Post on 21-Dec-2015
transcript
Evolution of Virulence
Matthew H. Bonds
The François-Xavier Bagnoud Center for Health and Human Rights
Harvard School of Public Health
Partners in Health
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
Background to Disease Evolution
1. Evolution of Virulence2. Antibiotic Resistance3. Disease Emergence
Background to Disease Evolution
1. Evolution of Virulence2. Antibiotic Resistance3. Disease Emergence
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”
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
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
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
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.
What is the ESS for a Pathogen?
What is the ESS for a Pathogen?
A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.
What is the ESS for a Pathogen?
A strategy adopted by some kind of pathogen, forwhich an alternative (mutant) strategy, cannotinvade.
dI
dtSI ( v)I
What is the ESS for a Pathogen?
A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.
dI
dtSI ( v)I 0
What is the ESS for a Pathogen?
A strategy adopted by some kind of pathogen, forwhich an alternative (mutant) strategy, cannot invade.
S * v
1RII *
What is the ESS for a Pathogen?
A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.
v
R0
What is the ESS for a Pathogen?
A strategy adopted by some kind of pathogen, for which an alternative (mutant) strategy, cannot invade.
v
R0
A strategy that maximizes the Basic Reproductive Ratio is evolutionarily stable (Anderson and May, 1982)
ESS for a Pathogen?
v
R0
What are the evolutionary tradeoffs faced by pathogens?
ESS for a Pathogen?
v
R0
What are the evolutionary tradeoffs faced by pathogens?
Pathogens should evolve to maximize the transmission rate and minimize the disease-induced death rate.
ESS for a Pathogen?
v
R0
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! ?
ESS for a Pathogen?
(v) v
R0
ESS for a Pathogen?
(v) v
R0
(v) v
ESS for a Pathogen?
(v) v
R0
(v) v
(v)
v
Tradeoff between transmission and killing the host
ESS for a Pathogen?
v
vR0
dR0dv
0
(v)
v
Maximize Ro with respect to v
v*
v*
*
ESS for Multiple Pathogens?
v
vR0
dR0dv
0
(v)
v
Maximize Ro with respect to v
v*
v*
*
ESS for Multiple Pathogens?
(v) v
R0
ESS for Multiple Pathogens?
(v1) v1 v2
R0
ESS for Multiple Pathogens?
v1 v1 v2
R01
gv2 v2
v1 v2R0
2
ESS for Multiple Pathogens?
v1 v1 v2
R01
Maximize Ro with respect to v
v1* v2
dR01
dv10
v2* ( v1)
gv2 v2
v1 v2R0
2
dR02
dv20
ESS for Multiple Pathogens?
v1* v2
dR01
dv10
v2* ( v1)
dR02
dv20
ESS for Multiple Pathogens?
v1* v2
dR01
dv10
v2* ( v1)
dR02
dv20
v *1
v2
v1
v1(v2)
ESS for Multiple Pathogens?
v *1
v2
v1
v1(v2)
v1* v2
dR01
dv10
v2* ( v1)
dR02
dv20
v2(v1)
ESS for Multiple Pathogens?
v *1
v2
v1
v1(v2)
v1* v2
dR01
dv10
v2* ( v1)
dR02
dv20
v *2
v2(v1)
ESS for Multiple Pathogens?
v *1
v2
v1
v1(v2)
v1* v2
dR01
dv10
v2* ( v1)
dR02
dv20
v *2
v2(v1)
CoESS
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.