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An outbreak of artemisinin resistant falciparum malaria in Eastern Thailand.

Imwong M, Jindakhad T, Kunasol C, Sutawong K, Vejakama P, Dondorp AM - Sci Rep (2015)

Bottom Line: Mutations in the Kelch13 marker for artemisinin resistance were present in 93% of samples, mainly C580Y from 2 major clusters as identified by microsatellite typing.Resistance markers for antifolates and chloroquine were also highly prevalent.Careful monitoring of ACT efficacy and additional genetic epidemiological studies are warranted to guide the public health response to the outbreak.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

ABSTRACT
Artemisinin resistant falciparum malaria is an increasing problem in Southeast Asia, but has not been associated with increased transmission of the disease, yet. During a recent outbreak in 2014 in Ubon Ratchatani, Eastern Thailand, parasites from 101 patients with falciparum malaria were genotyped for antimalarial drug resistance markers. Mutations in the Kelch13 marker for artemisinin resistance were present in 93% of samples, mainly C580Y from 2 major clusters as identified by microsatellite typing. Resistance markers for antifolates and chloroquine were also highly prevalent. Most strains (91%) carried single copy number PfMDR1, suggesting sustained sensitivity to mefloquine, the partner drug in the local first-line artemisinin combination therapy (ACT). The high prevalence of artemisinin resistance in this recent malaria outbreak suggests but does not prove a causative role in increased transmission. Careful monitoring of ACT efficacy and additional genetic epidemiological studies are warranted to guide the public health response to the outbreak.

No MeSH data available.


Related in: MedlinePlus

(a) Pie charts representing proportions of mutations or gene-amplification in five resistance genes (Pfkelch, pfcrt, pfdhfr, pfdhps and pfmdr1) observed in P. falciparum isolates from Ubon Ratchathani. A total of 101 samples were genotyped, but full genotyping of all resistance markers was not accomplished in all samples (see denominators shown next to pie charts) The map was created using Adobe® Photoshop® CS6 version 13.1.2 × 64 software (Copyright© 1990–2012 Adobe Systems Incorporated). (b) Bar chart representing the patterns observed in the five antimalarial drug resistance genes assessed in this study.
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f1: (a) Pie charts representing proportions of mutations or gene-amplification in five resistance genes (Pfkelch, pfcrt, pfdhfr, pfdhps and pfmdr1) observed in P. falciparum isolates from Ubon Ratchathani. A total of 101 samples were genotyped, but full genotyping of all resistance markers was not accomplished in all samples (see denominators shown next to pie charts) The map was created using Adobe® Photoshop® CS6 version 13.1.2 × 64 software (Copyright© 1990–2012 Adobe Systems Incorporated). (b) Bar chart representing the patterns observed in the five antimalarial drug resistance genes assessed in this study.

Mentions: Figure 1 provides a summary of the molecular resistance markers identified in this study. A total of 101 patients presenting with uncomplicated falciparum malaria in Buntharik district hospital were studied, but full genotyping of all resistance markers was not accomplished in all samples. Full length sequencing of P. falciparum PfKelch gene was assessed in samples from 88 patients presenting with uncomplicated falciparum malaria (Fig. 1A). Point mutations in the propeller region of the gene were found in 82/88 (93%) of samples. The major mutant type was C580Y (65/88: 74%) followed by R539T (17/88: 19%). A small number of samples showed multiple genotypes suggesting polyclonal infections: C580Y/C in 5/88 (6%) and R539T/R in 2/88 (2%) of patient samples.


An outbreak of artemisinin resistant falciparum malaria in Eastern Thailand.

Imwong M, Jindakhad T, Kunasol C, Sutawong K, Vejakama P, Dondorp AM - Sci Rep (2015)

(a) Pie charts representing proportions of mutations or gene-amplification in five resistance genes (Pfkelch, pfcrt, pfdhfr, pfdhps and pfmdr1) observed in P. falciparum isolates from Ubon Ratchathani. A total of 101 samples were genotyped, but full genotyping of all resistance markers was not accomplished in all samples (see denominators shown next to pie charts) The map was created using Adobe® Photoshop® CS6 version 13.1.2 × 64 software (Copyright© 1990–2012 Adobe Systems Incorporated). (b) Bar chart representing the patterns observed in the five antimalarial drug resistance genes assessed in this study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663761&req=5

f1: (a) Pie charts representing proportions of mutations or gene-amplification in five resistance genes (Pfkelch, pfcrt, pfdhfr, pfdhps and pfmdr1) observed in P. falciparum isolates from Ubon Ratchathani. A total of 101 samples were genotyped, but full genotyping of all resistance markers was not accomplished in all samples (see denominators shown next to pie charts) The map was created using Adobe® Photoshop® CS6 version 13.1.2 × 64 software (Copyright© 1990–2012 Adobe Systems Incorporated). (b) Bar chart representing the patterns observed in the five antimalarial drug resistance genes assessed in this study.
Mentions: Figure 1 provides a summary of the molecular resistance markers identified in this study. A total of 101 patients presenting with uncomplicated falciparum malaria in Buntharik district hospital were studied, but full genotyping of all resistance markers was not accomplished in all samples. Full length sequencing of P. falciparum PfKelch gene was assessed in samples from 88 patients presenting with uncomplicated falciparum malaria (Fig. 1A). Point mutations in the propeller region of the gene were found in 82/88 (93%) of samples. The major mutant type was C580Y (65/88: 74%) followed by R539T (17/88: 19%). A small number of samples showed multiple genotypes suggesting polyclonal infections: C580Y/C in 5/88 (6%) and R539T/R in 2/88 (2%) of patient samples.

Bottom Line: Mutations in the Kelch13 marker for artemisinin resistance were present in 93% of samples, mainly C580Y from 2 major clusters as identified by microsatellite typing.Resistance markers for antifolates and chloroquine were also highly prevalent.Careful monitoring of ACT efficacy and additional genetic epidemiological studies are warranted to guide the public health response to the outbreak.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

ABSTRACT
Artemisinin resistant falciparum malaria is an increasing problem in Southeast Asia, but has not been associated with increased transmission of the disease, yet. During a recent outbreak in 2014 in Ubon Ratchatani, Eastern Thailand, parasites from 101 patients with falciparum malaria were genotyped for antimalarial drug resistance markers. Mutations in the Kelch13 marker for artemisinin resistance were present in 93% of samples, mainly C580Y from 2 major clusters as identified by microsatellite typing. Resistance markers for antifolates and chloroquine were also highly prevalent. Most strains (91%) carried single copy number PfMDR1, suggesting sustained sensitivity to mefloquine, the partner drug in the local first-line artemisinin combination therapy (ACT). The high prevalence of artemisinin resistance in this recent malaria outbreak suggests but does not prove a causative role in increased transmission. Careful monitoring of ACT efficacy and additional genetic epidemiological studies are warranted to guide the public health response to the outbreak.

No MeSH data available.


Related in: MedlinePlus