Immuno-epidemiology of coccidiosis

1. Immuno-epidemiology of coccidiosis Don Klinkenberg Maite Severins Hans Heesterbeek

2. Coccidiosis • Caused by Eimeria spp • Protozoan • Intestinal infection • sometimes lesions • main problem: production loss • Seven species in chickens • location in the intestine • no cross-immunity

3. Parasite classification • After lecture notes by Kretschmar (micro/macro):

4. Essential characteristics • Transmission through environment • Dose-dependent infectivity • Slowly acquired immune response • stronger upon re-infection • reduces parasite excretion • Within-host dynamics!

5. This presentation • Model of within-host dynamics • relation between uptake and excretion of infectious material (oocysts) • interaction with immune system • Model of between-host dynamics (I) • coupling excretion and uptake of oocysts • interaction chickens and environment • Model of between-host dynamics (II)

6. Within-host model • Eimeria characteristics: • transmission through oocysts • Eimeria parasitises gut epithelial cells • limited number of asexual generations

7. Oocyst uptake (W) Sporozoites Oocyst excretion (Z) Schizont I (X(1)) Gamont Merozoites I (u(1)) Merozoites II (u(2)) Schizont II (X(2)) Eimeria cycle

8. Oocyst uptake (W) Oocyst excretion (Z) Schizont I (X(1)) Schizont II (X(2)) Eimeria cycle

9. Oocyst uptake (W) Schizont I (X(1)) Schizont II (X(2)) Oocyst excretion (Z) Eimeria cycle

10. Adding immunity • Primarily T cell immunity • Immunity evoked by schizonts • Immunity inhibits schizont development • Keeping the model simple: one immunity variable Y

11. Oocyst uptake (W) Oocyst excretion (Z) Schizont I (X(1)) + Immunity (Y) – – + Schizont II (X(2)) Eimeria cycle with immunity

12. Eimeria cycle with immunity Oocyst uptake (W) Schizont I (X(1)) – + Schizont II (X(2)) Immunity (Y) + – Oocyst excretion (Z)

13. Eimeria cycle with immunity Oocyst uptake (W) Schizont I (X(1)) – + Schizont II (X(2)) Immunity (Y) + – Oocyst excretion (Z)

14. Eimeria cycle with immunity

15. Model summary • Discrete time • Two asexual schizont generations • T cell immunity against schizont development

16. Model analysis • Compare model experiments to data • relation single dose and excretion • saturation followed by decrease • excretion during trickle infections • excretion terminates after some time • immunising effect of trickle and single immunisation • trickle immunisation gives better protection

17. Single dose and excretion E. tenella

18. Model analysis • Model experiments • single dose and excretion • relation between W0 and Z4 • trickle infections • trickle vs single immunisation

19. Analysis: single dose

20. Analysis: single dose E. tenella

21. Analysis: single dose E. acervulina

22. Analysis: single dose E. maxima

23. Model analysis • Model experiments • single dose and excretion • relation between W0 and Z4 • b > 0 (naïve immunity growth) • m≠ 1 (non-linear immune effectiveness) • trickle infections & immunisation • conclusions on g and a

24. Conclusions within-host model • Simple model of parasite input-output behaviour • Single immunity variable can explain experimental data • Solid basis for studying re-infection and between-host transmission

25. Between-host model • Relate excretion to uptake with oocyst level in environment V • Simplifying assumption: average chicken

26. Oocyst uptake (W) Oocyst excretion (Z) Schizont I (X(1)) + Immunity (Y) – – + Schizont II (X(2)) Eimeria cycle

27. outside the chickens Environmental oocysts (V) × 1 × a0 Oocyst excretion (Z) Oocyst uptake (W) × 1 × a1 Immunity (Y) Gamont (G) + Schizont I (X(1)) + – – × l2 × l1 Schizont II (X(2)) inside the chickens Eimeria cycle

28. Two new parameters • Per time step of ca. 2 days • Uptake rate a0 • estimate from a single experiment: 0.01 • Oocyst degradation rate • estimate from couple of articles: 0.5

29. Interesting variables • Oocyst level in environment • decrease due to degradation (+ uptake) • increase due to excretion • Immunity level in average chicken • increase due to presence of schizonts • decrease by fixed rate • Number of infected cells as measure of damage • numbers of schizonts and gamonts

30. Basic dynamics

31. outside the chickens Environmental oocysts (V) × 1 × a0 Oocyst excretion (Z) Oocyst uptake (W) × 1 × a1 Immunity (Y) Gamont (G) + Schizont I (X(1)) + – – × l2 × l1 Schizont II (X(2)) inside the chickens 5 5 0 4 2 1 3 3 2

32. Dynamics in single chicken cohort • First dose of each infection generation most important • major change compared to previous dose • fast decay of oocysts in environment • Dynamics can be described in terms of infection generations

33. Damage in single chicken cohort • Cumulative damage ≈ maximum damage logdmax logv0

34. Conclusion on damage • Production damage is reflected by the maximum number of infected cells • Damage may take local minimum with intermediate oocyst level V0 • Mechanism • maximum damage if a single infection generation dominates • minimum when generation dominance switches

35. Damage in single chicken cohort • Cumulative damage ≈ maximum damage logdmax 1 3 2 4 schizonts II gamonts logv0

36. Discussion of the model • Single ‘average’ chicken • Deterministic model • No spatial effects

37. Different approach • Individual chickens • Stochastic model • Spatial model • Cost: • No continuous infection/immune level

38. Individual based model • Patches interact with walking chickens • Patches • oocyst level empty, low, medium, high (0; 103; 105; 107) • level rises if chicken excretes higher level • level falls after 14 days without excretion

39. Individual based model • Chickens • walk or ‘shuffle’ each hour • pick up maximum daily exposure (0, 101; 3; 5) • excrete once per day depending on • uptake -4 days • level of immunity (no, partial, full) • regulated by excretion templates • immunity level may increase depending on • time since first dose • number and level of doses

40. Example: fit to data (Galmes)