1921
Volume 77, Issue 6_Suppl
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

As chloroquine and sulfadoxine-pyrimethamine (SP) are replaced by more effective artemisinin-based combination therapies (ACTs), strategies for monitoring (and, if possible, deterring) drug-resistant malaria must be updated and optimized. methods for measuring resistance will be critical for confirming and characterizing resistance to ACTs. Molecular markers are useful for tracking the emergence and dissemination of resistance and guiding treatment policy where resistance is low or moderate. Genomic approaches may help identify molecular markers for resistance to artemisinins and their partner drugs. Studies of reported ACT treatment failure should include assessing factors other than resistance that affect efficacy, including pharmacokinetics. Longitudinal clinical trials are particularly useful for comparing the benefits and risks of repeated treatment in high transmission settings. The malaria research and control community should not fail to exploit this opportunity to apply the lessons of the last 50 years to extend the useful therapeutic lives of ACTs.

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2017-09-20
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References

  1. Rieckmann KH, McNamara JV, Frischer H, Stockert TA, Carson PE, Powell RD, 1968. Effects of chloroquine, quinine, and cycloguanil upon the maturation of asexual erythrocytic forms of two strains of Plasmodium falciparum in vitro. Am J Trop Med Hyg 17 : 661–671.
  2. Nguyen-Dinh P, Payne D, 1980. Pyrimethamine sensitivity in Plasmodium falciparum: determination in vitro by a modified 48-hour test. Bull World Health Organ 58 : 909–912.
  3. Plowe CV, 2003. Monitoring antimalarial drug resistance: making the most of the tools at hand. J Exp Biol 206 : 3745–3752.
  4. Aubouy A, Mayombo J, Keundjian A, Bakary M, Le BJ, Deloron P, 2004. Short report: lack of prediction of amodiaquine efficacy in treating Plasmodium falciparum malaria by in vitro tests. Am J Trop Med Hyg 71 : 294–296.
  5. Borrmann S, Binder RK, Adegnika AA, Missinou MA, Issifou S, Ramharter M, Wernsdorfer WH, Kremsner PG, 2002. Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon: implications for the validity of tests in vitro vs. in vivo. Trans R Soc Trop Med Hyg 96 : 660–663.
  6. 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.
  7. Price RN, Cassar C, Brockman A, Duraisingh M, van Vugt M, White NJ, Nosten F, Krishna S, 1999. The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand. Antimicrob Agents Chemother 43 : 2943–2949.
  8. Price RN, Uhlemann AC, Van VM, Brockman A, Hutagalung R, Nair S, Nash D, Singhasivanon P, Anderson TJ, Krishna S, White NJ, Nosten F, 2006. Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Clin Infect Dis 42 : 1570–1577.
  9. Bzik DJ, Li WB, Horii T, Inselburg J, 1987. Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene. Proc Natl Acad Sci USA 84 : 8360–8364.
  10. Brooks DR, Wang P, Read M, Watkins WM, Sims PF, Hyde JE, 1994. Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: dihydropteroate synthase gene in lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine. Eur J Biochem 224 : 397–405.
  11. Foote SJ, Thompson JK, Cowman AF, Kemp DJ, 1989. Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum. Cell 57 : 921–930.
  12. Wellems TE, Walker-Jonah A, Panton LJ, 1991. Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7. Proc Natl Acad Sci USA 88 : 3382–3386.
  13. Peterson DS, Walliker D, Wellems TE, 1988. Evidence that a point mutation in dihydrofolate reductase- thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA 85 : 9114–9118.
  14. Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Bir Singh SA, Naude B, Deitsch KW, Su X, Wootton JC, Roepe PD, Wellems TE, 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6 : 861–871.
  15. Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF, 1990. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature 345 : 255–258.
  16. Su X, Kirkman LA, Fujioka H, Wellems TE, 1997. Complex polymorphisms in an ∼330 kDa protein are linked to chloroquine-resistant P. falciparum in Southeast Asia and Africa. Cell 91 : 593–603.
  17. Cowman AF, Galatis D, Thompson JK, 1994. Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine. Proc Natl Acad Sci USA 91 : 1143–1147.
  18. Wu Y, Kirkman LA, Wellems TE, 1996. Transformation of Plasmodium falciparum malaria parasites by homologous integration of plasmids that confer resistance to pyrimethamine. Proc Natl Acad Sci USA 93 : 1130–1134.
  19. Sidhu AB, Verdier-Pinard D, Fidock DA, 2002. Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 298 : 210–213.
  20. Triglia T, Wang P, Sims PG, Hyde JE, Cowman AF, 1998. Allelic exchange at the endogenous genomic locus in Plasmodium falciparum proves the role of dihyropteroate synthase in sulfadoxine-resistant malaria. EMBO J 17 : 3807–3815.
  21. Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF, 2000. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403 : 906–909.
  22. Cortese JF, Plowe CV, 1998. Antifolate resistance due to new and known Plasmodium falciparum dihydrofolate reductase mutants expressed in yeast. Mol Biochem Parasitol 94 : 205–214.
  23. Plowe CV, Cortese JF, Djimdé A, Nwanyanwu OC, Watkins WM, Winstanley PA, Estrada-Franco JG, Mollinedo RE, Avila JC, Cespedes JL, Carter D, Doumbo OK, 1997. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 176 : 1590–1596.
  24. Wang P, Lee C-S, Bayoumi R, Djimdé A, Doumbo O, Swedberg G, Dao LD, Mshinda H, Tanner M, Watkins WM, Sims PFG, Hyde JE, 1997. Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. Mol Biochem Parasitol 89 : 161–177.
  25. Djimdé A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 : 257–263.
  26. Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RA, Rogerson SJ, Lescano AG, Molyneux ME, Winstanley PA, Chimpeni P, Taylor TE, Plowe CV, 2002. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis 185 : 380–388.
  27. Djimdé A, Doumbo OK, Steketee RW, Plowe CV, 2001. Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet 358 : 890–891.
  28. Djimdé AA, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV, 2003. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg 69 : 558–563.
  29. Dzinjalamala FK, Macheso A, Kublin JG, Taylor TE, Barnes KI, Molyneux ME, Plowe CV, Smith PJ, 2005. Blood folate concentrations and in vivo sulfadoxine-pyrimethamine failure in Malawian children with uncomplicated Plasmodium falciparum malaria. Am J Trop Med Hyg 72 : 267–272.
  30. Wellems TE, Plowe CV, 2001. Chloroquine-resistant malaria. J Infect Dis 184 : 770–776.
  31. Mockenhaupt FP, Ehrhardt S, Eggelte TA, Gana-Nsiire P, Stollberg K, Mathieu A, Markert M, Otchwemah RN, Bienzle U, 2005. Chloroquine-treatment failure in northern Ghana: roles of pfcrt T76 and pfmdr1 Y86. Ann Trop Med Parasitol 99 : 723–732.
  32. Mayengue PI, Ndounga M, Davy MM, Tandou N, Ntoumi F, 2005. In vivo chloroquine resistance and prevalence of the Pfcrt codon 76 mutation in Plasmodium falciparum isolates from the Republic of Congo. Acta Trop 95 : 219–225.
  33. Khalil IF, Alifrangis M, Tarimo DS, Staalso T, Satti GMH, Theander TG, Ronn AM, Bygbjerg IC, 2005. The roles of the pfcrt 76T and pfmdr1 86Y mutations, immunity and the initial level of parasitaemia, in predicting the outcome of chloroquine treatment in two areas with different transmission intensities. Ann Trop Med Parasitol 99 : 441–448.
  34. Tinto H, Sanou B, Dujardin JC, Ouedragogo JB, Van Overmeir C, Erhart A, Van Marck E, Guiguemde TR, D’Alessandro U, 2005. Short report: usefulness of the Plasmodium falciparum chloroquine resistance transporter T76 genotype failure index for the estimation of in vivo chloroquine resistance in Burkina Faso. Am J Trop Med Hyg 73 : 171–173.
  35. Kyabayinze D, Cattamanchi A, Kamya MR, Rosenthal PJ, Dorsey G, 2003. Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria. Am J Trop Med Hyg 69 : 247–252.
  36. Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H, 2004. Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg 71 : 696–702.
  37. Happi CT, Gbotosho GO, Folarin OA, Akinboye DO, Yusuf BO, Ebong OO, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM, 2005. Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria. Acta Trop 95 : 183–193.
  38. Francis D, Nsobya SL, Talisuna A, Yeka A, Kamya MR, Machekano R, Dokomajilar C, Rosenthal PJ, Dorsey G, 2006. Geographic differences in antimalarial drug efficacy in Uganda are explained by differences in endemicity and not by known molecular markers of drug resistance. J Infect Dis 193 : 978–986.
  39. White N, 2004. Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria: sulfadoxine-pyrimethamine is not working in Malawi. BMJ 328 : 1259.
  40. Happi CT, Gbotosho GO, Folarin OA, Akinboye DO, Yusuf BO, Ebong OO, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM, 2005. Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria. Acta Trop 95 : 183–193.
  41. Schneider AG, Premji Z, Felger I, Smith T, Abdulla S, Beck HP, Mshinda H, 2002. A point mutation in codon 76 of pfcrt of P. falciparum is positively selected for by Chloroquine treatment in Tanzania. Infect Genet Evol 1 : 183–189.
  42. Djimdé AA, Dolo A, Ouattara A, Diakite S, Plowe CV, Doumbo OK, 2004. Molecular diagnosis of resistance to antimalarial drugs during epidemics and in war zones. J Infect Dis 190 : 853–855.
  43. Kublin JG, Cortese JF, Njunju EM, Ra GM, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE, Plowe CV, 2003. Re-emergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187 : 1870–1875.
  44. Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV, 2006. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 355 : 1959–1966.
  45. 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.
  46. 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.
  47. Ferdig MT, Cooper RA, Mu J, Deng B, Joy DA, Su XZ, Wellems TE, 2004. Dissecting the loci of low-level quinine resistance in malaria parasites. Mol Microbiol 52 : 985–997.
  48. Volkman SK, Sabeti PC, Decaprio D, Neafsey DE, Schaffner SF, Milner DA Jr, Daily JP, Sarr O, Ndiaye D, Ndir O, Mboup S, Duraisingh MT, Lukens A, Derr A, Stange-Thomann N, Waggoner S, Onofrio R, Ziaugra L, Mauceli E, Gnerre S, Jaffe DB, Zainoun J, Wiegand RC, Birren BW, Hartl DL, Galagan JE, Lander ES, Wirth DF, 2007. A genome-wide map of diversity in Plasmodium falciparum. Nat Genet 39 : 113–119.
  49. Mu J, Ferdig MT, Feng X, Joy DA, Duan J, Furuya T, Subramanian G, Aravind L, Cooper RA, Wootton JC, Xiong M, Su XZ, 2003. Multiple transporters associated with malaria parasite responses to chloroquine and quinine. Mol Microbiol 49 : 977–989.
  50. Sabeti PC, Schaffner SF, Fry B, Lohmueller J, Varilly P, Shamovsky O, Palma A, Mikkelsen TS, Altshuler D, Lander ES, 2006. Positive natural selection in the human lineage. Science 312 : 1614–1620.
  51. Rathod PK, Ganesan K, Hayward RE, Bozdech Z, DeRisi JL, 2002. DNA microarrays for malaria. Trends Parasitol 18 : 39–45.
  52. White NJ, Van VM, Ezzet F, 1999. Clinical pharmacokinetics and pharmacodynamics and pharmacodynamics of artemether-lumefantrine. Clin Pharmacokinet 37 : 105–125.
  53. Giao PT, de Vries PJ, 2001. Pharmacokinetic interactions of antimalarial agents. Clin Pharmacokinet 40 : 343–373.
  54. Khaliq Y, Gallicano K, Tisdale C, Carignan G, Cooper C, McCarthy A, 2001. Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers. Br J Clin Pharmacol 51 : 591–600.
  55. Ridtitid W, Wongnawa M, Mahatthanatrakul W, Chaipol P, Sunbhanich M, 2000. Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol 52 : 1265–1269.
  56. Schippers EF, Hugen PW, Den HJ, Burger DM, Hoetelmans RM, Visser LG, Kroon FP, 2000. No drug-drug interaction between nelfinavir or indinavir and mefloquine in HIV-1-infected patients. AIDS 14 : 2794–2795.
  57. WHO, 1973. Chemotherapy of Malaria and Resistance to Antimalarials. Geneva: World Health Organization.
  58. WHO, 1996. Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated Falciparum Malaria in Areas with Intense Transmission. Geneva: World Health Organization, Division of Control of Tropical Diseases.
  59. WHO, 2003. Assessment and Monitoring of Antimalarial Efficacy for the Treatment of Uuncomplicated Falciparum Malaria. Geneva: World Health Organization.
  60. Dorsey G, Njama D, Kamya MR, Cattamanchi A, Kyabayinze D, Staedke SG, Gasasira A, Rosenthal PJ, 2002. Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial. Lancet 360 : 2031–2038.
  61. White NJ, 2006. Editorial: clinical trials in tropical diseases: a politically incorrect view. Trop Med Int Health 11 : 1483–1484.
  62. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitie MA, Dubovsky F, Menendez C, Tornieporth N, Ballou WR, Thompson R, Cohen J, 2004. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364 : 1411–1420.
  63. Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Sagara I, Dicko A, Diemert DJ, Heppner DG, Stewart VA, Angov E, Soisson L, Leach A, Tucker K, Lyke KE, Plowe CV, 2006. Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial. PLoS Clin Trials 1 : e34.
  64. Withers MR, McKinney D, Ogutu BR, Waitumbi JN, Milman JB, Apollo OJ, Allen OG, Tucker K, Soisson LA, Diggs C, Leach A, Wittes J, Dubovsky F, Stewart VA, Remich SA, Cohen J, Ballou WR, Holland CA, Lyon JA, Angov E, Stoute JA, Martin SK, Heppner DG, 2006. Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children. PLoS Clin Trials 1 : e32.
  65. Hutagalung R, Paiphun L, Ashley EA, McGready R, Brockman A, Thwai KL, Singhasivanon P, Jelinek T, White NJ, Nosten FH, 2005. A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multidrug resistant Plasmodium falciparum on the western border of Thailand. Malar J 4 : 46.
  66. Tran TH, Dolecek C, Pham PM, Nguyen TD, Nguyen TT, Le HT, Dong TH, Tran TT, Stepniewska K, White NJ, Farrar J, 2004. Dihydroartemisinin-piperaquine against multidrug-resistant Plasmodium falciparum malaria in Vietnam: randomised clinical trial. Lancet 363 : 18–22.
  67. Mutabingwa T, Nzila A, Mberu E, Nduati E, Winstanley P, Hills E, Watkins W, 2001. Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania. Lancet 358 : 1218–1223.
  68. Sulo J, Chimpeni P, Hatcher J, Kublin JG, Plowe CV, Molyneux ME, Marsh K, Taylor TE, Watkins WM, Winstanley PA, 2002. Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial. Lancet 360 : 1136–1143.
  69. Farnert A, Arez AP, Babiker HA, Beck HP, Benito A, Bjorkman A, Bruce MC, Conway DJ, Day KP, Henning L, Mercereau-Puijalon O, Ranford-Cartwright LC, Rubio JM, Snounou G, Walliker D, Zwetyenga J, do Rosario VE, 2001. Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study. Trans R Soc Trop Med Hyg 95 : 225–232.
  70. Viriyakosol S, Siripoon N, Petcharapirat C, Petcharapirat P, Jarra W, Brown KN, Snounou G, 1995. Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studies. Bull World Health Organ 73 : 85–95.
  71. Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G, 2003. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg 68 : 133–139.
  72. Escalante AA, Lal AA, Ayala FJ, 1998. Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum. Genetics 149 : 189–202.
  73. Su XZ, Wellems TE, 1996. Toward a high-resolution Plasmodium falciparum linkage map: polymorphic markers from hundreds of simple sequence repeats. Genomics 33 : 430–444.
  74. Mwangi JM, Omar SA, Ranford-Cartwright LC, 2006. Comparison of microsatellite and antigen-coding loci for differentiating recrudescing Plasmodium falciparum infections from reinfections in Kenya. Int J Parasitol 36 : 329–336.
  75. Nyachieo A, Van OC, Laurent T, Dujardin JC, D’Alessandro U, 2005. Plasmodium falciparum genotyping by microsatellites as a method to distinguish between recrudescent and new infections. Am J Trop Med Hyg 73 : 210–213.
  76. Greenhouse B, Myrick A, Dokomajilar C, Woo JM, Carlson EJ, Rosenthal PJ, Dorsey G, 2006. Validation of microsatellite markers for use in genotyping polyclonal Plasmodium falciparum infections. Am J Trop Med Hyg 75 : 836–842.
  77. Watkins WM, Mosobo M, 1993. Treatment of Plasmodium falciparum malaria with pyrimethamine- sulfadoxine: selective pressure for resistance is a function of long elimination half-life. Trans R Soc Trop Med Hyg 87 : 75–78.
  78. Mockenhaupt FP, Ehrhardt S, Eggelte TA, Gana-Nsiire P, Stollberg K, Mathieu A, Markert M, Otchwemah RN, Bienzle U, 2005. Chloroquine-treatment failure in northern Ghana: roles of pfcrt T76 and pfmdr1 Y86. Ann Trop Med Parasitol 99 : 723–732.
  79. Mayengue PI, Ndounga M, Davy MM, Tandou N, Ntoumi F, 2005. In vivo chloroquine resistance and prevalence of the Pfcrt codon 76 mutation in Plasmodium falciparum isolates from the Republic of Congo. Acta Trop 95 : 219–225.
  80. Khalil IF, Alifrangis M, Tarimo DS, Staalso T, Satti GMH, Theander TG, Ronn AM, Bygbjerg IC, 2005. The roles of the pfcrt 76T and pfmdr1 86Y mutations, immunity and the initial level of parasitaemia, in predicting the outcome of chloroquine treatment in two areas with different transmission intensities. Ann Trop Med Parasitol 99 : 441–448.
  81. Tinto H, Sanou B, Dujardin JC, Ouedragogo JB, Van Overmeir C, Erhart A, Van Marck E, Guiguemdé TR, D’Alessandro U, 2005. Short report: Usefulness of the Plasmodium falciparum chloroquine resistance transporter T76 genotype failure index for the estimation of in vivo chloroquine resistance in Burkina Faso. Am J Trop Med Hyg 73 : 171–173.
  82. Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H, 2004. Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg 71 : 696–702.
  83. Happi CT, Gbotosho GO, Folarin OA, Akinboye DO, Yusuf BO, Ebong OO, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM, 2005. Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria. Acta Trop 95 : 183–193.
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  • Received : 17 Jan 2007
  • Accepted : 02 Apr 2007

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