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Investigating antigenic variation and other parasite–host interactions in Plasmodium falciparum infections in naïve hosts

Published online by Cambridge University Press:  16 April 2004

M. L. GATTON  and
Q. CHENG
M. L. GATTON
Affiliation:
Australian Centre for International and Tropical Health & Nutrition, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Qld 4029, Australia
Q. CHENG
Affiliation:
Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Gallipoli Barracks, Enoggera, Qld 4051, Australia
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Abstract

Mathematical models of the in-host dynamics of malaria infections provide a valuable tool to explore aspects of the host–parasite interaction that are not possible to investigate experimentally. This paper presents predictions of several important parameter values for 2 parasite strains/groups: parasite PfEMP1 switching rates, dynamics of host anti-PfEMP1 antibodies and parameters related to specific and non-specific host immune responses. A stochastic simulation model of the in-host dynamics of Plasmodium falciparum infections in naïve hosts was used to make these predictions. This model incorporates a novel process to simulate antigenic variation by the parasite, and specific and non-specific immune responses by the host. Comparison of model output to a range of published statistics indicated that the model is capable of reproducing the features of clinical P. falciparum infections, including the characteristic recrudescent behaviour. Using the model, we explored the hypothesized switching mechanism of a fast overall rate of antigenic variation early in an infection and found that it is compatible with chronic infections when the var genes are split into 2 groups; fast and slow switching.

Keywords

malariaPlasmodium falciparummathematical modellingin-host dynamics
Type
Research Article
Information
Parasitology , Volume 128 , Issue 4 , April 2004 , pp. 367 - 376
Copyright
© 2004 Cambridge University Press

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References

REFERENCES

ANDREWS, K. T. & LANZER, M. (2002). Maternal malaria: Plasmodium falciparum sequestration in the placenta. Parasitology Research 88, 715–723.CrossRefGoogle Scholar
BIGGAR, R. J., COLLINS, W. E. & CAMPBELL, C. C. (1980). The serological response to primary malaria infection in urban Ghanaian infants. American Journal of Tropical Medicine and Hygiene 29, 720–724.CrossRefGoogle Scholar
BORST, P., BITTER, W., McCULLOCH, R., VAN LEEUWEN, F. & RUDENKO, G. (1995). Antigenic variation in malaria. Cell 82, 1–4.CrossRefGoogle Scholar
BULL, P. C., LOWE, B. S., KORTOK, M., MOLYNEUX, C. S., NEWBOLD, C. I. & MARSH, K. (1998). Parasite antigens on the infected red cell surface are targets for naturally acquired immunity. Nature, Medicine 4, 358–360.CrossRefGoogle Scholar
CHENG, Q., LAWRENCE, G., REED, C., STOWERS, A., RANFORD-CARTWRIGHT, L., CREASEY, A., CARTER, R. & SAUL, A. (1997). Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines. American Journal of Tropical Medicine and Hygiene 57, 495–500.CrossRefGoogle Scholar
COLLINS, W. E. & JEFFERY, G. M. (1999 a). A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity during primary infection. American Journal of Tropical Medicine and Hygiene 61 (Suppl.), 4–19.Google Scholar
COLLINS, W. E. & JEFFERY, G. M. (1999 b). A retrospective examination of the patterns of recrudescence in patients infected with Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 61 (Suppl.), 44–48.Google Scholar
CRAIG, A. & SCHERF, A. (2001). Molecules on the surface of the Plasmodium falciparum infected erythrocyte and their role in malaria pathogenesis and immune evasion. Molecular and Biochemical Parasitology 115, 129–143.CrossRefGoogle Scholar
DUFFY, M. F., BROWN, G. V., BASUKI, W., KREJANY, E. O., NOVIYANTI, R., COWMAN, A. F. & REEDER, J. C. (2002). Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Molecular Microbiology 43, 1285–1293.CrossRefGoogle Scholar
GATTON, M. L. & CHENG, Q. (2002). Evaluation of the pyrogenic threshold for P. falciparum in naïve individuals. American Journal of Tropical Medicine and Hygiene 66, 467–473.CrossRefGoogle Scholar
GATTON, M. L., PETERS, J., FOWLER, E. & CHENG, Q. (2003). Switching rates of Plasmodium falciparum var genes: faster than we thought? Trends in Parasitology 19, 202–208.Google Scholar
JAMES, S. P., NICOL, W. D. & SHUTE, P. G. (1932). A study of induced malignant tertian malaria. Proceedings of the Royal Society of Medicine 25, 1153–1186.Google Scholar
JEFFERY, G. M., YOUNG, M. D., BURGESS, R. W. & EYLES, D. E. (1959). Early activity in sporozoite-induced Plasmodium falciparum infections. Annals of Tropical Medicine and Parasitology 53, 51–58.CrossRefGoogle Scholar
KINYANJUI, S., BULL, P. B., NEWBOLD, C. I. & MARSH, K. (2003). Kinetics of antibody responses to Plasmodium falciparum-infected erythrocyte variant surface antigens. Journal of Infectious Diseases 187, 667–674.CrossRefGoogle Scholar
MOLINEAUX, L. & DIETZ, K. (1999). Review of intra-host models of malaria. Parassitologia 41, 221–231.Google Scholar
MOLINEAUX, L., DIEBNER, H. H., EICHNER, M., COLLINS, W. E., JEFFERY, G. M. & DIETZ, K. (2001). Plasmodium falciparum parasitaemia described by a new mathematical model. Parasitology 122, 379–391.CrossRefGoogle Scholar
NOVIYANTI, R., BROWN, G. V., WICKHAM, M. E., DUFFY, M. F., COWMAN, A. F. & REEDER, J. C. (2001). Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion. Molecular and Biochemical Parasitology 114, 227–237.CrossRefGoogle Scholar
OFORI, M. F., DODOO, D., STAALSOE, T., KURTZHALS, J. A. L., KORAM, K., THEANDER, T. G., AKANMORI, B. D. & HVIID, L. (2002). Malaria-induced acquisition of antibodies to Plasmodium falciparum variant surface antigens. Infection and Immunity 70, 2982–2988.CrossRefGoogle Scholar
PAGET-McNICOL, S., GATTON, M., HASTINGS, I. & SAUL, A. (2002). The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling. Parasitology 124, 225–235.Google Scholar
PETERS, J., FOWLER, E., GATTON, M., CHEN, N., SAUL, A. & CHENG, Q. (2002). High diversity and rapid changeover of expressed var genes during acute phase of Plasmodium falciparum infections in human volunteers. Proceedings of the National Academy of Sciences, USA 99, 10689–10694.CrossRefGoogle Scholar
POMBO, D. J., LAWRENCE, G., HIRUNPETCHARAT, C., RZEPCZK, C., BRYDEN, M., CLOONAN, N., ANDERSON, K., MAHAKUNKIJCHAROEN, Y., MARTIN, L. B., WILSON, D., ELLIOTT, S., ELLIOTT, S., EISEN, D. P., WEINBERG, J. B., SAUL, A. & GOOD, M. F. (2002). Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet 360, 610–617.CrossRefGoogle Scholar
SIMPSON, J. A., AARONS, L., COLLINS, W. E., JEFFERY, G. M. & WHITE, N. J. (2002). Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection. Parasitology 124, 247–263.CrossRefGoogle Scholar
SMITH, J. D., CRAIG, A. G., KRIEK, N., HUDSON-TAYLOR, D., KYES, S., FAGEN, T., PINCHES, R., BARUCH, D. I., NEWBOLD, C. I. & MILLER, L. H. (2000). Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proceedings of the National Academy of Sciences, USA 97, 1766–1771.CrossRefGoogle Scholar