3: R 0

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