Prevalence of K13-propeller polymorphisms in Plasmodium falciparum from China-Myanmar border in 2007–2012

Malaria Journal - Tập 14 - Trang 1-6 - 2015
Zenglei Wang1, Sony Shrestha1, Xiaolian Li1, Jun Miao1, Lili Yuan1,2, Mynthia Cabrera1, Caitlin Grube1, Zhaoqing Yang2, Liwang Cui1
1Department of Entomology, The Pennsylvania State University, University Park, USA
2Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China

Tóm tắt

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. 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. 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%). 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.

Tài liệu tham khảo

WHO. World malaria report 2014. Geneva: World Health Organization; 2014. http://www.who.int/malaria/publications/world_malaria_report_2014/en/ 2014. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, et al. Evidence of artemisinin-resistant malaria in Western Cambodia. N Engl J Med. 2008;359:2619–20. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361:455–67. Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505:50–5. Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, et al. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis. 2013;13:1043–9. Straimer JGN, Witkowski B, Amaratunga C, Duru V, Ramadani AP, Dacheux M, et al. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science. 2015;347:428–31. Ghorbal M, Gorman M, Macpherson CR, Martins RM, Scherf A, Lopez-Rubio JJ. Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat Biotechnol. 2014;32:819–21. Nyunt MH, Hlaing T, Oo HW, Tin-Oo LK, Phway HP, Wang B, et al. Molecular assessment of artemisinin-resistance markers, polymorphisms in the K13 propeller and a multidrug-resistance gene, in eastern and western border areas of Myanmar. Clin Infect Dis. 2014, doi:10.1093/cid/ciu1160. Takala-Harrison S, Jacob CG, Arze C, Cummings MP, Silva JC, Dondorp AM, et al. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia. J Infect Dis. 2014, doi:10.1093/infdis/jiu491. Thriemer K, Hong N, Rosanas-Urgell A, Phuc BQ, Ha-do M, Pockele E. Delayed parasite clearance after treatment with dihydroartemisinin-piperaquine in Plasmodium falciparum malaria patients in Central Vietnam. Antimicrob Agents Chemother. 2014;58(12):7049–55. Mohon A, Alam MS, Bayih AG, Folefoc A, Shahinas D, Haque R. Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009–2013). Malar J. 2014;13:431. doi:10.1186/1475-2875-13-431. Conrad MD, Bigira V, Kapisi J, Muhindo M, Kamya MR, Havlir DV, et al. Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children. Plos One. 2014;9:e105690. Taylor SM, Parobeck CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, et al. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis. 2014;211:680–8. doi: 10.1093/infdis/jiu467. Kamau E, Campino S, Amenga-Etego L, Drury E, Ishengoma D, Johnson K, et al. K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa. J Infect Dis. 2014, doi: 10.1093/infdis/jiu608. Torrentino-Madamet M, Fall B, Benoit N, Camara C, Amalvict R, Fall M. Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013. Malar J. 2014;13:472. doi:410.1186/1475-2875-1113-1472. Isozumi R, Uemura H, Kimata I, Ichinose Y, Logedi J, Omar AH, et al. Novel mutations in K13 propeller gene of artemisinin-resistant Plasmodium falciparum. Emerg Infect Dis. 2015;21:40–2. doi:10.3201/eid2103.140898. Cui L, Su XZ. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Rev Anti Infect Ther. 2009;7:999–1013. Sun X, Zhang Z, Wang J, Deng Y, Yang Y, Lasi J, et al. Therapeutic efficacy and safety of compound dihydroartemisinin/piperaquine for uncomplicated Plasmodium falciparum infection in Laiza city of Myanmar bordering on China. Chin J Parasitol Parasit Dis. 2011;29:372–5. Huang F, Tang L, Yang H, Zhou S, Sun X, Liu H. Therapeutic efficacy of artesunate in the treatment of uncomplicated Plasmodium falciparum malaria and anti-malarial, drug-resistance marker polymorphisms in populations near the China-Myanmar border. Malar J. 2012;11:278. WHO. Global plan for artemisinin resistance containment (GPARC). 2011. http://who.int/malaria/publications/atoz/9789241500838/en/. Wang Z, Parker D, Meng H, Wu L, Li J, Zhao Z, et al. In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes. PLoS One. 2012;7:e30927. Kaneko O, Kimura M, Kawamoto F, Ferreira MU, Tanabe K. Plasmodium falciparum: allelic variation in the merozoite surface protein 1 gene in wild isolates from southern Vietnam. Exp Parasitol. 1997;86:45–57. Snounou G, Zhu X, Siripoon N, Jarra W, Thaithong S, Brown KN, et al. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg. 1999;93:369–74. Roper C, Richardson W, Elhassan IM, Giha H, Hviid L, Satti GM, et al. Seasonal changes in the Plasmodium falciparum population in individuals and their relationship to clinical malaria: a longitudinal study in a Sudanese village. Parasitology. 1998;116:501–10. Meng H, Zhang R, Yang H, Fan Q, Su X, Miao J, et al. In vitro sensitivity of Plasmodium falciparum clinical isolates from the China-Myanmar border area to quinine and association with polymorphism in the Na+/H+ exchanger. Antimicrob Agents Chemother. 2010;54:4306–13. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30:2725–9. Kelley LA, Sternberg MJE. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc. 2009;4:363–71. Yuan LL, Zhao H, Wu LO, Li XM, Parker D, Xu SH, et al. Plasmodium falciparum populations from northeastern Myanmar display high levels of genetic diversity at multiple antigenic loci. Acta Trop. 2013;125:53–9. Feng J, Zhou D, Lin Y, Xiao H, Yan H, Xia Z. Amplification of pfmdr1, pfcrt, pvmdr1 and K13-propeller polymorphism associated with Plasmodium falciparum and Plasmodium vivax at the China-Myanmar border. Antimicrob Agents Chemother 2015, doi: 10.1128/AAC.04843-14 Tun KM, Imwong M, Lwin KM, Win AA, Hlaing TM, Hlaing T, et al. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infect Dis. 2015, doi:10.1016/S1473-3099(15)70032-0. Huang F, Tang L, Yang H, Zhou S, Liu H, Li J, et al. Molecular epidemiology of drug resistance markers of Plasmodium falciparum in Yunnan Province, China. Malar J. 2012;11:243.