Hostname: page-component-8448b6f56d-qsmjn Total loading time: 0 Render date: 2024-04-19T20:30:03.077Z Has data issue: false hasContentIssue false

The within-host cellular dynamics of bloodstage malaria: theoretical and experimental studies

Published online by Cambridge University Press:  06 April 2009

C. Hetzel*
Affiliation:
Infection and Immunity Section, Department of Biology, Imperial College, London SW7 2BB, UK
R. M. Anderson
Affiliation:
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK
*
*Corresponding author. Tel: 0171 594 5405. Fax: 0171 584 9075. E-mail: c.hetzel@ic.ac.uk

Summary

The properties of a mathematical model of bloodstage infection with a single strain of malaria were investigated. Analysing the cell population dynamics in the absence of a host immune response we demonstrate a relationship between host and parasite parameters that defines a criterion for the successful invasion and persistence of the parasite. Important parameters are the rates of merozoite production and death and those of erythrocyte production, death and invasion. We present data from experiments designed to evaluate the erythrocyte invasion rate in a rodent malaria system. The model generates patterns of parasitaemia in good qualitative agreement with those seen in Plasmodium berghei infections. The sole force behind the rise and fall in parasitaemia in the model without immunity is the density of susceptible erythrocytes, suggesting that resource availability is an important determinant of the initial pattern of infection in vivo. When we incorporate a simple immune response into the model we find that immunity against the infected cell is much more effective at suppressing parasite abundance than immunity against the merozoite. Simulations reveal oscillating temporal patterns of parasite abundance similar to P. c. chabaudi infection, challenging the concept that antigenic variation is the sole mechanism behind recrudescing patterns of infection.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1996

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

REFERENCES

Agur, Z., Abiri, D. & Van Der Ploeg, L. H. T. (1989). Ordered appearance of antigenic variants of african trypanosomes explained in mathematical model based on a stochastic switch process and immune selection against putative switch intermediates. Proceedings of the National Academy of Sciences, USA 86, 9626–30.CrossRefGoogle ScholarPubMed
Anderson, R. M. & May, R. M. (1992). Infectious Diseases of Humans: Dynamics and Control. Oxford: Oxford University Press.Google Scholar
Anderson, R. M., May, R. M. & Gupta, s. (1989). Nonlinear phenomena in host–parasite interactions. Parasitology 99 (Suppl 1), S59–S79.Google Scholar
Carlsson, J., Helmby, H., Hill, A. V. S., Brewster, D., Greenwood, B. M. & Wahlgren, M. (1990). Human cerebral malaria: association with erythrocyte resetting and lack of anti-rosetting antibodies. Lancet 336, 1457–60.CrossRefGoogle Scholar
Dearsley, A. L., Sinden, R. E. & Self, I. A. (1990). Sexual development in malaria parasites: gametocyte production, fertility and infectivity to the mosquito vector. Parasitology 100, 359–68.CrossRefGoogle Scholar
Eling, W. M. C., Van Zon, A. A. J. C. & Jerusalem, C. (1977). The course of a Plasmodium berghei infection in six different mouse strains. Parasitology Research 54, 2945.Google Scholar
Finley, R. W., Mackey, L. J. & Lambert, P. H. (1982). Virulent Plasmodium berghei malaria: prolonged survival and decreased cerebral pathology in cell-deficient nude mice. Journal of Immunology 129, 2213–18.Google Scholar
Garnham, P. C. C. (1966). Malaria Parasites and other Haemosporidia. Oxford: Blackwell Scientific Publishers.Google Scholar
Gravenor, M. B., Mclean, A. R. & Kwiatkowski, D. (1995). The regulation of malaria parasitaemia: parameter estimates for a population model. Parasitology 110, 115–22.Google Scholar
Hellriegel, B. (1992). Modelling the immune response to malaria with ecological concepts: short-term behaviour against long-term equilibrium. Proceedings of the Royal Society of London, B 250, 249–56.Google Scholar
Jarra, W. & Brown, K. N. (1989). Invasion of mature and immature erythrocytes of CBA/Ca mice by a cloned line of Plasmodium chabaudi chabaudi. Parasitology 99, 157–63.Google Scholar
Jayawardena, A. N., Targett, G. A. T., Leuchars, E., Carter, R. L., Doenhoff, M. J. & Davies, A. J. S. (1975). T cell activation in murine malaria. Nature, London 258, 149–51.Google Scholar
Killick-Kendrick, R. & Peters, W. (1978). Rodent Malaria. London: Academic Press.Google Scholar
Kwiatkowski, D. & Nowak, M. A. (1991). Periodic and chaotic host–parasite interactions in human malaria. Proceedings of the National Academy of Sciences, USA 88, 5111–13.CrossRefGoogle ScholarPubMed
Lamb, J. R., Skidmore, B. J., Green, N., Chiller, J. M. & Feldman, M. (1983). Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza haemagglutinin. Journal of Experimental Medicine 157, 1434–47.CrossRefGoogle Scholar
Langhorne, J., Simon-Haarhaus, B. & Meding, S. J. (1990). The role of CD4+ T cells in the protective immune response to Plasmodium chabaudi in vivo. Immunology Letters 25, 101–8.CrossRefGoogle ScholarPubMed
Matis, L. A., Glimcher, L. H., Paul, W. E. & Schwartz, R. H. (1983). Magnitude of the response of histocompatibility-restricted T cell clones is a function of the product of the concentrations of antigen and la molecules. Proceedings of the National Academy of Sciences, USA 80, 6019–23.Google Scholar
May, R. M. (1974). Stability and Complexity in Model Ecosystems. Princeton, NJ: Princeton University Press.Google Scholar
McAllister, R. O. (1977). Time dependent loss of invasive ability of Plasmodium berghei merozoites in vitro. Journal of Parasitology 63, 455–63.CrossRefGoogle Scholar
McLean, S. A., MacDougall, L. M. & Phillips, R. S. (1990). Early appearance of variant parasites in Plasmodium chabaudi infections. Parasite Immunology 12, 97103.CrossRefGoogle ScholarPubMed
Meding, S. J. & Langhorne, J. (1991). CD4+T cells and B cells are necessary for the transfer of protective immunity to Plasmodium chabaudi chabaudi. European Journal of Immunology 21, 1433–8.CrossRefGoogle Scholar
Mons, B., Janse, C. J., Boorsma, E. G. & Van Der Kaay, H. J. (1985). Synchronized erythrocytic schizogony and gametocytogenesis of Plasmodium berghei in vivo and in vitro. Parasitology 91, 423–30.CrossRefGoogle ScholarPubMed
Nowak, M. A., May, R. M. & Anderson, R. M. (1990). The evolutionary dynamics of HIV-1 quasispecies and the development of immunodeficiency disease. AIDS 4, 1095–103.Google Scholar
Roberts, D. J., Craig, A. G., Berendt, A. R., Pinches, R., Nash, G., Marsh, K. & Newbold, C. I. (1992). Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature, London 357, 689–92.CrossRefGoogle ScholarPubMed
Roth, R. L. & Herman, R. (1979). Plasmodium berghei: correlation of in vitro erythrophagocytosis with the dynamics of early onset anaemia and reticulocytosis. Experimental Parasitology 47, 169–79.CrossRefGoogle ScholarPubMed
Russell, E. s. & Bernstein, S. E. (1966). Blood and blood formation. In Biology of the Laboratory Mouse, 2nd Edn (ed. Green, E. L.). New York: McGraw-Hill.Google Scholar
Stevenson, M. M., Ghadirian, E., Phillips, N. C., Rae, D. & Podoba, J. E. (1989). Role of mononuclear phagocytes in elimination of Plasmodium chabaudi AS infection. Parasite Immunology 11, 529–44.CrossRefGoogle ScholarPubMed
Suss, G., Eichmann, K., Kury, E., Lincke, A. & Langhorne, J. (1988). The role of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stage of Plasmodium chabaudi. Infection and Immunity 56, 3081–8.CrossRefGoogle Scholar
Vanderberg, J. P. (1977). Plasmodium berghei: quantification of sporozoites ejected by mosquitoes feeding on a rodent host. Experimental Parasitology 42, 169–81.Google Scholar
Weatherall, D. J. (1988). The anaemia of malaria. In Malaria: Principles and Practice of Malariology (ed. Wernsdorfer, W. H. & McGregor, I. A.). Edinburgh: Churchill-Livingstone.Google Scholar
Zuckerman, A. (1957). Blood loss and replacement in plasmodial infections. I. Plasmodium berghei in untreated rats of varying age and in adult rats with erythropoietic mechanisms manipulated before inoculation. Journal of Infectious Diseases 100, 172206.Google Scholar