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dc.contributor.authorRungniran Sugaramen_US
dc.contributor.authorKanokon Suwannasinen_US
dc.contributor.authorChanon Kunasolen_US
dc.contributor.authorVivek Bhakta Mathemaen_US
dc.contributor.authorNicholas P.J. Dayen_US
dc.contributor.authorPrayuth Sudathipen_US
dc.contributor.authorPreecha Prempreeen_US
dc.contributor.authorArjen M. Dondorpen_US
dc.contributor.authorMallika Imwongen_US
dc.contributor.otherChurchill Hospitalen_US
dc.contributor.otherThailand Ministry of Public Healthen_US
dc.contributor.otherMahidol Universityen_US
dc.identifier.citationMalaria Journal. Vol.19, No.1 (2020)en_US
dc.description.abstract© 2020 The Author(s). Background: Resistance to anti-malarials is a major threat to the control and elimination of malaria. Sulfadoxine-pyrimethamine (SP) anti-malarial treatment was used as a national policy for treatment of uncomplicated falciparum malaria in Thailand from 1973 to 1990. In order to determine whether withdrawal of this antifolate drug has led to restoration of SP sensitivity, the prevalence of genetic markers of SP resistance was assessed in historical Thai samples. Methods: Plasmodium falciparum DNA was collected from the Thailand-Myanmar, Thailand-Malaysia and Thailand-Cambodia borders during 2008-2016 (N = 233). Semi-nested PCR and nucleotide sequencing were used to assess mutations in Plasmodium falciparum dihydrofolate reductase (pfdhfr), P. falciparum dihydropteroate synthase (pfdhps). Gene amplification of Plasmodium falcipaurm GTP cyclohydrolase-1 (pfgch1) was assessed by quantitative real-time PCR. The association between pfdhfr/pfdhps mutations and pfgch1 copy numbers were evaluated. Results: Mutations in pfdhfr/pfdhsp and pfgch1 copy number fluctuated overtime through the study period. Altogether, 14 unique pfdhfr-pdfhps haplotypes collectively containing quadruple to octuple mutations were identified. High variation in pfdhfr-pfdhps haplotypes and a high proportion of pfgch1 multiple copy number (51% (73/146)) were observed on the Thailand-Myanmar border compared to other parts of Thailand. Overall, the prevalence of septuple mutations was observed for pfdhfr-pfdhps haplotypes. In particular, the prevalence of pfdhfr-pfdhps, septuple mutation was observed in the Thailand-Myanmar (50%, 73/146) and Thailand-Cambodia (65%, 26/40) border. In Thailand-Malaysia border, majority of the pfdhfr-pfdhps haplotypes transaction from quadruple (90%, 9/10) to quintuple (65%, 24/37) during 2008-2016. Within the pfdhfr-pfdhps haplotypes, during 2008-2013 the pfdhps A/S436F mutation was observed only in Thailand-Myanmar border (9%, 10/107), while it was not identified later. In general, significant correlation was observed between the prevalence of pfdhfr I164L (φ = 0.213, p-value = 0.001) or pfdhps K540E/N (φ = 0.399, p-value ≤ 0.001) mutations and pfgch1 gene amplification. Conclusions: Despite withdrawal of SP as anti-malarial treatment for 17 years, the border regions of Thailand continue to display high prevalence of antifolate and anti-sulfonamide resistance markers in falciparum malaria. Significant association between pfgch1 amplification and pfdhfr (I164L) or pfdhps (K540E) resistance markers were observed, suggesting a compensatory mutation.en_US
dc.rightsMahidol Universityen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleMolecular characterization of Plasmodium falciparum antifolate resistance markers in Thailand between 2008 and 2016en_US
Appears in Collections:Scopus 2020

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