Prevalence of K13-propeller polymorphisms in Plasmodium falciparum from China-Myanmar border in 2007-2012.
BACKGROUND
The recent emergence and spread of artemisinin resistance in the Greater Mekong Subregion poses a great threat to malaria control and elimination. A K13-propeller gene (K13), PF3D7_1343700, has been associated lately with artemisinin resistance both in vitro and in vivo. This study aimed to investigate the K13 polymorphisms in Plasmodium falciparum parasites from the China-Myanmar border area where artemisinin use has the longest history.


METHODS
A total of 180 archived P. falciparum isolates containing 191 parasite clones, mainly collected in 2007-2012 from the China-Myanmar area, were used to obtain the full-length K13 gene sequences.


RESULTS
Seventeen point mutations were identified in 46.1% (88/191) parasite clones, of which seven were new. The F446I mutation predominated in 27.2% of the parasite clones. The C580Y mutation that is correlated with artemisinin resistance was detected at a low frequency of 1.6%. Collectively, 43.1% of the parasite clones contained point mutations in the kelch domain of the K13 gene. Moreover, there was a trend of increase in the frequency of parasites carrying kelch domain mutations through the years of sample collection. In addition, a microsatellite variation in the N-terminus of the K13 protein was found to have reached a high frequency (69.1%).


CONCLUSIONS
This study documented the presence of mutations in the K13 gene in parasite populations from the China-Myanmar border. Mutations present in the kelch domain have become prevalent (>40%). A predominant mutation F446I and a prevalent microsatellite variation in the N-terminus were identified, but their importance in artemisinin resistance remains to be elucidated.
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. zxw11@psu.edu.
Zenglei
Z
Wang
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. szs17@psu.edu.
Sony
S
Shrestha
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. xul11@psu.edu.
Xiaolian
X
Li
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. jum23@psu.edu.
Jun
J
Miao
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. luy16@psu.edu.|Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, 650500, China. luy16@psu.edu.
Lili
L
Yuan
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. mxc92@psu.edu.
Mynthia
M
Cabrera
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. chg125@psu.edu.
Caitlin
C
Grube
Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, 650500, China. zhaoqingy@yahoo.com.
Zhaoqing
Z
Yang
Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. luc2@psu.edu.
Liwang
L
Cui
D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D002681:China; D009154:Mutation; D002052:Myanmar; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D015800:Protozoan Proteins; C031327:artemisinin