Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 2619–2620.
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NPJ, Lindegardh N, Socheat D, White NJ, 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455–467.
Lon C, Manning JE, Vanachayangkul P, So M, Sea D, Se Y, Gosi P, Lanteri C, Chaorattanakawee S, Sriwichai S, Chann S, Kuntawunginn W, Buathong N, Nou S, Walsh DS, Tyner SD, Juliano JJ, Lin J, Spring M, Bethell D, Kaewkungwal J, Tang D, Chuor CM, Satharath P, Saunders D, 2014. Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial. PLoS One 9: e93138.
Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, ler Moo C, Al-Saai S, Dondorp AM, Lwin KM, Singhasivanon P, Day NPJ, White NJ, Anderson TJC, Nosten F, 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 1960–1966.
Takala-Harrison S, Jacob CG, Arze C, Cummings MP, Silva JC, Dondorp AM, Fukuda MM, Hien TT, Mayxay M, Noedl H, Nosten F, Kyaw MP, Nhien NTT, Imwong M, Bethell D, Se Y, Lon C, Tyner SD, Saunders DL, Ariey F, Mercereau-Puijalon O, Menard D, Newton PN, Khanthavong M, Hongvanthong B, Starzengruber P, Fuehrer H-P, Swoboda P, Khan WA, Phyo AP, Nyunt MM, Nyunt MH, Brown TS, Adams M, Pepin CS, Bailey J, Tan JC, Ferdig MT, Clark TG, Miotto O, MacInnis B, Kwiatkowski DP, White NJ, Ringwald P, Plowe CV, 2015. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in southeast Asia. J Infect Dis 211: 670–679.
Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Ménard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale J-C, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Ménard D, 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.
Straimer J, Gnädig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, Dacheux M, Khim N, Zhang L, Lam S, Gregory PD, Urnov FD, Mercereau-Puijalon O, Benoit-Vical F, Fairhurst RM, Ménard D, Fidock DA, 2015. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347: 428–431.
Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, Lim P, Mead D, Oyola SO, Dhorda M, Imwong M, Woodrow C, Manske M, Stalker J, Drury E, Campino S, Amenga-Etego L, Thanh T-NN, Tran HT, Ringwald P, Bethell D, Nosten F, Phyo AP, Pukrittayakamee S, Chotivanich K, Chuor CM, Nguon C, Suon S, Sreng S, Newton PN, Mayxay M, Khanthavong M, Hongvanthong B, Htut Y, Han KT, Kyaw MP, Faiz MA, Fanello CI, Onyamboko M, Mokuolu OA, Jacob CG, Takala-Harrison S, Plowe CV, Day NP, Dondorp AM, Spencer CCA, McVean G, Fairhurst RM, White NJ, Kwiatkowski DP, 2015. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet 47: 226–234.
MalariaGEN Plasmodium falciparum Community Project, 2016. Genomic epidemiology of artemisinin resistant malaria. eLife 5: e08714.
Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han K-T, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ; Tracking Resistance to Artemisinin Collaboration (TRAC), 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, Ringwald P, 2013. Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother 57: 818–826.
Lin JT, Patel JC, Kharabora O, Sattabongkot J, Muth S, Ubalee R, Schuster AL, Rogers WO, Wongsrichanalai C, Juliano JJ, 2013. Plasmodium vivax isolates from Cambodia and Thailand show high genetic complexity and distinct patterns of P. vivax multidrug resistance gene 1 (pvmdr1) polymorphisms. Am J Trop Med Hyg 88: 1116–1123.
Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M, Prasetyorini B, Kenangalem E, Piera KA, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN, 2008. Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. J Infect Dis 198: 1558–1564.
Eldin de Pécoulas P, Basco LK, Tahar R, Ouatas T, Mazabraud A, 1998. Analysis of the Plasmodium vivax dihydrofolate reductase–thymidylate synthase gene sequence. Gene 211: 177–185.
Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, Tagbor H, Williams J, Bojang K, Njie F, Desai M, Kariuki S, Gutman J, Mathanga DP, Mårtensson A, Ngasala B, Conrad MD, Rosenthal PJ, Tshefu AK, Moormann AM, Vulule JM, Doumbo OK, Ter Kuile FO, Meshnick SR, Bailey JA, Juliano JJ, 2015. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis 211: 680–688.
Taylor SM, Parobek CM, Aragam N, Ngasala BE, Mårtensson A, Meshnick SR, Juliano JJ, 2013. Pooled deep sequencing of Plasmodium falciparum isolates: an efficient and scalable tool to quantify prevailing malaria drug-resistance genotypes. J Infect Dis 208: 1998–2006.
Popovici J, Kao S, Eal L, Bin S, Kim S, Ménard D, 2015. Reduced polymorphism in the Kelch propeller domain in Plasmodium vivax isolates from Cambodia. Antimicrob Agents Chemother 59: 730–733.
Langmead B, Salzberg SL, 2012. Fast gapped-read alignment with Bowtie 2. Nat Methods 9: 357–359.
R Core Team, 2016. R: A Language and Environment for Statistical Computing. Available at: https://www.R-project.org/. Accessed March 28, 2016.
Lysholm F, Andersson B, Persson B, 2011. An efficient simulator of 454 data using configurable statistical models. BMC Res Notes 4: 449.
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Abstract Views | 660 | 331 | 29 |
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The emergence of artemisinin resistance among Plasmodium falciparum in the Greater Mekong subregion threatens malaria control interventions and is associated with multiple unique mutations in K13 (PF3D7_1343700). The aim of this study was to survey Cambodian Plasmodium vivax for mutations in the K13 ortholog (K12, PVX_083080) that might similarly confer artemisinin resistance. Extracted DNA from Cambodian isolates collected between 2009 and 2012 was pooled by province and year and submitted for next-generation sequencing. Single-nucleotide polymorphisms (SNPs) were identified using a pile-up approach that detected minority SNPs. Among the 14 pools, we found six unique SNPs, including three nonsynonymous SNPs, across six codons in K12. However, none of the SNPs were orthologous to artemisinin resistance–conferring mutations in PF3D7_1343700, and nonsynonymous changes did not persist through time within populations. These results suggest a lack of selection in the P. vivax population in Cambodia due to artemisinin drug pressure.
Authors' addresses: Nicholas F. Brazeau, University of North Carolina School of Medicine, Chapel Hill, NC, E-mail: nbrazeau@med.unc.edu. Nicholas Hathaway, School of Medicine, University of Massachusetts Medical School, Worcester, MA, E-mail: nickjhathaway@gmail.com. Christian M. Parobek, Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC, E-mail: christian_parobek@med.unc.edu. Jessica T. Lin, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, E-mail: jessica_lin@med.unc.edu. Jeffrey A. Bailey, Division of Transfusion Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, and Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester, MA, E-mail: jeffrey.bailey@umassmed.edu. Chanthap Lon and David L. Saunders, Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mails: chanthapl@afrims.org and david.l.saunders.mil@mail.mil. Jonathan J. Juliano, Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, E-mail: jonathan_juliano@med.unc.edu.
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 2619–2620.
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NPJ, Lindegardh N, Socheat D, White NJ, 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455–467.
Lon C, Manning JE, Vanachayangkul P, So M, Sea D, Se Y, Gosi P, Lanteri C, Chaorattanakawee S, Sriwichai S, Chann S, Kuntawunginn W, Buathong N, Nou S, Walsh DS, Tyner SD, Juliano JJ, Lin J, Spring M, Bethell D, Kaewkungwal J, Tang D, Chuor CM, Satharath P, Saunders D, 2014. Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial. PLoS One 9: e93138.
Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, ler Moo C, Al-Saai S, Dondorp AM, Lwin KM, Singhasivanon P, Day NPJ, White NJ, Anderson TJC, Nosten F, 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 1960–1966.
Takala-Harrison S, Jacob CG, Arze C, Cummings MP, Silva JC, Dondorp AM, Fukuda MM, Hien TT, Mayxay M, Noedl H, Nosten F, Kyaw MP, Nhien NTT, Imwong M, Bethell D, Se Y, Lon C, Tyner SD, Saunders DL, Ariey F, Mercereau-Puijalon O, Menard D, Newton PN, Khanthavong M, Hongvanthong B, Starzengruber P, Fuehrer H-P, Swoboda P, Khan WA, Phyo AP, Nyunt MM, Nyunt MH, Brown TS, Adams M, Pepin CS, Bailey J, Tan JC, Ferdig MT, Clark TG, Miotto O, MacInnis B, Kwiatkowski DP, White NJ, Ringwald P, Plowe CV, 2015. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in southeast Asia. J Infect Dis 211: 670–679.
Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Ménard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale J-C, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Ménard D, 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.
Straimer J, Gnädig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, Dacheux M, Khim N, Zhang L, Lam S, Gregory PD, Urnov FD, Mercereau-Puijalon O, Benoit-Vical F, Fairhurst RM, Ménard D, Fidock DA, 2015. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347: 428–431.
Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, Lim P, Mead D, Oyola SO, Dhorda M, Imwong M, Woodrow C, Manske M, Stalker J, Drury E, Campino S, Amenga-Etego L, Thanh T-NN, Tran HT, Ringwald P, Bethell D, Nosten F, Phyo AP, Pukrittayakamee S, Chotivanich K, Chuor CM, Nguon C, Suon S, Sreng S, Newton PN, Mayxay M, Khanthavong M, Hongvanthong B, Htut Y, Han KT, Kyaw MP, Faiz MA, Fanello CI, Onyamboko M, Mokuolu OA, Jacob CG, Takala-Harrison S, Plowe CV, Day NP, Dondorp AM, Spencer CCA, McVean G, Fairhurst RM, White NJ, Kwiatkowski DP, 2015. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet 47: 226–234.
MalariaGEN Plasmodium falciparum Community Project, 2016. Genomic epidemiology of artemisinin resistant malaria. eLife 5: e08714.
Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han K-T, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ; Tracking Resistance to Artemisinin Collaboration (TRAC), 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, Ringwald P, 2013. Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother 57: 818–826.
Lin JT, Patel JC, Kharabora O, Sattabongkot J, Muth S, Ubalee R, Schuster AL, Rogers WO, Wongsrichanalai C, Juliano JJ, 2013. Plasmodium vivax isolates from Cambodia and Thailand show high genetic complexity and distinct patterns of P. vivax multidrug resistance gene 1 (pvmdr1) polymorphisms. Am J Trop Med Hyg 88: 1116–1123.
Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M, Prasetyorini B, Kenangalem E, Piera KA, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN, 2008. Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. J Infect Dis 198: 1558–1564.
Eldin de Pécoulas P, Basco LK, Tahar R, Ouatas T, Mazabraud A, 1998. Analysis of the Plasmodium vivax dihydrofolate reductase–thymidylate synthase gene sequence. Gene 211: 177–185.
Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, Tagbor H, Williams J, Bojang K, Njie F, Desai M, Kariuki S, Gutman J, Mathanga DP, Mårtensson A, Ngasala B, Conrad MD, Rosenthal PJ, Tshefu AK, Moormann AM, Vulule JM, Doumbo OK, Ter Kuile FO, Meshnick SR, Bailey JA, Juliano JJ, 2015. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis 211: 680–688.
Taylor SM, Parobek CM, Aragam N, Ngasala BE, Mårtensson A, Meshnick SR, Juliano JJ, 2013. Pooled deep sequencing of Plasmodium falciparum isolates: an efficient and scalable tool to quantify prevailing malaria drug-resistance genotypes. J Infect Dis 208: 1998–2006.
Popovici J, Kao S, Eal L, Bin S, Kim S, Ménard D, 2015. Reduced polymorphism in the Kelch propeller domain in Plasmodium vivax isolates from Cambodia. Antimicrob Agents Chemother 59: 730–733.
Langmead B, Salzberg SL, 2012. Fast gapped-read alignment with Bowtie 2. Nat Methods 9: 357–359.
R Core Team, 2016. R: A Language and Environment for Statistical Computing. Available at: https://www.R-project.org/. Accessed March 28, 2016.
Lysholm F, Andersson B, Persson B, 2011. An efficient simulator of 454 data using configurable statistical models. BMC Res Notes 4: 449.
Past two years | Past Year | Past 30 Days | |
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Abstract Views | 660 | 331 | 29 |
Full Text Views | 286 | 8 | 0 |
PDF Downloads | 99 | 14 | 0 |