Artemisinin-resistant malaria: Research challenges, opportunities, and public health implications

American Journal of Tropical Medicine and Hygiene

Volumn 87, Issue 2, 2012, Pages 231-241

  Fairhurst, Rick M ^a   Nayyar, Gaurvika M L ^b   Breman, Joel G ^b   Hallett, Rachel ^c   Vennerstrom, Jonathan L ^d   Duong, Socheat ^e   Ringwald, Pascal ^f   Wellems, Thomas E ^a   Plowe, Christopher V ^g   Dondorp, Arjen M ^h  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^d UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^e Ministry of Health Cambodia   (Cambodia)

^f WORLD HEALTH ORGANIZATION   (Switzerland)

^g University of Maryland School of Medicine Center for Vaccine Development   (United States)

^h MAHIDOL UNIVERSITY   (Thailand)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; AMODIAQUINE; AMODIAQUINE PLUS ARTESUNATE; ANTIMALARIAL AGENT; ARTEMETHER PLUS BENFLUMETOL; ARTEMISININ; ARTEMISININ DERIVATIVE; ARTESUNATE; ARTESUNATE PLUS MEFLOQUINE; BENFLUMETOL; CHLOROQUINE; CLATHRIN; CLATHRIN ADAPTOR PROTEIN MU SUBUNIT; DIHYDROARTEMISININ PLUS PIPERAQUINE; GLYCOPROTEIN P; MEFLOQUINE; MEMBRANE PROTEIN; MOLECULAR MARKER; PYRIMETHAMINE PLUS SULFADOXINE; QUININE; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; UBIQUITIN THIOLESTERASE; UNCLASSIFIED DRUG;

ANTIMALARIAL ACTIVITY; ANTIMALARIAL DRUG RESISTANCE; CONFERENCE PAPER; CONSENSUS DEVELOPMENT; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG SENSITIVITY; EVIDENCE BASED MEDICINE; GAMETOCYTE; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC VARIABILITY; HEALTH PROGRAM; HOSPITALIZATION; HOST PARASITE INTERACTION; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; LABORATORY TEST; MALARIA CONTROL; MALARIA FALCIPARUM; MEDICAL EXPERT; MEDICAL INFORMATION; MONOTHERAPY; MULTICENTER STUDY (TOPIC); PARASITE PREVALENCE; PLASMODIUM FALCIPARUM; PUBLIC HEALTH; SCIENTIFIC LITERATURE; SINGLE NUCLEOTIDE POLYMORPHISM; STRUCTURE ACTIVITY RELATION; TRANSLATIONAL RESEARCH; TREATMENT DURATION; TREATMENT RESPONSE; WORLD HEALTH ORGANIZATION;

ANIMALS; ANTIMALARIALS; ARTEMISININS; DRUG RESISTANCE; HUMANS; MALARIA, FALCIPARUM; PLASMODIUM FALCIPARUM; PUBLIC HEALTH;

EID: 84864883641     PISSN: 00029637     EISSN: None     Source Type: Journal    
DOI: 10.4269/ajtmh.2012.12-0025     Document Type: Conference Paper

References (87)

1. Johanson E, Cibulskis R, Steketee R, 2010. Malaria Funding & Resource Utilization: The First Decade of Roll Back Malaria. Geneva, Switzerland: Roll Back Malaria
2. WHO, 2011. Learning to outwit malaria. WHO Bulletin 89: 10-11.
3. Tanner M, Savigny D, 2008. Malaria eradication back on the table. Bull World Health Organ 86: 81-160.
4. WHO, 2010. Global Report on Antimalarial Efficacy and Drug Resistance: 2000-2010. Geneva: World Health Organization.
5. Trape J, 2001. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg 64 (1-2 Suppl): 12-17.
6. Dondorp AM, Yeung S, White L, Nguon C, Day NP, Socheat D, von Seidlein L, 2010. Artemisinin resistance: current status and scenarios for containment. Nat Rev Microbiol 8: 272.
7. Dondorp AM, Fanello CI, Hendriksen ICE, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, Kivaya E, Agbenyega T, Nguah SB, Evans J, Gesase S, Kahabuka C, Mtove G, Nadjm B, Deen J, Mwanga-Amumpaire J, Nansumba M, Karema C, Umulisa N, Uwimana A, Mokuolu OA, Adedoyin OT, Johnson WB, Tshefu AK, Onyamboko MA, Sakulthaew T, Ngum WP, Silamut K, Stepniewska K, Woodrow CJ, Bethell D, Wills B, Oneko M, Peto TE, von Seidlein L, Day NP, White NJ; AQUAMAT group, 2010. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomized trial. Lancet 376: 1647-1657.
8. SEAQUAMAT, 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomized trial. Lancet 366: 717-725.
9. WHO, 2010. Marketing of Oral Artemisinin-Based Monotherapy Medicines at Country Level. Available at: http://www.who.int/malaria/monotherapy-NDRAs.pdf. Accessed February 15, 2011.
10. WHO, 2005. Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000-2010. Geneva: World Health Organization,
11. WHO, 2010. Marketing of Oral Artemisinin-Based Monotherapy Medicines. Geneva: WHO. Available at: http://www.who.int/malaria/monotherapy-manufacturers. pdf. Accessed February 15, 2011.
12. 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: 455-467.
13. Anderson TJ, Nair S, Nkhoma S, Williams JT, Imwong M, Yi P, Socheat D, Das D, Chotivanich K, Day NP, White NJ, Dondorp AM, 2010. High heritability of malaria parasite clearance rate indicates a genetic basis for artemisinin resistance in Western Cambodia. J Infect Dis 201: 1326-1330.
14. WHO, 2011. Global Plan for Artemisinin Resistance Containment (GPARC). Geneva: World Health Organization.
15. PATH, 2011. Staying the Course? Malaria Research and Development in a Time of Economic Uncertainty. Seattle, WA: PATH.
16. Stepniewska K, Ashley E, Lee SJ, Anstey N, Barnes KI, Binh TQ, D'Alessandro U, Day NP, de Vries PJ, Dorsey G, Guthmann JP, Mayxay M, Newton PN, Olliaro P, Osorio L, Price RN, Rowland M, Smithuis F, Taylor WR, Nosten F, White NJ, 2010. In vivo parasitological measures of artemisinin susceptibility. J Infect Dis 201: 570-579.
17. WHO, 2011. Update on Artemisinin Resistance. Geneva: World Health Organization.
18. Price R, van Vugt M, Nosten F, Luxemburger C, Brockman A, Phaipun L, Chongsuphajaisiddhi T, White N, 1998. Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria. Am J Trop Med Hyg 59: 883-888. (Pubitemid 29028916)
19. White N, 2011. The parasite clearance curve. Malar J 10: 278.
20. Flegg J, Guerin P, White N, Stepniewska K, 2011. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J 10: 339.
21. Chotivanich K, Udomsangpetch R, McGready R, Proux S, Newton P, Pukrittayakamee S, Looareesuwan S, White NJ, 2002. Central role of the spleen in malaria parasite clearance. J Infect Dis 185: 1538-1541. (Pubitemid 34507982)
22. Seidlein VL, Drakeley C, Greenwood B, Walraven G, Targett G, 2001. Risk factors for gametocyte carriage in Gambian children. Am J Trop Med Hyg 65: 523-527. (Pubitemid 33134586)
23. Barnes KI, Little F, Mabuza A, Mngomezulu N, Govere J, Durrheim D, Roper C, Watkins B, White NJ, 2008. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J Infect Dis 197: 1605-1613. (Pubitemid 351706492)
24. Price R, Nosten F, Simpson JA, Luxemburger C, Phaipun L, ter Kuile F, van Vugt M, Chongsuphajaisiddhi T, White NJ, 1999. Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am J Trop Med Hyg 60: 1019-1023. (Pubitemid 29296230)
25. Sutherland CJ, Alloueche A, Curtis J, Drakeley CJ, Ord R, Duraisingh M, Greenwood BM, Pinder M, Warhurst D, Targett GA, 2002. Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes. Am J Trop Med Hyg 67: 578-585. (Pubitemid 36014913)
26. Méndez F, Herrera S, Murrain B, Gutiérrez A, Moreno LA, Manzano M, Muñoz A, Plowe CV, 2007. Selection of antifolate-resistant Plasmodium falciparum by sulfadoxine-pyrimethamine treatment and infectivity to Anopheles mosquitoes. Am J Trop Med Hyg 77: 438-443. (Pubitemid 351844315)
27. Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewska K, Barends M, Brockman A, Anderson T, McGready R, Phaiphun L, Proux S, van Vugt M, Hutagalung R, Lwin KM, Phyo AP, Preechapornkul P, Imwong M, Pukrittayakamee S, Singhasivanon P, White NJ, Nosten F, 2009. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS ONE 4: e4551.
28. Wernsdorfer WH, 1980. Field evaluation of drug resistance in malaria. In vitro micro-test. Acta Trop 37: 222-227. (Pubitemid 11192487)
29. Noedl H, Attlymar B, Wernsdorfer W, Kollaritsch H, Miller RS, 2004. A histidine-rich protein 2-based malaria drug sensitivity assay for field use. Am J Trop Med Hyg 71: 711-714. (Pubitemid 40075618)
30. WHO, 2001. In vitro Micro Test for the Assessment of the Response to Plasmodium to Chloroquine, Mefloquine, Amodiaquine, Sulfadoxine/Pyrimethamine and Artemisinin. Geneva: World Health Organization.
31. Saralamba S, Pan-Ngum W, Maude RJ, Lee SJ, Tarning J, Lindegårdh 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: 397-402.
32. Witkowski B, Lelièvre J, Barragán 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: 1872-1877.
33. Codd A, Teuscher F, Kyle DE, Cheng Q, Gatton ML, 2011. Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure. Malar J 10: 56.
34. Teuscher F, Gatton ML, Chen N, Peters J, Kyle DE, Cheng Q, 2010. Artemisinin-induced dormancy in Plasmodium falciparum: duration, recovery rates, and implications in treatment failure. J Infect Dis 202: 1362-1368.
35. Plowe CV, Roper C, Barnwell JW, Happi CT, Joshi HH, Mbacham W, Meshnick SR, Mugittu K, Naidoo I, Price RN, Shafer RW, Sibley CH, Sutherland CJ, Zimmerman PA, Rosenthal PJ, 2007. World Antimalarial Resistance Network (WARN) III: molecular markers for drug resistant malaria. Malar J 6: 121.
36. Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Coulibaly D, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344: 257-263. (Pubitemid 32108530)
37. Sidhu AB, Verdier-Pinard D, Fidock DA, 2002. Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 298: 210-213.
38. Johnson DJ, Fidock DA, Mungthin M, Lakshmanan V, Sidhu AB, Bray PG, Ward SA, 2004. Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol Cell 15: 867-877. (Pubitemid 39277984)
39. Holmgren G, Gil JP, Ferreira PM, Veiga MI, Obonyo CO, Björkman A, 2006. Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infect Genet Evol 6: 309-314. (Pubitemid 43785813)
40. Sisowath C, Petersen I, Veiga MI, Martensson A, Premji Z, Björkman A, Fidock DA, Gil JP, 2009. In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemetherlumefantrine in Africa. J Infect Dis 199: 750-757.
41. Valderramos SG, Valderramos JC, Musset L, Purcell LA, Mercereau-Puijalon O, Legrand E, Fidock DA, 2010. Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype in Plasmodium falciparum. PLoS Pathog 6: e1000887.
42. Duraisingh MT, von Seidlein LV, Jepson A, Jones P, Sambou I, Pinder M, Warhurst DC, 2000. Linkage disequilibrium between two chromosomally distinct loci associated with increased resistance to chloroquine in Plasmodium falciparum. Parasitology 121 (Pt 1): 1-7. (Pubitemid 30616105)
43. 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: 438-447. (Pubitemid 39036891)
44. Sidhu AB, Valderramos SG, Fidock DA, 2005. pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum. Mol Microbiol 57: 913-926. (Pubitemid 41139856)
45. Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Björkman A, Gil JP, 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 191: 1014-1017. (Pubitemid 40349821)
46. Humphreys GS, Merinopoulos I, Ahmed J, Whitty CJ, Mutabingwa TK, Sutherland CJ, Hallett RL, 2007. Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrob Agents Chemother 51: 991-997. (Pubitemid 46355285)
47. Veiga MI, Ferreira PE, Jornhagen L, Malmberg M, Kone A, Schmidt BA, Petzold M, Björkman A, Nosten F, Gil JP, 2011. Novel polymorphisms in Plasmodium falciparum ABC transporter genes are associated with major ACT antimalarial drug resistance. PloS One 6: e20212.
48. Mu J, Ferdig MT, Feng X, Joy DA, Duan J, Furuya T, Subramanian G, Aravind L, Cooper RA, Wooton JC, Xiong M, Su XZ, 2003. Multiple transporters associated with malaria parasite responses to chloroquine and quinine. Mol Microbiol 49: 977-989. (Pubitemid 36981343)
49. Anderson TJ, Nair S, Qin H, Singlam S, Brockman A, Paiphun L, Nosten F, 2005. Are transporter genes other than the chloroquine resistance locus (pfcrt) and multidrug resistance gene (pfmdr) associated with antimalarial drug resistance? Antimicrob Agents Chemother 49: 2180-2188. (Pubitemid 40734444)
50. Dahlstrom S, Ferreira PE, Veiga MI, Sedighi N, Wiklund L, Martensson A, Färnert A, Sisowath C, Osório L, Darhan H, Andersson B, Kaneko A, Conseil G, Björkman A, Gil P, 2009. Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa. J Infect Dis 200: 1456-1464.
51. Hunt P, Afonso A, Creasey A, Culleton R, Sidhu AB, Logan J, Valderramos SG, McNae I, Cheesman S, do Rosario V, Carter R, Fidock DA, Cravo P, 2007. Gene encoding a deubiquitinating enzyme is mutated in artesunate- and chloroquine-resistant rodent malaria parasites. Mol Microbiol 65: 27-40. (Pubitemid 46934481)
52. Deplaine G, Lavazec C, Bischoff E, Natalang O, Perrot S, Guillotte-Blisnick M, Coppée JY, Pradines B, Mercereau-Puijalon O, David PH, 2011. Artesunate tolerance in transgenic Plasmodium falciparum parasites over-expressing a tryptophan rich protein. Antimicrob Agents Chemother 55: 2576-2584.
53. Mok S, Imwong M, Mackinnon M, 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.
54. Imwong M, Dondorp AM, Nosten F, Yi P, Mungthin M, Hanchana S, Das D, Phyo AP, Lwin KM, Pukrittayakamee S, Lee SJ, Saisung S, Koecharoen K, Nguon C, Day NP, Socheat D, White NJ, 2010. Exploring the contribution of candidate genes to artemisinin resistance in Plasmodium falciparum. Antimicrob Agents Chemother 54: 2886-2892.
55. Mu J, Myers RA, Jiang H, Liu S, Ricklefs S, Waisberg M, Chotivanich K, Wilairatana P, Krudsood S, White NJ, Udomsangpetch R, Cui L, Ho M, Ou F, Li H, Song J, Li G, Wang X, Seila S, Sokunthea S, Socheat D, Sturdevant DE, Porcella SF, Fairhurst RM, Wellems TE, Awadalla P, Su XZ, 2010. Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Med 42: 268-271.
56. Beez D, Sanchez CP, Stein WD, Lanzer M, 2010. Genetic predisposition favors the acquisition of stable artemisinin resistance in malaria parasites. Antimicrob Agents Chemother 55: 50-55.
57. Yuan J, Cheng KC-C, Johnson RL, Huang R, Pattaradilokrat S, Liu A, Guha R, Fidock DA, Inglese J, Wellems TE, Austin CP, Su XZ, 2011. Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets. Science 333: 724-729.
58. Jefford CW, Vicente MGH, Jacquier Y, Favarger F, Mareda J, Millasson-Schmidt P, Brunner G, Burger U, 1996. The deoxygenation and isomerization of artemisinin and artemether and their relevance to antimalarial action. Helv Chim Acta 79: 1475-1487.
59. Meshnick SR, 2002. Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol 32: 1655-1660. (Pubitemid 35339455)
60. O'Neill PM, Posner GH, 2004. A medicinal chemistry perspective on artemisinin and related endoperoxides. JMed Chem 47: 2945-2964. (Pubitemid 38702690)
61. Robert A, Cazelles J, Meunier B, 2001. Characterization of the alkylation product of heme by the antimalarial drug artemisinin. Angew Chem Int Ed 40: 1954-1957. (Pubitemid 32525107)
62. Hartwig CL, Rosenthal AS, D'Angelo J, Griffin CE, Posner GH, Cooper RA, 2009. Accumulation of artemisinin trioxane derivatives within neutral lipids of Plasmodium falciparum malaria parasites is endoperoxide-dependent. Biochem Pharmacol 77: 322-336.
63. Klonis N, Crespo-Ortiz MP, Bottova I, Abu-Bakar N, Kenny S, Rosenthal PJ, Tilley L, 2011. Artemisinin activity against Plasmodium falciparum requires hemoglobin uptake and digestion. Proc Natl Acad Sci USA 108: 11405-11410.
64. Kaiser M, Wittlin S, Nehrbass-Stuedli A, Dong Y, Wang X, Hemphill A, Matile H, Brun R, Vennerstrom JL, 2007. Peroxide bond-dependent antiplasmodial specificity of artemisinin and OZ277 (RBx11160). Antimicrob Agents Chemother 51: 2991-2993. (Pubitemid 47206243)
65. Haynes RK, Chan W-C, Wong H-N, Li K-Y, Wu W-K, Fan K-M, Sung HH, Williams ID, Prosperi D, Melato S, Coghi P, Monti D, 2010. Facile oxidation of leucomethylene blue and dihydroflavins by artemisinins: relationship with flavoenzyme function and antimalarial mechanism of action. ChemMedChem 5: 1282-1299.
66. Wang J, Huang L, Li J, Fan Q, Long Y, Li Y, Zhou B, 2010. Artemisinin directly targets malarial mitochondria through its specific mitochondrial activation. PLoS ONE 5: e9582.
67. Eckstein-Ludwig U, Webb RJ, van Goethem IDA, East JM, Lee AG, Kimura M, O'Neill PM, Bray PG, Ward SA, Krishna S, 2003. Artemisinins target the SERCA of Plasmodium falciparum. Nature 424: 957-961. (Pubitemid 37051688)
68. Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala MT, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon O, 2005. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet 366: 1960-1963. (Pubitemid 41713986)
69. Bhisutthibhan J, Pan X-Q, Hossler PA, Walker DJ, Yowell CA, Carlton J, Dame JB, Meshnick SR, 1998. The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin. J Biol Chem 273: 16192-16198. (Pubitemid 28311392)
70. Bakar NA, Klonis N, Hanssen E, Chan C, Tilley L, 2010. Digestive-vacuole genesis and endocytic processes in the early intraerythrocytic stages of Plasmodium falciparum. J Cell Sci 123: 441-450.
71. Dluzewski AR, Ling IT, Hopkins JM, Grainger M, Margos G, Mitchell GH, Holder AA, Bannister LH, 2008. Formation of the food vacuole in Plasmodium falciparum: a potential role for the 19 kDa fragment of merozoite surface protein 1 (MSP1 (19)). PLoS ONE 3: e3085.
72. Bethell D, Se Y, Lon C, Tyner S, Saunders D, Sriwichai S, Darapiseth S, Teja-Isavadharm P, Khemawoot P, Schaecher K, Ruttvisutinunt W, Lin J, Kuntawungin W, Gosi P, Timmermans A, Smith B, Socheat D, Fukuda MM, 2011. Artesunate dose escalation for the treatment of uncomplicated malaria in a region of reported artemisinin resistance: a randomized clinical trial. PLoS ONE 6: e19283.
73. MMV, 2009. Medicines for Malaria Venture Concept Note - May 2009. Geneva: Medicines for Malaria Venture.
74. 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.
75. WWARN, 2011. Asia Regional Center Activities: Tracking Resistance to Artemisinin Collaboration (TRAC). Available at: http://www.wwarn.org/about-us/ regional-centres/asia-regional-centre. Accessed August 1, 2011.
76. Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, et al., 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 1960-1966.
77. Naidoo I, Roper C, 2010. Following the path of most resistance: dhps K540E dispersal in African Plasmodium falciparum. Trends Parasitol 26: 447-456.
78. Mita T, Venkatesan M, Ohashi J, Culleton R, Takahashi N, Tsukahara T, Ndounga M, Dysoley L, Endo H, Hombhanje F, Ferreira MU, Plowe CV, Tanabe K, 2011. Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations. J Infect Dis 204: 1980-1988.
79. WHO, Battling Malaria Drug Resistance Along the Thai-Cambodian Border. Available at: http://www.who.int/malaria/diagnosis-treatment/arcp/containment- project/en/index.html. Accessed May 28, 2011.
80. Meankaew P, Kaewkungwal J, Khamsiriwatchara A, Khunthong P, Singhasivanon P, Satimai W, 2010. Application of mobiletechnology for disease and treatment monitoring of malaria in the "Better Border Healthcare Programme". Malar J 9: 237.
81. WHO, Battling Malaria Drug Resistance Along the Thai-Cambodian Border. Geneva: World Health Organization. Available at: http://www.who.int/malaria/ diagnosis-treatment/arcp/achievements/en/index.html. Accessed May 30, 2011.
82. Maude R, Pontavornpinyo W, Saralamba S, Aguas R, Yeung S, Dondorp A, Day NP, White NJ, White LJ, 2009. The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia. Malar J 8: 31.
83. MalEra Consultative Group on Drugs, 2011. A research agenda for malaria eradication: drugs. PLoS Med 8: e1000402.
84. Song J, Socheat D, Tan B, Dara P, Deng C, Sokunthea S, Seila S, Ou F, Jian H, Li G, 2010. Rapid and effective malaria control in Cambodia through mass administration of artemisinin-piperaquine. Malar J 9: 57.
85. Nayyar GML, Breman JG, Newton PN, Herrington J, 2012. Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa. The Lancet Infectious Diseases 12: 488-496.
86. White NJ, 2008. Qinghaosu (artemisinin): the price of success. Science 320: 330-334. (Pubitemid 351555649)
87. WHO, 2010. Essential medicines: regulatory action needed to stop the sale of oral artemisinin-based monotherapy. WHO Drug Information Bulletin. Volume 24. Geneva: World Health Organization.