Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-19T23:11:09.400Z Has data issue: false hasContentIssue false

The development of resistance to metachloridine in Plasmodium gallinaceum in Chicks

Published online by Cambridge University Press:  06 April 2009

Ann Bishop
Affiliation:
Molteno Institute, University of Cambridge
Elspeth W. McConnachie
Affiliation:
Molteno Institute, University of Cambridge

Extract

1. An increase in resistance to metachloridine of more than 100-fold was obtained within a few weeks in a strain of Plasmodium gallinaceum treated with gradually increasing doses of the drug and maintained in young chicks by blood-inoculation at intervals of 2–3 days.

2. There was no evidence that the rapid development of resistance arose by the selection of highly resistant individuals present in the normal population.

3. Two strains of P. gallinaceum passaged through chicks treated with 0·025 mg. doses of the drug gradually became resistant to greater concentrations than that to which they had been exposed, though their growth rate decreased when they were inoculated into birds receiving higher doses of the drug.

4. In both strains maintained in birds treated with 0·025 mg. doses of the drug, resistance reached a maximum beyond which it did not increase.

5. Cross-resistance tests failed to show any relationship in mode of action between meta-chloridine and pamaquin, mepacrine, quinine or chloroquine. A strain of P. gallinaceum, highly resistant to metachloridine, showed slight resistance to sulphadiazine, sulphapyridine and sulphathiazole, but none to sulphanilamide or proguanil.

We are indebted to the Cyanamid Products Ltd., London, for the gift of the Folvite used in these experiments.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1953

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adams, A. R. D. & Seaton, D. R. (1949). Resistance to paludrine developed by a strain of Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 42, 314.Google Scholar
Alexander, H. F. & Leidy, G. (1947). Mode of action of streptomycin on type b H. influenzae. J. Exp. Med. 85, 329.CrossRefGoogle ScholarPubMed
Beerstecher, E. & Shive, W. (1947). Prevention of phenylalanine synthesis by tyrosine. J. Biol. Chem. 167, 527.CrossRefGoogle ScholarPubMed
Bishop, A. (1951). Drug-resistance in Malaria. Brit. Med. Bull. 8, 47.CrossRefGoogle ScholarPubMed
Bishop, A. & Birkett, B. (1947). Acquired resistance to paludrine in Plasmodium gallinaceum. Acquired resistance and persistence after passage through the mosquito. Nature, Lond., 159, 884.CrossRefGoogle Scholar
Bishop, A. & Birkett, B. (1948). Drug-resistance in Plasmodium gallinaceum, and the persistence of paludrine-resistance after mosquito transmission. Parasitology, 39, 126.CrossRefGoogle ScholarPubMed
Bishop, A. & McConnachie, E. W. (1948). Resistance to sulphadiazine and ‘paludrine’ in the malaria parasite of the fowl (P. gallinaceum). Nature, Lond., 162, 541.CrossRefGoogle ScholarPubMed
Bishop, A. & McConnachie, E. W. (1950 a). Sulpha-diazine-resistance in Plasmodium gallinaceum and its relation to other antimalarial compounds. Parasitology, 40, 163.CrossRefGoogle ScholarPubMed
Bishop, A. & McConnachie, E. W. (1950 b). Cross-resistance between sulphanilamide and paludrine (proguanil) in a strain of Plasmodium gallinaceum resistant to sulphanilamide. Parasitology, 40, 175.CrossRefGoogle Scholar
Bishop, A. & McConnachie, E. W. (1952 a). Failure to produce resistance to chloroquine in Plasmodium gallinaceum in chicks. Parasitology, 42, 52.CrossRefGoogle ScholarPubMed
Bishop, A. & McConnachie, E. W. (1952 b). Pamaquin-resistance in a strain of Plasmodium gallinaceum and its relationship to other antimalarial drugs. Parasitology, 42, 57.CrossRefGoogle Scholar
Brackett, S. & Waletzky, E. (1946). The antimalarial activity of metachloridine (2-metanilamido-5-chloro-pyrimidine) and other metanilamide derivatives in test infections with Plasmodium gallinaceum. J. Parasit. 32, 325.CrossRefGoogle Scholar
Cooper, W. C., Coatney, G. R. & Imboden, C. A. (1950). Studies in human malaria. XXIII. Acquired resistance to chlorguanide in the Chesson strain of Plasmodium vivax. J. Nat. Malaria Soc. 9, 59.Google Scholar
Demerec, M. (1948). Origin of bacterial resistance to antibiotics. J. Bact. 56, 63.CrossRefGoogle ScholarPubMed
Edeson, J. F. B. & Field, J. W. (1950). Proguanil-resistant falciparum malaria in Malaya. Brit. Med. J. 1, 147.CrossRefGoogle ScholarPubMed
English, A. R. & McCoy, E. (1951). A study of streptomycin resistance in Micrococcus pyogenes var. aureus. J. Bact. 61, 51.CrossRefGoogle ScholarPubMed
Field, J. W. & Edeson, J. F. B. (1949). Paludrine-resistant falciparum malaria. Trans. R. Soc. Trop. Med. Hyg. 43, 233.CrossRefGoogle ScholarPubMed
Fulton, J. D. & Yorke, W. (1941). Studies in chemotherapy. XXIX. The development of plasmoquine-resistance in Plasmodium knowlesi. Ann. Trop. Med. Parasit. 35, 233.CrossRefGoogle Scholar
Fulton, J. D. & Yorke, W. (1943). Studies in Chemotherapy. Further observations on plasmoquine-resistance in Plasmodium knowlesi. Ann. Trop. Med. Parasit. 37, 41.CrossRefGoogle Scholar
Gibson, M. I. & Gibson, F. (1951). Development of resistance to dihydrostreptomycin by Bacterium coli. Nature, Lond., 167, 113.CrossRefGoogle ScholarPubMed
Van Goor, W. T., Lodens, J. G. & Gomez, J. A. (1950). Clinical prophylaxis with proguanil and nivaquine in a community in Java. Docum. neerl. indones. Morb. trop. 2, 341.Google Scholar
Greenberg, J. (1949 a). Inhibition of the antimalarial activity of chlorguanide by pteroylglutamic acid. Proc. Soc. Exp. Biol., N.Y., 71, 306.CrossRefGoogle ScholarPubMed
Greenberg, J. (1949 b). The potentiation of the antimalarial activity of chlorguanide by p−aminobenzoic acid competitors. J. Pharmacol. 97, 238.Google ScholarPubMed
Greenberg, J., Boyd, B. L. & Josephson, E. S. (1948). Synergistic effect of chlorguanide and sulfadiazine against Plasmodium gallinaceum in the chick. J. Pharmacol. 94, 60.Google ScholarPubMed
Hawking, F. & Perry, W. L. M. (1948). Resistance to proguanil (paludrine) in a mammalian malaria parasite (Plasmodium cynomolgi). Lancet, ii, 850.CrossRefGoogle Scholar
Hughes, C. O. & Brackett, S. (1946). The prevention of sporozoite-induced infections of Plasmodium cathemerium in the canary by metachloridine. J. Parasit. 32, 340.CrossRefGoogle ScholarPubMed
Klein, R. & Kimelmann, L. J. (1946). The role of spontaneous variants in the acquisition of streptomycin resistance by the Shigellae. J. Bact. 52, 471.CrossRefGoogle ScholarPubMed
Knoppers, A. T. (1947). Acquired resistance (twofold) to quinine in Plasmodium gallinaceum. Nature, Lond., 160, 606.CrossRefGoogle ScholarPubMed
Knoppers, A. T. (1949). Twofold quinine resistance of Plasmodium gallinaceum, induced by regular administration of the drug. Docum. neerl. indones. Morb. trop. 1, 55.Google ScholarPubMed
Linz, R. & Lane, L. (1949). Au sujet de la résistance bactérienne à la streptomyeine après action de concentrations minimes de streptomycine. C.R. Soc. Biol., Paris, 143, 726.Google Scholar
Lourie, E. M. & Seaton, D. R. (1949). Resistance to paludrine developed by a strain of Plasmodium vivax. Trans. R. Soc. Trop. Med. Hyg. 42, 315.Google Scholar
Meads, M. & Haslam, N. M. (1949). Quantitative studies on the origin and characteristics of streptomycin-fast variants of Klebsiella pneumoniae. J. Immunol. 63, 1.CrossRefGoogle ScholarPubMed
Mitchison, J. A. (1951). The segregation of streptomycin-resistant variants of Mycobacterium tuberculosis into groups with characteristic levels of resistance. J. Gen. Microbiol. 5, 596.CrossRefGoogle ScholarPubMed
Newcombe, H. B. & Hawirko, R. (1949). Spontaneous mutation to streptomycin resistance and dependence in Escherichia coli. J. Bact. 57, 565.CrossRefGoogle ScholarPubMed
Olitzki, A. L. (1952). The determination of the most probable numbers of streptomycin-fast cells in Brucella cultures and their variability in growing and ageing cultures. J. Gen. Microbiol. 6, 166.CrossRefGoogle Scholar
Rollo, I. M. (1951). A 2:4-diamino pyrimidine in the treatment of proguanil-resistant laboratory malarial strains. Nature, Lond., 168, 333.CrossRefGoogle Scholar
Schmidt, L. H., Genther, C. S., Fradkin, R. & Squires, W. (1949). Development of resistance to chlorguanide (paludrine) during treatment of infections with Plasmodium cynomolgi. J. Pharmacol. 95, 382.Google ScholarPubMed
Seaton, D. R. (1951). Failure to induce chlorquine-resistance in Plasmodium gallinaceum. Ann. Trop. Med. Parasit. 45, 99.CrossRefGoogle ScholarPubMed
Seaton, D. R. & Adams, A. R. D. (1949). Acquired resistance to proguanil in Plasmodium gallinaceum. Lancet, ii, 323.CrossRefGoogle Scholar
Seaton, D. R. & Lottrie, E. M. (1949). Acquired resistance to proguanil (paludrine) in Plasmodium vivax. Lancet, i, 394.CrossRefGoogle Scholar
Silver, H. K. & Kempe, C. H. (1947). Resistance to streptomycin. A study of the mechanisms of its development. J. Immunol. 57, 263.CrossRefGoogle ScholarPubMed
Thompson, P. E. (1948). On the ability of Plasmodium lophurae to acquire resistance to chlorguanide, camoquin and chloroquine. J. Infect. Dis. 83, 250.CrossRefGoogle ScholarPubMed
Williamson, J., Bertram, D. S. & Lourie, E. M. (1947). Acquired resistance to paludrine in Plasmodium gallinaceum. Effects of paludrine and other antimalarials. Nature, Lond., 159, 885.CrossRefGoogle Scholar
Williamson, J. & Lourie, E. M. (1947). Acquired paludrine-resistance in Plasmodium gallinaceum. I. Development of resistance to paludrine and failure to develop resistance to certain other antimalarials. Ann. Trop. Med. Parasit. 41, 278.CrossRefGoogle ScholarPubMed
Yegian, D. & Vanderlinde, R. J. (1948). A quantitative analysis of the resistance of mycobacteria to streptomycin. J. Bact. 56, 177.CrossRefGoogle ScholarPubMed