1. The construction and analysis of epidemic trees with reference to the 2001 UK FMDV outbreak Dan Haydon, Dept Zoology, University of Guelph, On. Ca.

2. Provide case reproduction ratios from outbreak data as it arises Explore the consequences of applying stricter control measures Woolhouse, MEJ., Topping, M.C., Haydon, D.T. and 8 others. 2001. Foot-and-mouth disease under control in the UK. Nature 411, 258-259. Haydon, D.T., Topping, M.C., Shaw, D.J., Matthews, L., Friar, J.K., Wilesmith, J., and Woolhouse, M.E.J. 2003. The construction and analysis of epidemic trees with reference to the 2001 UK foot-and-mouth outbreak. Proceedings: Biological Sciences (The Royal Society, UK) 270, 121-127.

3. Number of infected premises ∞ skiingMove to Guelph

5. time 5 km 3 km 13 km 0.5 km 1.5 km Reporting date Culling date Infection date Always pick the closest Pick candidates with equal probability Pick candidates with probabiltiy weighted by distance

6. time 1 7 0 0 0 0 0 1 4 1 0 1 0 0 0 0 0

9. b)

10. time Parent reporting date Estimated parent infection date Daughter reporting date Parent Infected – daughter reporting interval

11. 93% 60%

13. 20 th Feb. Time

14. 20 th Feb. 23 rd Feb. Time NMB

15. 20 th Feb. 23 rd Feb. X X Time NMB

16. 20 th Feb. 23 rd Feb. Time NMB

18. Between 20 th – evening of 23 rd of February: 17 IPs infected at distance greater than 20km 16 of these IPs have positive contact tracing 13 were infected by animal movements from markets

19. time

24. 20 th Feb. 23 rd Feb. Time NMB X X

25. 20 th Feb. 23 rd Feb. Time NMB

26. 20 th Feb. Time

28. Week Number of new infections

29. The government, however, dismisses Woolhouse's figures as an overestimate. It also argues that it could not have acted any faster than it did. "A national ban was imposed as soon as it became clear that there was a national problem," a spokesman for the Department for Environment Food and Rural Affairs told New Scientist. But he did add that such a ban would be imposed immediately if any future outbreak occurred. New Scientist vol. 176 issue 2372 (07 December 2002)

30. What the foot and mouth virus looks like (not actual size)

31. 1.5% yr -1 1.0% yr -1 1.4% yr -1 1.0% yr -1 1.1% yr -1 0.4% yr -1

32. Wildtype virus Mutant virus Assume: Simple exponential population growth Simple Poisson mutation process (no back mutation) Mutants are either tolerated and equally fit as wildtype or not tolerated at all WITHIN HOST POPULATION DYNAMICS Haydon, D.T., Samuel, A.R., and Knowles, N.J. (2001). The generation and persistence of genetic variation in foot-and-mouth disease virus. Preventative Veterinary Medicine 51, 111-124.

34. 0 10 20 30 40 50 10 -3 10 -4 10 -5 10 -6 Viral Generations (t) Error Rate (per base per replication cycle) The fraction of mutant capsid genes in an infected animal?

35. observed rates of change in the field are 0.5 - 1.5 % yr -1 corresponding to 10 - 30 nucleotide changes in capsids genes yr -1 plausible that the bulk of virus excreted by infected animals differs by at least one point mutation to capsid genes from that which ‘went in’ therefore sequential chains of infection of 10 - 30 animals yr -1 could give rise to observed rates of change

36. Uncertainty surrounds many of the critical parameters governing the generation of genetic variation during a single infection In particular: the mutation rate the number of viral generations the viability of variants However, if variation is generated at the rate anticipated, then transmission networks may be traced at a much finer resolution than practiced to date

37. Group 1Group 2Group 3Group 4 Introduce infection Hughes, G.J., Mioulet, V., Haydon, D.T., Kitching, P.R., Donaldson, A.I., and Woolhouse, M.E.J. (2002). Serial passage of foot-and-mouth disease virus in sheep reveals declining levels of viraemia through time. Journal of General Virology 83, 1907-1914.

38. 07 98 83 06 97 90 82 05 96 89 81 04 95 8880 03 94 8779 0286 78 85 77 Inoculum Group 1 Group 2 Group 3 Group 4 01 93 84 76 00 92 9991 NOT DONE Inoculum a Inoculum b Ø 487 23 487 23 1,2 487 23 487 577 23 487 23 487 577 23 487 23 487 577 23 1,2 487 23 487 577 23 487 577 23 487 577 23 23 1,2 487 577 1,2 487 NOT INFECTED