Transmission and Cross-Mating of High-Level Resistance Plasmodium falciparum Dihydrofolate Reductase Haplotypes in The Gambia

Amani Kheir Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman; Medical Research Council, Laboratories, Banjul, The Gambia; School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

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Davis Nwakanma Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman; Medical Research Council, Laboratories, Banjul, The Gambia; School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

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Aisha Al-Gazali Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman; Medical Research Council, Laboratories, Banjul, The Gambia; School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

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Yagut Akbarova Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman; Medical Research Council, Laboratories, Banjul, The Gambia; School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

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Salma Al-Saai Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman; Medical Research Council, Laboratories, Banjul, The Gambia; School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

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Göte Swedberg Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman; Medical Research Council, Laboratories, Banjul, The Gambia; School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

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Hamza A. Babiker Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman; Medical Research Council, Laboratories, Banjul, The Gambia; School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

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A high-level pyrimethamine resistance Plasmodium falciparum lineage with triple dihydrofolate reductase (dhfr) mutations prevails across Africa. However, additional minority lineages were seen. We examined transmission success of mutant dhfr haplotypes among 22 children in The Gambia and 60 infected Anopheles gambiae mosquitoes fed on their blood. Additional polymorphic genes of the gametocyte-specific protein (pfg377) and merozoite surface protein-1 (MSP-1) were examined. Similarities were seen between pfg377 and MSP-1 alleles in children and mosquitoes and evidence of cross-mating between different parasite genotypes was seen in some infected mosquitoes, reflecting high transmission success of existing clones. With regard to dhfr, 16 haplotypes were seen among the children: 2 carried double mutations and 14 carried triple mutations. However, only nine haplotypes, all with triple mutations, were detected among mosquitoes. A single triple-mutant dhfr haplotype, similar to that in other countries in Africa, predominated among children (42%) and mosquitoes (60%), supporting the hypothesis of migration of this haplotype across Africa. However, evidence of cross-mating between the above haplotypes signifies the role of local evolution.

Author Notes

*Address correspondence to Hamza A. Babiker, Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, PO Box 35, Alk-Khod, Oman. E-mail: h.babiker@squ.edu.com

Financial support: This work was supported by the Medical Research Council, United Kingdom; the Swedish International Development Cooperation Agency; and Sultan Qaboos University, Oman.

Authors' addresses: Amani Kheir and Göte Swedberg, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsalal, Sweden. Davis Nwakanma, Medical Research Council Laboratories, Banjul, The Gambia. Yagut Akbarova, Salma Al-Saai, and Aisha Al-Gazali, Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman. Hamza A. Babiker, Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Alk-Khjod, Oman and School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.

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