Why are pathogens not more virulent? Conventional wisdom (and one of the key mathematical models in the ecological and evolutionary theory of infectious diseases) is that evolution removes excessively lethal Strains. Pathogens that kill their hosts too rapidly shorten their own infectious periods and hence have lower evolutionary fitness than less lethal strains. If so, what happens when vaccines protect hosts from death? Gould immunization enable the circulation of strains that would once have been removed by natural selection? That would increase the net virulence of pathogen population experienced by unvaccinated hosts. The 'evolutionary risk'of public and animal health measures cannot be directly assessed in clinical trials because pathogen evolution will be seen only after population-wide implementation. We have recently shown experimentally that vaccination does indeed make possible the onward transmission of hyperpathogenic strains of Marek's disease virus (MDV) in poultry. We seek to now to dissect the effects of immunization on the ecology of transmission in this farm animal system, so as to evaluate the impact of contemporary and next generation vaccines on the future evolution of this disease. We will fuse experimental measurements of virus transmission from vaccinated and unvaccinated birds, field investigations of farm epidemiology and mathematical evolutionary-epidemiological models. Our primary objective is to dissect the selective forces imposed by immunization and other management pratices on MDV virulence, and to evaluate their evolutionary and epidemiological consequences. This will make it possible to use evolutionary epidemiological models to analyze evolutionary trajectories and to assess the evolutionary consequences of contrasting management strategies on the evolution of MDV and other pathogens. The biology and ecological context of MDV offer unprecedented scientific opportunities.
We aim to make MDV a canonical case study of pathogen adaptation and disease emergence in response to human-induced environmental change.

Public Health Relevance

Our work will make it possible to evaluate the risk that some types of vaccines allow pathogens to circulate which are so virulent that they would normally be removed by natural selection. The emergence of high-path farm animal diseases can have implications for animal and human health (e.g. avian influenza) - and it is also possible next generation human vaccines might drive the evolution of more virulent pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM105244-02
Application #
8554371
Study Section
Special Emphasis Panel (ZRG1-IDM-U (55))
Program Officer
Eckstrand, Irene A
Project Start
2012-09-28
Project End
2017-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$237,728
Indirect Cost
$75,363
Name
Pennsylvania State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802