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Whither Disease Ecology Multi -host, Multi Parasite in Wildlife 3 Points to think about Ecology & Disease. R 0 o R N o t ?. HUD. DOB. Grouse. Wolf. Maasai. Rats Tenrec. Sheep. Mouse. - PowerPoint PPT Presentation
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Whither Disease EcologyMulti-host, Multi Parasite in Wildlife3 Points to think about Ecology & Disease
R0 oR Not ?HUD DOB
Grouse
MaasaiWolf
RatsTenrec
SheepMouse
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!Spurious correlations do not prove cause & effect why should models?
4
Parasite
Free LivingStages
Host Deaths
Births
19871988198919901991199219931994199519961997
1
10
100
1000
1000019871988198919901991199219931994199519961997
1
10
100
1000
10000
1. Killer Experiments : Needs an Experimental test
200 500 800 3000 6000 10000
Worms
0
2
4
6
8
10
Broo
d si
ze
E
C
E
E E
EE
EC
CC C
CC
C
E
Hudson et al. 1992 J.Anim Ecol
0 5 10 15 2010
100
1000
10000
Years
Num
bers
2
Step 1
Step 3
0
2
4
6
8
10
1000 10000
Worms
Broo
d si
ze
Do parasites reduce fecundity?
5
Underlying RockRainfall
Peat Depth
Predation
Viral Pathogens
Social Behavior
Ticks
Hares
Deer & Sheep
Aggression Relatedness
Host Density
Raptors
Corvids
Foxes
Grazing
Unstable Dynamics
Stable Dynamics
Sunshine
Cover
Survival
Fecundity
Dispersal
Food Quality
Parasite
Hudson et al. 2002 Phil Trans Roy Soc
Community Impact
1. Parasites embedded in the Community System
12
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 hostsSo depauperate communities more likely to transmit
1. The Dilution Hypothesis: In desperate need of Experimental tests
Borrelia
Ixodes vectors
Density of Competent Host Dens
ity o
f Non
Com
pete
nt H
ost
Norman et al 1999
C
NC
NC
NC NC
NC
6
Biodiversity reduces risk of exposure to zoonotic infections
Generalized: The Competent Hosts are The Resilient hostsSo depauperate communities more likely to transmit
1. The Dilution Hypothesis: In desperate need of Experimental tests
Borrelia
Ixodes vectors
Experimental manipulation?
1. Predictions: Norman model 2. Experimentally Remove competent3. Negative Control: Remove non
competent – Chipmunk
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
Protein
Indirect-Comp:Immuno
Modulated
Transmission
Dynamics
Pandemic
CommunityInteraction
Julius Jauregg 1857-1940
Hypothesis: Coinfections generate transmission heterogeneities
Within HostModels
Between HostModels
9
0 50 100 150 200 250
010
000
2000
030
000
4000
0
1977 2013
T. retortaeformis
Bordetella bronchiseptica
Myxoma Virus
RHD Virus
Graphidium strigosum
Trichostrongylus retortaeformis
Passalurus ambiguous
Mosgovoyla pectinata
Cittotaenia denticulata
Month
inte
nsity
2 4 6 8 10 12 14 16 18
01
23
45
67
89 M2
M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M2M3M4M5M6M7M8M9M10
M3
2. Multiscale Issues: Coinfection, heterogeneity and transmission
Rabbits
10
Single Parasite Immune Pathway Models(Note: Chronic Infections)
Thakar et al. 2012 Plos Comp Biol
Bordetella bronchiseptica Trichsotrongylus retortaeformis
2. Multiscale Issues: Coinfection, heterogeneity and transmission
Compartment I = Local Response Compartment II = Systemic Response 11
Thakar et al. 2012 PLOS Comp Biol
Co-infection Immune Pathway Model – No Direct
The Co-infection Hypothesis: Prevalence changes with coinfection
Common Cytokines
Lung Small Intestine
12
[ ]Knock out node experiments ~ Parasite activity from simulations -= Key nodes for persistence
Bordetella
Worm +Bordetella
Bordetella+Worm
Worm
IL12 II stimulates Th1 response is necessary for bacteria clearance IL10 ..stimulated subversely by bacteria as a regulatory cytokine
[ ]13
Broad Spectrum Systemic Anthlemintic:1. Kills Helminths, Mites, Bed bugs,
Lice, Ticks2. Toxic to some genotypes3. Stimulates immune response
Bordetella bronchiseptica
Myxoma Virus
RHD Virus
Graphidium strigosum
Trichostrongylus retortaeformis
Passalurus ambiguous
Mosgovoyla pectinata
Cittotaenia denticulata
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
Grenfell 2002
Epidemic Fadeout
16
Trichostrongylus life cycle
M1
b
Parasite
Free LivingStages
Host Deaths
Births
Dobson & Hudson Model
M2
T
a
γ
μThreshold Host Density ~ Persistence
HT = M1 γ β(λ-M1)
Critical Community Size
Host Replenishment
R0= βλH . (α+b+μP) (γ+βH)
R0= T 1
M1M2
Simple, Direct, Monoxenic Life Cylce
3: R0 , Dynamics & Persistence: The Alternative Hypotheses
Epidemic Fadeout
17
R0
Free living larvae life expectancy
No Arrested Development
Arrested Development
3. Persistence Mechanisms: Arrested Development = Hypobiosis
b
Parasite
Free LivingStages
Host Deaths
Births
Dobson & Hudson Model
M2
T
a
γ
μ
AD
18
1. Macroparasite Complex Life Cycles: Heteroxenic
Opisthorcis life cycle
R0= T1 T2 T3 1
M1M2 M3
HT= lower
M1M2
M3
T1
T2
T3
Dobson, Hudson & Lyles 1992
Geoff Parker : Complex life cycle evolved to increase R0. Reduced larval mortality & increased adult body size leads to high fecundity
~ Complex Life Cycles ~ Indirect ~ Heteroxenic
19
Chicken Pox ~ Shingles
Rabies ~ Multiple Host Species?
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 heterogeneitiesPoint 3: R0 is but one hypothesis ~ Persistence
4. What happens After Disease Invasion? … Bighorn Sheep
Mycoplasma ovipneumoniae [= M.ovi]
Wild Lamb Experimental Infection
2121
Cassirer et al . 201337
4. What happens After Disease Invasion? Host or Pathogen?
22
Keypoint 4: Alternative hypotheses: Pathogen evolution:Host selection ~ those with long infectious periods
~ but not humans
4. What happens After Invasion? … Pathogen or Host Selection ?
Phocine Distemper Virus Rabbit Hemorrhagic Virus Mycoplasma in Bighorns