Virulence vs. Transmission Trade-off

R_0 Fitness

• R_0 = The expected number of secondary cases produced by a single infected individual in a completely susceptible population

• Fitness of a pathogen can be measured by R_0

• R_0 = S*beta*L

R_0 Considering Virulence

• L (length of infectious period) is inversely related to:

  • Rate of recovery of the infection v

  • The host’s pathogen- induced mortality rate (i.e., virulence) alpha the host’s natural mortality rate mu

• R_0 = (Beta*N)/(mu+alpha+v)

• R_0 would be maximized if alpha is minimized, or as alpha → 0

  • Natural selection favors lower alpha (ideally alpha = 0)

  • Fits the hypothesis that virulence for emergent new pathogens will decrease over time

Virulence-Transmission Trade-Off

• The harm that a pathogen inflicts on its host through a decrease in host fitness is an unavoidable cost to the pathogen for using the host resources for replication

• The cost increases mortality rates, which translates into a shorter infection period in the population

• Overall transmission should be the greatest at intermediate levels of virulence, which balances the costs of within-host replication and benefits of infectious period length

R_0 and Virulence-Transmission Trade-Off

• Recovery and transmission rates are functions of virulence

• Host may recover more quickly from less virulent strains

• Decreasing alpha (virulence) may not necessarily increase R_0 because v_alpha will increase as well

R_0 = ((Beta_alpha)*N)/(mu+alpha+v_alpha)

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• Virulent strains could be better at transmission (beta) because there is more in-host replication (higher “viral load”)

• Positive relationship between within-host replication rate and transmission (beta)

• Positive relationship between within-host replication rate and host resources used

• Virulence is positively coupled with transmission probability (I.e., when one increase/decreases, the other is doing the same)

Virulence-Transmission Summary

• It all parameters were independent, benign parasites would evolve

• Natural selection would favor highly transmissible, incurable commendable or even mutualists

• On the other hand, if transmission and virulence were positively coupled, some level of virulence will be favored

• In other words, if higher virulence were linked to increased rate of transmission, there would be a trade-off between this benefit versus the cost of reducing the time that an infected individual could transmit its pathogen

Case Study: Myxoma Virus

• Pox virus introduced into Australia to control European rabbit populations

• Vectored by mosquitos and fleas, skin lesions

• Initially the virus was extremely virulent (e.g., 90%+ mortality)

• Subsequently, there was a sharp drop in virulence (~50% mortality)

  
  

Virulence of Myxoma Virus

1. High survival = Low virulence

2. Australian field strains injected into lab rabbits dropped to intermediate levels

3. Wild strains 30/42 never as virulent as artificially lab strains

Transmission & Mortality in Myxoma

• Positive coupling: notably focused between transmission and virus-induced mortality

• Trade off between virulence and transmission:

  • highly virulent forms killed too quickly, low virulent forms were too attenuated (mild) had fewer lesions and lower viral load → each extreme reduced the chance of being picked up by vector

• intermediate virulence:

  • “Happy medium” was selected for, rather than more benign forms

    
    

    
    

Expected “Intermediate Virulence”

• Changes in rates of infectious transmission will select for parasite strains or species with different levels of virulence

• Assumed parasite virulence is constrained solely by the need to keep the host alive long enough to facilitate transmission to next host

Vector Borne vs Direct Transmission

• Vectored diseases should have a higher optimal virulence than directly transmitted ones

• Immobilizing the host does not prevent, and may even enhance, transmission

• Evidence that insect-vectored diseases are more virulent (e.g., higher mortality rates)

More Hypothetical Predictions

• Diseases that spread by “cultural vectors” should also tend to high virulence

• Cultural vectors are any mixture of behavior and environmental conditions that allow immobilized hosts to transmit infections

• For example, diarrheal pathogens can be passed through drinking water systems (an immobilized victim can still infect lots of people if contaminated materials get into drinking water)

Case Study: Broad Street Epidemic

• Cholera was thought to be caused by miasma (bad air)

• Discovered could be spread by water in London (1853)

• In one week, 600+ people near Broad Street died of Cholera

• Mapping locations of cholera cases, John Snow determined the source was a single water pump

• When the pump was closed, the epidemic ceased

• Discovery likely led to the “birth of epidemiology”