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