Dihydrofolate reductase (DHFR; EC18.104.22.168) is a known target enzyme for antifolate agents, which are used as alternative chemotherapeutics for chloroquine-resistant malaria. Mutations in the dhfr gene of Plasmodium vivax are thought to be associated with resistance to the antifolate drugs. In this study, we have analyzed genetic variations in the dhfr genes of clinical isolates of P. vivax (n=21) in Myanmar, to monitor antifolate resistance in this country. Sequence variations within the entire dhfr gene were highly restricted to codons from 57 to 117, and the GGDN tandem repeat region. Double (S58R and S117N/T) or quadruple mutations (F57L/I, S58R, T61M, and S117N/T), which may be closely related to the drug resistance, were recognized in most of the isolates (20/21 cases). Our results suggest that antifolate-resistant P. vivax is becoming widespread in Myanmar, as it also is in the neighboring countries in Southeast Asia. It appears that the drug resistance situation may be worsening in the country.
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This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, the Republic of Korea (03-PJ1-PG1-CH01-0001). The authors are grateful to health personnel of Department of Health (Vector Borne Diseases Control Project and Basic Health in the respected townships) and Department of Medical Research (Upper Myanmar), for their active cooperation in this study.
Byoung-Kuk Na and Hyeong-Woo Lee have contributed equally to the work.
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Na, B., Lee, H., Moon, S. et al. Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar. Parasitol Res 96, 321–325 (2005). https://doi.org/10.1007/s00436-005-1364-0
- Plasmodium vivax
- Dihydrofolate reductase
- Point mutations