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Replication, differentiation, growth and the virulence of Trypanosoma brucei infections

Published online by Cambridge University Press:  06 April 2009

C. M. R. Turner
Affiliation:
Parasitology Laboratory I.B.L.S., Joseph Black Building, University of Glasgow, Glasgow G12 8QQ
N. Aslam
Affiliation:
Parasitology Laboratory I.B.L.S., Joseph Black Building, University of Glasgow, Glasgow G12 8QQ
C. Dye
Affiliation:
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT

Summary

This study had 2 objectives: first, to investigate how the processes of slender form replication, of differentiation from dividing slender to non-dividing stumpy forms, and of stumpy mortality, combine to determine the initial (acute-phase) growth rate of Trypanosoma brucei populations; second, to determine how acute-phase growth rates influence parasite densities during the subsequent, chronic phase of infection. During the acute phase, slender and stumpy populations both grew approximately exponentially, the latter more slowly than the former. Mathematical models showed how this difference in slender and stumpy growth rates can be explained in terms of heterogeneous replication and differentiation rates. Stumpy life-expectancy was determined for one stock and found to be age-dependent with a half-life of 48–72 h, much larger than observed population doubling times of 5–10 h. A comparison of cloned stocks showed that the highest parasite densities during the chronic phase were associated with the highest acute-phase growth rates of both the whole parasite population and of the subpopulation of slender forms. By contrast, high chronic-phase parasitaemias artificially produced following rapid syringe passage were associated with low acute-phase growth rates of slender forms. Syringe-passaging is a laboratory procedure which selects for virulent parasites, but these parasites behave differently from naturally virulent stocks.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1995

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References

REFERENCES

Aslam, N. & Turner, C. M. R. (1992). The relationship of variable antigen expression and population growth rates in Trypanosoma brucei. Parasitology Research 78, 661–4.CrossRefGoogle ScholarPubMed
Bajyana Songa, E., Hamers, R., Rickman, R., Nantulya, V. M., Mulla, A. F. & Magnus, E. (1991). Evidence for widespread asymptomatic Trypanosoma rhodesiense human infection in the Luangwa Valley (Zambia). Tropical Medicine and Parasitology 42, 389–93.Google Scholar
Barry, J. D., Le Ray, D. & Herbert, W. J. (1979). Infectivity and virulence of Trypanosoma (Trypanozoon) brucei for mice. IV. Dissociation of virulence and variable antigen type in relation to pleomorphism. Journal of Comparative Pathology 89, 465–70.CrossRefGoogle ScholarPubMed
Barry, J. D. & Turner, C. M. R. (1991). The dynamics of antigenic variation and growth in African trypanosomes. Parasitology Today 7, 207–11.CrossRefGoogle ScholarPubMed
Black, S. J., Hewett, R. S. & Sendashonga, C. N. (1982). Trypanosoma brucei variable surface antigen is released by degenerating parasites but not by actively dividing parasites. Parasite Immunology 4, 233–44.CrossRefGoogle Scholar
Black, S. J., Sendashonga, C. N., O'Brien, C., Borowy, N. K., Naessens, M., Webster, P. & Murray, M. (1985). Regulation of parasitaemia in mice infected with Trypanosoma brucei. Current Topics in Microbiology and Immunology 117, 93118.Google ScholarPubMed
Giffin, B. F., McCann, P. P., Bitonti, A. J. & Bacchi, C. J. (1986). Polyamine depletion following exposure to DL-α-difluromethylornithine both in vivo and in vitro initiates morphological alterations and mitochondrial activation in a monomorphic strain of Trypanosma brucei brucei. Journal of Protozoology 32, 238–43.CrossRefGoogle Scholar
Godfrey, D. G. (1960). Types of Trypanosoma congolense. II. Differences in the course of infection. Annals of Tropical Medicine and Parasitology 55, 154–66.CrossRefGoogle Scholar
Greenblatt, H. C., Diggs, C. L., & Rosenstreich, D. L. (1984). Trypanosoma rhodesiense: analysis of the genetic control of resistance among mice. Infection and Immunity 44, 107–11.CrossRefGoogle ScholarPubMed
Hamm, B., Schindler, A., Mecke, D. & Duszenko, M. (1990). Differentiation of Trypanosoma brucei bloodstream trypomastigotes from long slender to short stumpy-like forms in axenic culture. Molecular and Biochemical Parasitology 40, 1322.CrossRefGoogle ScholarPubMed
Herbert, W. J., Mucklow, M. G. & Lennox, B. (1975). The cause of death in acute murine trypanosomiasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 69, 4.Google ScholarPubMed
Herbert, W. J. & Parratt, D. (1979). Virulence of trypanosomes in the vertebrate host. In Biology of the Kinetoplastida, vol. 2. (ed. Lumsden, W. H. R. & Evans, D. A.), pp. 481521. London: Academic Press.Google Scholar
Hoare, C. A. (1972). The Trypanosomes of Mammals: a Zoological Monograph. Oxford: Blackwell Scientific Publications.Google Scholar
Inverso, J. A., De Gee, A. L. W. & Mansfield, J. M. (1988). Genetics of resistance to the African trypanosomes. VII. Trypanosome virulence is not linked to variable surface glycoprotein expression. Journal of Immunology 140, 289–93.CrossRefGoogle Scholar
Inverso, J. A. & Mansfield, J. M. (1983). Genetics of resistance to the African trypanosomes. II. Differences in virulence associated with VSSA expression among clones of Trypanosoma rhodesiense. Journal of Immunology 130, 412–19.CrossRefGoogle Scholar
Levine, R. F. & Mansfield, J. M. (1981). Genetics of resistance to African trypanosomes: role of the H-2 locus in determining resistance to infection with Trypanosoma rhodesiense. Infection and Immunity 34, 513–18.CrossRefGoogle ScholarPubMed
Murray, M. & Morrison, w. I. (1979). Parasitaemia and host susceptibility to African trypanosomiasis. In Pathogenicity of Trypanosomes (ed. Losos G. & Chouinard A.), pp. 7181. IDRC No. 132e.Google Scholar
Roelants, G. E. & Pinder, M. (1987). The virulence of Trypanosoma congolense can be determined by the antibody response of inbred strains of mice. Parasite Immunology 9, 379–88.CrossRefGoogle ScholarPubMed
Sacks, D. L., Selkirk, M., Ogilvie, B. M. & Askonas, B. A. (1980). Intrinsic immunosuppressive activity of different trypanosome strains varies with parasite virulence. Nature, London 283, 476–8.CrossRefGoogle ScholarPubMed
Turner, C. M. R. (1990). The use of experimental artefacts in African trypanosome research. Parasitology Today 6, 1417.CrossRefGoogle ScholarPubMed
Turner, C. M. R., Hunter, C. A., Barry, J. D. & Vickerman, K. (1986). Similarity in variable antigen type composition of Trypanosoma brucei rhodesiense populations in different sites within the mouse host. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 824–30.CrossRefGoogle ScholarPubMed
Vickerman, K., Myler, P. J. & Stuart, K. D. (1993). African trypanosomiasis. In Immunology and Molecular Biology of Parasitic Infections, 3rd Edn (ed. Warren, K. S.), pp. 170212. Oxford: Blackwell Scientific Publications.Google Scholar