W7 L2 virulence

Question 1

How do disease outbreaks end

Answer 1

• Changes in the host:
• Development of resistance
• Destruction of population
• Changes in the pathogen:
• Cessation of transmission
• Reduction in virulence (harm)

Question 2

Acquisition of resistance In host

Answer 2

• Rapid evolution of pathogens can limit adaptive response
• Selection on ‘standing variation’ may increase pathogen resistance, sometimes with important ongoing effects
• Acquired immune systems (vertebrate antibody response, bacterial/archaeal CRISPR) play central roles in pathogen resistance

Question 3

Population loss

Answer 3

• Of most concern in populations with very low genetic diversity - crop monocultures, but also severely endangered species
• Fixation of an optimal phenotype in a given environment does not assist long-term survival in a changing world

Question 4

Selection pressure on virulence

Answer 4

• Does a pathogen benefit from killing its host? What about causing serious but temporary illness?
• The ‘law of declining virulence’ -evolutionary pressure to develop towards commensalism to avoid risk of killing host
• In the early twentieth century, adaptation to the host was regarded by some as so systematic that pathogenicity was itself evidence of a novel interaction

Question 5

Myxoma virus in Australia

Answer 5

• Biological control as a means of reducing the numbers of rabbits in Australia was first considered in the late nineteenth century
• The mosquito-borne myxoma virus causes benign skin tumours in its natural host, the cottontail rabbits
• After numerous unsuccessful attempts, myxoma was established in Australia by late 1951, initially showing 99.8% lethality
• Five virulence grades were observed in the 1950s, with the’intermediate’ strain III the most successful
• This could represent the start of further
  decline in virulence, but…
• Lethality of myxoma virus in Australia has since increased - isolates from the 1990s, but not from the 1950s, induce immune collapse in susceptible rabbits

Question 6

Trade off in pathogen

Answer 6

• Numerous factors drove a shift toward embrace of trade-offs in explaining pathogen evolution, e.g. the emergence of AIDS, evidence of increasing virulence in dengue
• Introduction of more complex mathematical modelling to ecological questions also played an important role

Question 7

What connects increases in virulence and increase in transmission

Answer 7

• Some studies have assumed that higher transmission by more virulent pathogens is a consequence of greater infection duration alone
• In some cases, virulence may be the result of higher pathogen load, which can increase transmission rates
• However, under certain circumstances virulence can also decrease transmission

Question 8

complicating factor in the trade offs

Answer 8

• Competition within pathogen populations
• Mode of transmission affects how debilitating a pathogen can ‘afford’ to be
• Host evolution in response to disease may modify the selective pressures acting on pathogens
• Immune system-modifying technology can produce a more variable selective landscape for pathogens

Question 9

Inter-pathogen competition

Answer 9

• Competition between pathogens often favours those which reproduce most effectively - this will often increase virulence
• Bacterial meningitis - caused by the spread of various (usually harmless) bacterial species from the nose and upper throat into the blood and cerebrospinal fluid
• Greater habitat flexibility provides a short-term advantage in competition with other bacteria, but ultimately leads to a dead-end

Question 10

Indirect pathogen spread

Answer 10

• Many diseases can be transmitted through water supplies, especially in areas where water treatment is limited
• Vector-borne diseases are transmitted between individuals of the ‘primary’ host species by an ‘intermediate’ host (e.g. Anopheles mosquitoes in the case of malaria)

Question 11

Pathogen effects on host evolution

Answer 11

• Clear signs of unusually rapid evolution in many rabbit genes encoding immune system proteins following exposure to myxoma virus
• Increased virulence in myxoma was likely a response to such host shifts - further biological control methods (calicivirus) have since been introduced

Question 12

The role of the immune system and how does pathigen bypass it

Answer 12

• The immune system is able to clear many infections, though some pathogens are able to escape immune surveillance in various ways:
• Exploiting niches not under immune surveillance (e.g. malaria liver stages)
• Synthesis of proteins which block innate immune processes (e.g. bacterial inflammatory suppression)
• Synthesis of proteins which block acquired immune processes (e.g. HIV Nef prevents display of intracellular proteins for MHC checking)

Question 13

Evolutionary responses to vaccination

Answer 13

• ‘Leaky’ vaccines reduce disease virulence within vaccinated individuals, but do not prevent transmission - vaccinated individuals could serve as reservoirs for strains lethal in unvaccinated individuals
• Faster immune response could also favour rapidly reproducing strains
• Clearest example of increased virulence in response to vaccination is Marek’s disease virus in chickens

Question 14

Can we manipulate virulence evolution

Answer 14

• Some policies which have been proposed as means of reducing virulence levels are beneficial for other reasons (e.g. improving water sanitation)
• Others, such as avoiding use of vaccines which cannot suppress pathogen transmission at very high levels, would likely do substantial harm
• What level of confidence would we need in our understanding of how transmission and virulence are related in a given context to support the latter approaches?