Amani M A Bakhiet1,2, Mohamed H Abdelraheem3, Amani Kheir4, Samia Omer5, Linda Gismelseed6, Abdel-Muhsin A Abdel-Muhsin2,7, Ahmed Naiem1, Ahmed Al Hosni1, Amani Al Dhuhli1, Maymona Al Rubkhi1, Salama Al-Hamidhi1, Amal Gadalla8, Moawia Mukhtar6,9, Ali A Sultan10, Hamza A Babiker1. 1. Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Al Khoudh, Oman. 2. Sudan Academy of Sciences, Department of Epidemiology and Molecular Biology, Khartoum, Sudan. 3. Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Al Khoudh, Oman. 4. Ahfad University for Women, Omdurman, Sudan. 5. Tropical Medicine Research Institute, Khartoum, Sudan. 6. Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. 7. Department of Biology, Faculty of Science, University of Hail, Kingdom of Saudi Arabia. 8. Division of Population Medicine, School of Medicine, College of Biomedical Sciences, Cardiff University, Cardiff, UK. 9. Bioscience Research, Institute, Ibn Sina University, Khartoum, Sudan. 10. Department of Microbiology and Immunology, Weill Cornell Medicine - Qatar, Qatar Foundation - Education City, Doha, Qatar.
Abstract
BACKGROUND: Malaria control efforts in Sudan rely heavily on case management. In 2004, health authorities adopted artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. However, some recent surveys have reported ACT failure and a prevalent irrational malaria treatment practice. Here we examine whether the widespread use of ACT and failure to adhere to national guidelines have led to the evolution of drug resistance genes. METHODS: We genotyped known drug resistance markers (Pfcrt, Pfmdr-1, Pfdhfr, Pfdhps, Pfk13 propeller) and their flanking microsatellites among Plasmodium falciparum isolates obtained between 2009 and 2016 in different geographical regions in Sudan. Data were then compared with published findings pre-ACT (1992-2003). RESULTS: A high prevalence of Pfcrt76T, Pfmdr-1-86Y, Pfdhfr51I, Pfdhfr108N, Pfdhps37G was observed in all regions, while no Pfk13 mutations were detected. Compared with pre-ACT data, Pfcrt-76T and Pfmdr-1-86Y have decayed, while Pfdhfr-51I, Pfdhfr-108N and Pfdhps-437G strengthened. Haplotypes Pfcrt-CVIET, Pfmdr-1-NFSND/YFSND, Pfdhfr-ICNI and Pfdhps-SGKAA predominated in all sites. Microsatellites flanking drug resistance genes showed lower diversity than neutral ones, signifying high ACT pressure/selection. CONCLUSIONS: Evaluation of P. falciparum drug resistance genes in Sudan matches the drug deployment pattern. Regular monitoring of these genes, coupled with clinical response, should be considered to combat the spread of ACT resistance.
BACKGROUND:Malaria control efforts in Sudan rely heavily on case management. In 2004, health authorities adopted artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. However, some recent surveys have reported ACT failure and a prevalent irrational malaria treatment practice. Here we examine whether the widespread use of ACT and failure to adhere to national guidelines have led to the evolution of drug resistance genes. METHODS: We genotyped known drug resistance markers (Pfcrt, Pfmdr-1, Pfdhfr, Pfdhps, Pfk13 propeller) and their flanking microsatellites among Plasmodium falciparum isolates obtained between 2009 and 2016 in different geographical regions in Sudan. Data were then compared with published findings pre-ACT (1992-2003). RESULTS: A high prevalence of Pfcrt76T, Pfmdr-1-86Y, Pfdhfr51I, Pfdhfr108N, Pfdhps37G was observed in all regions, while no Pfk13 mutations were detected. Compared with pre-ACT data, Pfcrt-76T and Pfmdr-1-86Y have decayed, while Pfdhfr-51I, Pfdhfr-108N and Pfdhps-437G strengthened. Haplotypes Pfcrt-CVIET, Pfmdr-1-NFSND/YFSND, Pfdhfr-ICNI and Pfdhps-SGKAA predominated in all sites. Microsatellites flanking drug resistance genes showed lower diversity than neutral ones, signifying high ACT pressure/selection. CONCLUSIONS: Evaluation of P. falciparum drug resistance genes in Sudan matches the drug deployment pattern. Regular monitoring of these genes, coupled with clinical response, should be considered to combat the spread of ACT resistance.
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