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The relationship between duration of infection with Trypanosoma brucei in mice and the efficacy of chemotherapy

Published online by Cambridge University Press:  06 April 2009

F. W. Jennings
Affiliation:
Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Gloasgow G61 1QH.
D. D. Whitelaw
Affiliation:
Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Gloasgow G61 1QH.
G. M. Urquhart
Affiliation:
Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Gloasgow G61 1QH.

Extract

Relapse of infection after drug treatment of trypanosome infections under conditions precluding re-infection has usually been ascribed to drug resistance on the part of the parasite or to under-dosage of the drug. With Trypanosoma brucei infection in mice we have obtained evidence of another type of relapse. In infections resulting from the inoculation of 1 × 105 trypanosomes, derived from a stabilate T. brucei TREU 667, treatment with diminazene aceturate (Berenil) at 40 mg/kg at either 3 or 7 days after infection elicited a permanent cure. If, however, treatment was delayed later than 14 days after infection, then all the mice relapsed. These relapses generally occurred between 20 and 50 days after treatment, but some mice remained aparasitaemic for up to 60 days. The relapsed infections were apparently not due to the survival of ‘drug-resistant’ trypanosomes, as infections derived from a stabilate isolated from a relapsed Berenil-treated mouse were also permanently cured with Berenil if treated 3 days after infection; however, if treatment was delayed until 21 days post-infection, all the mice relapsed. The cause of relapse was not related to the number of parasites inoculated, as infection resulting from initial inocula of 1 × 105 to 1 × 108 trypanosomes were all cured if treated at 3 days after infection, and all eventually relapsed if treatment was delayed until day 21. This type of relapse phenomenon was not confined to T. brucei TREU 667 but also occurred with 5 other stabi-lates of T. brucei after Berenil treatment. Treatment of T. brucei TREU 667 infections with Ethidium and Prothidium at dose levels of 7.5 and 10 mg/kg respectively was also followed by relapse if treatment was delayed for 3 weeks after infection. The possible causes of relapse under these conditions, and its implications in the study of the natural disease, are discussed.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1977

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References

Apted, F. I. C. (1970). Treatment of human trypanosomiasis. In The African Trypanosomiases (ed. Mulligan, H. W.), pp. 684725. London: George Allen and Unwin.Google Scholar
Browning, C. H. & Calver, K. M. (1943). The effect of the stage of infection on the chemotherapeutic response of T. congolense and on the immunity following cure. Journal of Pathology and Bacteriology 55, 393–4.Google Scholar
Calver, K. M. (1945). Chemotherapeutic studies on experimental T. congolense infections. Ph.D. thesis, University of Glasgow. Reviewed by E. M. Lourie, Tropical Diseases Bulletin 42, 704–9.Google Scholar
Fairolough, R. (1963). Observations on the use of Berenil against trypanosomiasis of cattle in Kenya. Veterinary Record 75, 1107–12.Google Scholar
Fiennes, R. N. T-W. (1950 a). The cattle trypanosomiases: some considerations of pathology and immunity. Annals of Tropical Medical Parasitology 44, 4254.CrossRefGoogle ScholarPubMed
Fiennes, R. N. T-W. (1950 b). The cattle trypanosomiases: cryptic trypanosomiasis. Annals of Tropical Medical Parasitology 44, 222–37.CrossRefGoogle ScholarPubMed
Fink, E. & Dann, O. (1974). The specific curative and prophylactic activity of diamidines against T. rhodesiense and T. congolense. In Control Programs for Trypanosomes and their Vectors. Revue d'élevage et de médicine veterinaire de pays tropicaux pp. 297300. Office International des Epizooties.Google Scholar
Goodwin, L. G. & Rollo, I. M. (1955). Bovine trypanosomiasis in Africa. In Biochemistry and Physiology of Protozoa Vol 2. (ed. Hutner, S. H.Lwoff, A.), pp. 255–63. New York and London: Academic Press.Google Scholar
Gray, A. R. & Roberts, C. J. (1971). The cyclical transmission of strains of Trypanosoma congolense and T. vivax resistant to normal therapeutic doses of trypanocidal drugs. Parasitology 63, 6789.CrossRefGoogle Scholar
Lanham, S. M. & Godfrey, D. G. (1970). Isolation of salivarian trypanosomes of man and other mammals using DEAE-cellulose. Experimental Parasitology 28, 521–34.CrossRefGoogle ScholarPubMed
Lumsden, W. H. R., Herbert, W. J. & Hardy, G. J. C. (1965). In vivo prophylactic activity of Berenil against trypanosomes in mice. Veterinary Record 77, 147–8.Google ScholarPubMed
Lumsden, W. H. R., Herbert, W. J. & McNeillage, G. J. C. (1973). Techniques with Trypanosomes, pp. 95–9. London: Churchill Livingstone.Google Scholar
Maclennan, K. J. R. (1970). Practical application measures for the control of tsetse-borne trypanosomiasis of livestock. In The African Trypanosomiases (ed. Mulligan, H. W.), pp. 799821. London: Allen and Unwin.Google Scholar
Maclennan, K. J. R. (1971). The aparasitaemic interval following diminazine aceturate therapy of a relapsing strain of T. vivax infecting cattle. Tropical Animal Health and Production 3, 208–12.CrossRefGoogle ScholarPubMed
Maclennan, K. J. R. (1973). Additional notes on the aparasitaemic interval following subcurative treatment with diminazene of T. vivax infection in cattle. Transactions of the Royal Society of Tropical Medicine and Hygiene 67, 282.Google Scholar
Maclennan, K. J. R. & Na'isa, B. K. (1970). Relapsing Trypanosoma vivax infections in Nigerian Zebu cattle treated with diminazine aceturate. Tropical Animals Health and Production 2, 189–95.CrossRefGoogle Scholar
Mwambu, P. M. & Mayende, J. S. P. (1975). In vivo comparison of the sensitivity of Ethidium (homidium bromide, B. Vet. C) of Trypanosoma brucei subgroup trypanosomes isolated from cattle, game animals and tsetse flies. Transactions of the Royal Society of Tropical Medicine and Hygiene 69, 276–7.Google Scholar
Ormerod, W. E. & Venkatesan, S. (1970). The choroid plexus in African sleeping sickness. Lancet 2, 777.CrossRefGoogle ScholarPubMed
Ormerod, W. E. & Venkatesan, S. (1971 a). The occult visceral phase of mammalian trypanosomes with special reference to the life cycle of Trypanosoma (trypanozoon) brucei, Transactions of the Royal Society of Tropical Medicine and Hygiene 65, 722–35.CrossRefGoogle Scholar
Ormerod, W. E. & Venkatesan, S. (1971 b). An amastigote phase of the sleeping sickness trypanosome. Transactions of the Royal Society of Tropical Medicine and Hygiene 65, 736–41.CrossRefGoogle ScholarPubMed
Raether, W., Hajdu, P., Seidenath, H. & Damm, D. (1972). Pharmakokinetische und chemoprophylaktische Untersuchungen mit Berenil an Wister-Ratten (Trypanosoma rhodesiense). Zeitschrift fũr Tropenmedizin und Parasitologie 23, 418–27.Google Scholar
Schwetz, J.; (1928). Un stade leishmaniaoide dans revolution du Tr. Vivax-Cazalboui et du Tr. Congolense-dimorphon chez l'hote vertebre (bovides). Annales de la Société belge de médecine tropicale 8, 315–7.Google Scholar
Schwetz, J. & Fornara, L. (1929). Y a-t-il des formes d'evolution des trypanosomes chez l'hote vertébre? Bulletin de la Société de pathologie exotique 22, 862–71.Google Scholar
Soltys, M. A. & Woo, P. (1969). Multiplication of Trypanosoma brucei and Trypanosoma congolense in vertebrate hosts. Transactions of the Royal Society of Tropical Medicine and Hygiene 63, 490–4.CrossRefGoogle ScholarPubMed
Soltys, M. A. & Woo, P. (1970). Further studies on tissue forms of Trypanosoma brucei in a vertebrate host. Transactions of the Royal Society of Tropical Medicine and Hygiene 64, 692–4.CrossRefGoogle Scholar
Soltys, M. A., Woo, P. & Gillick, A. C. (1969). A preliminary note on the separation and infectivity of tissue forms of Trypanosoma brucei. Transactions of the Royal Society of Tropical Medicine and Hygiene 63, 495–6.CrossRefGoogle ScholarPubMed
Taylor, B. J. (1972). Cryostorage in polythene tubing. Transactions of the Royal Society of Tropical Medicine and Hygiene 66, 544.Google ScholarPubMed
Van Hoeve, K. & Cunningham, M. P. (1964). Prophylactic activity of Berenil against trypanosomes in treated cattle. Veterinary Record 76, 260.Google Scholar
Van Hoeve, K. & Grainge, E. G. (1966). The drug sensitivity after two cyclical transmissions of a T. rhodesiense isolate resistant to Ethidium. East African Trypanosome Research Organization Annual Report for 1965, pp. 62, 63–4.Google Scholar
Williamson, J. (1970). Review of chemotherapeutic and chemoprophylactic agents. In The African Trypanosomiases, (ed. Mulligan, H. W.), pp. 125221. London: Allen and Unwin.Google Scholar
Williamson, J. (1976). Chemotherapy of African trypanosomiasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 117–19.CrossRefGoogle ScholarPubMed
Zahalsky, A. C. & Weinberg, R. L. (1976). Immunity to monomorphic Trypanosoma brucei: humoral response. Journal of Parasitology 62, 1519.CrossRefGoogle ScholarPubMed