Transcript Oct 12 Lecture 12 Evolution of Virulence

Lecture 15
Evolution of virulence I
Today and next class:
• Midterm next Thursday.
• The “conventional wisdom” on virulence
• Modern theories for how virulence evolves
and is maintained
Today and next class:
• R0: the “Basic reproductive number” of a
pathogen
• The trade-off hypothesis and Paul Ewald’s
view: route and timing of transmission
determines virulence
• Transmission and virulence de-coupled:
coincidental evolution
• Transmission and virulence de-coupled:
Short-sighted evolution
evolution of virulence
•
Virulence is the harm done by a pathogen to the
host following an infection; parasite-mediated
morbidity and mortality in infected hosts
•
“Harm” here can mean specific symptoms and
pathologies (clinician’s definition) or a reduction in
host fitness (population biologist’s definition)
•
Virulence varies dramatically among pathogens
•
Some, like cholera and smallpox, are often lethal
•
Others, like herpes viruses and cold viruses, may
produce no symptoms at all
Evolution of virulence
•
Why are some microbes commensal and others
pathogenic?
•
What causes qualitative and quantitative variation
in disease symptoms?
•
There are three (modern) general models to
explain the evolution of virulence, the trade-off
hypothesis, the coincidental evolution
hypothesis, and the short-sighted evolution
hypothesis
•
Plus one old-fashioned idea that persists…
The conventional wisdom
1. Think globally, act locally.
2. Given enough time a state of peaceful coexistence
eventually becomes established between any host and
parasite.
-Rene Dubos
Quic kT i me™ and a
T IFF (Unc ompres s ed) dec ompres s or
are needed t o s ee thi s pi c ture.
The conventional wisdom
•
Biologists traditionally believed that all pathogen
populations would evolve toward ever-lower
virulence
•
Why?
Damage to the host must ultimately be detrimental to
the interests of the pathogens that live within it.
The conventional wisdom
•
The logic behind this view is pleasing to human
sensibilities: a fully-evolved parasite would not
harm the host it needs for its survival, proliferation,
and transmission
•
The corollary is that pathogenesis is evidence of
recent associations between parasites and their
hosts. Virulence is an indication that not enough
time has elapsed for a benign association to
evolve…Is this view correct?
The conventional wisdom
•
Many observations are consistent with the
conventional wisdom: Legionnaire’s disease,
Lyme disease, Ebola fever, and SARS are
consequences of human infection with symbionts
of other species that have recently jumped into
humans
•
In other older diseases, like rabies, humans play a
negligible role in the transmission of the parasite
The conventional wisdom
•
Other observations don’t fit so well, however.
•
For some virulent pathogens like Neisseria
gonorrhoeae humans are the unique or dominant
host and vector
•
For other, like the agents of malaria and
tuberculosis, there is evidence of a long
association with humans
•
Is “long” not long enough, or could it be that some
pathogens evolve to become increasingly
virulent?
The conventional wisdom
•
The conventional wisdom runs up against a big
problem when it comes to articulating the
mechanism responsible for the alleged
evolutionary pressure toward benign associations
•
For a parasite to evolve to become gentle and
prudent in its treatment of its host requires some
form of group selection since natural selection
operating at the level of the individual parasite
often favors virulence
The conventional wisdom
•
In the 1980s, evolutionary biologists realized that if
transmission and virulence were positively
coupled, natural selection acting on individuals
could favor the evolution and maintenance of
some level of virulence
•
It comes down to elucidating the relationship
between the rate of parasite-mediated mortality
and the rate of transmission. If the relationship is
positive, some level of virulence may be favored
•
In other words, if killing your host is correlated with
higher transmission, natural selection may well
favor virulence
Some basic epidemiological theory:
The compartmental approach distinguishes various
classes of hosts during an epidemic, and then tracks the
movement of individual hosts from one class to another:
Susceptible individuals S
Exposed individuals E
Infective individuals I
Removed individuals R
R0: The basic reproductive rate
The fundamental epidemiological quantity
R0 represents the average number of secondary
infections generated by one primary case in a susceptible
population
Can be used to estimate the level of immunization or
behavioural change required to control an epidemic
What R0 is required for an outbreak to persist?
What R0 must be brought about if an intervention is to be
successful?
R0: The basic reproductive rate
= rate constant of infectious transfer (transmissibility)
= density of the susceptible host population
= rate of parasite-induced mortality (virulence)
= rate of parasite-independent mortality
= rate of recovery
The post intervention R0 values were < 1.
What do you think happenned?
The trade-off hypothesis for the
evolution of virulence
•
The trade-off hypothesis: Natural selection should
strike an optimal balance between the costs and
benefits of harming hosts
•
There is a (virulence-related) trade-off between rate of
transmission and duration of infection
•
A virulent strain of parasite may increase in frequency
if, in the process of killing its hosts, it sufficiently
increases its chance of being transmitted
•
If all parameters were independent, benign
parasites would evolve
•
Natural selection would favor highly transmissible,
incurable commensals or even mutualists
•
On the other hand, if transmission and virulence
were positively coupled, some level of virulence
will be favored
•
In other words, if higher virulence were linked to
increased rate of transmission, there would be a
trade-off between this benefit versus the cost of
reducing the time that an infected individual could
transmit its pathogen.
= rate constant of infectious transfer (transmissibility)
= density of the susceptible host population
= rate of parasite-induced mortality (virulence)
= rate of parasite-independent mortality
= rate of recovery
The classis example: Myxoma virus
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Pox virus introduced into Australia to control
European rabbit populations
Vectored by mosquitos and fleas, skin lesions
Initially the virus was extremely virulent (99%)
mortality
A sharp drop in virulence was initially observed
However, the circulating virus remained much more
virulent than lab strains
Positive coupling between transmission and virusinduced mortality
Myxoma virus
•
Trade-off between virulence and transmission: highly
virulent forms killed too quickly, reducing chance of
being picked up by vector
•
Viruses that were too attenuated (mild) had fewer
lesions and lower viral load, again translating into
less chance of being picked up by vector
•
Happy medium selected for, rather than ever-more
benign forms
Paul Ewald’s view
•
Changes in rates of infectious transmission will
select for parasite strains or species with different
levels of virulence
•
Assumes parasite virulence is constrained solely
by the need to keep the host alive long enough to
facilitate transmission to the next host
•
How should this perspective apply to pathogens
with different modes of transmission (e.g. direct
versus indirect transmission)?
Paul Ewald’s view
•
All else being equal, vectored diseases ought to
have a higher optimal virulence than directlytransmitted ones since immobilizing the host does
not prevent (and may even enhance) transmission
•
There does seem to be some support for the idea
that insect-vectored diseases are more virulent