TY - JOUR
T1 - Evolution of Plasmodium falciparum drug resistance genes following artemisinin combination therapy in Sudan
AU - Bakhiet, Amani M.A.
AU - Abdelraheem, Mohamed H.
AU - Kheir, Amani
AU - Omer, Samia
AU - Gismelseed, Linda
AU - Abdel-Muhsin, Abdel Muhsin A.
AU - Naiem, Ahmed
AU - Al Hosni, Ahmed
AU - Al Dhuhli, Amani
AU - Al Rubkhi, Maymona
AU - Al-Hamidhi, Salama
AU - Gadalla, Amal
AU - Mukhtar, Moawia
AU - Sultan, Ali A.
AU - Babiker, Hamza A.
N1 - Funding Information:
Funding: This work was supported by the Third World Organization for Women in Science, Trieste, Italy (fellowship to Amani M. A. Bakhiet; 3240219354), as well as Sultan Qaboos University, Oman.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - Pfcrt
KW - Pfdhfr
KW - Pfdhps
KW - Pfk13
KW - Pfmdr-1
KW - Plasmodium falciparum
KW - Sudan
KW - malaria
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U2 - 10.1093/trstmh/trz059
DO - 10.1093/trstmh/trz059
M3 - Article
C2 - 31369106
AN - SCOPUS:85074674981
SN - 0035-9203
VL - 113
SP - 693
EP - 700
JO - Transactions of the Royal Society of Tropical Medicine and Hygiene
JF - Transactions of the Royal Society of Tropical Medicine and Hygiene
IS - 11
ER -
