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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

Geographic distribution of the K13 propeller alleles in Thailand in 2007.Pie charts show K13 propeller allele frequencies among 417 parasite isolates in 10 Thailand provinces. The different alleles are color coded. The results are shown on top of the clinical burden map of P. falciparum in Thailand in 2007 (Malaria Atlas Project) [34]. Light grey areas are P. falciparum malaria free and dark grey areas have an unstable risk of malaria transmission (i.e. annual case incidence, or API, is reported at less than 1 per 10,000). Map shows mean estimate for the clinical burden in the range from 0 (light green) to 10,000 (dark green/blue) clinical cases per year. The clinical burden predictions are based on a Bayesian geostatistical model.
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ppat.1004789.g001: Geographic distribution of the K13 propeller alleles in Thailand in 2007.Pie charts show K13 propeller allele frequencies among 417 parasite isolates in 10 Thailand provinces. The different alleles are color coded. The results are shown on top of the clinical burden map of P. falciparum in Thailand in 2007 (Malaria Atlas Project) [34]. Light grey areas are P. falciparum malaria free and dark grey areas have an unstable risk of malaria transmission (i.e. annual case incidence, or API, is reported at less than 1 per 10,000). Map shows mean estimate for the clinical burden in the range from 0 (light green) to 10,000 (dark green/blue) clinical cases per year. The clinical burden predictions are based on a Bayesian geostatistical model.

Mentions: All 417 patient samples were either wild type or had a single mutation in the K13 propeller domain. Twelve percent (50/417) carried one of seven mutant alleles (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F) in the K13 propeller domain, including two mutations (R575K and S621F) that have not been reported previously in Thailand. The C580Y mutant allele, which is a predominant allele in Cambodia, accounted for 52% (26/50) of all mutant alleles identified in our study population. The C580Y allele frequencies were higher along the Thai-Cambodian border, in Chanthaburi (N = 5/10, 50% C580Y), Trat (N = 5/12, 42% C580Y), and Sisaket (N = 8/13, 62% C580Y) provinces compared to the provinces along the Thai-Myanmar border, Chumporn (N = 2/12, 17% C580Y), Ranong (N = 3/40, 8% C580Y), Kanchanaburi (N = 6/40, 15% C580Y), and Tak (N = 1/171, 1% C580Y). Interestingly, the R539T alleles were only found in eastern Thailand near the Cambodian border in Trat (N = 1/12, 8% R539T) and Sisaket (N = 2/13, 16% R539T) provinces. Besides the C580Y mutation, four previously identified mutations (R575K, P574L, E556D, and N458Y) as well as one novel K13 propeller allele not reported yet (S621F), were found in western parts of Thailand. The R575K and S621F alleles were only present along the Thai-Myanmar border in Prachuap (N = 6/33, 18% R575K), Kanchanaburi (N = 4/40, 10% R575K), and Tak (N = 1/132, 1% S621F), provinces. The P574L allele was present in Ranong (N = 4/40, 10%), followed by 8% (N = 1/12) prevalence in Chumporn and 3% (N = 1/33) in Prachuap. All parasite isolates from the northwestern province of Mae Hong Son (N = 42/42) and southeastern province of Yala (N = 40/40) carried the wild type K13 propeller allele. Overall, these results show the presence of parasites harboring single non-synonymous mutations in the K13 propeller domain as early as 2007 in eight Thai provinces (Fig 1).


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)

Geographic distribution of the K13 propeller alleles in Thailand in 2007.Pie charts show K13 propeller allele frequencies among 417 parasite isolates in 10 Thailand provinces. The different alleles are color coded. The results are shown on top of the clinical burden map of P. falciparum in Thailand in 2007 (Malaria Atlas Project) [34]. Light grey areas are P. falciparum malaria free and dark grey areas have an unstable risk of malaria transmission (i.e. annual case incidence, or API, is reported at less than 1 per 10,000). Map shows mean estimate for the clinical burden in the range from 0 (light green) to 10,000 (dark green/blue) clinical cases per year. The clinical burden predictions are based on a Bayesian geostatistical model.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1004789.g001: Geographic distribution of the K13 propeller alleles in Thailand in 2007.Pie charts show K13 propeller allele frequencies among 417 parasite isolates in 10 Thailand provinces. The different alleles are color coded. The results are shown on top of the clinical burden map of P. falciparum in Thailand in 2007 (Malaria Atlas Project) [34]. Light grey areas are P. falciparum malaria free and dark grey areas have an unstable risk of malaria transmission (i.e. annual case incidence, or API, is reported at less than 1 per 10,000). Map shows mean estimate for the clinical burden in the range from 0 (light green) to 10,000 (dark green/blue) clinical cases per year. The clinical burden predictions are based on a Bayesian geostatistical model.
Mentions: All 417 patient samples were either wild type or had a single mutation in the K13 propeller domain. Twelve percent (50/417) carried one of seven mutant alleles (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F) in the K13 propeller domain, including two mutations (R575K and S621F) that have not been reported previously in Thailand. The C580Y mutant allele, which is a predominant allele in Cambodia, accounted for 52% (26/50) of all mutant alleles identified in our study population. The C580Y allele frequencies were higher along the Thai-Cambodian border, in Chanthaburi (N = 5/10, 50% C580Y), Trat (N = 5/12, 42% C580Y), and Sisaket (N = 8/13, 62% C580Y) provinces compared to the provinces along the Thai-Myanmar border, Chumporn (N = 2/12, 17% C580Y), Ranong (N = 3/40, 8% C580Y), Kanchanaburi (N = 6/40, 15% C580Y), and Tak (N = 1/171, 1% C580Y). Interestingly, the R539T alleles were only found in eastern Thailand near the Cambodian border in Trat (N = 1/12, 8% R539T) and Sisaket (N = 2/13, 16% R539T) provinces. Besides the C580Y mutation, four previously identified mutations (R575K, P574L, E556D, and N458Y) as well as one novel K13 propeller allele not reported yet (S621F), were found in western parts of Thailand. The R575K and S621F alleles were only present along the Thai-Myanmar border in Prachuap (N = 6/33, 18% R575K), Kanchanaburi (N = 4/40, 10% R575K), and Tak (N = 1/132, 1% S621F), provinces. The P574L allele was present in Ranong (N = 4/40, 10%), followed by 8% (N = 1/12) prevalence in Chumporn and 3% (N = 1/33) in Prachuap. All parasite isolates from the northwestern province of Mae Hong Son (N = 42/42) and southeastern province of Yala (N = 40/40) carried the wild type K13 propeller allele. Overall, these results show the presence of parasites harboring single non-synonymous mutations in the K13 propeller domain as early as 2007 in eight Thai provinces (Fig 1).

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