Publication: Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan
Accepted Date
2013-03-11
Issued Date
2013-03-15
Copyright Date
2013
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
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Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Awab GR, Pukrittayakamee S, Jamornthanyawat N, Yamin F, Dondorp AM, Day NP, et al. Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan. Malar J. 2013 Mar 15;12:96.
Suggested Citation
Awab, Ghulam R, Sasithon Pukrittayakamee, ศศิธร ผู้กฤตยาคามี, Natsuda Jamornthanyawat, นาถสุดา จามรธัญญวาท, Yamin, Fazel, Dondorp, Arjen M., Day, Nicholas P.J., White, Nicholas J., Woodrow, Charles J., Mallika Imwong, มัลลิกา อิ่มวงศ์ Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan. Awab GR, Pukrittayakamee S, Jamornthanyawat N, Yamin F, Dondorp AM, Day NP, et al. Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan. Malar J. 2013 Mar 15;12:96.. doi:10.1186/1475-2875-12-96 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/691
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Title
Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan
Corresponding Author(s)
Other Contributor(s)
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU)
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine
Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics
Mahidol University. Center for Emerging and Neglected Infectious Diseases
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine
Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics
Mahidol University. Center for Emerging and Neglected Infectious Diseases
Abstract
BACKGROUND: Artesunate plus sulphadoxine-pyrimethamine (AS+SP) is now first-line
treatment for Plasmodium falciparum infection in several south Asian countries,
including Afghanistan. Molecular studies provide a sensitive means to investigate
the current state of drug susceptibility to the SP component, and can also
provide information on the likely efficacy of other potential forms of
artemisinin-combination therapy.
METHODS: During the years 2007 to 2010, 120 blood spots from patients with P.
falciparum malaria were obtained in four provinces of Afghanistan. PCR-based
methods were used to detect drug-resistance mutations in dhfr, dhps, pfcrt and
pfmdr1, as well as to determine copy number of pfmdr1.
RESULTS: The majority (95.5%) of infections had a double mutation in the dhfr
gene (C59R, S108N); no mutations at dhfr positions 16, 51 or 164 were seen. Most
isolates were wild type across the dhps gene, but five isolates from the
provinces of Kunar and Nangarhar in eastern Afghanistan had the triple mutation
A437G / K540E / A581G; all five cases were successfully treated with three
receiving AS+SP and two receiving dihydroartemisinin-piperaquine. All isolates
showed the pfcrt SVNMT chloroquine resistance haplotype. Five of 79 isolates had
the pfmdr1 N86Y mutation, while 52 had pfmdr1 Y184F; positions 1034, 1042 and
1246 were wild type in all isolates. The pfmdr1 gene was not amplified in any
sample.
CONCLUSIONS: This study indicates that shortly after the adoption of AS+SP as
first-line treatment in Afghanistan, most parasites had a double mutation
haplotype in dhfr, and a small number of isolates from eastern Afghanistan
harboured a triple mutation haplotype in dhps. The impact of these mutations on
the efficacy of AS+SP remains to be assessed in significant numbers of patients,
but these results are clearly concerning since they suggest a higher degree of SP
resistance than previously detected. Further focused molecular and clinical
studies in this region are urgently required.