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Malaria Cycle

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

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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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