Abstract
New antimalarial drugs are required, partly because of the emergence of drug resistant strains of malaria parasites and partly because better compounds are needed to cure relapsing tertian malaria. In reviewing the diverse modes of action of currently used anti-malarials, against a background of the pathogenesis of malaria, attention is drawn to deficiencies in our knowledge. Even less do we understand how the malaria parasite becomes resistant to certain drugs, in particular chloroquine. New approaches to the problem include the application of combinations of existing antimalarials, and the search for new drugs on an unprecedentedly vast scale. Out of over a quarter million compounds that have recently been screened, a handful are now in clinical trial and are showing great promise for the treatment of multiple resistant falciparum malaria. The paper concludes by summarizing current recommendations for the prophylaxis and therapy of malaria due to drug resistant parasites.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bruce-Chwatt L. J. Malaria. Epidemiology. Br Med J. 1971 Apr 10;2(5753):91–93. doi: 10.1136/bmj.2.5753.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferone R., Burchall J. J., Hitchings G. H. Plasmodium berghei dihydrofolate reductase. Isolation, properties, and inhibition by antifolates. Mol Pharmacol. 1969 Jan;5(1):49–59. [PubMed] [Google Scholar]
- Ferone R. Dihydrofolate reductase from pyrimethamine-resistant Plasmodium berghei. J Biol Chem. 1970 Feb 25;245(4):850–854. [PubMed] [Google Scholar]
- Fitch C. D. Chloroquine resistance in malaria: a deficiency of chloroquine binding. Proc Natl Acad Sci U S A. 1969 Dec;64(4):1181–1187. doi: 10.1073/pnas.64.4.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fitch C. D. Plasmodium falciparum in owl monkeys: drug resistance and chloroquine binding capacity. Science. 1970 Jul 17;169(3942):289–290. doi: 10.1126/science.169.3942.289. [DOI] [PubMed] [Google Scholar]
- Howells R. E., Peters W., Homewood C. A., Warhurst D. C. Theory for the mechanism of chloroquine resistance in rodent malaria. Nature. 1970 Nov 14;228(5272):625–628. doi: 10.1038/228625a0. [DOI] [PubMed] [Google Scholar]
- Macomber P. B., O'Brien R. L., Hahn F. E. Chloroquine: physiological basis of drug resistance in Plasmodium berghei. Science. 1966 Jun 3;152(3727):1374–1375. doi: 10.1126/science.152.3727.1374. [DOI] [PubMed] [Google Scholar]
- McGregor I. A. Immunology of malarial infection and its possible consequences. Br Med Bull. 1972 Jan;28(1):22–27. doi: 10.1093/oxfordjournals.bmb.a070886. [DOI] [PubMed] [Google Scholar]
- Neva F. A., Sheagren J. N., Shulman N. R., Canfield C. J. Malaria: host-defense mechanisms and complications. Ann Intern Med. 1970 Aug;73(2):295–306. doi: 10.7326/0003-4819-73-2-295. [DOI] [PubMed] [Google Scholar]
- PETERS W., FLETCHER K. A., STAEUBLI W. PHAGOTROPHY AND PIGMENT FORMATION IN A CHLOROQUINE-RESISTANT STRAIN OF PLASMODIUM BERGHEI VINCKE AND LIPS, 1948. Ann Trop Med Parasitol. 1965 Mar;59:126–134. doi: 10.1080/00034983.1965.11686290. [DOI] [PubMed] [Google Scholar]
- Peters W. The chemotherapy of rodent malaria. XIV. The action of some sulphonamides alone or with folic reductase inhibitors against malaria vectors and parasites. 4. The response of normal and drug-resistant strains of Plasmodium berghei. Ann Trop Med Parasitol. 1971 Jun;65(2):123–129. [PubMed] [Google Scholar]
- Ramkaran A. E., Peters W. Infectivity of chloroquine resistant Plasmodium berghei to Anopheles stephensi enhanced by chloroquine. Nature. 1969 Aug 9;223(5206):635–636. doi: 10.1038/223635a0. [DOI] [PubMed] [Google Scholar]
- Warhurst D. C., Robinson B. L., Howells R. E., Peters W. The effect of cytotoxic agents on autophagic vacuole formation in chloroquine-treated malaria parasites (Plasmodium berghei). Life Sci II. 1971 Jul 8;10(13):761–771. doi: 10.1016/0024-3205(71)90208-6. [DOI] [PubMed] [Google Scholar]