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

被引:18
|
作者
Bakhiet, Amani M. A. [1 ,2 ]
Abdelraheem, Mohamed H. [3 ]
Kheir, Amani [4 ]
Omer, Samia [5 ]
Gismelseed, Linda [6 ]
Abdel-Muhsin, Abdel-Muhsin A. [2 ,7 ]
Naiem, Ahmed [1 ]
Al Hosni, Ahmed [1 ]
Al Dhuhli, Amani [1 ]
Al Rubkhi, Maymona [1 ]
Al-Hamidhi, Salama [1 ]
Gadalla, Amal [8 ]
Mukhtar, Moawia [6 ,9 ]
Sultan, Ali A. [10 ]
Babiker, Hamza A. [1 ]
机构
[1] Sultan Qaboos Univ, Fac Med & Hlth Sci, Dept Biochem, Al Khoud, Oman
[2] Sudan Acad Sci, Dept Epidemiol & Mol Biol, Khartoum, Sudan
[3] Sultan Qaboos Univ, Fac Med & Hlth Sci, Dept Microbiol & Immunol, Al Khoud, Oman
[4] Ahfad Univ Women, Omdurman, Sudan
[5] Trop Med Res Inst, Khartoum, Sudan
[6] Univ Khartoum, Inst Endem Dis, Khartoum, Sudan
[7] Univ Hail, Fac Sci, Dept Biol, Hail, Saudi Arabia
[8] Cardiff Univ, Coll Biomed Sci, Sch Med, Div Populat Med, Cardiff, S Glam, Wales
[9] Ibn Sina Univ, Biosci Res Inst, Khartoum, Sudan
[10] Qatar Fdn Educ City, Dept Microbiol & Immunol, Weill Cornell Med Qatar, Doha, Qatar
关键词
malaria; Pfcrt; Pfdhfr; Pfdhps; Pfk13; Pfmdr-1; Plasmodium falciparum; Sudan; PLUS SULFADOXINE-PYRIMETHAMINE; ARTEMETHER-LUMEFANTRINE; MOLECULAR MARKERS; HIGH-LEVEL; IN-VIVO; MALARIA; MUTATIONS; POLYMORPHISMS; SURVEILLANCE; HAPLOTYPES;
D O I
10.1093/trstmh/trz059
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
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.
引用
收藏
页码:693 / 700
页数:8
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