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The regulation of malaria parasitaemia: parameter estimates for a population model

Published online by Cambridge University Press:  06 April 2009

M. B. Gravenor ,
A. R. Mclean  and
D. Kwiatkowski
M. B. Gravenor
Affiliation:
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS
A. R. Mclean
Affiliation:
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS
D. Kwiatkowski
Affiliation:
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU
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Summary

Classical studies of non-immune individuals infected with Plasmodium falciparum reveal that the infection may be regulated for long periods at a relatively stable parasite density, despite the enormous growth potential of a parasite that continually replicates within host erythrocytes. This suggests that the parasite population may be controlled by density-dependent mechanisms, and in theory the most obvious of these is competition between parasites for host erythrocytes. Here we evaluate the role of this mechanism in the regulation of parasitaemia, by modelling the basic population interaction between parasites and erythrocytes in a form that allows all the essential parameters to be estimated from clinical data. Our results show that competition cannot account for the total regulation of P. falciparum, but when combined with immune mechanisms it may play a more important role than is generally supposed. Further analysis of the model indicates that in the long term, parasite replication at low parasite densities can contribute significantly to the high degree of anaemia observed in natural infection, a conclusion which is not obvious from simple clinical observation.

Keywords

malariaerythrocytecompetitionregulationmodellingmalariatherapy
Type
Research Article
Information
Parasitology , Volume 110 , Issue 2 , February 1995 , pp. 115 - 122
Copyright
Copyright © Cambridge University Press 1995

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References

REFERENCES

Abdalla, S., Weatherall, D. J., Wickramasinghe, S. N. & Hughes, M. (1980). The anaemia of Plasmodium falciparum malaria. British Journal of Haematology 46, 171–83.CrossRefGoogle Scholar
Anderson, R. M., May, R. M. & Gupta, S. (1989). Nonlinear phenomena in host-parasite interactions. Parasitology 99 (Suppl.), S59–S79.CrossRefGoogle ScholarPubMed
Boyd, M. F. (1940). On strains and races of malaria parasites. American Journal of Tropical Medicine 20, 69–80.Google Scholar
Covell, G. & Nicoll, W. D. (1951). Clinical, chemotherapeutic and immunological studies on induced malaria. British Medical Bulletin 8, 51–5.CrossRefGoogle ScholarPubMed
Esan, G. J. (1975). Haematological aspects of malaria. Clinics in Haematology 4, 247–56.CrossRefGoogle ScholarPubMed
Fleming, A. F. (1981) Haematological manifestations of malaria and other parasitic diseases. Clinics in Haematology 10, 983–1011.CrossRefGoogle ScholarPubMed
Garnham, P. C. C. (1966). Malarial Parasites and Other Haemosporidia. Oxford: Blackwell Scientific Publications.Google Scholar
Glynn, J. R. & Bradley, D. J. (1995). Inoculum size, incubation period and severity of malaria. Analysis of data from malariatherapy records. Parasitology 110, 7–19.CrossRefGoogle Scholar
Gupta, S., Hill, A. V. S., Kwiatkowski, D., Greenwood, B. M. & Day, K. P. (1994). Parasite virulence and disease patterns in Plasmodium falciparum malaria. Proceedings of the National Academy of Sciences, USA 91, 3715–19.CrossRefGoogle ScholarPubMed
Hellriegel, B. (1992). Modelling the immune response to malaria. Proceedings of the Royal Society of London, B 250, 249–56.Google ScholarPubMed
Hetzel, C. (1993). The dynamics of the immune response to infection: mathematical models and experimental investigations. Ph.D. thesis, University of London.Google Scholar
Jarra, W. & Brown, K. N. (1989 a). Invasion of mature and immature erythrocytes of CBA/Ca mice by a cloned line of Plasmodium chabaudi chabaudi. Parasitology 99, 157–63.CrossRefGoogle ScholarPubMed
Jarra, W. & Brown, K. N. (1989 b). Protective immunity to malaria: studies with cloned lines of rodent malaria in CBA/Ca mice. IV. The specificity of mechanisms resulting in crisis and resolution of the primary acute phase parasitaemia of Plasmodium chabaudi chabaudi and P. yoelii yoelii. Parasitic Immunology 11, 1–13.CrossRefGoogle ScholarPubMed
Kitchen, S. F. (1949). Symptomatology: general considerations. In Malariology, Vol. 2 (ed. Boyd, M. F.), pp. 966–1045. Philadelphia: Saunders.Google Scholar
Kwiatkowski, D. (1989). Febrile temperatures can synchronize the growth of Plasmodium falciparum in vitro. Journal of Experimental Medicine 169, 357–61.CrossRefGoogle ScholarPubMed
Kwiatkowski, D. & Nowak, M. (1991). Periodic and chaotic host-parasite interactions in human malaria. Proceedings of the National Academy of Sciences, USA 88, 5111–13.CrossRefGoogle ScholarPubMed
Marsh, K. & Howard, R. J. (1986). Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants. Science 231, 150–3.CrossRefGoogle ScholarPubMed
Newbold, C. I., Pinches, R., Roberts, D. J. & Marsh, K. (1992). Plasmodium falciparum: the human antibody response to the infected red cell surface is predominantly variant specific. Experimental Parasitology 75, 281–92.CrossRefGoogle Scholar
Philips, R. E., Looareesuwan, S., Warrell, D. A., Lee, S. H., Karbwang, J. K., Warrell, M. J., White, N. J., Swasdichai, D. & Weatherall, D. J. (1986). The importance of anaemia in cerebral and uncomplicated falciparum malaria: role of complications, dyserythropoiesis and iron sequestration. Quarterly Journal of Medicine, New Series 58, no. 227, 305–23.Google Scholar
Roberts, D. J., Craig, A. G., Berendt, A. R., Pinches, G. N., Marsh, K. & Newbold, C. I. (1992). Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature, London 357, 689–92.CrossRefGoogle ScholarPubMed
Segel, L. & Slemrod, M. (1989). The quasi-steady-state assumption: a case study in perturbation. Society for Industrial and Applied Mathematics Review 31, 446–77.Google Scholar
Winckel, Ch. W. F. (1941). Are the experimental data of therapeutic malaria applicable to conditions obtaining in nature ? American Journal of Tropical Medicine 21, 789–94.Google Scholar