Evolution of Pathogen Virulence

1
Evolution of Pathogen Virulence

• Functionally Dependent Life-History Traits
• Pathogen-Strain Competition
• Spatially Structured Transmission
• Superinfection
• Limit Virulence

2
Evolution and Epidemiology

• Dynamics Host-Pathogen System
• Governed by Evolved Parameters
• In Turn, Population Dynamics Defines Context
• For Selective Evolution
• Adaptive Dynamics Interplay of Ecology,
  Evolution
  
• Major Advance in Population Biology

3
Virulence

• Property Host-Parasite Interaction
• Parasites 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
• and
• (2a) Hosts Mortality Rate Increases
• and/or
• (2b) Rate of Clearance by Immune System
  Increases
  
• and/or
• (2c) Hosts Fecundity Declines

5
Virulence Trade-Off

• Antagonistic Pleiotropy
• Pathogen Increases Propagule Production (Hence,
  Infection Transmission) Rate
  
• Duration of Infectious Period Decreases
• Evidence Reviewed

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

9
Cross-Protective Immunity

• Assume Homogeneous Mixing/Mean-Field Model
• Density-dependent Transmission Dybamics
• Optimally Virulent Strain, Max R0
• Minimizes Equilibrium Density Susceptible Hosts
• No Strain Coexistence (Pure ESS)

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
Natural Selection Optimize ?
13
Natural Selection Optimize ?
14
Natural Selection Optimize ?von Baalen
Sabelis (1995, Am Nat)
15
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

16
Contact Structure, Van Baalen (2000)
17
SPATIAL SUPERINFECTION
18
SPATIAL SUPERINFECTION

• Virulent Can Displace Avirulent Strain
• Transmission (Virulence) No Recovery
• Key Superinfection (Virulence Difference)
• Within Between-Host Competition
• Neighborhood Size 8, 48

19
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

20
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

21
Mean-Field Solution

• Host Alone,
• Endemic Strain,
• Invasion Analysis
• Virulent Invades
• Avirulent Invades

?(?i) (?i)?/? 0
22
Mean-Field Results

• Pairwise Invasion
• Evolution to
• Criticality
• Coexistence
• Niche Difference

23
Spatial Model Results

• Increased Virulence
• Decreased Infection
• Increased Clustering
• Pair Correlation Model OK

24
Adaptive Dynamics Spatial Process

• Pair Approximation
• Convergent Stable
• Evolutionarily Stable
• (Local ESS)
• Virulence Constrained
• By Structure

25
Adaptive Dynamics Spatial Process

• Simulation
• Max Virulence Lower
• Local ESS Reduced

26
Adaptive Dynamics Spatial Process

• Weaker Competitive Asymmetry Via
• Superinfection
• Reduce ESS
• Reduce Coexistence

27
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

28
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

29
Basic Conceptual Models

• Virulence Diversity Among Host-Pathogen Systems
• Coexisting Strains, Single Pathogen,
• Varying in Virulence
• Hyperparasites Hypovirulence
• Sterilizing Pathogens

30
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?

31
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

32
Basic Conceptual Models

• Coevolution of Pathogens and Human Culture
• Adoption of Agriculture
• Urbanization
• Antibiotics,
• Disease Prevalence and Host Social Group Size