1. Modelling infectious agents in food webs Hans Heesterbeek

2. Small selection of examples from Selakovic, de Ruiter & H, submitted review

3. It would be hard to study the ecology of a natural system without this being influenced by infectious agents Only in recent decades have we started to explore these explicitly Theory to think about these influences is lagging behind

4. Picture collage: Ricardo Holdo Photo’s: John Fryxell Changes in the Serengeti ecosystem: increased tree cover since 1980’s

5. Serengeti ecosystem & rinderpest Holdo et al. PLoS Biology, 2009, 7(9), e1000210 Cascade: rinderpest disappears tree density increases in the ecosystem Via “the effect of rinderpest on a herbivore that does not even consume trees” (Holdo et al)

6. Unhealthy herd effect Work of Spencer Hall/Meghan Duffy Pictures and example from Duffy et al., Functional Ecol., 2011 Daphnia Predator produces chemical that induces larger body size in its prey, Daphnia. Larger Daphnia are more susceptible to a fungal parasite because of their increased feeding rate Larger infected Daphnia produce more fungal spores Body size and spore yield of Daphnia in presence of chemical compared to absence Chaoborus

7. CDV and Babesia in Serengeti lions

8. Dynamics lion population ’75-’05 From: Munson et al, 2008, PLoS One C,D: number of buffalo carcasses in lion diet Extensive herbivore deaths after extreme drought in 1993 (S) and 2000 (N) Red bars: outbreaks of CDV with massive lion mortality 1994, 2001 Grey bars: ‘silent’ outbreaks of CDV detected by serology (retrosp.)

9. Nematomorph parasites in crickets (community) Sato et al., Ecol. Lett. 2012

10. Savanah ecosystem of Kruger National Park, SA From: Han Olff et al. Phil. Trans. R. Soc. B 2009;364:1755-1779

11. Infectious agents are species Prey Pred. Para- site 1 Prey Patho- gen 2 Suggests effects on topology, connectivity, path length, ‘complexity’

12. Arctic food web Beckerman & Petchey J. Anim. Ecol. 2009 Kevin Lafferty Salt marsh food web Yellow = parasite species Red = host species PNAS, 2008, Ecol. Lett, 2008

13. Pelagic food web of sub-arctic lake Takvatn with only predator-prey interaction (top) and including parasite species and their links (bottom) Amundsen et al J. Anim Ecol. 2009

14. US-Army General: “it’s dangerous because it creates the illusion of understanding” (New York Times)

15. Three approaches to food webs Possible ways to think about infectious agents in food web; I is “pathogen”; II is “parasite”

16. Type of questions for modelling ecological questionsepidemiological questions Study infectious agents as a biological species to determine its role in ecosystems. How do infectious agents influence (shape, determine?) food-web topology & ultimately stability? What is their role in persistence and evolution of the ecosystem? What is their contribution to energy flow through the system? Are there essential differences between an agent-host link and a consumer- resource link? How are species of infectious agents distributed over trophic levels? What are the effects of loss/gain or increase/decrease of species (succession?)? How do infectious agents influence/cause trophic cascades? Study the effects of an infectious agents on its host species in their ecosystem (and vice versa). Under what conditions can an infectious agent invade the ecosystem? How does the ecosystem context influence evolution of virulence, and jumps to new host species? How are control measures aimed at a specific host influenced by the ecosystem context? How is long- term persistence influenced by host and non-host interaction and dynamics? How does the prevalence over host species change with ecosystem change? What are possible mechanisms for a positive or negative “dilution effect”?

17. Two approaches to infectious agents in food webs Direct approach: agent as separate species/node Indirect approach: agent only through its effect in splitting host species split into epidemiological (infected) states

18. Roots Detritus Phytophagous Nematodes Saprophytic Fungi Bacteria Collembolans Noncrypto- stigmatic Mites Cryptostigmatic Mites Fungivorous Nematodes Bacteriophagous Nematodes Bacteriophagous Enchytraeids Mites Flagellates Amoebae Predaceous Nematodes Predaceous Mites Predaceous Collembolans Nematode Feeding Mites Energy flow soil food web picture: Peter de Ruiter Measurements of feeding, energy flow, biomass, interaction strength

19. top predators resource basal resources predatory collembola nematophagous mites predatory nematodes collembola cryptostigmatic mites non-cryptostigmatic mites fungivorous nematodes bacteriophagous nematodes bacteriophagous mites predatory nematodes fungivorous nematodes bacteriophagous nematodes fungivorous nematodes bacteriophagous nematodes phytophagous nematodes amoebae fungivorous nematodes flagellates bacteriophagous nematodes phytophagous nematodes flagellates phytophagous nematodes bacteria fungi bacteria fungi bacteria detritus roots detritus consumer predatory mites predatory collembola predatory mites nematophagous mites predatory collembola nematophagous mites predatory mites predatory nematodes predatory collembola nematophagous mites amoebae predatory nematodes amoebae collembola cryptostimatic mites non-cryptostigmatic mites fungivorous nematodes flagellates bacteriophagous nematodes bacteriophagous mites enchytraeids phytophagous nematodes fungi bacteria Distribution of interaction strengths and biomass within a food web maintains stability with increasing complexity A.M. Neutel, et al., Science (2002) & Nature (2007) How do infectious agents influence this? Theory based on steady state situation of biomass distribution over species: “only” the ecological questions can be studied

20. Effects of prey on their predator Effects of predators on their prey Self-limiting effects (diagonal) 0.017 0.019 0.021 0.015 -0.085-0.15-1.5 0.021 -0.085 0.015-0.085-1.50.015 0.022 0.024 -0.32-0.29-2.8 -0.32 -0.28-2.8 -0.16-0.14-1.4 -0.0850.019 -0.19-0.0850.022 -0.093-0.11-0.0850.024 -0.16 -13-11 -0.085-18 0.023 -0.085 -19-8.5-7.5 -0.24-0.11-0.093 -8.5-7.5 3 12456789 1 2 3 4 5 7 8 9 6 real Top species basal species

21. Direct approach: challenges Infectious agent as a species, with links to host species Is an agent-host link “the same” as a predator-prey link in a topological analysis? – Agent consumes part of resource, but even when agent kills host, this host is still available as prey for predators. So how to account for this? – Some parasite stages and most pathogens inside host How to make this precise before studying effects on path lengths, complexity, nr. of trophic levels, … ? Much of the current theory restricted to systems in steady state (e.g. with respect to biomass distribution)

22. Intermediate view Structure host species by epidemiological state Incorporate effects through interaction strengths Study food-web dynamics with “weighted” interaction strength driven by changes in distribution over epi-states Prey Susc. Pred. Susc. Pred. Infect Pred. Recov. Pred. Predator

23. Intermediate approach: challenges Similarities to network models on which infection spreads: – Network is known and fixed – But: it is the dynamic strength of the link that describes the system – This strength changes depending on within-species dynamics of infectious agent in the species involved in the link – The strength itself influences the between-species dynamics How to model (let alone analyse) this feed back?

24. Indirect approach More pragmatic and close to the ecological and epidemiological modelling we know Basically: take a predator-prey model and add allow different infected states for each host species

25. Developments in math. biology Hadeler & Freedman, 1989: parasite mediates coexistence between predator and prey Chattopadhyay & Arino, 1999: similar with disease in prey, probably coined “eco-epidemiology” Venturino, 1994, 1995, 2002: Lotka-Volterra with infection Han & Hethcote, 2001: one predator/one prey with infection Hsieh & Hsiao, 2008: similar Haque & Venturino, 2006: similar Han & Pugliese, 2009: similar Malchow and others 2005-2008 (papers + book): spatial predator-prey with infection Hilker and others, 2006-2010 (5 papers): Allee effect and infection, stabilizing predator-prey oscillations, bio-control Morozov, 2012: one predator/ one prey and infection

26. Pathogen can mediate coexistence between consumer and resource when feeding rate too high

27. Consumer-resource dynamics n species, population sizes N i P i set of consumers species for which species i is a resource – Consumption rate Φ ij N j – Positive effect on species j: e ji Φ ji N i Q i set of species that are consumed by species i Density dependent birth and death From: Roberts & Heesterbeek, J. Math. Biol. March 2013

28. Ecological stability Steady state solutions Jacobian matrix C, community matrix:

29. Adding an infectious agent (SI)

30. Stability in combined system Jacobian matrix J is, for a particular steady state, given by Order by total population sizes N i, followed by the sizes of all infected states in the system C is the community matrix, as given before H is the epidemiological matrix; this matrix is related to the next-generation matrix (NGM)

31. D gives influence of changes in the ecology of individuals due to epidemiology (i.e. their infected state) – E.g. changes in feeding behaviour, fecundity, … B gives the influence of changes in the epidemiology of infected individuals due to ecology (e.g. population size N i ) – E.g. changes in the influence of density dependence for infected individuals, compared to uninfected In the infection-free steady state (invasion problem), matrix B = 0, the zero matrix For endemic states, B is typically not the zero matrix

32. Stability: spectral bound of J Regard J for the infection-free steady state: – Consequence: B = O = zero matrix Stability problem decouples in product of ecological stability (governed by C) x epidemiological stability (governed by H) H describes the influence of any infected state on each infected state – H = T + Σ – T the transmission matrix, Σ the transition matrix – Next-generation matrix with large domain: In SI-example: K L = K, next-gen. matrix; in all cases: R 0 = spectral radius of K L

33. Matrix H for the ‘general’ model

34. Epidemiological stability H = T + Σ for pred.-prey with infection in both Epidemiological stability depends on feeding rate ϕ

35. Wildebeest-grass-rinderpest H is a 1 x 1 ‘matrix’ (only one infected state) R 0 = β/(μ 2 + α) Epidemiological stability does not depend on ϕ in this example

36. Stability is balance between ecology and epidemiology Consumer extinct due to infection

37. Serengeti ecosystem & rinderpest Data from Holdo et al. PLoS Biology, 2009, 7(9), e1000210 Rinderpest regulated wildebeest to a low steady state level Vaccination of cattle around the park lowered infection success in wildebeest R 0 decreased to below 1 Wildebeest settled in high steady state; grass in low state Afterthought: more tree and shrub cover could lead to increase of tsetse flies which could lead to more sleeping sickness in cattle and humans

38. Eco-epi approach: agenda Deriving useful analytical results for the stability of non- trivial states (B not equal zero matrix) What happens in periodic environments? Stability related to adding one host or non-host species? Exploring the dilution effect (Pete’s lecture!) How is overall system stability related to relevant indicators related to matrix C, D, B, H Parasites with i life stages (Andy’s question and conjecture: hope to deal with that in the coming weeks)

39. Summary On your wish list of future extensions for your work: add multiple species and community dynamics!

40. The web of interactions between microparasite species within a community of infectious agents in one rodent host species (bank vole), showing the magnitude of effects. Sandra Telfer et al. Science 2010;330:243-246

41. How and what to model? Within host: using ideas from metabolic/gene regulatory networks? Relevant questions? Relevant experiments or empirical set ups? Individual level: how is susceptibility and infectivity for agent A mediated by agents B, C, D, …? Does influence remain when an agent has been cleared? Immune response. Population level: how does dynamics of agents B, C, D, … and their distribution over the host species influence the invasion and spread of A into that community? How to model the above? Stratify by history of infection?