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Malaria Cycle

Explore the complex dynamics of Variant Surface Antigens (VSAs) expressed by malaria parasites within and between hosts. Investigate why VSA_SM is antigenically conserved and present in every parasite. Analyze switching matrices, transmission dynamics, and the impact of VSAs on disease progression. Consider research questions, mathematical models, and potential extensions for understanding VSA dynamics in malaria.

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Malaria Cycle

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  1. (Marsh et al, 2004) Malaria Cycle (Hviid, 2004)

  2. Variant Surface Antigens (VSA) • Parasite proteins expressed by iRBCs. • Each parasite has a repertoire of ~60 var genes for PfEMP1, where each iRBC expresses one type. • PfEMP1 regulates the adhesion properties. • Major target for the adaptive immune system.

  3. VSA_SM (Severe Malaria) • An antigenically conserved group, in time and space, associated with severe disease. • Positively selected in naive hosts. • Each parasite seems to contain VSA_SM. (Bull et al, 2000)

  4. Why is VSA_SM antigenically conserved? Why does every parasite contain VSA_SM? Research questions

  5. Within-host dynamics • After release of the merozoites by the liver, the whole repertoire of VSAs are expressed. • In a few days, all the iRBCs tend to express the same VSA. • During infection, the iRBCs can clonally switch to express a different VSA (switching matrix)

  6. Between-host dynamics • Vector transmission • High transmissibility • High diversity • Multiple infections during lifetime (SIS)

  7. Model • VSAs: 1, 2, 3, 4, ... • Parasites: {1,2}, {1,3}, {2,3}, ... • Stronger VSA: 1 > 2 > 3 > 4 > ... • Upon infection by a parasite, the strongest VSA for which there is no immunity will be expressed • After clearance, the host has build up immunity against the expressed VSA • SIR-model with homogeneous mixing • Equilibrium analysis Within-host Between-host

  8. Flow diagram

  9. Results (2 loci) 5 VSA, 2 loci

  10. Results (2 loci)

  11. Results (1 locus) 5 VSA, 1 locus

  12. Frequency VSA_SM (VSA 1) Variable # VSA, 2 loci

  13. Results (superinfection and scaled mu) 5 vsa, 2 loci, superinfection, high birth/death rate

  14. Extensions • Superinfection. • VSA dependent disease dynamics. • Cross-immunty between the VSAs. • Immunity based on number of infections. • Recombination in the parasite. • VSA_UM without adaptive immunity

  15. Conclusions • (Very much work in progress) • In the basic model, it cannot be explained why each parasite should contain some VSA_SM. The conservedness could be explained by its lower prevalence. • Extensions could show that each parasite contains some VSA_SM, but its conservedness is harder to explain. • Epidemiological data on VSA expression is needed

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