1921
Volume 95, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

Artemisinin-based combination therapies (ACTs) are the cornerstone of current strategies for fighting malaria. Over the last decade, ACTs have played a major role in decreasing malaria burden. However, this progress is being jeopardized by the emergence of artemisinin-resistant parasites. Artemisinin resistance was first detected in western Cambodia in 2008 and has since been observed in neighboring countries in southeast Asia. The problem of antimalarial drug resistance has recently worsened in Cambodia, with reports of parasites resistant to piperaquine, the latest generation of partner drug used in combination with dihydroartemisinin, leading to worrying rates of clinical treatment failure. The monitoring and the comprehension of both types of resistance are crucial to prevent the spread of multidrug-resistant parasites outside southeast Asia, and particularly to Africa, where the public health consequences would be catastrophic. To this end, new tools are required for studying the biological and molecular mechanisms underlying resistance to antimalarial drugs and for monitoring the geographic distribution of the resistant parasites. In this review, we detail the major advances in our understanding of resistance to artemisinin and piperaquine and define the challenges that the malaria community will have to face in the coming years.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.16-0234
2016-12-07
2018-12-15
Loading full text...

Full text loading...

/deliver/fulltext/14761645/95/6/1228.html?itemId=/content/journals/10.4269/ajtmh.16-0234&mimeType=html&fmt=ahah

References

  1. World Health Organization, 2015. World Malaria Report 2015. Geneva, Switzerland: World Health Organization. [Google Scholar]
  2. RTS,S Clinical Trials Partnership Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, Kabwende AL, Adegnika AA, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Machevo S, Acacio S, Bulo H, Sigauque B, Macete E, Alonso P, Abdulla S, Salim N, Minja R, Mpina M, Ahmed S, Ali AM, Mtoro AT, Hamad AS, Mutani P, Tanner M, Tinto H, D'Alessandro U, Sorgho H, Valea I, Bihoun B, Guiraud I, Kaboré B, Sombié O, Guiguemdé RT, Ouédraogo JB, Hamel MJ, Kariuki S, Oneko M, Odero C, Otieno K, Awino N, McMorrow M, Muturi-Kioi V, Laserson KF, Slutsker L, Otieno W, Otieno L, Otsyula N, Gondi S, Otieno A, Owira V, Oguk E, Odongo G, Woods JB, Ogutu B, Njuguna P, Chilengi R, Akoo P, Kerubo C, Maingi C, Lang T, Olotu A, Bejon P, Marsh K, Mwambingu G, Owusu-Agyei S, Asante KP, Osei-Kwakye K, Boahen O, Dosoo D, Asante I, Adjei G, Kwara E, Chandramohan D, Greenwood B, Lusingu J, Gesase S, Malabeja A, Abdul O, Mahende C, Liheluka E, Malle L, Lemnge M, Theander TG, Drakeley C, Ansong D, Agbenyega T, Adjei S, Boateng HO, Rettig T, Bawa J, Sylverken J, Sambian D, Sarfo A, Agyekum A, Martinson F, Hoffman I, Mvalo T, Kamthunzi P, Nkomo R, Tembo T, Tegha G, Tsidya M, Kilembe J, Chawinga C, Ballou WR, Cohen J, Guerra Y, Jongert E, Lapierre D, Leach A, Lievens M, Ofori-Anyinam O, Olivier A, Vekemans J, Carter T, Kaslow D, Leboulleux D, Loucq C, Radford A, Savarese B, Schellenberg D, Sillman M, Vansadia P, ; , 2012. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med 367: 22842295.[Crossref] [Google Scholar]
  3. Eyles DE, Hoo CC, Warren M, Sandosham AA, , 1963. Plasmodium falciparum resistant to chloroquine in Cambodia. Am J Trop Med Hyg 12: 840843. [Google Scholar]
  4. Young MD, Contacos PG, Stitcher JE, Millar JW, , 1963. Drug resistance in Plasmodium falciparum from Thailand. Am J Trop Med Hyg 12: 305314. [Google Scholar]
  5. Hofler W, , 1980. Sulfadoxine-pyrimethamine resistant falciparum malaria from Cambodia [in German]. Dtsch Med Wochenschr 105: 350351. [Google Scholar]
  6. Hurwitz ES, Johnson D, Campbell CC, , 1981. Resistance of Plasmodium falciparum malaria to sulfadoxine-pyrimethamine (‘Fansidar’) in a refugee camp in Thailand. Lancet 1: 10681070.[Crossref] [Google Scholar]
  7. Boudreau EF, Webster HK, Pavanand K, Thosingha L, , 1982. Type II mefloquine resistance in Thailand. Lancet 2: 1335.[Crossref] [Google Scholar]
  8. Smithuis FM, van Woensel JB, Nordlander E, Vantha WS, ter Kuile FO, , 1993. Comparison of two mefloquine regimens for treatment of Plasmodium falciparum malaria on the northeastern Thai-Cambodian border. Antimicrob Agents Chemother 37: 19771981.[Crossref] [Google Scholar]
  9. Denis MB, Tsuyuoka R, Poravuth Y, Narann TS, Seila S, Lim C, Incardona S, Lim P, Sem R, Socheat D, Christophel EM, Ringwald P, , 2006. Surveillance of the efficacy of artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria in Cambodia. Trop Med Int Health 11: 13601366.[Crossref] [Google Scholar]
  10. 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: 26192620.[Crossref] [Google Scholar]
  11. 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 NP, Lindegardh N, Socheat D, White NJ, , 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.[Crossref] [Google Scholar]
  12. Saunders DL, Vanachayangkul P, Lon C, , 2014. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med 371: 484485.[Crossref] [Google Scholar]
  13. Leang R, Taylor WR, Bouth DM, Song L, Tarning J, Char MC, Kim S, Witkowski B, Duru V, Domergue A, Khim N, Ringwald P, Menard D, , 2015. Evidence of falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia: dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother 59: 47194726.[Crossref] [Google Scholar]
  14. Mita T, Tanabe K, Kita K, , 2009. Spread and evolution of Plasmodium falciparum drug resistance. Parasitol Int 58: 201209.[Crossref] [Google Scholar]
  15. Roper C, Pearce R, Nair S, Sharp B, Nosten F, Anderson T, , 2004. Intercontinental spread of pyrimethamine-resistant malaria. Science 305: 1124.[Crossref] [Google Scholar]
  16. Trape JF, , 2001. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg 64: 1217. [Google Scholar]
  17. Trape JF, Pison G, Preziosi MP, Enel C, Desgrees du Lou A, Delaunay V, Samb B, Lagarde E, Molez JF, Simondon F, , 1998. Impact of chloroquine resistance on malaria mortality. C R Acad Sci III 321: 689697.[Crossref] [Google Scholar]
  18. Muheki C, McIntyre D, Barnes KI, , 2004. Artemisinin-based combination therapy reduces expenditure on malaria treatment in KwaZulu Natal, South Africa. Trop Med Int Health 9: 959966.[Crossref] [Google Scholar]
  19. World Health Organization, 2001. Antimalarial Drug Combination Therapy. Geneva, Switzerland: World Health Organization. [Google Scholar]
  20. Amaratunga C, Lim P, Suon S, Sreng S, Mao S, Sopha C, Sam B, Dek D, Try V, Amato R, Blessborn D, Song L, Tullo GS, Fay MP, Anderson JM, Tarning J, Fairhurst RM, , 2016. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis 16: 357365.[Crossref] [Google Scholar]
  21. Hien TT, Thuy-Nhien NT, Phu NH, Boni MF, Thanh NV, Nha-Ca NT, Thai le H, Thai CQ, Toi PV, Thuan PD, Long le T, Dong le T, Merson L, Dolecek C, Stepniewska K, Ringwald P, White NJ, Farrar J, Wolbers M, , 2012. In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam. Malar J 11: 355.[Crossref] [Google Scholar]
  22. Kyaw MP, Nyunt MH, Chit K, Aye MM, Aye KH, Aye MM, Lindegardh N, Tarning J, Imwong M, Jacob CG, Rasmussen C, Perin J, Ringwald P, Nyunt MM, , 2013. Reduced susceptibility of Plasmodium falciparum to artesunate in southern Myanmar. PLoS One 8: e57689.[Crossref] [Google Scholar]
  23. 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 NP, White NJ, Anderson TJ, Nosten F, , 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 19601966.[Crossref] [Google Scholar]
  24. Huang F, Takala-Harrison S, Jacob CG, Liu H, Sun X, Yang H, Nyunt MM, Adams M, Zhou S, Xia Z, Ringwald P, Bustos MD, Tang L, Plowe CV, , 2015. A single mutation in K13 predominates in southern China and is associated with delayed clearance of Plasmodium falciparum following artemisinin treatment. J Infect Dis 212: 16291635.[Crossref] [Google Scholar]
  25. Flegg JA, Guerin PJ, White NJ, Stepniewska K, , 2011. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J 10: 339.[Crossref] [Google Scholar]
  26. White LJ, Flegg JA, Phyo AP, Wiladpai-ngern JH, Bethell D, Plowe C, Anderson T, Nkhoma S, Nair S, Tripura R, Stepniewska K, Pan-Ngum W, Silamut K, Cooper BS, Lubell Y, Ashley EA, Nguon C, Nosten F, White NJ, Dondorp AM, , 2015. Defining the in vivo phenotype of artemisinin-resistant falciparum malaria: a modelling approach. PLoS Med 12: e1001823.[Crossref] [Google Scholar]
  27. 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 KT, 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; , 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411423.[Crossref] [Google Scholar]
  28. Maiga AW, Fofana B, Sagara I, Dembele D, Dara A, Traore OB, Toure S, Sanogo K, Dama S, Sidibe B, Kone A, Thera MA, Plowe CV, Doumbo OK, Djimde AA, , 2012. No evidence of delayed parasite clearance after oral artesunate treatment of uncomplicated falciparum malaria in Mali. Am J Trop Med Hyg 87: 2328.[Crossref] [Google Scholar]
  29. Beshir KB, Sutherland CJ, Sawa P, Drakeley CJ, Okell L, Mweresa CK, Omar SA, Shekalaghe SA, Kaur H, Ndaro A, Chilongola J, Schallig HD, Sauerwein RW, Hallett RL, Bousema T, , 2013. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. J Infect Dis 208: 20172024.[Crossref] [Google Scholar]
  30. Witkowski B, Khim N, Chim P, Kim S, Ke S, Kloeung N, Chy S, Duong S, Leang R, Ringwald P, Dondorp AM, Tripura R, Benoit-Vical F, Berry A, Gorgette O, Ariey F, Barale JC, Mercereau-Puijalon O, Menard D, , 2013. Reduced artemisinin susceptibility of Plasmodium falciparum ring stages in western Cambodia. Antimicrob Agents Chemother 57: 914923.[Crossref] [Google Scholar]
  31. Klonis N, Xie SC, McCaw JM, Crespo-Ortiz MP, Zaloumis SG, Simpson JA, Tilley L, , 2013. Altered temporal response of malaria parasites determines differential sensitivity to artemisinin. Proc Natl Acad Sci USA 110: 51575162.[Crossref] [Google Scholar]
  32. Mok S, Imwong M, Mackinnon MJ, Sim J, Ramadoss R, Yi P, Mayxay M, Chotivanich K, Liong KY, Russell B, Socheat D, Newton PN, Day NP, White NJ, Preiser PR, Nosten F, Dondorp AM, Bozdech Z, , 2011. Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription. BMC Genomics 12: 391.[Crossref] [Google Scholar]
  33. Saralamba S, Pan-Ngum W, Maude RJ, Lee SJ, Tarning J, Lindegardh N, Chotivanich K, Nosten F, Day NP, Socheat D, White NJ, Dondorp AM, White LJ, , 2011. Intrahost modeling of artemisinin resistance in Plasmodium falciparum . Proc Natl Acad Sci USA 108: 397402.[Crossref] [Google Scholar]
  34. Amaratunga C, Witkowski B, Dek D, Try V, Khim N, Miotto O, Menard D, Fairhurst RM, , 2014. Plasmodium falciparum founder populations in western Cambodia have reduced artemisinin sensitivity in vitro. Antimicrob Agents Chemother 58: 49354937.[Crossref] [Google Scholar]
  35. Witkowski B, Lelievre J, Barragan MJ, Laurent V, Su XZ, Berry A, Benoit-Vical F, , 2010. Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism. Antimicrob Agents Chemother 54: 18721877.[Crossref] [Google Scholar]
  36. Cheeseman IH, Miller BA, Nair S, Nkhoma S, Tan A, Tan JC, Al Saai S, Phyo AP, Moo CL, Lwin KM, McGready R, Ashley E, Imwong M, Stepniewska K, Yi P, Dondorp AM, Mayxay M, Newton PN, White NJ, Nosten F, Ferdig MT, Anderson TJ, , 2012. A major genome region underlying artemisinin resistance in malaria. Science 336: 7982.[Crossref] [Google Scholar]
  37. Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S, Rockett KA, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Duong S, Nguon C, Chuor CM, Saunders D, Se Y, Lon C, Fukuda MM, Amenga-Etego L, Hodgson AV, Asoala V, Imwong M, Takala-Harrison S, Nosten F, Su XZ, Ringwald P, Ariey F, Dolecek C, Hien TT, Boni MF, Thai CQ, Amambua-Ngwa A, Conway DJ, Djimdé AA, Doumbo OK, Zongo I, Ouedraogo JB, Alcock D, Drury E, Auburn S, Koch O, Sanders M, Hubbart C, Maslen G, Ruano-Rubio V, Jyothi D, Miles A, O'Brien J, Gamble C, Oyola SO, Rayner JC, Newbold CI, Berriman M, Spencer CC, McVean G, Day NP, White NJ, Bethell D, Dondorp AM, Plowe CV, Fairhurst RM, Kwiatkowski DP, , 2013. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat Genet 45: 648655.[Crossref] [Google Scholar]
  38. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Menard 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, Menard D, , 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 5055.[Crossref] [Google Scholar]
  39. Straimer J, Gnadig 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, Menard D, Fidock DA, , 2015. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347: 428431.[Crossref] [Google Scholar]
  40. Ghorbal M, Gorman M, Macpherson CR, Martins RM, Scherf A, Lopez-Rubio JJ, , 2014. Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat Biotechnol 32: 819821.[Crossref] [Google Scholar]
  41. Nyunt MH, Hlaing T, Oo HW, Tin-Oo LL, 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: 12081215.[Crossref] [Google Scholar]
  42. 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: 670679.[Crossref] [Google Scholar]
  43. Talundzic E, Okoth SA, Congpuong K, Plucinski MM, Morton L, Goldman IF, Kachur PS, Wongsrichanalai C, Satimai W, Barnwell JW, Udhayakumar V, , 2015. Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign. PLoS Pathog 11: e1004789.[Crossref] [Google Scholar]
  44. 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: 415421.[Crossref] [Google Scholar]
  45. Huang F, Takala-Harrison S, Jacob CG, Liu H, Sun X, Yang H, Nyunt MM, Adams M, Zhou S, Xia Z, Ringwald P, Bustos MD, Tang L, Plowe CV, , 2015. A single mutation in K13 predominates in southern China and is associated with delayed clearance of Plasmodium falciparum following artemisinin treatment. J Infect Dis 212: 16291635.[Crossref] [Google Scholar]
  46. Wang Z, Shrestha S, Li X, Miao J, Yuan L, Cabrera M, Grube C, Yang Z, Cui L, , 2015. Prevalence of K13-propeller polymorphisms in Plasmodium falciparum from China-Myanmar border in 2007–2012. Malar J 14: 168.[Crossref] [Google Scholar]
  47. Wang Z, Wang Y, Cabrera M, Zhang Y, Gupta B, Wu Y, Kemirembe K, Hu Y, Liang X, Brashear A, Shrestha S, Li X, Miao J, Sun X, Yang Z, Cui L, , 2015. Artemisinin resistance at the China-Myanmar border and association with mutations in the K13 propeller gene. Antimicrob Agents Chemother 59: 69526959.[Crossref] [Google Scholar]
  48. Ye R, Hu D, Zhang Y, Huang Y, Sun X, Wang J, Chen X, Zhou H, Zhang D, Mungthin M, Pan W, , 2016. Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border. Sci Rep 6: 20100.[Crossref] [Google Scholar]
  49. Mishra N, Prajapati SK, Kaitholia K, Bharti RS, Srivastava B, Phookan S, Anvikar AR, Dev V, Sonal GS, Dhariwal AC, White NJ, Valecha N, , 2015. Surveillance of artemisinin resistance in Plasmodium falciparum in India using the kelch13 molecular marker. Antimicrob Agents Chemother 59: 25482553.[Crossref] [Google Scholar]
  50. 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.[Crossref] [Google Scholar]
  51. Conrad MD, Bigira V, Kapisi J, Muhindo M, Kamya MR, Havlir DV, Dorsey G, Rosenthal PJ, , 2014. Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children. PLoS One 9: e105690.[Crossref] [Google Scholar]
  52. Cooper RA, Conrad MD, Watson QD, Huezo SJ, Ninsiima H, Tumwebaze P, Nsobya SL, Rosenthal PJ, , 2015. Lack of artemisinin resistance in Plasmodium falciparum in Uganda based on parasitological and molecular assays. Antimicrob Agents Chemother 59: 50615064.[Crossref] [Google Scholar]
  53. 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.[Crossref] [Google Scholar]
  54. Isozumi R, Uemura H, Kimata I, Ichinose Y, Logedi J, Omar AH, Kaneko A, , 2015. Novel mutations in K13 propeller gene of artemisinin-resistant Plasmodium falciparum . Emerg Infect Dis 21: 490492.[Crossref] [Google Scholar]
  55. 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: 13521355. [Google Scholar]
  56. Ouattara A, Kone A, Adams M, Fofana B, Maiga AW, Hampton S, Coulibaly D, Thera MA, Diallo N, Dara A, Sagara I, Gil JP, Bjorkman A, Takala-Harrison S, Doumbo OK, Plowe CV, Djimde AA, , 2015. Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali. Am J Trop Med Hyg 92: 12021206.[Crossref] [Google Scholar]
  57. 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, Martensson 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: 680688.[Crossref] [Google Scholar]
  58. Torrentino-Madamet M, Fall B, Benoit N, Camara C, Amalvict R, Fall M, Dionne P, Ba Fall K, Nakoulima A, Diatta B, Dieme Y, Menard D, Wade B, Pradines B, , 2015. Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013. Malar J 13: 472.[Crossref] [Google Scholar]
  59. Ménard D, Khim N, Beghain J, Adegnika AA, Shafiul-Alam M, Amodu O, Rahim-Awab G, Barnadas C, Berry A, Boum Y, Bustos MD, Cao J, Chen JH, Collet L, Cui L, Thakur GD, Dieye A, Djallé D, Dorkenoo MA, Eboumbou-Moukoko CE, Espino FE, Fandeur T, Ferreira-da-Cruz MF, Fola AA, Fuehrer HP, Hassan AM, Herrera S, Hongvanthong B, Houzé S, Ibrahim ML, Jahirul-Karim M, Jiang L, Kano S, Ali-Khan W, Khanthavong M, Kremsner PG, Lacerda M, Leang R, Leelawong M, Li M, Lin K, Mazarati JB, Ménard S, Morlais I, Muhindo-Mavoko H, Musset L, Na-Bangchang K, Nambozi M, Niaré K, Noedl H, Ouédraogo JB, Pillai DR, Pradines B, Quang-Phuc B, Ramharter M, Randrianarivelojosia M, Sattabongkot J, Sheikh-Omar A, Silué KD, Sirima SB, Sutherland C, Syafruddin D, Tahar R, Tang LH, Touré OA, Tshibangu-wa-Tshibangu P, Vigan-Womas I, Warsame M, Wini L, Zakeri S, Kim S, Eam R, Berne L, Khean C, Chy S, Ken M, Loch K, Canier L, Duru V, Legrand E, Barale JC, Stokes B, Straimer J, Witkowski B, Fidock DA, Rogier C, Ringwald P, Ariey F, Mercereau-Puijalon O, KARMA Consortium; , 2016. A worldwide map of plasmodium falciparum K13-propeller polymorphisms. N Engl J Med 374: 24532464.[Crossref] [Google Scholar]
  60. Muwanguzi J, Henriques G, Sawa P, Bousema T, Sutherland CJ, Beshir KB, , 2016. Lack of K13 mutations in Plasmodium falciparum persisting after artemisinin combination therapy treatment of Kenyan children. Malar J 15: 36.[Crossref] [Google Scholar]
  61. 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 TN, 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 CC, McVean G, Fairhurst RM, White NJ, Kwiatkowski DP, , 2015. Genetic architecture of artemisinin-resistant Plasmodium falciparum . Nat Genet 47: 226234.[Crossref] [Google Scholar]
  62. Mbengue A, Bhattacharjee S, Pandharkar T, Liu H, Estiu G, Stahelin RV, Rizk SS, Njimoh DL, Ryan Y, Chotivanich K, Nguon C, Ghorbal M, Lopez-Rubio JJ, Pfrender M, Emrich S, Mohandas N, Dondorp AM, Wiest O, Haldar K, , 2015. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature 520: 683687.[Crossref] [Google Scholar]
  63. Adams J, Kelso R, Cooley L, , 2000. The kelch repeat superfamily of proteins: propellers of cell function. Trends Cell Biol 10: 1724.[Crossref] [Google Scholar]
  64. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M, , 1999. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13: 7686.[Crossref] [Google Scholar]
  65. Li X, Zhang D, Hannink M, Beamer LJ, , 2004. Crystal structure of the Kelch domain of human Keap1. J Biol Chem 279: 5475054758.[Crossref] [Google Scholar]
  66. Prag S, Adams JC, , 2003. Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals. BMC Bioinformatics 4: 42.[Crossref] [Google Scholar]
  67. Zhang DD, Hannink M, , 2003. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol 23: 81378151.[Crossref] [Google Scholar]
  68. Bauer AK, Hill T, 3rd Alexander CM, , 2013. The involvement of NRF2 in lung cancer. Oxid Med Cell Longev 2013: 746432.[Crossref] [Google Scholar]
  69. Rojanawatsirivej C, Vijaykadga S, Amklad I, Wilairatna P, Looareesuwan S, , 2003. Monitoring the therapeutic efficacy of antimalarials against uncomplicated falciparum malaria in Thailand. Southeast Asian J Trop Med Public Health 34: 536541. [Google Scholar]
  70. Nelson AL, Purfield A, McDaniel P, Uthaimongkol N, Buathong N, Sriwichai S, Miller RS, Wongsrichanalai C, Meshnick SR, , 2005. pfmdr1 genotyping and in vivo mefloquine resistance on the Thai–Myanmar border. Am J Trop Med Hyg 72: 586592. [Google Scholar]
  71. Price RN, Uhlemann AC, Brockman A, McGready R, Ashley E, Phaipun L, Patel R, Laing K, Looareesuwan S, White NJ, Nosten F, Krishna S, , 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364: 438447.[Crossref] [Google Scholar]
  72. Alker AP, Lim P, Sem R, Shah NK, Yi P, Bouth DM, Tsuyuoka R, Maguire JD, Fandeur T, Ariey F, Wongsrichanalai C, Meshnick SR, , 2007. Pfmdr1 and in vivo resistance to artesunate-mefloquine in falciparum malaria on the Cambodian-Thai border. Am J Trop Med Hyg 76: 641647. [Google Scholar]
  73. Denis MB, Tsuyuoka R, Lim P, Lindegardh N, Yi P, Top SN, Socheat D, Fandeur T, Annerberg A, Christophel EM, Ringwald P, , 2006. Efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Cambodia. Trop Med Int Health 11: 18001807.[Crossref] [Google Scholar]
  74. Janssens B, van Herp M, Goubert L, Chan S, Uong S, Nong S, Socheat D, Brockman A, Ashley EA, Van Damme W, , 2007. A randomized open study to assess the efficacy and tolerability of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Cambodia. Trop Med Int Health 12: 251259.[Crossref] [Google Scholar]
  75. WHO, 2012. National Treatment Guidelines for Malaria in the Kingdom of Cambodia. Geneva, Switzerland: World Health Organization. [Google Scholar]
  76. Leang R, Canavati SE, Khim N, Vestergaard LS, Borghini Fuhrer I, Kim S, Denis MB, Heng P, Tol B, Huy R, Duparc S, Dondorp AM, Menard D, Ringwald P, , 2016. Efficacy and safety of pyronaridine-artesunate for treatment of uncomplicated Plasmodium falciparum malaria in western Cambodia. Antimicrob Agents Chemother 60: 38843890.[Crossref] [Google Scholar]
  77. Rueangweerayut R, Phyo AP, Uthaisin C, Poravuth Y, Binh TQ, Tinto H, Penali LK, Valecha N, Tien NT, Abdulla S, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L, Pyronaridine-Artesunate Study Team; , 2012. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. N Engl J Med 366: 12981309.[Crossref] [Google Scholar]
  78. Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L, , 2013. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J 12: 70.[Crossref] [Google Scholar]
  79. Kayentao K, Doumbo OK, Penali LK, Offianan AT, Bhatt KM, Kimani J, Tshefu AK, Kokolomami JH, Ramharter M, de Salazar PM, Tiono AB, Ouedraogo A, Bustos MD, Quicho F, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L, , 2012. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial. Malar J 11: 364.[Crossref] [Google Scholar]
  80. Ramharter M, Kurth F, Schreier AC, Nemeth J, Glasenapp I, Belard S, Schlie M, Kammer J, Koumba PK, Cisse B, Mordmuller B, Lell B, Issifou S, Oeuvray C, Fleckenstein L, Kremsner PG, , 2008. Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon. J Infect Dis 198: 911919.[Crossref] [Google Scholar]
  81. Tshefu AK, Gaye O, Kayentao K, Thompson R, Bhatt KM, Sesay SS, Bustos DG, Tjitra E, Bedu-Addo G, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L, Pyronaridine-Artesunate Study Team; , 2010. Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial. Lancet 375: 14571467.[Crossref] [Google Scholar]
  82. Duru V, Khim N, Leang R, Kim S, Domergue A, Kloeung N, Ke S, Chy S, Eam R, Khean C, Loch K, Ken M, Lek D, Beghain J, Ariey F, Guerin PJ, Huy R, Mercereau-Puijalon O, Witkowski B, Menard D, , 2015. Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations. BMC Med 13: 305.[Crossref] [Google Scholar]
  83. 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.[Crossref] [Google Scholar]
  84. Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, Se Y, Chann S, Ittiverakul M, Sia-Ngam P, Kuntawunginn W, Arsanok M, Buathong N, Chaorattanakawee S, Gosi P, Ta-Aksorn W, Chanarat N, Sundrakes S, Kong N, Heng TK, Nou S, Teja-Isavadharm P, Pichyangkul S, Phann ST, Balasubramanian S, Juliano JJ, Meshnick SR, Chour CM, Prom S, Lanteri CA, Lon C, Saunders DL, , 2015. Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis 15: 683691.[Crossref] [Google Scholar]
  85. Eastman RT, Dharia NV, Winzeler EA, Fidock DA, , 2011. Piperaquine resistance is associated with a copy number variation on chromosome 5 in drug-pressured Plasmodium falciparum parasites. Antimicrob Agents Chemother 55: 39083916.[Crossref] [Google Scholar]
  86. Lim P, Dek D, Try V, Eastman RT, Chy S, Sreng S, Suon S, Mao S, Sopha C, Sam B, Ashley EA, Miotto O, Dondorp AM, White NJ, Su XZ, Char MC, Anderson JM, Amaratunga C, Menard D, Fairhurst RM, , 2013. Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in western, northern, and eastern Cambodia, 2011–2012: Association with molecular markers. Antimicrob Agents Chemother 57: 52775283.[Crossref] [Google Scholar]
  87. Veiga MI, Ferreira PE, Malmberg M, Jornhagen L, Bjorkman A, Nosten F, Gil JP, , 2012. pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine. Antimicrob Agents Chemother 56: 36153619.[Crossref] [Google Scholar]
  88. Takala-Harrison S, Clark TG, Jacob CG, Cummings MP, Miotto O, Dondorp AM, Fukuda MM, Nosten F, Noedl H, Imwong M, Bethell D, Se Y, Lon C, Tyner SD, Saunders DL, Socheat D, Ariey F, Phyo AP, Starzengruber P, Fuehrer HP, Swoboda P, Stepniewska K, Flegg J, Arze C, Cerqueira GC, Silva JC, Ricklefs SM, Porcella SF, Stephens RM, Adams M, Kenefic LJ, Campino S, Auburn S, MacInnis B, Kwiatkowski DP, Su XZ, White NJ, Ringwald P, Plowe CV, , 2013. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in southeast Asia. Proc Natl Acad Sci USA 110: 240245.[Crossref] [Google Scholar]
  89. van Schalkwyk DA, Sutherland CJ, , 2015. Malaria resistance to non-artemisinin partner drugs: how to reACT. Lancet Infect Dis 15: 621623.[Crossref] [Google Scholar]
  90. Pelleau S, Moss EL, Dhingra SK, Volney B, Casteras J, Gabryszewski SJ, Volkman SK, Wirth DF, Legrand E, Fidock DA, Neafsey DE, Musset L, , 2015. Adaptive evolution of malaria parasites in French Guiana: reversal of chloroquine resistance by acquisition of a mutation in pfcrt. Proc Natl Acad Sci USA 112: 1167211677.[Crossref] [Google Scholar]
  91. Wells TN, Hooft van Huijsduijnen R, Van Voorhis WC, , 2015. Malaria medicines: a glass half full? Nat Rev Drug Discov 14: 424442.[Crossref] [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.16-0234
Loading
/content/journals/10.4269/ajtmh.16-0234
Loading

Data & Media loading...

  • Received : 24 Mar 2016
  • Accepted : 12 Sep 2016

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error