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MOLECULAR SURVEILLANCE OF MUTATIONS IN DIHYDROFOLATE REDUCTASE AND DIHYROPTEROATE SYNTHASE GENES OF PLASMODIUM FALCIPARUM IN ETHIOPIA

Point mutations in the genes for dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) of Plasmodium falciparum isolates are associated with sulfadoxine/pyrimethamine (SP) treatment failure, respectively. This study was conducted to assess the prevalence of SP resistance in P. falciparum isolates collected at the Jimma Health Center in southwestern Ethiopia. In this study, the genetic profile of P. falciparum isolates with respect to DHFR and DHPS genes was assessed in 124 individuals. The prevalence of single, double, and multiple mutations in these genes was calculated. The sequence profile showed that all samples carried a double mutation at the positions 51 and 108 (I51N108) in the DHFR gene. Sixty-seven (54.03%) of the isolates had an additional third mutation at position 59, resulting in the triple mutant I51R59N108. All isolates carried mutations G437 and E540 in the DHPS gene. Two isolates (1.61%) had additional mutations at codon 581 (A581).

Received May 20, 2005. Accepted for publication July 14, 2005.

Acknowledgments: We thank the Graduate School of Addis Ababa University for organizing the study, Almaz Demissei (Jimma Health Centre) for recruiting patients, and Andrea Weierich and Velia Grummes for technical help at the Sequencing Facility of the Institute for Tropical Medicine.

Financial support: This work was supported by grants to Tamirat Gebru-Woldearegai from the Deutscher Akademischer Austausch Dienst and by the Professor Josef und Erika Hesselbach Stiftung to Jürgen F. J. Kun.

^* Address correspondence to Jürgen F. J. Kun, Institute for Tropical Medicine, Department of Parasitology, University of Tübingen, Wilhelmstr. 27, 72074 Tübingen, Germany. E-mail: juergen.kun{at}uni-tuebingen.de

Authors’ addresses: Tamirat Gebru-Woldearegai, Institute for Tropical Medicine, Department of Parasitology, University of Tübingen, Wilhelmstr. 27, 72074 Tübingen, Germany, Telephone: 49-7071-298-2195, Fax: 49-7071-294-684, E-mail: tamiratgw2002{at}yahoo.com (present address: P.O. Box 70226, Addis Ababa, Ethiopia, Telephone: 251-9-645-665). Asrat Hailu, P.O. Box 28017/1000, Addis Ababa, Ethiopia, Telephone: 251-9-480-993, Fax: 251-1-513099, E-mail: hailu_a2004{at}yahoo.com. Martin P. Grobusch, Institute for Tropical Medicine, Department of Parasitology, University of Tübingen, Wilhelmstr. 27, 72074 Tübingen, Germany, Telephone: 49-7071-298-0234, Fax: 49-7071-294-684 (present address: Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2196, Johannesburg, South Africa, Telephone: 27-11-489-8537, Fax: 27-11-489-8511, E-mail: grobuschm{at}pathology.wits.ac.za). Jürgen F. J. Kun, Institute for Tropical Medicine, Department of Parasitology, University of Tübingen, Wilhelmstr. 27, 72074 Tübingen, Germany, Telephone: 49-7071-298-2191, Fax: 49-7071-294-684, E-mail: juergen.kun{at}uni-tuebingen.de.