Molecular Approaches to the Spreading Problem of Drug Resistant Malaria

  • Christopher V. Plowe
  • Thomas E. Wellems
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 390)

Abstract

In 1891, only ten years after Jean Louis Alphonse Laveran first discovered the human malaria parasite, Paul Ehrlich observed that methylene blue specifically stained malaria parasites, and he reasoned that the dye might have potential as an antimalarial treatment. When a 21 year old man with fever, chills, a headache and parasites in his blood failed to improve after a week of observation, Erlich began daily infusions of 0.5g of methylene blue. This regimen caused the patient’s fever to clear quickly and his parasitemia to resolve by the eighth day of treatment. Similar results were obtained in a second case, the only ill effect of the treatment being blue urine.1

Keywords

Methylene Blue Malaria Parasite Antimalarial Activity Chloroquine Resistance Human Malaria Parasite 
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.
    P. Guttman and P. Ehrlich, Ueber die wirkung des methylenblau bei malaria, Berlin Klin Wochenschr. 28: 953–956 1891.Google Scholar
  2. 2.
    L.J. Bruce-Chwatt(ed.), R.H. Black, C.J. Canfield, D.F. Clyde, W. Peters, and W.H. Wernsdorfer, Chemotherapy of Malaria, World Health Organization, Geneva, 1986.Google Scholar
  3. 3.
    D.F. Clyde, Variations in response of malaria parasites to drugs in Asia and Oceania, Med. Trop. Cooperaz. Sviluppo 3: 3–22 (1987).Google Scholar
  4. 4.
    D.F. Clyde, Genesis of chloroquine-resistant Plasmodium falciparum in the American region, Med Trop Cooperaz Sviluppo 3: 41–44 1987.Google Scholar
  5. 5.
    A.S. Jones, Mass treatment with pyrimethamine. A study of resistance and cross resistance resulting from a field trial in the hyperendemic malarious area of Makueni, Kenya, September 1952-September 1953, Trans R Soc Trop Med Hyg 52: 547–561 (1958).PubMedCrossRefGoogle Scholar
  6. 6.
    T. Wilson and J.F.B. Edeson, Treatment of acute malaria with pyrimethamine, British Medical Journal 1: 253–255 (1953).PubMedCrossRefGoogle Scholar
  7. 7.
    P.B. Bloland, E.M. Lackritz, P.N. Kazembe, J.B.O. Were, R. Steketee, and C.C. Campbell, Beyond chloroquine: Implications of drug resistance for evaluating malaria therapy efficacy and treatment policy in Africa. J Infect Dis. 167: 932937 (1993).Google Scholar
  8. 8.
    World Health Organization Technical Report Series, World Health Organization, Geneva, (1990).Google Scholar
  9. 9.
    F. Gay, D.G. Bustos, B. Diquet, L. Rojas Rivero, M. Litaudon, C. Pichet, M. Danis, and M. Gentilini, Cross-resistance between mefloquine and halofantrine [letter], Lancet 336: 1262 (1990).Google Scholar
  10. 10.
    S.R. Meshnick, Y.Z. Yang, V. Lima, F. Kuypers, S. Kamchonwongpaisan, and Y. Yuthavong, Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu), Antimicrob. Agents Chemother. 37: 1108–1114 (1993).CrossRefGoogle Scholar
  11. 11.
    T.T. Hien and N.J. White, Qinghaosu, Lancet 341: 603–608 (1993).CrossRefGoogle Scholar
  12. 12.
    N.J. White, D. Waller, J. Crawley, F. Nosten, D. Chapman, D. Brewster, and B.M. Greenwood, Comparison of artemether and chloroquine for severe malaria in Gambian children, Lancet 339: 317–321 (1992).PubMedCrossRefGoogle Scholar
  13. 13.
    S. Looareesuwan, C. Viravan, S. Vanijanonta, P. Wilairatana, P. Suntharasamai, P. Charoenlarp, K. Arnold, D. Kyle, C. Canfield, and K. Webster, Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria, Lancet 339: 821–824 (1992).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Looareesuwan, P. Wilairatana, S. Vanijanonta, D. Kyle, and K. Webster, Efficacy of quinine-tetracycline for acute uncomplicated falciparum malaria in Thailand [letter], Lancet 339: 369 (1992).Google Scholar
  15. 15.
    G. Watt, L. Loesuttivibool, G.D. Shanks, E.F. Boudreau, A.E. Brown, K. Pavanand, H.K. Webster, and S. Wechgritaya, Quinine with tetracycline for the treatment of drug-resistant falciparum malaria in Thailand, Am. J. Trop. Med. Hyg. 47: 108–111 (1992).PubMedGoogle Scholar
  16. 16.
    C.C. Campbell, Challenges facing antimalarial therapy in Africa, J. Infect. Dis. 163: 1207–1211 (1991).PubMedCrossRefGoogle Scholar
  17. 17.
    A.F.G. Slater and A. Cerami, Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites, Nature 355: 167–169 (1992).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Yayon, Z.I. Cabantchik, and H. Ginsburg, Susceptibility of human malaria parasites to chloroquine is pH dependent, Proc. Natl. Acad. Sci. U. S. A. 82: 2784–2788 (1985).PubMedCrossRefGoogle Scholar
  19. 19.
    D.J. Krogstad, I.Y. Gluzman, D.E. Kyle, A.M. Oduola, S.K. Martin, W.K. Milhous, and P.H. Schlesinger, Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance, Science 238: 1283–1285 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    P.G. Bray, R.E. Howells, G.Y. Ritchie, and S.A. Ward, Rapid chloroquine efflux phenotype in both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. A correlation of chloroquine sensitivity with energy-dependent drug accumulation, Biochem. Pharmacol. 44: 1317–1324 (1992).Google Scholar
  21. 21.
    S.K. Martin, A.M. Oduola, and W.K. Milhous, Reversal of chloroquine resistance in Plasmodium falciparum by verapamil, Science 235: 899–901 (1987).PubMedCrossRefGoogle Scholar
  22. 22.
    A.J. Bitonti, A. Sjoerdsma, P.P. McCann, D.E. Kyle, A.M. Oduola, R.N. Rossan, W.K. Milhous, and D.E. Davidson, Jr., Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine, Science 242: 1301–1303 (1988).PubMedCrossRefGoogle Scholar
  23. 23.
    M. Warsame, W.H. Wernsdorfer, and A. Bjorkman, Lack of effect of desipramine on the response to chloroquine of patients with chloroquine-resistant falciparum malaria, Trans. R. Soc. Trop. Med. Hyg. 86: 235–236 (1992).PubMedCrossRefGoogle Scholar
  24. 24.
    A.J. Bitonti and P.P. McCann, Desipramine and cyproheptadine for reversal of chloroquine resistance in Plasmodium falciparum (letter), Lancet 2: 1282–1283 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    C.M. Wilson, A.E. Serrano, A. Wasley, M.P. Bogenschutz, A.H. Shankar, and D.F. Wirth, Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum, Science 244: 1184–1186 (1989).PubMedCrossRefGoogle Scholar
  26. 26.
    S.J. Foote, J.K. Thompson, A.F. Cowman, and D.J. Kemp, Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum, Cell 57: 921–930 (1989).PubMedCrossRefGoogle Scholar
  27. 27.
    S.J. Foote, D.E. Kyle, R.K. Martin, A.M. Oduola, K. Forsyth, D.J. Kemp, and A.F. Cowman, Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum, Nature 345: 255–258 (1990).PubMedCrossRefGoogle Scholar
  28. 28.
    T.E. Wellems, L.J. Panton, I.Y. Gluzman, V.E. do Rosario, R.W. Gwadz, A. Walker-Jonah, and D.J. Krogstad, Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross, Nature 345: 253–255 (1990).PubMedCrossRefGoogle Scholar
  29. 29.
    C.M. Wilson, S.K. Volkman, S. Thaithong, R.K. Martin, D.E. Kyle, W.K. Milhous, and D.F. Wirth, Amplification of pfmdr 1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand. Mol. Biochem. Parasitol. 57: 151–160 (1993).PubMedCrossRefGoogle Scholar
  30. 30.
    F.M. Awad-el-Kariem, M.A. Miles, and D.C. Warhurst, Chloroquine-resistant Plasmodium falciparum isolates from the Sudan lack two mutations in the pfmdrl gene thought to be associated with chloroquine resistance, Trans. R. Soc. Trop. Med. Hyg. 86: 587–589 (1992).PubMedCrossRefGoogle Scholar
  31. 31.
    T.E. Wellems, A. Walker-Jonah, and L.J. Panton, Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7, Proc. Natl. Acad. Sci. U. S. A. 88: 3382–3386 (1991).PubMedCrossRefGoogle Scholar
  32. 32.
    D.S. Peterson, D. Walliker, and T.E. Wellems, Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria, Proc. Nati. Acad. Sci. U. S. A. 85: 9114–9118 (1988).CrossRefGoogle Scholar
  33. 33.
    A.F. Cowman, M.J. Morry, B.A. Biggs, G.A. Cross, and S.J. Foote, Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum, Proc. Natl. Acad. Sci. U. S. A. 85: 9109–9113 (1988).PubMedCrossRefGoogle Scholar
  34. 34.
    J.W. Zolg, J.R. Plitt, G. Chen, and S. Palmer, Point mutations in the dihydrofolate reductase-thymidylate synthase gene as the molecular basis for pyrimethamine resistance in Plasmodiumfalciparum, Mol. Biochem. Parasitol. 36: 253–262 (1989).CrossRefGoogle Scholar
  35. 35.
    D.S. Peterson, W.K. Milhous, and T.E. Wellems, Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria, Proc. Natl. Acad. Sci. U. S. A. 87: 3018–3022 (1990).PubMedCrossRefGoogle Scholar
  36. 36.
    S.J. Foote, D. Galatis, and A.F. Cowman, Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance, Proc. Natl. Acad. Sci. U. S. A. 87: 3014–3017 (1990).PubMedCrossRefGoogle Scholar
  37. 37.
    D.S. Peterson, S.M. di Santi, M. Povoa, V.S. Calvosa, V.E. do Rosario, and T.E. Wellems, Prevalence of the dihydrofolate reductase Asn-108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the Brazilian Amazon, Am. J. Trop. Med. Hyg. 45: 492–497 (1991).PubMedGoogle Scholar
  38. 38.
    W.K. Milhous, D.S. Peterson, T.E. Wellems, E.K. Lehnert, L. Gerena, S.L. Andersen, and B.G. Schuster, New alternatives to cycloguanil and pyrimethamine, Programs & Abstracts of the 40th Annual Meeting of the American Society of Tropical Medicine & Hygiene 45: (1991). (Abstract)Google Scholar
  39. 39.
    C.J. Canfield, W.K. Milhous, A.L. Ager, R.N. Rossan, T.R. Sweeney, N.J. Lewis, and D.P. Jacobus, PS-15: A potent orally active antimalarial from a new class of folic acid antagonists, Am. J. Trop. Med. Hyg. 49: 121–126 (1993).PubMedGoogle Scholar
  40. 40.
    D.R. Brooks, P. Wang, M. Read, W.M. Watkins, P.F.G. Sims, and J.E. Hyde, Sequence variation of the hydroxymethyldihydropterin pyrophospohkinasedihydropteroate synthase gene in lines of the human malaria parasite, Plasmodiumfalciparum, with differing resistance to sulfadoxine, Eur J Biochem. 224: 397–405 (1994).PubMedCrossRefGoogle Scholar
  41. 41.
    T. triglia and A.F. Cowman, Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum, Proc Natl Acad Sci USA. 85: 7149–7153 (1994).CrossRefGoogle Scholar
  42. 42.
    M.J. Gardner, D.H. Williamson, and R.J.M. Wilson, A circular DNA in malaria parasites encodes an RNA polymerase like that of prokaryotes and chloroplasts, Mol. Biochem. Parasitol. 44: 115–124 (1991).CrossRefGoogle Scholar
  43. 43.
    A.A. Gajadhar, W.C. Marquardt, R. Hall, J. Gunderson, E.V. Ariztia-Carmona, and M.L. Sogin, Ribosomal RNA sequences of Sarcocystis muris, Theileria annulata and Crypthecodinium cohnii reveal evolutionary relationships among apicomplexans, dinoflagellates, and ciliates, Mol. Biochem. Parasitol. 45: 147–154 (1991).CrossRefGoogle Scholar
  44. 44.
    A.B. Vaidya, R. Akella, and K. Suplick, Sequences similar to genes for two mitochondrial proteins and portions of ribosomal RNA in tandemly arrayed 6-kilobase-pair DNA of a malarial parasite, Mol. Biochem. Parasitol. 35: 97–108 (1989).CrossRefGoogle Scholar
  45. 45.
    R. Kiatfuengfoo, T. Suthiphongchai, P. Prapunwattana, and Y. Yuthavong, Mitochondria as the site of action of tetracycline on Plasmodium falciparum, Mol. Biochem. Parasitol. 34: 109–115 (1989).CrossRefGoogle Scholar
  46. 46.
    P.G. Kremsner, Clindamycin in malaria treatment, J. Antimicrob. Chemother. 25: 9–14 (1990).PubMedCrossRefGoogle Scholar
  47. 47.
    M. Strath, T. Scott-Finnigan, M. Gardner, D. Williamson, and I. Wilson, Antimalarial activity of rifampicin in vitro and in rodent models, Trans. R. Soc. Trop. Med. Hyg. 87: 211–216 (1993).PubMedCrossRefGoogle Scholar
  48. 48.
    W.E. Gutteridge, Antimalarial drugs currently in development, J. R. Soc. Med. 82 Suppl 17:63–6; discuss (1989).Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Christopher V. Plowe
    • 1
  • Thomas E. Wellems
    • 1
  1. 1.Laboratory of Malaria ResearchNational Institute of Allergy & Infectious Diseases National Institutes of HealthBethesdaUSA

Personalised recommendations