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R 0 o R No t ? HUD DOB Grouse Wolf Mouse Maasai Rats Tenrec Sheep Peter Hudson, Kezia Manlove, Emily Almberg, Paul Cross, Francis Cassirer, …..and of course: Andy Dobson Discussion: Isabella Cattadori & Jamie Lloyd Smith Deep Thanks to: RAPIDD, NIH, NSF, MAF, Key Point 1: Vaccinating with Lemons: Save America Eat More Citrus Fruit ……… 3 1: Spurious Correlations : The Need for a Killer Experiment “If we Import 4,500 Tons of Lemons per annum we could eradicate all Highway Fatalities!” Only 24.8 million Lemons = 0.1 lemons per person! 4 1. Killer Experiments : Needs an Experimental test Do parasites reduce fecundity? 10 8 Deaths Host E Step 1 Brood size Births Brood size 8 10 E E 6 E 4 C 2 0 Parasite 4 2 E EC E 6 0 1000 10000 CC C E C Worms C C 200 500 800 3000 6000 10000 Worms Hudson et al. 1992 J.Anim Ecol 10000 1000 100 Free Living Stages 10 Numbers 10000 1 19871988198919901991199219931994199519961997 2 10000 1000 1000 100 Step 3 100 10 10 0 5 10 Years 15 20 1 19871988198919901991199219931994199519961997 5 1. Parasites embedded in the Community System Community Impact Grazing Stable Dynamics Rainfall Underlying Rock Food Quality Sunshine Peat Depth Survival Fecundity Raptors Predation Cover Corvids Foxes Parasite Host Density Ticks Deer & Sheep Viral Pathogens Hares Dispersal Social Behavior Aggression Relatedness Unstable Dynamics Hudson et al. 2002 Phil Trans Roy Soc 12 1. The Dilution Hypothesis: In desperate need of Experimental tests Biodiversity reduces risk of exposure to zoonotic infections ~ Non competent hosts are a sink to infection (wasted bites) Generalized: The Competent Hosts are The Resilient hosts Density of Non Competent Host So depauperate communities more likely to transmit NC NC NC C Borrelia NC Ixodes vectors NC Density of Competent Host Norman et al 1999 6 1. The Dilution Hypothesis: In desperate need of Experimental tests Biodiversity reduces risk of exposure to zoonotic infections Generalized: The Competent Hosts are The Resilient hosts So depauperate communities more likely to transmit Borrelia Ixodes vectors 7 Key Point 1: Neither correlations or models provide proof …. We need perturbation experiments to reveal mechanisms…… 8 2. Multiscale Issues: Coinfection, heterogeneity and transmission Pandemic Between Host Models Dynamics Transmission Within Host Models Julius Jauregg 1857-1940 Community Interaction Indirect-Comp: Immuno Modulated Protein 9 8 7 6 5 4 3 2 1 0 intensity T. retortaeformis M2 M3 M4 M5 M6 M7 M8 M9 M10 2 4 6 8 10 12 14 16 0 10 20 30 40 9 2. Multiscale Issues: Coinfection, heterogeneity and transmission 18 Month 0 1977 Bordetella bronchiseptica Cittotaenia denticulata 5 0 1 0 1 0 5 2 0 0 2 0 5 0 Rabbits 2013 Trichostrongylus retortaeformis Graphidium strigosum Mosgovoyla pectinata Myxoma Virus RHD Virus Passalurus ambiguous 10 2. Multiscale Issues: Coinfection, heterogeneity and transmission Single Parasite Immune Pathway Models (Note: Chronic Infections) Bordetella bronchiseptica Compartment I = Local Response Compartment II = Systemic Response Trichsotrongylus retortaeformis 11 Thakar et al. 2012 Plos Comp Biol The Co-infection Hypothesis: Prevalence changes with coinfection Co-infection Immune Pathway Model – No Direct Lung Small Intestine Common Cytokines 12 Thakar et al. 2012 PLOS Comp Biol Knock out node experiments ~ Parasite activity from simulations -= Key nodes for persistence Bordetella Bordetella+ Worm Worm Worm + Bordetella IL12 II stimulates Th1 response is necessary for bacteria clearance IL10 ..stimulated subversely by bacteria as a regulatory cytokine 13 Bordetella bronchiseptica Cittotaenia denticulata Myxoma Virus RHD Virus Trichostrongylus retortaeformis Graphidium strigosum Mosgovoyla pectinata Passalurus ambiguous Broad Spectrum Systemic Anthlemintic: 1. Kills Helminths, Mites, Bed bugs, Lice, Ticks 2. Toxic to some genotypes 3. Stimulates immune response 14 Key Point 2: Coinfections introduce important transmission heterogeneities? How & When? 3: R0: Whence the Alternative Hypotheses: Persistence R0 ~ initial spread, likelihood of epidemic, vaccination proportion BUT Selection does not always maximize R0: e.g. Superinfection NEED to test other hypotheses & Models – Persistence R0 = Transmission* Infectious Period (1/mortality) R0 with High transmission * Low infectious period = Low Transmission * High infectious period But Different dynamics & Persistence likelihood Epidemic Fadeout Grenfell 2002 16 3: R0 , Dynamics & Persistence: The Alternative Hypotheses Simple, Direct, Monoxenic Life Cylce Births a Deaths Host b Parasite μ T M1 Free Living Stages Threshold Host Density ~ Persistence HT = M1 γ β(λ-M1) Dobson & Hudson Model γ Epidemic Fadeout Critical Community Size Host Replenishment M2 Trichostrongylus life cycle 17 3. Persistence Mechanisms: Arrested Development = Hypobiosis 5 R0 4 3 2 Arrested Development Births a Host No Arrested Development Deaths b 1 0 Parasite AD 0 5 10 15 20 25 30 Free living larvae life expectancy μ T Free Living Stages Dobson & Hudson Model γ M2 18 1. Macroparasite Complex Life Cycles: Heteroxenic ~ Complex Life Cycles ~ Indirect ~ Heteroxenic T3 Geoff Parker : Complex life cycle evolved to increase R0. Reduced larval mortality & increased adult body size leads to high fecundity M3 T1 T2 M2 M1 Opisthorcis life cycle R0= T1 T2 T3 M1M2 M3 HT= lower Dobson, Hudson & Lyles 1992 19 Key Point 3: Maximizing R0 is but one Hypothesis.. Alternative: Persistence Persistence Mechanisms in Neuro infections 20 Point 1: Need for Experiments Point 2: Coinfections generate heterogeneities Point 3: R0 is but one hypothesis ~ Persistence 4. What happens After Disease Invasion? … Bighorn Sheep Wild Lamb Experimental Infection Mycoplasma ovipneumoniae [= M.ovi] 21 21 pr(s 0.0 2001 2005 4. What happens After Disease Invasion? Host or1997 Pathogen? year B 2009 1.0 pr(fade-out) 0.8 0.6 0.4 0.2 0.0 2 37 Cassirer et al . 2013 4 6 8 10 12 14 16 years since invasion 22 4. What happens After Invasion? … Pathogen or Host Selection ? Keypoint 4: Alternative hypotheses: Pathogen evolution: Host selection ~ those with long infectious periods ~ but not humans Phocine Distemper Virus Rabbit Hemorrhagic Virus Mycoplasma in Bighorns