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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

Dendrogram showing inter-strain relatedness of P. falciparum strains carrying the C580Y Pfkelch mutation obtained from patients with a first presentation of uncomplicated falciparum malaria in Buntharik district hospital in Ubon Ratchatani province in eastern Thailand.Complete microsatellite typing was successful in 57/65 (88%) of parasite strains with the C580Y mutation. Microsatellite types were compared to 20 typed strains from Guinea16. Cluster analysis was based on typing of 9 microsatellites using genetic similarity indexes obtained by unweighted pair group method arithmetic averages (UPGMA). The analysis revealed 2 separate clusters within the Ubon Ratchathani isolates.
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f2: Dendrogram showing inter-strain relatedness of P. falciparum strains carrying the C580Y Pfkelch mutation obtained from patients with a first presentation of uncomplicated falciparum malaria in Buntharik district hospital in Ubon Ratchatani province in eastern Thailand.Complete microsatellite typing was successful in 57/65 (88%) of parasite strains with the C580Y mutation. Microsatellite types were compared to 20 typed strains from Guinea16. Cluster analysis was based on typing of 9 microsatellites using genetic similarity indexes obtained by unweighted pair group method arithmetic averages (UPGMA). The analysis revealed 2 separate clusters within the Ubon Ratchathani isolates.

Mentions: Microsatellite typing and subsequent cluster analysis by UPGMA was performed on all 65 parasite strains containing the C580Y Pfkelch mutation obtained from patients at the moment of first presentation. Complete typing was successful in 57 samples, whereas in the remainder the quantity of parasite DNA was too limited. Results are presented as a dendrogram in Fig. 2. Previous published microsatellite genetic patterns of 20 P. falciparum strains from Guinea16 were included in the dendrogram as an outgroup. The dendrogram indicated that the P. falciparum strains obtained from patients in Ubon Ratchathani were closely related and could be divided into 2 clusters. The P. falciparum from Guinea clearly diverged from the Thai isolates.


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)

Dendrogram showing inter-strain relatedness of P. falciparum strains carrying the C580Y Pfkelch mutation obtained from patients with a first presentation of uncomplicated falciparum malaria in Buntharik district hospital in Ubon Ratchatani province in eastern Thailand.Complete microsatellite typing was successful in 57/65 (88%) of parasite strains with the C580Y mutation. Microsatellite types were compared to 20 typed strains from Guinea16. Cluster analysis was based on typing of 9 microsatellites using genetic similarity indexes obtained by unweighted pair group method arithmetic averages (UPGMA). The analysis revealed 2 separate clusters within the Ubon Ratchathani isolates.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Dendrogram showing inter-strain relatedness of P. falciparum strains carrying the C580Y Pfkelch mutation obtained from patients with a first presentation of uncomplicated falciparum malaria in Buntharik district hospital in Ubon Ratchatani province in eastern Thailand.Complete microsatellite typing was successful in 57/65 (88%) of parasite strains with the C580Y mutation. Microsatellite types were compared to 20 typed strains from Guinea16. Cluster analysis was based on typing of 9 microsatellites using genetic similarity indexes obtained by unweighted pair group method arithmetic averages (UPGMA). The analysis revealed 2 separate clusters within the Ubon Ratchathani isolates.
Mentions: Microsatellite typing and subsequent cluster analysis by UPGMA was performed on all 65 parasite strains containing the C580Y Pfkelch mutation obtained from patients at the moment of first presentation. Complete typing was successful in 57 samples, whereas in the remainder the quantity of parasite DNA was too limited. Results are presented as a dendrogram in Fig. 2. Previous published microsatellite genetic patterns of 20 P. falciparum strains from Guinea16 were included in the dendrogram as an outgroup. The dendrogram indicated that the P. falciparum strains obtained from patients in Ubon Ratchathani were closely related and could be divided into 2 clusters. The P. falciparum from Guinea clearly diverged from the Thai isolates.

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