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Artemisinin derivatives are first-line antimalarial drugs in Thailand. No firm evidence of clinically relevant artemisinin resistance exists. When used as monotherapy, artesunate has been associated with a high treatment failure (recrudescence) rate, which could be due to low-level artemisinin resistance. To understand the causes of recrudescence, we retrospectively studied a cohort of 104 malaria patients treated with artesunate monotherapy, 32 of whom recrudesced. There was no difference in in vitro artesunate sensitivities between 6 nonrecrudescent isolates and 16 paired admission and recrudescent isolates. Paired admission and recrudescent isolates from 10 patients were genotyped; only 3 had pfmdr1 mutations. Patients with admission parasitemias >10,000 per µl had a 9-fold higher likelihood of recrudescence (adjusted odds ratio) compared with patients with lower parasitemias. This study suggests (1) recrudescence after treatment with artesunate is not the result of inherent parasite resistance, and (2) admission parasitemia may be useful in choosing therapeutic options.
Received May 7, 2002. Accepted for publication September 30, 2002.
Acknowledgments: We are grateful to the patients for their cooperation. We thank Donglin Zeng (Department of Biostatistics, University of North Carolina School of Public Health) for statistical help.
Financial support: This work was supported by grants from the U.S. National Institutes of Health (R21 AI45426 and R01 AI51320).
Authors’ addresses: Wanida Ittarat and Panthip Rattanasinganchan, Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand, Telephone: 66-2-4197169, Fax: 66-2-4124110, E-mail: mtwit{at}mucc.mahidol.ac.th. Amy L. Pickard, Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, NC 27599, Telephone: 919-968-9651, E-mail: apickard{at}email.unc.edu. Polrat Wilairatana and Sornchai Looareesuwan, Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10700, Thailand, Telephone: 66-2-2469000, Fax: 66-2-2469013. Kathryn Emery, c/o Foxman Research Group, Room 2038 University of Michigan School of Public Health, 109 S. Observatory, Ann Arbor, MI 48109, Fax: 734-936-6732, E-mail: emeryk{at}umich.edu. Jonathan Low, 1500 E. Medical Center Drive, Box 0944, Dock 5, 6431 CCGC, Ann Arbor, MI 48109, Telephone: 734-936-0876, Fax: 734-647-9271, E-mail: jlowz{at}umich.edu. Rachanee Udomsangpetch, Department of Experimental Patho-biology, Faculty of Science, Mahidol University, Bangkok, 10700, Thailand, Telephone: 66-2-2461358, Fax: 66-2-2477050. Steven R Meshnick, Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, NC 27599-7435, Telephone: 919-966-7414, Fax: 919-966-2089, E-mail: meshnick{at}unc.edu
Reprint requests: Steven R. Meshnick, Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill NC 27599-7435, Telephone: 919-966-7414, Fax: 919-966-2089, E-mail: meshnick{at}unc.edu
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