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Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign.

Talundzic E, Okoth SA, Congpuong K, Plucinski MM, Morton L, Goldman IF, Kachur PS, Wongsrichanalai C, Satimai W, Barnwell JW, Udhayakumar V - PLoS Pathog. (2015)

Bottom Line: A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F).The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders.In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

View Article: PubMed Central - PubMed

Affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America; Atlanta Research and Education Foundation, Atlanta VA Medical Center, Atlanta, Georgia, United States of America.

ABSTRACT
The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria. Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance. A total of 417 patient samples from the year 2007, collected during malaria surveillance studies across ten provinces in Thailand, were genotyped for the candidate Plasmodium falciparum molecular marker of artemisinin resistance K13. Parasite genotypes were examined for K13 propeller mutations associated with artemisinin resistance, signatures of positive selection, and for evidence of whether artemisinin-resistant alleles arose independently across Thailand. A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F). Notably, the R575K and S621F mutations have previously not been reported in Thailand. The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders. It appears these two haplotypes may have independent evolutionary origins. In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

No MeSH data available.


Related in: MedlinePlus

Heterozygosity valley around K13 propeller alleles in Thailand.The expected heterozygosity of parasite isolates with: (A) the C580Y mutation (N = 26) and wild type alleles (N = 82); (B) the C580Y from the east (N = 10) and west (N = 16). Diversity was reduced at all 9 K13 propeller microsatellite loci for C580Y compared to wild type alleles. The mean He in (A) for C580Y (0.3526 ± 0.08), wild type (0.6246 ± 0.06), neutral (0.7650 ± 0.05); (B) C580Y east (0.2755 ± 0.05) and C580Y west (0.4360 ± 0.03 ± 0.03). The error bars indicate ± standard deviation (SD).
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ppat.1004789.g003: Heterozygosity valley around K13 propeller alleles in Thailand.The expected heterozygosity of parasite isolates with: (A) the C580Y mutation (N = 26) and wild type alleles (N = 82); (B) the C580Y from the east (N = 10) and west (N = 16). Diversity was reduced at all 9 K13 propeller microsatellite loci for C580Y compared to wild type alleles. The mean He in (A) for C580Y (0.3526 ± 0.08), wild type (0.6246 ± 0.06), neutral (0.7650 ± 0.05); (B) C580Y east (0.2755 ± 0.05) and C580Y west (0.4360 ± 0.03 ± 0.03). The error bars indicate ± standard deviation (SD).

Mentions: Using the nine microsatellite loci flanking the K13 propeller gene, expected heterozygosity (He) was calculated for the C580Y and wild type alleles (Fig 3). The N458Y, R539T, P574L, R575K and S621F alleles were excluded as there were limited samples to carry out the analysis. The C580Y allele (N = 26, mean He = 0.3526 ± 0.08) showed a 56% reduction (p = 0.0046) in heterozygosity as compared to wild type alleles (N = 22, mean He = 0.6246 ± 0.06) (Fig 3A). No significant difference (p = 0.2240) in heterozygosity was found when comparing western C580Y alleles (N = 10, mean He = 0.4360 ± 0.03) to eastern C580Y alleles (N = 15, mean He = 0.2755 ± 0.05) (Fig 3B). Mean He between the wild type and different mutant alleles were compared using the Mann-Whitney U test.


Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign.

Talundzic E, Okoth SA, Congpuong K, Plucinski MM, Morton L, Goldman IF, Kachur PS, Wongsrichanalai C, Satimai W, Barnwell JW, Udhayakumar V - PLoS Pathog. (2015)

Heterozygosity valley around K13 propeller alleles in Thailand.The expected heterozygosity of parasite isolates with: (A) the C580Y mutation (N = 26) and wild type alleles (N = 82); (B) the C580Y from the east (N = 10) and west (N = 16). Diversity was reduced at all 9 K13 propeller microsatellite loci for C580Y compared to wild type alleles. The mean He in (A) for C580Y (0.3526 ± 0.08), wild type (0.6246 ± 0.06), neutral (0.7650 ± 0.05); (B) C580Y east (0.2755 ± 0.05) and C580Y west (0.4360 ± 0.03 ± 0.03). The error bars indicate ± standard deviation (SD).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383523&req=5

ppat.1004789.g003: Heterozygosity valley around K13 propeller alleles in Thailand.The expected heterozygosity of parasite isolates with: (A) the C580Y mutation (N = 26) and wild type alleles (N = 82); (B) the C580Y from the east (N = 10) and west (N = 16). Diversity was reduced at all 9 K13 propeller microsatellite loci for C580Y compared to wild type alleles. The mean He in (A) for C580Y (0.3526 ± 0.08), wild type (0.6246 ± 0.06), neutral (0.7650 ± 0.05); (B) C580Y east (0.2755 ± 0.05) and C580Y west (0.4360 ± 0.03 ± 0.03). The error bars indicate ± standard deviation (SD).
Mentions: Using the nine microsatellite loci flanking the K13 propeller gene, expected heterozygosity (He) was calculated for the C580Y and wild type alleles (Fig 3). The N458Y, R539T, P574L, R575K and S621F alleles were excluded as there were limited samples to carry out the analysis. The C580Y allele (N = 26, mean He = 0.3526 ± 0.08) showed a 56% reduction (p = 0.0046) in heterozygosity as compared to wild type alleles (N = 22, mean He = 0.6246 ± 0.06) (Fig 3A). No significant difference (p = 0.2240) in heterozygosity was found when comparing western C580Y alleles (N = 10, mean He = 0.4360 ± 0.03) to eastern C580Y alleles (N = 15, mean He = 0.2755 ± 0.05) (Fig 3B). Mean He between the wild type and different mutant alleles were compared using the Mann-Whitney U test.

Bottom Line: A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F).The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders.In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

View Article: PubMed Central - PubMed

Affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America; Atlanta Research and Education Foundation, Atlanta VA Medical Center, Atlanta, Georgia, United States of America.

ABSTRACT
The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria. Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance. A total of 417 patient samples from the year 2007, collected during malaria surveillance studies across ten provinces in Thailand, were genotyped for the candidate Plasmodium falciparum molecular marker of artemisinin resistance K13. Parasite genotypes were examined for K13 propeller mutations associated with artemisinin resistance, signatures of positive selection, and for evidence of whether artemisinin-resistant alleles arose independently across Thailand. A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F). Notably, the R575K and S621F mutations have previously not been reported in Thailand. The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders. It appears these two haplotypes may have independent evolutionary origins. In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

No MeSH data available.


Related in: MedlinePlus