DISEASE E&E (Virulence)

Question 1

Virulence score:

Answer 1

-pathogens differ greatly in morbidity and mortality
-low: common virus
-high: malaria

Question 2

There is no grand theory of virulence because pathogens differ greatly in their:

Answer 2

-taxonomic diversity
-evolutionary history in human hosts
-mode of transmission

Question 3

Variation in virulence among strains of same pathogen:

Answer 3

-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

Question 4

H1N1 and H5N1 strains of influenza:

Answer 4

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

Question 5

Parasite/pathogen ecological definition

Answer 5

-an infectious agent that decreases host fitness

Question 6

Virulence definition:

Answer 6

-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

Question 7

Mortality rates of uninfected an infected hosts:

Answer 7

-uninfected: rates of mu
-infected: mu + alpha (pathogen induced mortality: virulence)

Question 8

Avirulence theory:

Answer 8

-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

Question 9

Modern virulence theory:

Answer 9

-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

Question 10

R0 for pathogen with virulence:

Answer 10

-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)

Question 11

Virulence-transmission trade-off:

Answer 11

-reduction in host-survival (virulence) is an unavoidable consequence of pathogen replication
-this negative association=evolutionary trade-off for the pathogen

Question 12

Virulence-transmission trade-off: graph

Answer 12

-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

Question 13

Pathogen with low vs. high abundance:

Answer 13

-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

Question 14

Relationship between parasite fitness (R0) and virulence:

Answer 14

-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

Question 15

Linear or accelerating relationships between transmission and virulence:

Answer 15

-no intermediate optimum

Question 16

Stages of HIV infection:

Answer 16

1. Infected but not infectious
2. Infectious but not ill
3. AIDS

Question 17

infected but not ill:

Answer 17

-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)

Question 18

Once develop AIDS:

Answer 18

-decrease sexual activity because they are too ill

Question 19

SPVL:

Answer 19

-set-point viral load
-enormous variation of HIV in humans during infectious period
>100-10 million
-is the viral copies per mL of blood

Question 20

SPVL affects:

Answer 20

1. Transmission
2. Duration of infectious stage

Question 21

HIV transmission increases with SPVL:

Answer 21

-concave relationship between viral load and transmission
-certain plateaus of transmission for ranges of viral load

Question 22

Duration of asymptomatic infection and SPVL:

Answer 22

-decreases with SPVL
-HIV transmission occurs in infectious period
-low SPVL: longer infection period=more time to transmit HIV than individuals with high SPVL

Question 23

Intermediate SPVL:

Answer 23

-patients with it have the highest lifetime transmission potential (LTP)

Question 24

LTP:

Answer 24

-lifetime transmission potential
=number of people one infected person could infect over duration of the infectious period
=transmission rate x duration of infectious period

Question 25

Low SPVL=

Answer 25

-lower LTP
>due to transmission rate per sex act is low

Question 26

High SPVL=

Answer 26

> duration of infectious period is too short

Question 27

Summary of HIV example:

Answer 27

-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)

Question 28

Virulence-clearance trade-off:

Answer 28

-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

Question 29

Clearance rate (v):

Answer 29

-rate at which host immune system clears infection

Question 30

Avirulent strain: virulence-clearance trade-off

Answer 30

-low virulence (alpha)
-high clearance rate
*cleared too quickly

Question 31

Virulent strain: virulence-clearance trade-off

Answer 31

-high virulence (alpha)
-not cleared by the host immune system
*but high virulence causes host death

Question 32

MYXV: virulence-clearance trade-off

Answer 32

-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

Question 33

R0 and virulence for MYXV (in wild rabbit populations in Australia):

Answer 33

-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

Question 34

MYXV in Australian rabbits:

Answer 34

-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

Question 35

Myxomatosis as biocontrol

Answer 35

-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%

Question 36

Drop in rabbit size (MYXV)

Answer 36

-changed optimal virulence and clearance
-induced strong evolution in rabbit population
*test on avirulence theory=contradicted

Question 37

Virulence of MYXV:

Answer 37

-evolved over time
-decreased in 1950s (support avirulence theory
-increased over time (1960-1990)
*increase in virulence=contradicts avirulence theory

Question 38

Explanation of decrease in MYXV virulence?

Answer 38

-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

Question 39

Evolution of resistance in rabbit hosts:

Answer 39

-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

Question 40

When host evolves higher resistance to parasite:

Answer 40

*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

Question 41

MYXV example: summary

Answer 41

-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