Advertisement

Antimalarial Drug Resistance: Clinical Perspectives

  • Philip J. Rosenthal
Part of the Infectious Disease book series (ID)

Malaria is one of the most important infectious diseases in the world, and the problem appears to be worsening. An important contributor to our continued inability to control malaria is the increasing resistance of malaria parasites to available drugs. New drugs are greatly needed, but the continued use of some agents against which resistance has already developed is inevitable. As we attempt to improve methods for malaria surveillance and control, it is important to standardize methods for the assessment of antimalarial drug resistance. Such efforts include the establishment of standard means of assessing responses to antimalarial treatment, the discrimination of recrudescence due to drug resistance from reinfection after treatment, the characterization of molecular mediators of drug resistance in fi eld isolates, and the establishment of improved systems for the in vitro analysis of the drug susceptibility of fi eld isolates.

Keywords

Plasmodium Falciparum Antimalarial Drug Falciparum Malaria Vivax Malaria Uncomplicated Malaria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Breman JG. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg 2001;64(suppl):1–11.PubMedGoogle Scholar
  2. 2.
    Meshnick SR and Dobson MJ. The history of antimalarial drugs. In: Rosenthal PJ, ed. Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Totowa, NJ: Humana Press, 2001, pp 15–25.Google Scholar
  3. 3.
    Olliaro P, Nevill C, LeBras J, Ringwald P, Mussano P, Garner P and Brasseur P. Systematic review of amodiaquine treatment in uncomplicated malaria. Lancet 1996;348:1196–201.PubMedCrossRefGoogle Scholar
  4. 4.
    White NJ. The treatment of malaria. N Engl J Med 1996;335: 800–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Meshnick SR. Artemisinin and its derivatives. In: Rosenthal PJ, ed. Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Totowa, NJ: Humana Press, 2001, pp 191–201.Google Scholar
  6. 6.
    Klayman DL. Qinghaosu (artemisinin): an antimalarial drug from China. Science 1985;228:1049–55.PubMedCrossRefGoogle Scholar
  7. 7.
    White NJ, Nosten F, Looareesuwan S, Watkins WM, Marsh K, Snow RW, Kokwaro G, Ouma J, Hien TT, Molyneux ME, Taylor TE, Newbold CI, Ruebush TK, II, Danis M, Greenwood BM, Anderson RM and Olliaro P. Averting a malaria disaster. Lancet 1999;353:1965–7.PubMedCrossRefGoogle Scholar
  8. 8.
    White NJ and Pongtavornpinyo W. The de novo selection of drug-resistant malaria parasites. Proc R Soc Lond B Biol Sci 2003; 270:545–54.CrossRefGoogle Scholar
  9. 9.
    Staedke SG, Kamya MR, Dorsey G, Gasasira A, Ndeezi G, Charlebois ED and Rosenthal PJ. Amodiaquine, sulfadoxine/ pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial. Lancet 2001;358:368–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Dorsey G, Njama D, Kamya MR, Cattamanchi A, Kyabayinze D, Staedke SG, Gasasira A and Rosenthal PJ. Sulfadoxine/pyrimeth-amine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial. Lancet 2002;360:2031–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Rwagacondo CE, Niyitegeka F, Sarushi J, Karema C, Mugisha V, Dujardin JC, Van Overmeir C, van den Ende J and D'Alessandro U. Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate. Am J Trop Med Hyg 2003;68:743–7.PubMedGoogle Scholar
  12. 12.
    von Seidlein L, Milligan P, Pinder M, Bojang K, Anyalebechi C, Gosling R, Coleman R, Ude JI, Sadiq A, Duraisingh M, Warhurst D, Alloueche A, Targett G, McAdam K, Greenwood B, Walraven G, Olliaro P and Doherty T. Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial. Lancet 2000;355:352–7.CrossRefGoogle Scholar
  13. 13.
    Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E and Taylor WR. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial. Lancet 2002;359:1365–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Lang T and Greenwood B. The development of Lapdap, an affordable new treatment for malaria. Lancet Infect Dis 2003;3:162–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Lefevre G, Looareesuwan S, Treeprasertsuk S, Krudsood S, Silachamroon U, Gathmann I, Mull R and Bakshi R. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg 2001;64:247–56.PubMedGoogle Scholar
  16. 16.
    Wongsrichanalai C, Pickard AL, Wernsdorfer WH and Meshnick SR. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2002; 2:209–18.PubMedCrossRefGoogle Scholar
  17. 17.
    Hall SA and Wilks NE. A trial of chloroquine-medicated salt for malaria suppression in Uganda. Am J Trop Med Hyg 1967; 16:429–42.PubMedGoogle Scholar
  18. 18.
    Wellems TE and Plowe C V. Chloroquine-resistant malaria. J Infect Dis 2001;184:770–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD and Wellems TE. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 2000;6:861–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV and Coulibaly D. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 2001;344:257–63.PubMedCrossRefGoogle Scholar
  21. 21.
    Sidhu AB, Verdier-Pinard D and Fidock DA. Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 2002;298:210–3.PubMedCrossRefGoogle Scholar
  22. 22.
    Reed MB, Saliba KJ, Caruana SR, Kirk K and Cowman AF. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 2000;403:906–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Brasseur P, Guiguemde R, Diallo S, Guiyedi V, Kombila M, Ringwald P and Olliaro P. Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa. Trans R Soc Trop Med Hyg 1999;93:645–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Dorsey G, Fidock DA, Wellems TE and Rosenthal PJ. Mechanisms of quinoline resistance. In: Rosenthal PJ, ed. Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Totowa, NJ: Humana Press, 2001, pp 153–72.Google Scholar
  25. 25.
    Pukrittayakamee S, Supanaranond W, Looareesuwan S, Vanijanonta S and White NJ. Quinine in severe falciparum malaria: evidence of declining efficacy in Thailand. Trans R Soc Trop Med Hyg 1994;88:324–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Nosten F, ter Kuile F, Chongsuphajaisiddhi T, Luxemburger C, Webster HK, Edstein M, Phaipun L, Thew KL and White NJ. Mefloquine-resistant falciparum malaria on the Thai-Burmese border. Lancet 1991;337:1140–3.PubMedCrossRefGoogle Scholar
  27. 27.
    Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Brockman A, McGready R, ter Kuile F, Looareesuwan S and White NJ. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet 2000;356: 297–302.PubMedCrossRefGoogle Scholar
  28. 28.
    Sibley CH, Hyde JE, Sims PF, Plowe CV, Kublin JG, Mberu EK, Cowman AF, Winstanley PA, Watkins WM and Nzila AM. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 2001;17:582–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Plowe C V. Folate antagonists and mechanisms of resistance. In: Rosenthal PJ, ed. Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Totowa, NJ: Humana Press, 2001, pp 173–90.Google Scholar
  30. 30.
    Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D and Sharp B. Antifolate antimalarial resistance in southeast Africa: a population-based analysis. Lancet 2003;361:1174–81.PubMedCrossRefGoogle Scholar
  31. 31.
    Peterson DS, Milhous WK and Wellems TE. Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. Proc Natl Acad Sci U S A 1990;87:3018–22.PubMedCrossRefGoogle Scholar
  32. 32.
    Vaidya AB. Atovaquone-proguanil combination. In: Rosenthal PJ, ed. Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Totowa, NJ: Humana Press, 2001, pp 203–18.Google Scholar
  33. 33.
    Canfield CJ, Pudney M and Gutteridge WE. Interactions of atovaquone with other antimalarial drugs against Plasmodium falciparum in vitro. Exp Parasitol 1995;80:373–81.PubMedCrossRefGoogle Scholar
  34. 34.
    Fivelman QL, Butcher GA, Adagu IS, Warhurst DC and Pasvol G. Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria. Malar J 2002;1:1.PubMedCrossRefGoogle Scholar
  35. 35.
    Peters W and Robinson BL. The chemotherapy of rodent malaria. LVI. Studies on the development of resistance to natural and synthetic endoperoxides. Ann Trop Med Parasitol 1999;93:325–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE and Plowe CV. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 2003;187:1870–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Murphy GS, Basri H, Purnomo, Andersen EM, Bangs MJ, Mount DL, Gorden J, Lal AA, Purwokusumo AR, Harjosuwarno S, et al. Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet 1993;341:96–100.PubMedCrossRefGoogle Scholar
  38. 38.
    Nomura T, Carlton JM, Baird JK, del Portillo HA, Fryauff DJ, Rathore D, Fidock DA, Su X, Collins WE, McCutchan TF, Wootton JC and Wellems TE. Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria. J Infect Dis 2001;183:1653–61.PubMedCrossRefGoogle Scholar
  39. 39.
    Pukrittayakamee S, Chantra A, Simpson JA, Vanijanonta S, Clemens R, Looareesuwan S and White NJ. Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrob Agents Chemother 2000;44:1680–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Imwong M, Pukrittayakamee S, Renia L, Letourneur F, Charlieu JP, Leartsakulpanich U, Looareesuwan S, White NJ and Snounou G. Novel point mutations in the dihydrofolate reductase gene of Plasmodium vivax: evidence for sequential selection by drug pressure. Antimicrob Agents Chemother 2003;47:1514–21.PubMedCrossRefGoogle Scholar
  41. 41.
    Smoak BL, DeFraites RF, Magill AJ, Kain KC and Wellde BT. Plasmodium vivax infections in U.S. Army troops: failure of pri-maquine to prevent relapse in studies from Somalia. Am J Trop Med Hyg 1997;56:231–4.Google Scholar
  42. 42.
    World Health Organization. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Geneva: World Health Organization, 2003.Google Scholar
  43. 43.
    Rieckmann KH. Monitoring the response of malaria infections to treatment. Bull World Health Organ 1990;68:759–60.PubMedGoogle Scholar
  44. 44.
    World Health Organization. Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated Falciparum Malaria in Areas with Intense Transmission. Geneva: World Health Organization, 1996.Google Scholar
  45. 45.
    Dorsey G, Kamya MR, Ndeezi G, Babirye JN, Phares CR, Olson JE, Katabira ET and Rosenthal PJ. Predictors of chloroquine treatment failure in children and adults with falciparum malaria in Kampala, Uganda. Am J Trop Med Hyg 2000;62:686–92.PubMedGoogle Scholar
  46. 46.
    Viriyakosol S, Siripoon N, Petcharapirat C, Petcharapirat P, Jarra W, Thaithong S, Brown KN and Snounou G. Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studies. Bull World Health Organ 1995;73:85–95.PubMedGoogle Scholar
  47. 47.
    Cattamanchi A, Kyabayinze D, Hubbard A, Kamya MR, Rosenthal PJ and Dorsey G. 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 2003;68:133–9.PubMedGoogle Scholar
  48. 48.
    Ohrt C, Mirabelli-Primdahl L, Looareesuwan S, Wilairatana P, Walsh D and Kain KC. Determination of failure of treatment of Plasmodium falciparum infection by using polymerase chain reaction single-strand conformational polymorphism fingerprinting. Clin Infect Dis 1999;28:847–52.PubMedCrossRefGoogle Scholar
  49. 49.
    Cheesman SJ, de Roode JC, Read AF and Carter R. Real-time quantitative PCR for analysis of genetically mixed infections of malaria parasites: technique validation and applications. Mol Biochem Parasitol 2003;131:83–91.PubMedCrossRefGoogle Scholar
  50. 50.
    Ferdig MT and Su XZ. Microsatellite markers and genetic mapping in Plasmodium falciparum. Parasitol Today 2000;16:307–12.PubMedCrossRefGoogle Scholar
  51. 51.
    Anderson TJ, Haubold B, Williams JT, Estrada-Franco JG, Richardson L, Mollinedo R, Bockarie M, Mokili J, Mharakurwa S, French N, Whitworth J, Velez ID, Brockman AH, Nosten F, Ferreira MU and Day KP. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol 2000;17:1467–82.PubMedGoogle Scholar
  52. 52.
    Warrell DA, Molyneux ME and Beales PF. Severe and complicated malaria. Trans R Soc Trop Med Hyg 1990;84(suppl 2):1–65.Google Scholar
  53. 53.
    Guthmann JP, Ruiz A, Priotto G, Kiguli J, Bonte L and Legros D. Validity, reliability and ease of use in the field of five rapid tests for the diagnosis of Plasmodium falciparum malaria in Uganda. Trans R Soc Trop Med Hyg 2002;96:254–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Craig MH, Bredenkamp BL, Williams CH, Rossouw EJ, Kelly VJ, Kleinschmidt I, Martineau A and Henry GF. Field and laboratory comparative evaluation of ten rapid malaria diagnostic tests. Trans R Soc Trop Med Hyg 2002;96:258–65.PubMedCrossRefGoogle Scholar
  55. 55.
    White NJ. The assessment of antimalarial drug efficacy. Trends Parasitol 2002;18:458–64.PubMedCrossRefGoogle Scholar
  56. 56.
    Jensen JB. In vitro culture of Plasmodium parasites. In: Doolan DL, ed. Malaria Methods and Protocols. Totowa, NJ: Humana Press, 2002, pp 477–88.CrossRefGoogle Scholar
  57. 57.
    Rieckmann KH, Campbell GH, Sax LJ and Mrema JE. Drug sensitivity of Plasmodium falciparum. An in-vitro microtechnique. Lancet 1978;1:22–3.PubMedCrossRefGoogle Scholar
  58. 58.
    Desjardins RE, Canfield CJ, Haynes JD and Chulay JD. Quantitative assessment of antimalarial activity in vitro by a semi-automated microdilution technique. Antimicrob Agents Chemother 1979;16:710–8.PubMedGoogle Scholar
  59. 59.
    Ringwald P, Bickii J and Basco LK. In vitro activity of antimalar-ials against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon. Am J Trop Med Hyg 1996;55:254–8.PubMedGoogle Scholar
  60. 60.
    Djimde A, Doumbo OK, Steketee RW and Plowe CV. Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet 2001;358:890–1.PubMedCrossRefGoogle Scholar
  61. 61.
    Duraisingh MT, Curtis J and Warhurst DC. Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion. Exp Parasitol 1998;89:1–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Dorsey G, Kamya MR, Singh A and Rosenthal PJ. Polymorphisms in the Plasmodium falciparum pfcrt and pfmdr-1 genes and clinical response to chloroquine in Kampala, Uganda. J Infect Dis 2001;183:1417–20.PubMedCrossRefGoogle Scholar
  63. 63.
    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 and Plowe C V. Molecular markers for failure of sulfadoxine-pyrimeth-amine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis 2002;185:380–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Kyabayinze D, Cattamanchi A, Kamya MR, Rosenthal PJ and Dorsey G. 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 2003;69:247–52.PubMedGoogle Scholar
  65. 65.
    Ridley RG. Medical need, scientific opportunity and the drive for antimalarial drugs. Nature 2002;415:686–93.PubMedCrossRefGoogle Scholar
  66. 66.
    Rosenthal PJ. Antimalarial drug discovery: old and new approaches. J Exp Biol 2003;206:3735–44.PubMedCrossRefGoogle Scholar
  67. 67.
    Nwaka S and Ridley RG. Virtual drug discovery and development for neglected diseases through public—private partnerships. Nat Rev Drug Discov 2003;2:919–28.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Philip J. Rosenthal
    • 1
  1. 1.Department of Medicine, San Francisco General HospitalUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations