DISEASE E&E (Virulence) Flashcards

(41 cards)

1
Q

Virulence score:

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Variation in virulence among strains of same pathogen:

A

-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

H1N1 and H5N1 strains of influenza:

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Parasite/pathogen ecological definition

A

-an infectious agent that decreases host fitness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Virulence definition:

A

-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mortality rates of uninfected an infected hosts:

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Avirulence theory:

A

-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Modern virulence theory:

A

-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

R0 for pathogen with virulence:

A

-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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Virulence-transmission trade-off:

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Virulence-transmission trade-off: graph

A

-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Pathogen with low vs. high abundance:

A

-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Relationship between parasite fitness (R0) and virulence:

A

-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Linear or accelerating relationships between transmission and virulence:

A

-no intermediate optimum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Stages of HIV infection:

A
  1. Infected but not infectious
  2. Infectious but not ill
  3. AIDS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

infected but not ill:

A

-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)

18
Q

Once develop AIDS:

A

-decrease sexual activity because they are too ill

19
Q

SPVL:

A

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

20
Q

SPVL affects:

A
  1. Transmission
  2. Duration of infectious stage
21
Q

HIV transmission increases with SPVL:

A

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

22
Q

Duration of asymptomatic infection and SPVL:

A

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

23
Q

Intermediate SPVL:

A

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

24
Q

LTP:

A

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

25
Low SPVL=
-lower LTP >due to transmission rate per sex act is low
26
High SPVL=
>duration of infectious period is too short
27
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)
28
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
29
Clearance rate (v):
-rate at which host immune system clears infection
30
Avirulent strain: virulence-clearance trade-off
-low virulence (alpha) -high clearance rate *cleared too quickly
31
Virulent strain: virulence-clearance trade-off
-high virulence (alpha) -not cleared by the host immune system *but high virulence causes host death
32
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
33
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
34
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
35
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%
36
Drop in rabbit size (MYXV)
-changed optimal virulence and clearance -induced strong evolution in rabbit population *test on avirulence theory=contradicted
37
Virulence of MYXV:
-evolved over time -decreased in 1950s (support avirulence theory -increased over time (1960-1990) *increase in virulence=contradicts avirulence theory
38
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
39
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
40
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
41
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