DISEASE E&E (Virulence) Flashcards
Virulence score:
-pathogens differ greatly in morbidity and mortality
-low: common virus
-high: malaria
There is no grand theory of virulence because pathogens differ greatly in their:
-taxonomic diversity
-evolutionary history in human hosts
-mode of transmission
Variation in virulence among strains of same pathogen:
-strains can differ in virulence
-virulence theory explains differences among strains rather than among pathogen species
-easier to explain differences between two things that are mostly the same
H1N1 and H5N1 strains of influenza:
H1N1
-mild symptoms and low CFR
-nose and throat (cannot cause serious disease)
H5N1
-circulates in birds and 60% CFR in humans
-infects lungs and causes rapid progression to pneumonia
>reduces person-to-person transmissibility
*evolutionary virulence theory provides general explain and not underly genetic mechanisms
Parasite/pathogen ecological definition
-an infectious agent that decreases host fitness
Virulence definition:
-pathogen-caused reduction in host fitness
-seen as a TRAIT of a pathogen, but measured in the host
Ex. reduction in host survival and/or host reproduction
Mortality rates of uninfected an infected hosts:
-uninfected: rates of mu
-infected: mu + alpha (pathogen induced mortality: virulence)
Avirulence theory:
-host is the environment of the parasite
-a ‘good’ parasite should not kill its host
-virulence is high in new host-parasite interactions
-over time parasite and host will adapt so that the virulence will decrease
*BUT, many endemic infectious diseases (ex. malaria, tuberculosis) have NOT EVOLVED to become less deadly
Modern virulence theory:
-uses epidemiological models to determine the optimal level of virulence for a pathogen
*critical component is trade-offs between pathogen traits of transmission (beta), recovery (v) and virulence (alpha)
-micro-evolutionary explanation for virulence: not concerned with genes
R0 for pathogen with virulence:
-assume that pathogen increases mortality by amount alpha (virulence)
>mortality rate=mu + alpha (for S or R hosts it is mu)
*pathogen should maximize R0: maximize beta, minimize v (recovery) and alpha (virulence)
Virulence-transmission trade-off:
-reduction in host-survival (virulence) is an unavoidable consequence of pathogen replication
-this negative association=evolutionary trade-off for the pathogen
Virulence-transmission trade-off: graph
-transmission (beta) increases with host exploitation (virulence, alpha)
-assumption: transmission is a decelerating function of virulence (parasite induced-mortality rate)
*after a certain point, increasing virulence has diminishing returns on transmission
*need to have a strategy to balance virulence and transmission rate
Pathogen with low vs. high abundance:
-low: long duration of infection (good), but low transmission (bad)
-high: high transmission (good), but host has a short lifespan (bad)
*optimal=balance virulence and abundance so that transmission success is maximized over lifetime of infection
Relationship between parasite fitness (R0) and virulence:
-maximum value of R0 occurs at an intermediate of virulence (parasite-induced host mortality rate)
>due to concave relationship between transmission rate and virulence
*pathogens should evolve an intermediate level of virulence that balances benefits of transmission and duration of infection
Linear or accelerating relationships between transmission and virulence:
-no intermediate optimum
Stages of HIV infection:
- Infected but not infectious
- Infectious but not ill
- AIDS
infected but not ill:
-duration is highly variable (2-15 years)
-most important for HIVE fitness as an infected individual can transmit HIV to partners and is healthy enough to engage in sexual activity
*virus persists at stable abundance in the host=set-point viral load (SPVL)
Once develop AIDS:
-decrease sexual activity because they are too ill
SPVL:
-set-point viral load
-enormous variation of HIV in humans during infectious period
>100-10 million
-is the viral copies per mL of blood
SPVL affects:
- Transmission
- Duration of infectious stage
HIV transmission increases with SPVL:
-concave relationship between viral load and transmission
-certain plateaus of transmission for ranges of viral load
Duration of asymptomatic infection and SPVL:
-decreases with SPVL
-HIV transmission occurs in infectious period
-low SPVL: longer infection period=more time to transmit HIV than individuals with high SPVL
Intermediate SPVL:
-patients with it have the highest lifetime transmission potential (LTP)
LTP:
-lifetime transmission potential
=number of people one infected person could infect over duration of the infectious period
=transmission rate x duration of infectious period
Low SPVL=
-lower LTP
>due to transmission rate per sex act is low
High SPVL=
> duration of infectious period is too short
Summary of HIV example:
-evolved intermediate virulence in human host to maximize its LT
*example of virulence-transmission trade-off
-higher virulence increases rate, but decreases duration of infectious period
-trade-off mediated by titer of HIV inside the host (SPVL)
Virulence-clearance trade-off:
-trade off between virulence (alpha) and clearance rate/recovery rate (v)
-could be mediated by pathogen abundance in host tissues
*optimal: balance virulence and clearance to maximize LR success
Clearance rate (v):
-rate at which host immune system clears infection
Avirulent strain: virulence-clearance trade-off
-low virulence (alpha)
-high clearance rate
*cleared too quickly
Virulent strain: virulence-clearance trade-off
-high virulence (alpha)
-not cleared by the host immune system
*but high virulence causes host death
MYXV: virulence-clearance trade-off
-negative relationship (trade-off) between virulence and clearance rate
-clearance/recovery is a decelerating function of parasite virulence
*intermediated virulence will produce highest lifetime fitness for parasite
R0 and virulence for MYXV (in wild rabbit populations in Australia):
-intermediate virulence=highest reproductive rate
-low virulence: didn’t kill host, but are rapidly cleared by host immune system
-high virulence: resist clearance by host, but kill host too quickly
*example of virulence-clearance trade-off
MYXV in Australian rabbits:
-myxoma virus
-rabbits were introduced to Australia in 1859
-population grew and caused severe damage to agriculture
-country imported MYXV to control rabbit population
*great example of how pathogen virulence can evolve over time
Myxomatosis as biocontrol
-Australian rabbits had no recent experience with myxomatosis
-develop skin tumors, blindness, fever and usually die within 14days
-transmitted by arthropod vectors and via direct contact
-600million to 100mill in 2 years
>CFR was 99%
Drop in rabbit size (MYXV)
-changed optimal virulence and clearance
-induced strong evolution in rabbit population
*test on avirulence theory=contradicted
Virulence of MYXV:
-evolved over time
-decreased in 1950s (support avirulence theory
-increased over time (1960-1990)
*increase in virulence=contradicts avirulence theory
Explanation of decrease in MYXV virulence?
-following the introduction of MYXV the population decreased
-lower population density=takes more time for infected and uninfected rabbits to contact each other
>selected for MXYV with less virulent and longer infectious period
>early death due to virulence=bigger problem than death due to clearance
Evolution of resistance in rabbit hosts:
-induced strong selection on wild rabbits to evolve resistance
-resistance increased from 1950s-1990s
-immune system evolved and became better at clearing MYXV
-MYXV evolved higher virulence to avoid clearance
When host evolves higher resistance to parasite:
*selects for higher pathogen virulence
-recovery rate resistant in ‘evolved’ rabbits is higher compared to susceptible ‘ancestral’ rabbits
-duration is shorter in ‘evolved’ rabbits
*to reach optimal level of recovery in wild rabbits, the virus can evolve a higher level of virulence
MYXV example: summary
-show virulence-clearance trade-off
-reduced host density selected for lower virulence
-higher host resistance selected for increased virulence
-evolution of increased virulence contradicts avirulence theory
