate (AS) or dihydroartemisinin (DHA) pharmacokinetics. Standard isotopic in-vitro sensitivity testing appeared not a sensitive method to detect decreased in-vivo sensitivity. No molecular markers for resistance could be identified. Mathematical modeling of the problem indicates that a malaria eradication program for Western Cambodia might be indicated.
Conclusion. There is reduced susceptibility of P. falciparum to artesunate in Western Cambodia. Further characterization and containment measures are needed urgently.
Arjen Dondorp, MD, PhD, Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand and  A. Dondorp, None.

Curriculum Vitae
Personalia
Family name: Dondorp
Christian names: Adrianus Mattheus (Arjen)
Date and place of birth: September 8th 1963 in Utrecht, The Netherlands
Marital status: Married to Marja Schilstra
Children: Lisa (1992) and Marten (1995)
Work Address: Mahidol-Oxford Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University
420/6 Rajvithi Road, Bangkok 10400, Thailand, Tel: 66-2-2036333, Fax: 66-2-3549169, E-mail: AMDondorp@yahoo.com

Work history
2001-present: Deputy Director and Head of Malaria Research, Mahidol-Oxford Research Unit (MORU), Bangkok, Thailand
2007-present: Honorary Consultant, John Radcliffe Hospital, Oxford, U.K.
2006-present: Honorary Consultant Infectious Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
2006-present: University Research Lectureship, Nuffield Dept of Medicine, Oxford University, Oxford, UK
2004-2007: Honorary Researcher, Dept of Physiology, Academic Medical Centre, Amsterdam, The Netherlands
Sept-Dec 2000: Intensive Care Physician, Department of Intensive Care Medicine, Academic Medical Centre, Amsterdam, the Netherlands
1999-2000: Fellowship in Intensive Care Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
1997-1999: Fellowship in Infectious Diseases, Academic Medical Centre, Amsterdam, The Netherlands.
1990-1997: Specialist training: Academic Medical Centre, Amsterdam, The Netherlands; and Red Cross Hospital, Beverwijk, The Netherlands
1987-1988: Research Trainee, Department of Neurology, Oregon Health Sciences University, Portland, OR, U.S.A.
Education and certification
2000: Registration as Intensive Care Physician
1999: PhD University of Amsterdam on thesis: 'On the pathophysiology of severe falciparum malaria, with special reference to red cell deformability’. Including clinical studies performed in Thailand (1995-1996) and Kenya (1997-1998)
1999: Registration as Infectious Diseases Physician
1997: Registration as 'Internist', Specialist Physician
1990: 'Artsexamen', Registration as Medical Doctor
1986: 'Doctoraal' in Medicine, 'with distinction', University of Amsterdam, The Netherlands.
1984: 'Kandidaats' in Medicine, 'with distinction', University of Amsterdam, The Netherlands.
1982: ‘Propaedeuse' in Medicine, 'with distinction', University of Amsterdam, The Netherlands.

Teaching activities
-DTM&H International Course, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand (yearly)
-Teaching Course in Intensive Care Medicine in Chittagong Medical College Hospital, Chittagong, Bangladesh; in collaboration with Royal United Hospital, Bath, UK (yearly)

Publications
Book chapters:
White NJ, Dondorp AM, Parigi D. “Malaria” in “Antimicrobial Therapy and Vaccines Volume II: Antimicrobial Agents”; Editors: Victor L. Yu, Geoffrey Edwards, Peggy S. McKinnon, Charles Peloquin, Gene D. Morse; Managing Editor: Brian A. Potoski; ISBN: 0-9700027-5-0; Web-version: www.anitmicrobe.org; Esun Technologies, LLC.
Dondorp A.M., Von Seidlein L. ,,Malaria“ in Cohen, Powderly and Opal - Infectious Diseases 3rd edition. Edinburgh: Elsevier; 2008 In press.

Selected Papers:
1. Charunwatthana P, Faiz MA, Ruangveerayut R, Maude R, Rahman MR, Roberts LJ, Moore K, Bin Yunus E, Hoque MG, Hasan MU, Lee SJ, Pukrittayakamee S, Newton PN, Day NPJ, White NJ, Dondorp AM. N-Acetylcysteine as adjunctive treatment in severe malaria: A randomized double blinded placebo controlled clinical trial. Crit Care Med. In press.
2. Dondorp AM, Lee SJ, Faiz MA, Mishra S, Price R, Tjitra E, Than M, Htut Y, Mohanty S, Yunus EB, Rahman R, Nosten F, Anstey NM, Day NP, Whi



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