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Evolution of Pathogen Virulence

Evolution of Pathogen Virulence

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Evolution of Pathogen Virulence

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  1. Evolution of Pathogen Virulence 1. Functionally Dependent Life-History Traits Pathogen-Strain Competition 2. Spatially Structured Transmission SuperinfectionDynamics Limits Virulence

  2. Evolution and epidemiology Population Dynamics Host-Pathogen System Governed by Evolved Parameters In Turn, Population Dynamics Defines Selective Pressures Driving Natural Selection Adaptive Dynamics: Interplay of Ecology, Evolution

  3. Virulence Property Host-Parasite Interaction: Highly Diverse among Diseases Parasite’s “Strategy” for Exploiting Host Affects Correlated Demographic Traits Often Measure Pathogenicity Consequences for Infected Host

  4. Increased Parasite Virulence Faster Consumption of Host Resources  (1) Pathogen Reproductive Rate Increases (2a) Host’s Mortality Rate Increases and/or (2b) Rate of Clearance by Immune System Increases and/or (2c) Host Reproduction Decreases

  5. Virulence Trade-Off Antagonistic Pleiotropy: One Gene Affects 2 Traits Pathogen Increases Propagule Production (Hence, Infection Transmission) Rate Duration of Infectious Period Decreases Trade-off

  6. How Does Virulence Evolve? Pathogen-Stain Competition  2 Strains Differ in Virulence (Resident, Mutant) Compete Between (and) Within Hosts 3 Modes of Strain Competition

  7. Pathogen-Strain Competition 1. Cross-Reactive Immunity Pre-emptive, Strictly Between-Host 2. Coinfection “Scramble,” Within & Between-Host 3. Superinfection Interference, Within & Between-Host

  8. Cross-Protective Immunity One Strain per Infected Host Strain Competition Between Hosts Only “Preemptive Competition” Disallows Within- Host Competition

  9. Cross-Protective Immunity Assume Homogeneous Mixing/Mean-Field Model “Optimally Virulent” Strain, Max R0 Minimizes Equilibrium Density Susceptible Hosts No Strain Coexistence (Pure ESS) Within-Host Competition More Complicated

  10. Cross-Protective Immunity Homogeneous Mixing, No Recovery Transmission-Infectious Period Trade-off () Transmission Efficiency, Direct Contact () Virulence, Extra Host Mortality  Host Exploitation Strategy: d/d > 0

  11. Natural Selection: Optimize  Invasion Dynamics (Conceptual Core) Can Rare Mutant  Invade Resident * at ecological equilibrium? This case: Max R0( ) : Background Host Mortality S: Susceptible Density

  12. General Epidemic: Infection & Population Growth SI Transmission Plus Host Birth, Death Resident Pathogen’s Dynamics Sets Resource Availability (Susceptible Density) for Mutant Strain of Pathogen

  13. Compartment Model & Virulence Susceptible, Infective Hosts Background Mortality: Both classes Virulence: Extra mortality, Infected hosts only Reproduction: Both classes; Hosts Born S

  14. Parameters b Per-capitum Birth • Transmission Rate (Mass Action)  Non-Disease Mortality (All) ( + ) Infective Mortality : Virulence > 0 No Recovery from Infection

  15. Dynamics of Epidemic = Birth, Infection Transmission, Death

  16. Assumptions When Rare, Mutant Pathogen Invades Host Population at Endemic Equilibrium R0 > 1 Invasion Criterion Endemic Infection: Set by Resident Pathogen

  17. Analysis : New Cases/Case When Invading Pathogen Rare Epidemiology: Invade All-Susceptible Population Evolutionary Ecology: Invade Host-Resident Strain at Endemic Equilibrium

  18. Analysis Transmission Rate: Infections/Time = Transmission Duration: Time = Transmission Ends at Host Death

  19. Mutant Invades: Recall: Note: ; Background Mortality & Virulence

  20. Natural Selection: Optimize 

  21. Natural Selection: Optimize 

  22. Natural Selection: Optimize von Baalen & Sabelis (1995, Am Nat)

  23. Natural Selection: Optimize  ^ ESS, Maximizes R0 ESS May Lead to Intermediate Virulence in Absence of Within-Host Competition No Strain-Coexistence Possible Under Well-mixed, Preemptive Competition

  24. Contact Structure, Van Baalen (2000)

  25. SPATIAL SUPERINFECTION

  26. SPATIAL SUPERINFECTION Virulent Can Displace “Avirulent” Strain Transmission (Virulence); No Recovery Key: Superinfection (Virulence Difference) Within & Between-Host Competition Neighborhood Size: 8, 48

  27. Develop Theory: Models 1. Mean-Field Analysis: Homogeneous Mixing 2. Pair Approximation: Local Correlation 3. Simulate Full Stochastic Spatial Model: Large-Scale Correlated Fluctuations, Strong Clustering Possible

  28. Develop Theory: Deduce Predictions Pairwise Invasion Analyses: Adaptive Dynamics Resident Strain at Ecological Equilibrium Can Invading Strain (Mutant) Advance? Assumed Time Scales Convergence Stability; Evolutionary Stability

  29. Mean-field solution Host Alone, Endemic Strain, Invasion Analysis Virulent Invades Avirulent Invades

  30. Mean-Field Results Pairwise Invasion Evolution to Criticality Coexistence: Niche Difference

  31. Spatial Model Results Increased Virulence Decreased Infection Increased Clustering Pair Correlation Model OK

  32. Adaptive dynamics spatial process Pair Approximation Convergent Stable Evolutionarily Stable (Local ESS) Virulence Constrained By Structure

  33. Adaptive dynamics spatial process Simulation Max Virulence Lower Local ESS Reduced

  34. Adaptive dynamics spatial process Weaker Competitive Asymmetry Via Superinfection Reduce ESS Reduce Coexistence

  35. predict 1. Spatial Structure Constrains Maximal Virulence Capable of Dynamic Persistence, Through Extinction of Highly Virulent Strains 2. Spatial Structure Reduces Evolutionarily Stable Level of Virulence 3. Larger Neighborhood Relaxes Constraint, Dynamic Penalty of Clustering Attenuated

  36. predict • Spatial Structure Promotes Coexistence: High Transmission/Virulence, Poor Interference Competitor and Low Transmission/Virulence, Advantage of Superinfection 5. Coexistence Increases with Neighborhood Size 6. Comp. Asymmetry Increases Coexistence

  37. Basic Conceptual models Virulence Diversity Among Host-Pathogen Systems Coexisting Strains, Single Pathogen, Varying in Virulence Hyperparasites & Hypovirulence Sterilizing Pathogens

  38. Basic Conceptual models Infection Transmission Mode Direct: Horizontal More Virulent Than Vertical Vector-Borne More Virulent Than Direct Contact FLP: “Curse of the Pharaoh,” More Virulent?

  39. Basic Conceptual models Within-Host Dynamics Parasite, Specific Immune Cell Densities Affects Between-Host Transmission Population Dynamics Host-Pathogen Coevolution Transmission, Resistance Virulence, Optimal Immune Response

  40. Basic Conceptual models Coevolution of Pathogens and Human Culture Adoption of Agriculture Urbanization Antibiotics, … Disease Prevalence and Host Social Group Size