Evolution of virulence

Why are some parasites so virulent and others so mild?

Conventional wisdom

“Given enough time a state of peaceful coexistence eventually becomes established between any host and parasite.” –Rene Dubos (1965)

“Disease usually represents the inconclusive negotiation for symbiosis…a biological misinterpretation of borders.” –Lewis Thomas (1972)

“The ideal of parasitism is actually commensalism”

-Paul D. Hoeprich (1989)

Pathogens have an evolutionary edge

• Rapid replication rate relative to host

• Many mechanisms of increasing genetic variability

• Sporulation and biofilms– Long-term durability in the environment

Segmented genome with recombining fragments

Variable repeats, e.g. ATATATATATAT

Cassette switching (Neisseria, trypanosomes)

Mechanisms of variation

Plasmids and viruses

“Competence” = picking up foreign DNA from environment

Parasite fitness is dependent upon transmission to susceptible hosts

Why virulence evolves• Correlation between replication rate of pathogen

and harm to host (presumed, poorly supported)

• Faster replication = better competition within hosts

• Slower replication = better competition between hosts??

• What is the evolutionarily stable strategy (ESS?)(Does this tradeoff sound familiar?)

What is required for a pathogen to invade a species and cause a new epidemic?

• The basic reproductive number (R0) must evolve to exceed 1.

• http://en.wikipedia.org/wiki/Basic_reproduction_number

How epidemics might be founded

• Following introduction to a host population, pathogens must be spread

• Could certain individuals serve as “stepping stones?”

• Persistent spread requires R0 > 1

• R0 may increase by changes in host density, altered host behavior, or increased genetic susceptibility

• Genetic changes in the pathogen could also alter R0

Survey of parasite strategies

• Direct transmission (host-to-host contact)

• Vectorborne (versus direct transmission)– Malaria, dengue, sleeping sickness, etc et– Human factors (contaminated water) can serve as a vector

• Vertical transmission (versus horizontal)– Lots of plant pathogens transmitted through

seed

• “Sit and wait” (durable pathogens)– Anthrax, baculoviruses

Other examples of pathogen strategy

• Intracellular immune avoidance = sit and wait– Mycobacterium tuberculosis and M. leprae– Legionella– Rickettssia pathogens (e.g typhus, Rocky Mtn spotted fever)

• Attendant-borne transmission = vectorborne– Group B Strep, Staph (esp. MRSA), Serratia, Klebsiella – Canine parvovirus– Agricultural pathogens (Cadang-cadang, Ilarviruses)

Parasite fitness is dependent upon transmission to susceptible hosts

Each of these strategies offer distinct evolutionary predictions

Is the current host-pathogen relationship optimal from the parasite’s perspective?

• Alternative hypotheses (sensu Ewald 1994): Restricted adaptation (insufficient time)Adaptive severity

• Mode of transmission– Is host mobility critical for transmission or not?

Why virulence may increase when hosts are dense

• (i) The extinction rate of virulent lineages may decline because ‘herd immunity’ is less likely to reduce the pool of susceptibles below a critical transmission threshold for parasite maintenance (Fine 1993).

• (ii) High host density may reduce the dependence on host mobility for transmission and permit greater host exploitation (Ewald 1994; Lenski & May 1994).

• (iii) Virulent variants may gain a numerical advantage during epidemic spread because of more frequent transmission (Anderson 1991).

• (iv) Transmission during the early stage of an infection may be enhanced.

Timing of transmission and the evolution of virulence of an insect virus

• System: Lymantria dispar (gypsy moth) NPV• Experimenters: 3 consecutive years of

Amherst College undergraduate honors students• Treatments: Early versus Late Transmission• Transmission simulated early versus late, 9 cycles of

transmission

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Early Late Gypchek

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Per

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larv

al m

oral

ityViruses transmitted early became more lethal

5 days post-inoculation Larval death or pupation0.1

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Time of Viral Harvest

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Late

12.2mg 14.5mg

14.0 days

721.3mg

25.9 days

1946.6mg

Viruses transmitted late were more productive

How do these dynamics play out in an ecologically structured population?

• Superinfection = two strains of the same pathogen co-infecting and competing within the same host

• Between host competition = parasite populations within different hosts will compete over the longer term– Parasites within hosts, while related, will still act selfishly

given sufficient genetic variance

• These two dynamics may play against each other in an ecological “metapopulation” setting

• What virus strategy will succeed when hosts are dense? When hosts are rare?