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Plasmodium falciparum resistance to sulfadoxine/pyrimethamine (S/P) is due to mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhfr) genes. Large-scale screening of the prevalence of these mutations could facilitate the surveillance of the level of S/P resistance in vivo. The prevalence of mutations in dhfr and dhps in relation to S/P efficacy was studied in four sites of differing endemicity in Sudan, Mozambique, and Tanzania. The sites were organized in order of increasing resistance and a significant increase in the prevalence of triple mutations in codons c51, c59, and c108 of dhfr was observed. A similar trend was observed when dhfr genotypes were combined with c437 of dhps. Since the differences in S/P resistance between the sites were minor, but nevertheless revealed major differences in dhfr genotype prevalence, the role of dhfr as a general molecular marker seems debatable. The differences may reflect variation in the duration and magnitude of S/P usage (or other antifolate drugs) between the sites. Thus, triple dhfr mutations may prove suitable only as a general guideline for detecting emerging S/P resistance in areas where S/P has been introduced recently. However, changes in susceptibility within the same area with moderate levels of resistance may be possible by longitudinal surveillance of a subset of dhfr/dhps mutations that has been associated with S/P resistance in vivo in a defined location.
Received March 17, 2003. Accepted for publication August 20, 2003.
Acknowledgments: We thank laboratory technicians Jimmy Weng and Gitte Hoff Jensen for excellent technical assistance in performing the RFLP-PCR. We also thank Anna Färnert for critical comments on this manuscript.
Financial support: This study was supported by the Danish International Development Agency (DANIDA) Research Council (RUF, grant no. 90892). The study in Tanzania was supported by DANIDA grant no. 104.Dan.8L as part of a Tanzanian-Danish collaboration under the Enhancement of Research Capacity (ENRECA) program. The study in Sudan was supported by DANIDA. The study in Mozambique was supported by the ENRECA program and the Danish Bilharziasis Laboratory.
Authors’ addresses: Michael Alifrangis and Insaf F. Khalil, Panum Institute, Institute of Medical Microbiology and Immunology, Building 24.2, Blegdamsvej 3, 2200 Copenhagen N, Denmark. Sonja Enosse, National Institute of Health, Ministry of Health, Maputo, Mozambique. Donath S. Tarimo, PO Box 65011, Dar es Salaam, Tanzania. Martha M. Lemnge, National Institute for Medical Research, Amani Research Centre, PO Box 4, Amani, Tanga, Tanzania. Richardo Thompson, National Institute of Health, Ministry of Health, Maputo, Mozambique. Ib C. Bygbjerg and Anita M. Rønn, Institute of Public Health, University of Copenhagen, Nørre Alle 4-6, 2200 Copenhagen N, Denmark.
Reprint requests: Michael Alifrangis, Panum Institute, Institute of Medical Microbiology and Immunology, Building 24.2, Blegdamsvej 3, 2200 Copenhagen N, Denmark, Telephone: 45-3-532-7676, Fax: 45-3-532-7851, E-mail: malif{at}biobase.dk.
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