Abstract | BACKGROUND: 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.
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Authors | Rungniran Sugaram, Kanokon Suwannasin, Chanon Kunasol, Vivek Bhakta Mathema, Nicholas P J Day, Prayuth Sudathip, Preecha Prempree, Arjen M Dondorp, Mallika Imwong |
Journal | Malaria journal
(Malar J)
Vol. 19
Issue 1
Pg. 107
(Mar 04 2020)
ISSN: 1475-2875 [Electronic] England |
PMID | 32127009
(Publication Type: Journal Article)
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Chemical References |
- Antimalarials
- DNA, Protozoan
- Drug Combinations
- Folic Acid Antagonists
- fanasil, pyrimethamine drug combination
- Sulfadoxine
- Pyrimethamine
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Topics |
- Antimalarials
(pharmacology)
- Cambodia
(epidemiology)
- DNA, Protozoan
(genetics)
- Dried Blood Spot Testing
- Drug Combinations
- Drug Resistance
(genetics)
- Folic Acid Antagonists
(pharmacology)
- Genotype
- Humans
- Malaria, Falciparum
(drug therapy, epidemiology)
- Mutation
- Plasmodium falciparum
(drug effects, genetics)
- Prevalence
- Pyrimethamine
(pharmacology)
- Sulfadoxine
(pharmacology)
- Thailand
(epidemiology)
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