K13 propeller domain mutations and pfmdr1 amplification in isolates of Plasmodium falciparum collected from Thai-Myanmar border area in 2006-2010
Language English Country Czech Republic Media electronic
Document type Journal Article
PubMed
31239407
DOI
10.14411/fp.2019.006
PII: 2019.006
Knihovny.cz E-resources
- Keywords
- PF3D7_1343700, artemisinin resistance, falciparum malaria, molecular marker, sequencing,
- MeSH
- Antimalarials pharmacology MeSH
- Artesunate pharmacology MeSH
- Drug Combinations MeSH
- Drug Resistance genetics MeSH
- Humans MeSH
- Mefloquine pharmacology MeSH
- Kelch Repeat MeSH
- Plasmodium falciparum drug effects genetics MeSH
- Polymerase Chain Reaction MeSH
- Multidrug Resistance-Associated Proteins analysis MeSH
- Protozoan Proteins analysis MeSH
- Sequence Analysis, DNA MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Myanmar MeSH
- Thailand MeSH
- Names of Substances
- Antimalarials MeSH
- Artesunate MeSH
- Drug Combinations MeSH
- Mdr1 protein, Plasmodium falciparum MeSH Browser
- Mefloquine MeSH
- Multidrug Resistance-Associated Proteins MeSH
- Protozoan Proteins MeSH
The K13 propeller domain mutation and pfmdr1 amplification have been proposed as useful molecular markers for detection and monitoring of artemisinin resistant Plasmodium falciparum Welch, 1897. Genomic DNA isolates of P. falciparum was extracted from 235 dried blood spot or whole blood samples collected from patients with uncomplicated falciparum malaria residing in areas along the Thai-Myanmar border during 2006-2010. Nested polymerase chain reaction (PCR) and sequencing were performed to detect mutations in K13 propeller domain of P. falciparum at codon 427-709. Pfmdr1 gene copy number was determined by SYBR Green I real-time PCR. High prevalence of pfmdr1 multiple copies was observed (42.5% of isolates). The presence of K13 mutations was low (40/235, 17.2%). Seventeen mutations had previously been reported and six mutations were newly detected. The C580Y was found in two isolates (0.9%). The F446I, N458Y and P574L mutations were commonly detected. Seven isolates had both K13 mutation and pfmdr1 multiple copies. It needs to be confirmed whether parasites harbouring both K13 mutation and pfmdr1 multiple copies and/or the observed new mutations of K13 propeller domain are associated with clinical artemisinin resistance.
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