1. Evolution of Virulence Matthew H. Bonds The François-Xavier Bagnoud Center for Health and Human Rights Harvard School of Public Health Partners in Health

2. Outline of Presentation 1.Background to Disease Evolution - Evolution of virulence - Antibiotic resistance - Disease emergence 2.Evolutionary Stable Strategies (ESS) 3.Evolution of Virulence - single infection - multiple infections

3. Background to Disease Evolution 1.Evolution of Virulence 2.Antibiotic Resistance 3.Disease Emergence

4. Background to Disease Evolution 1.Evolution of Virulence 2.Antibiotic Resistance 3.Disease Emergence

5. Background to Disease Evolution 1.Evolution: A change in genetic material in a population from generation to the next. - We say that organisms evolve to “maximize their fitness”

6. Background to Disease Evolution 1.Evolution: A change in genetic material in a population from generation to the next. - We say that organisms evolve to “maximize their fitness” 2. Fitness ≅ Reproductivity

7. Background to Disease Evolution 1.Evolution: A change in genetic material in a population from generation to the next. - We say that organisms evolve to “maximize their fitness” 2. Fitness ≅ Reproductivity = number of surviving offspring or number of reproductive offspring

8. Background to Disease Evolution 1.Evolution: A change in genetic material in a population from generation to the next. - We say that organisms evolve to “maximize their fitness” 2. Fitness ≅ Reproductivity = number of surviving offspring or number of reproductive offspring

9. Evolutionarily Stable Strategy Evolutionarily Stable Strategy (ESS): A strategy which, if adopted by a population, cannot be invaded by any alternative strategy that is initially rare. An ESS is a kind of Nash equilibrium.

10. What is the ESS for a Pathogen?

11. A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.

12. What is the ESS for a Pathogen? A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.

13. What is the ESS for a Pathogen? A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.

14. What is the ESS for a Pathogen? A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.

15. What is the ESS for a Pathogen? A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.

16. What is the ESS for a Pathogen? A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade. A strategy that maximizes the Basic Reproductive Ratio is evolutionarily stable (Anderson and May, 1982)

17. ESS for a Pathogen? What are the evolutionary tradeoffs faced by pathogens?

18. ESS for a Pathogen? What are the evolutionary tradeoffs faced by pathogens? Pathogens should evolve to maximize the transmission rate and minimize the disease-induced death rate.

19. ESS for a Pathogen? What are the evolutionary tradeoffs faced by pathogens? Pathogens should evolve to maximize the transmission rate and minimize the disease-induced death rate. There must be a tradeoff between transmission and virulence! ?

20. ESS for a Pathogen?

22. v Tradeoff between transmission and killing the host

23. ESS for a Pathogen? v Maximize Ro with respect to v v*

24. ESS for Multiple Pathogens? v Maximize Ro with respect to v v*

25. ESS for Multiple Pathogens?

28. Maximize Ro with respect to v

29. ESS for Multiple Pathogens?

33. CoESS

34. Summary The evolutionarily stable strategy for a pathogen is the strategy that maximizes its basic reproductive ratio Typically, the phenotype that we consider to be evolving is the disease-induced mortality rate (virulence) There may be a tradeoff between virulence and transmission The ESS level of virulence depends on coinfection. The host represents a common property resource, and the Co-evolutionarily stable strategy is the outcome of a prisoner’s dilemma.