Theoretical Ecology

, Volume 7, Issue 3, pp 299–311 | Cite as

Evolution of acuteness in pathogen metapopulations: conflicts between “classical” and invasion-persistence trade-offs

  • Sourya Shrestha
  • Ottar N. Bjørnstad
  • Aaron A. King


Classical life-history theory predicts that acute, immunizing pathogens should maximize between-host transmission. When such pathogens induce violent epidemic outbreaks, however, a pathogen’s short-term advantage at invasion may come at the expense of its ability to persist in the population over the long term. Here, we seek to understand how the classical and invasion-persistence trade-offs interact to shape pathogen life-history evolution as a function of the size and structure of the host population. We develop an individual-based infection model at three distinct levels of organization: within an individual host, among hosts within a local population, and among local populations within a metapopulation. We find a continuum of evolutionarily stable pathogen strategies. At one end of the spectrum—in large well-mixed populations—pathogens evolve to greater acuteness to maximize between-host transmission: the classical trade-off theory applies in this regime. At the other end of the spectrum—when the host population is broken into many small patches—selection favors less acute pathogens, which persist longer within a patch and thereby achieve enhanced between-patch transmission: the invasion-persistence trade-off dominates in this regime. Between these extremes, we explore the effects of the size and structure of the host population in determining pathogen strategy. In general, pathogen strategies respond to evolutionary pressures arising at both scales.


Evolution of infectious pathogens Invasion-persistence trade-off Metapopulation model Acute infections Individual-based model Bordetellae 



Financial support was provided by the Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, US Department of Homeland Security, and the Fogarty International Center, US National Institutes of Health. AAK acknowledges the support of the National Institutes of Health (grant #1-R01-AI-101155).


  1. Alizon S, van Baalen M (2005) Emergence of a convex trade-off between transmission and virulence. Am Nat 165(6):E155–E167. doi:10.1086/430053 PubMedCrossRefGoogle Scholar
  2. Antia R, Levin BR, May RM (1994) Within-host population dynamics and the evolution and maintenance of microparasite virulence. Am Nat 144(3):457–472CrossRefGoogle Scholar
  3. Ball F, Neal P (2002) A general model for stochastic SIR epidemics with two levels of mixing. Math Biosci 180:73–102. doi:10.1016/S0025-5564(02)00125-6 PubMedCrossRefGoogle Scholar
  4. Ball F, Mollison D, Scalia-Tomba G (1997) Epidemics with two levels of mixing. Ann Appl Probab 7:46–89. doi:10.1214/aoap/1034625252 CrossRefGoogle Scholar
  5. van Ballegooijen WM, Boerlijst MC (2004) Emergent trade-offs and selection for outbreak frequency in spatial epidemics. Proc Natl Acad Sci USA 101(52):18,246–18,250. doi:10.1073/pnas.0405682101 CrossRefGoogle Scholar
  6. Bjørnstad ON, Harvill ET (2005) Evolution and emergence of Bordetella in humans. Trends Microbiol 13(8):355–359. doi:10.1016/j.tim.2005.06.007 PubMedCrossRefGoogle Scholar
  7. Bjørnstad ON, Finkenstädt BF, Grenfell BT (2002) Dynamics of measles epidemics: estimating scaling of transmission rates using a time series SIR model. Ecol Monogr 72(2):169–184. doi:10.1890/0012-9615(2002)072[0169:DOMEES]2.0.CO;2 CrossRefGoogle Scholar
  8. Black F (1975) Infectious diseases in primitive societies. Science 187(4176):515–518. doi:10.1126/science.163483 PubMedCrossRefGoogle Scholar
  9. Black FL, Hierholzer WJ, Pinheiro F, Evans AS, Woodall JP, Opton EM, Emmons JE, West BS, Edsall G, Downs WG, Wallace GD (1974) Evidence for persistence of infectious agents in isolated human populations. Am J Epidemiol 100(3):230–250PubMedGoogle Scholar
  10. Boldin B, Diekmann O (2008) Superinfections can induce evolutionarily stable coexistence of pathogens. J Math Biol 56(5):635–672PubMedCrossRefGoogle Scholar
  11. Boots M, Sasaki A (1999) Small worlds and the evolution of virulence: infection occurs locally and at a distance. Proc R Soc Lond B 266(1432):1933–1933. doi:10.1098/rspb.1999.0869 CrossRefGoogle Scholar
  12. Boots M, Hudson PJ, Sasaki A (2004) Large shifts in pathogen virulence relate to host population structure. Science 303(5659):842–844. doi:10.1126/science.1088542 PubMedCrossRefGoogle Scholar
  13. Coombs D, Gilchrist M, Ball C (2007) Evaluating the importance of within- and between-host selection pressures on the evolution of chronic pathogens. Theor Popul Biol 72(4):576–591. doi:10.1016/j.tpb.2007.08.005 PubMedCrossRefGoogle Scholar
  14. Cross PC, Lloyd-Smith JO, Johnson PLF, Getz WM (2005) Duelling timescales of host movement and disease recovery determine invasion of disease in structured populations. Ecol Lett 8(6):587–595. doi:10.1111/j.1461-0248.2005.00760.x CrossRefGoogle Scholar
  15. Cross PC, Johnson PLF, Lloyd-Smith JO, Getz WM (2007) Utility of R 0 as a predictor of disease invasion in structured populations. J R Soc Interface 4:315–324. doi:10.1098/rsif.2006.0185 PubMedCentralPubMedCrossRefGoogle Scholar
  16. Ewald PW (1993) The evolution of virulence. Sci Am 268:8CrossRefGoogle Scholar
  17. Ferrari M, Perkins S, Pomeroy L, Bjørnstad O (2011) Pathogens, social networks, and the paradox of transmission scaling. Interdisciplinary perspectives on infectious diseases 2011:267,049. doi:10.1155/2011/267049
  18. Ganusov VV, Antia R (2003) Trade-offs and the evolution of virulence of microparasites: do details matter? Theor Popul Biol 64(2):211–220. doi:10.1016/S0040-5809(03)00063-7 PubMedCrossRefGoogle Scholar
  19. Gilchrist MA, Coombs D (2006) Evolution of virulence: Interdependence, constraints, and selection using nested models. Theor Popul Biol 69(2):145–153. doi:10.1016/j.tpb.2005.07.002 PubMedCrossRefGoogle Scholar
  20. Gilchrist MA, Sasaki A (2002) Modeling host-parasite coevolution: a nested approach based on mechanistic models. J Theor Biol 218(3):289–308. doi:10.1006/yjtbi.3076 PubMedCrossRefGoogle Scholar
  21. Grenfell BT (2001) Dynamics and epidemiological impact of microparasites. In: l Smith G, Irving WL, McCauley JW, Rowlands DJ (eds) New challenges to health: the threat of virus infection. Cambridge University Press, Cambridge, pp 33–52CrossRefGoogle Scholar
  22. Higham DJ (2008) Modeling and simulating chemical reactions. SIAM Rev 50(2):347–368. doi:10.1137/060666457 CrossRefGoogle Scholar
  23. Keeling MJ (2000) Evolutionary trade-offs at two time-scales: competition versus persistence. Proc R Soc Lond B 267:385–391. doi:10.1098/rspb.2000.1013 CrossRefGoogle Scholar
  24. King AA, Shrestha S, Harvell ET, Bjørnstad ON (2009) Evolution of acute infections and the invasion-persistence trade-off. Am Nat 173:446–455. doi:10.1086/597217 PubMedCentralPubMedCrossRefGoogle Scholar
  25. Levin S, Pimentel D (1981) Selection of intermediate rates of increase in parasite-host systems. Am Nat 117(3):308–315CrossRefGoogle Scholar
  26. May RM, Anderson RM (1983) Parasite-host coevolution. In: Futuyma D J, Slatkin M (eds) Coevolution, Sinauer. Mass, SunderlandGoogle Scholar
  27. Mira A, Pushker R, Rodriguez-Valera F (2006) The Neolithic revolution of bacterial genomes. Trends Microbiol 14(5):200–206. doi:10.1016/j.tim.2006.03.001 PubMedCrossRefGoogle Scholar
  28. Morozov A, Best A (2012) Predation on infected host promotes evolutionary branching of virulence and pathogens’ biodiversity. J Theor Bio 307:29–36CrossRefGoogle Scholar
  29. Pilyugin SS, Antia R (2000) Modeling immune responses with handling time. Bull Math Biol 62:869–890. doi:10.1006/bulm.2000.0181 PubMedCrossRefGoogle Scholar
  30. Rand DA, Keeling MJ, Wilson HB (1995) Invasion, stability and evolution to criticality in spatially extended, artificial host-pathogen ecologies. Proc R Soc Lond B 259:55–63. doi:10.1098/rspb.1995.0009 CrossRefGoogle Scholar
  31. Svennungsen TO, Kisdi E (2009) Evolutionary branching of virulence in a single-infection model. J Theor Bio 257(3):408–418CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Sourya Shrestha
    • 1
    • 2
  • Ottar N. Bjørnstad
    • 3
    • 5
  • Aaron A. King
    • 1
    • 2
    • 4
    • 5
  1. 1.Department of Ecology and Evolutionary BiologyUniversity of MichiganAnn ArborUSA
  2. 2.Center for the Study of Complex SystemsUniversity of MichiganAnn ArborUSA
  3. 3.Department of Entomology and BiologyPennsylvania State UniversityUniversity ParkUSA
  4. 4.Department of MathematicsUniversity of MichiganAnn ArborUSA
  5. 5.Fogarty International CenterNational Institutes of HealthBethesdaUSA

Personalised recommendations