World Health Organization, 2014. World Malaria Report. Geneva, Switzerland: World Health Organization.
World Health Organization, 2015. Guidelines for the Treatment of Malaria, 3rd edition. Geneva, Switzerland: World Health Organization.
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.
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 JC, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Ménard D, 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.
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 NT, 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 HP, 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.
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.
Kamau E, Campino S, Amenga-Etego L, Drury E, Ishengoma D, Johnson K, Mumba D, Kekre M, Yavo W, Mead D, Bouyou-Akotet M, Apinjoh T, Golassa L, Randrianarivelojosia M, Andagalu B, Maiga-Ascofare O, Amambua-Ngwa A, Tindana P, Ghansah A, MacInnis B, Kwiatkowski D, Djimde AA, 2014. K13-Propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa. J Infect Dis 211: 1352–1355.
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.
Ministry of Health, The Federal Democratic Republic of Ethiopia, 2010. National Strategic Plan for Malaria Prevention Control and Elimination in Ethiopia 2011–2015.
Ministry of Health, The Federal Democratic Republic of Ethiopia, 2010. Malaria Diagnosis and Treatment, Guideline for Health Workers in Ethiopia.
Sema M, Alemu A, Bayih A, Getie S, Getnet G, Guelig D, Burton R, LaBarre P, Pillai DR, 2015. Evaluation of non-instrumented nucleic acid amplification by loop-mediated isothermal amplification (NINA-LAMP) for the diagnosis of malaria in northwest Ethiopia. Malar J 14: 44.
Mohon AN, Alam MS, Bayih AG, Folefoc A, Shahinas D, Haque R, Pillai DR, 2014. Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009–2013). Malar J 13: 431.
Clamp M, Cuff J, Searle SM, Barton GJ, 2004. The Jalview Java alignment editor. Bioinformatics 20: 426–427.
Kelley LA, Sternberg MJE, 2009. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 4: 363–371.
Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN, 1993. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol 61: 315–320.
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 NTT, 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, for the Tracking Resistance to Artemisinin Collaboration, 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
Tun KM, Imwong M, Lwin KM, Win AA, Hlaing TM, Hlaing T, Lin K, Kyaw MP, Plewes K, Faiz MA, Dhorda M, Cheah PY, Pukrittayakamee S, Ashley EA, Anderson TJ, Nair S, McDew-White M, Flegg JA, Grist EP, Guerin P, Maude RJ, Smithuis F, Dondorp AM, Day NP, Nosten F, White NJ, Woodrow CJ, 2015. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infect Dis 15: 415–421.
Torrentino-Madamet M, Fall B, Benoit N, Camara C, Amalvict R, Fall M, Dionne P, Ba Fall K, Nakoulima A, Diatta B, Diemé Y, Ménard D, Wade B, Pradines B, 2014. Limited polymorphisms in K13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013. Malar J 13: 472.
Escobar C, Pateira S, Lobo E, Lobo L, Teodosio R, Dias F, Fernandes N, Arez AP, Varandas L, Nogueira F, 2015. Polymorphisms in Plasmodium falciparum K13-propeller in Angola and Mozambique after the introduction of the ACTs. PLoS One 10: e0119215.
Nyunt MH, Hlaing T, Oo HW, Tin-Oo L-LK, Phway HP, Wang B, Zaw NN, Han SS, Tun T, San KK, Kyaw MP, Han ET, 2014. Molecular assessment of artemisinin resistance markers, polymorphisms in the K13 propeller, and a multidrug-resistance gene in the eastern and western border areas of Myanmar. Clin Infect Dis 60: 1208–1215.
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Artemisinin combination therapy (ACT) is the first line to treat uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin treatment failures are on the rise in southeast Asia. Delayed parasite clearance after ACT is associated with mutations of the P. falciparum kelch 13 gene. Patients (N = 148) in five districts of northwest Ethiopia were enrolled in a 28-day ACT trial. We identified a unique kelch 13 mutation (R622I) in 3/125 (2.4%) samples. The three isolates with R622I were from Negade-Bahir and Aykel districts close to the Ethiopia–Sudan border. One of three patients with the mutant strain was parasitemic at day 3; however, all patients cleared parasites by day 28. Correlation between kelch 13 mutations and parasite clearance was not possible due to the low frequency of mutations in this study.
Financial support: Funding for this study was provided in part by Calgary Laboratory Services and Department of Medicine, University of Calgary.
Authors' addresses: Abebe Genetu Bayih and Abu Naser Mohon, Department of Pathology, University of Calgary, Alberta, Canada, E-mails: abebegenetu@gmail.com and manmohon@ucalgary.ca. Gebeyaw Getnet, Abebe Alemu, and Sisay Getie, Department of Medical Parasitology, University of Gondar, Gondar, Ethiopia, E-mails: ggebeyaw@yahoo.com, yanbule@gmail.com, and sisaygetie@yahoo.com. Dylan R. Pillai, Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada, E-mail: drpillai@ucalgary.ca.
World Health Organization, 2014. World Malaria Report. Geneva, Switzerland: World Health Organization.
World Health Organization, 2015. Guidelines for the Treatment of Malaria, 3rd edition. Geneva, Switzerland: World Health Organization.
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.
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 JC, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Ménard D, 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.
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 NT, 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 HP, 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.
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.
Kamau E, Campino S, Amenga-Etego L, Drury E, Ishengoma D, Johnson K, Mumba D, Kekre M, Yavo W, Mead D, Bouyou-Akotet M, Apinjoh T, Golassa L, Randrianarivelojosia M, Andagalu B, Maiga-Ascofare O, Amambua-Ngwa A, Tindana P, Ghansah A, MacInnis B, Kwiatkowski D, Djimde AA, 2014. K13-Propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa. J Infect Dis 211: 1352–1355.
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.
Ministry of Health, The Federal Democratic Republic of Ethiopia, 2010. National Strategic Plan for Malaria Prevention Control and Elimination in Ethiopia 2011–2015.
Ministry of Health, The Federal Democratic Republic of Ethiopia, 2010. Malaria Diagnosis and Treatment, Guideline for Health Workers in Ethiopia.
Sema M, Alemu A, Bayih A, Getie S, Getnet G, Guelig D, Burton R, LaBarre P, Pillai DR, 2015. Evaluation of non-instrumented nucleic acid amplification by loop-mediated isothermal amplification (NINA-LAMP) for the diagnosis of malaria in northwest Ethiopia. Malar J 14: 44.
Mohon AN, Alam MS, Bayih AG, Folefoc A, Shahinas D, Haque R, Pillai DR, 2014. Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009–2013). Malar J 13: 431.
Clamp M, Cuff J, Searle SM, Barton GJ, 2004. The Jalview Java alignment editor. Bioinformatics 20: 426–427.
Kelley LA, Sternberg MJE, 2009. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 4: 363–371.
Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN, 1993. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol 61: 315–320.
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 NTT, 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, for the Tracking Resistance to Artemisinin Collaboration, 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
Tun KM, Imwong M, Lwin KM, Win AA, Hlaing TM, Hlaing T, Lin K, Kyaw MP, Plewes K, Faiz MA, Dhorda M, Cheah PY, Pukrittayakamee S, Ashley EA, Anderson TJ, Nair S, McDew-White M, Flegg JA, Grist EP, Guerin P, Maude RJ, Smithuis F, Dondorp AM, Day NP, Nosten F, White NJ, Woodrow CJ, 2015. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infect Dis 15: 415–421.
Torrentino-Madamet M, Fall B, Benoit N, Camara C, Amalvict R, Fall M, Dionne P, Ba Fall K, Nakoulima A, Diatta B, Diemé Y, Ménard D, Wade B, Pradines B, 2014. Limited polymorphisms in K13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013. Malar J 13: 472.
Escobar C, Pateira S, Lobo E, Lobo L, Teodosio R, Dias F, Fernandes N, Arez AP, Varandas L, Nogueira F, 2015. Polymorphisms in Plasmodium falciparum K13-propeller in Angola and Mozambique after the introduction of the ACTs. PLoS One 10: e0119215.
Nyunt MH, Hlaing T, Oo HW, Tin-Oo L-LK, Phway HP, Wang B, Zaw NN, Han SS, Tun T, San KK, Kyaw MP, Han ET, 2014. Molecular assessment of artemisinin resistance markers, polymorphisms in the K13 propeller, and a multidrug-resistance gene in the eastern and western border areas of Myanmar. Clin Infect Dis 60: 1208–1215.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1357 | 1001 | 29 |
Full Text Views | 650 | 25 | 1 |
PDF Downloads | 384 | 30 | 1 |