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Evolution of Plasmodium falciparum drug resistance genes following artemisinin combination therapy in Sudan

Bakhiet, Amani M. A., Abdelraheem, Mohamed H., Kheir, Amani, Omer, Samia, Gismelseed, Linda, Abdel-Muhsin, Abdel-Muhsin A., Naiem, Ahmed, Al Hosni, Ahmed, Al Dhuhli, Amani, Al Rubkhi, Maymona, Al-Hamidhi, Salama, Gadalla, Amal, Mukhtar, Moawia, Sultan, Ali A. and Babiker, Hamza A. 2019. Evolution of Plasmodium falciparum drug resistance genes following artemisinin combination therapy in Sudan. Transactions of The Royal Society of Tropical Medicine and Hygiene 113 (11) , pp. 693-700. 10.1093/trstmh/trz059

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier / Oxford University Press (OUP)
ISSN: 0035-9203
Date of First Compliant Deposit: 4 February 2020
Date of Acceptance: 1 June 2019
Last Modified: 18 Jun 2020 13:03
URI: http://orca.cf.ac.uk/id/eprint/129306

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