West Nile Virus (WNV), a mosquito-borne virus of birds, emerged in North America in 1999; the invading strain was then displaced within a few years by a novel mutant. In order to understand this competitive displacement event, and to predict transmission of WNV in bird communities comprising hundreds of species, we collected data on bird and mosquito infections, bird community composition, and mosquito biting preferences from lab experiments, field observations, and citizen-science databases. We use a Bayesian framework, including a method for phylogenetic imputation applied to species with missing data, to synthesize information across the entire disease life cycle and throughout the community.

1. WNV biology Strain replacement Community spread Ecological synthesis References
Ecological synthesis across scales: West Nile virus
in individuals and communities
Ben Bolker
McMaster University
Departments of Mathematics & Statistics and Biology
24 June 2019

2. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

3. WNV biology Strain replacement Community spread Ecological synthesis References
Acknowledgements
People Morgan Kain
Support NSF Discovery Grant

4. WNV biology Strain replacement Community spread Ecological synthesis References
West Nile Virus
single stranded RNA virus
Flavivirus (dengue, yellow fever, Zika)
primary spread by Culex mosquitos
birds are primary hosts
(hundreds of species!)
I
S
I
S
1
2
WNV Life Cycle
(Infected Bird to Infected Bird)
Bird Titer
Profile
Bird
Survival
Mosquito
Incubation
Mosquito
to Bird
Transmission
Bird to
Mosquito
Transmission

5. WNV biology Strain replacement Community spread Ecological synthesis References

6. WNV biology Strain replacement Community spread Ecological synthesis References
WNV in North America
first detected in 1999 (NY99 strain)
related to 1997-1998 Israel strains
(single substitution in NS3 helicase)
spread rapidly 1999-2003
new WN02 strain rapidly displaced NY99
(single substitution in envelope gene)

7. WNV biology Strain replacement Community spread Ecological synthesis References
WNV phylogeny (Lanciotti et al., 2002)

8. WNV biology Strain replacement Community spread Ecological synthesis References
ecological impact: American crows (LaDeau et al., 2007)
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1980 1985 1990 1995 2000 2005
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counts/BBStransect

9. WNV biology Strain replacement Community spread Ecological synthesis References
spillover to mammals
humans, horses, cats, dogs, squirrels . . .
dead-end hosts
symptoms in ≈ 20% of human infections

10. WNV biology Strain replacement Community spread Ecological synthesis References
Human incidence
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annualincidence(US)
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US CDC

11. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

12. WNV biology Strain replacement Community spread Ecological synthesis References

13. WNV biology Strain replacement Community spread Ecological synthesis References
what drove WNV strain replacement?
estimated fitness (R0) difference > 3×
Consensus:
WNV02 > NY99 due to increased mosquito incubation rate
(Kilpatrick et al., 2008)
robins are the key contributor to WNV spread
(Kilpatrick et al., 2006)
bird species richness predicts human cases (dilution effect)

14. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

15. WNV biology Strain replacement Community spread Ecological synthesis References
I
S
I
S
A
B
Bird Titer
Profile
Bird
Survival
Mosquito
Incubation
Mosquito
to Bird
Transmission
Bird to
Mosquito
Transmission
1
2
3
4
5
13( ) x x2 15( ), 4 x
Ecological Parameters
(bite rate, mosquito: bird
ratio etc.)
=R0
WNV Life Cycle
(Infected Bird to Infected Bird)

16. WNV biology Strain replacement Community spread Ecological synthesis References
transmission from bird species i to j
(for virus genotype v at temperature C)
R0{ijCv} =
Tb
tb=1
B survtbv × B → M Transtbv × M bites/day
×
Tm
tm=1
M → B TranstmtbvC × M survCtm × M bites/day
× M : B Ratio × Prop Bi × M Bite Pref on Bi
× Prop Bj × M Bite Pref on Bj

17. WNV biology Strain replacement Community spread Ecological synthesis References
statistical methods
literature survey/scraping
for each component, fit hierarchical models
appropriate function (logistic, Gaussian, etc.)
fixed effects of genotype, day, titer, temperature
random effects of citation, experiment, bird species
all done in Stan (Carpenter et al., 2017)

18. WNV biology Strain replacement Community spread Ecological synthesis References
bird survival vs. time
House Finch American Robin
American Crow House Sparrow
0 2 4 6 8 0 2 4 6 8
0.0
0.5
1.0
0.0
0.5
1.0
Day
Survival
NY99
WN02
strain
NY99
WN02
sample size
1
5
10

19. WNV biology Strain replacement Community spread Ecological synthesis References
bird titer curves vs. time
House Finch American Robin
American Crow House Sparrow
0 2 4 6 8 0 2 4 6 8
0
5
10
15
0
5
10
15
Day
Titer(log10PFU)
Virus_Lineage
NY99
WN02

20. WNV biology Strain replacement Community spread Ecological synthesis References
transmission vs. titer
0.0
0.5
1.0
2 4 6 8 10 12
Titer(Log10)
BirdtoMosquitoTransmission
Sample Size
q
q
q
q
50
100
200
400
Virus Genotype
NY99
WN02

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mosquito-to-bird transmission
a
0.0
0.5
1.0
0 10 20 30 40 50
Day
MosquitotoBirdTransmission
Virus Genotype NY99 WN02
b
2 4 6 8 10 12
Titer
Temperature (0
C) 21 26

22. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

23. WNV biology Strain replacement Community spread Ecological synthesis References
R0 conclusions
House Finch American Robin
American Crow House Sparrow
0.1 1 10 0.1 1 10
NY99.16
WN02.16
NY99.26
WN02.26
NY99.16
WN02.16
NY99.26
WN02.26
R0
strain
NY99
WN02
Temperature
16
26

24. WNV biology Strain replacement Community spread Ecological synthesis References
fitness advantage of WN02
0.01 1 3 100
American Crow
House Sparrow
House Finch
American Robin
R0 advantage of WN02
Temperature
16
26

25. WNV biology Strain replacement Community spread Ecological synthesis References
incubation advantage of WN02?
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1.00
0 10 20 30 40
days post−infection
meantransmissionprobability
Strain
q
NY99
WN02
temp (C)
q
q
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q
q
q
q
18
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22
26
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30
32

26. WNV biology Strain replacement Community spread Ecological synthesis References

27. WNV biology Strain replacement Community spread Ecological synthesis References

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29. WNV biology Strain replacement Community spread Ecological synthesis References

30. WNV biology Strain replacement Community spread Ecological synthesis References

31. WNV biology Strain replacement Community spread Ecological synthesis References
conclusions
advantage of WN02 over NY99: still uncertain
missing hosts? ecological context?
could use more data on mosquito-to-bird transmission

32. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

33. WNV biology Strain replacement Community spread Ecological synthesis References
From species to community
that was fun, but . . .
monoculture estimates of R0
all but four species ignored/lumped into “other”
can only predict for a few specific communities
Extend to a wider spatial, temporal, phylogenetic range ??

34. WNV biology Strain replacement Community spread Ecological synthesis References
New components needed
community composition in space & time
recorded counts
detectability
biting preferences
titer profiles/survival/etc. (all species)

35. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

36. WNV biology Strain replacement Community spread Ecological synthesis References
21st century citizen science

37. WNV biology Strain replacement Community spread Ecological synthesis References
eBird data
complete checklists Jan 2000 - Dec 2017 (1.44 million)
aggregated to county
33,479 “communities” (county × month); 700 species
IUCN, Catalogue of Life for species name lookup

38. WNV biology Strain replacement Community spread Ecological synthesis References
detectability
1440 titles/abstracts → 12 papers → 469 species
(419 from Blancher et al. (2013))
adjusted for body mass

39. WNV biology Strain replacement Community spread Ecological synthesis References
phylogenetic imputation
information on species missing from our data set
estimate missing values based on closest relatives
(and other covariates, e.g. body size)
ancestral state reconstruction
machinery that lets this work (quickly) in lme4 package
use for most effects in the model

40. WNV biology Strain replacement Community spread Ecological synthesis References

41. WNV biology Strain replacement Community spread Ecological synthesis References

42. WNV biology Strain replacement Community spread Ecological synthesis References

43. WNV biology Strain replacement Community spread Ecological synthesis References

44. WNV biology Strain replacement Community spread Ecological synthesis References

45. WNV biology Strain replacement Community spread Ecological synthesis References

46. WNV biology Strain replacement Community spread Ecological synthesis References
biting preferences
mosquito biting survey by Hamer et al. (2009) (blood meal ID)
species composition uses a prior from eBird + survey from
Hamer et al.
Dirichlet-multinomial model in Stan
phylogenetically imputed biting preferences for other species

47. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

48. WNV biology Strain replacement Community spread Ecological synthesis References
seasonal effects (mostly temperature)

49. WNV biology Strain replacement Community spread Ecological synthesis References
poor match with human cases
no systematic sampling of WNV in birds
human spillover effects:
activity, mosquito density, . . .

50. WNV biology Strain replacement Community spread Ecological synthesis References
spatial (bird community) effects

51. WNV biology Strain replacement Community spread Ecological synthesis References
species-level effects on WNV

52. WNV biology Strain replacement Community spread Ecological synthesis References
dilution effect
18 22 26
100 200 300 100 200 300 100 200 300
1.5
2.0
2.5
Species Richness
CommunityR0

53. WNV biology Strain replacement Community spread Ecological synthesis References
caveats
mosquito ecology is important! missing data
(Rund et al., 2019b; Sedda et al., 2019; Rund et al., 2019a)
effects of nonlinearity + uncertainty on means and variances

54. WNV biology Strain replacement Community spread Ecological synthesis References
Outline
1 Natural and evolutionary history of WNV
2 Understanding WNV strain replacement
introduction
methods
conclusions
3 Community spread of WNV
intro
methods
conclusions
4 Ecological synthesis

55. WNV biology Strain replacement Community spread Ecological synthesis References
Being honest about uncertainty
propagate error all the way through
(Bayesian [or pseudo-Bayesian] methods)
account for full life cycle
put priors on everything (Elderd et al., 2006; Park et al., 2018)

56. WNV biology Strain replacement Community spread Ecological synthesis References
Coping with uncertainty
add covariates/auxiliary information
two-level priors (ABC)?

57. WNV biology Strain replacement Community spread Ecological synthesis References
Data scaling

58. WNV biology Strain replacement Community spread Ecological synthesis References
data vs. computation
Moore′s law:
T1 2 ≈ 1.5yr
$0.10
$10.00
$1,000.00
2005 2010 2015
Date
Sequencingcostpermegabase(US$)

59. WNV biology Strain replacement Community spread Ecological synthesis References
industrial vs. artisanal
limitations
data
computation
algorithms
code complexity
theory?
judgement/creativity?

60. WNV biology Strain replacement Community spread Ecological synthesis References
References
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database, version 2.0. PIF technical series no 6.
Carpenter, B., Gelman, A., et al., 2017. J. Stat. Software.
Elderd, B.D., Dukic, V.M., and Dwyer, G., 2006. PNAS, 103(42):15693 –15697.
doi:10.1073/pnas.0600816103.
Hamer, G.L., Kitron, U.D., et al., 2009. Am J Trop Med Hyg, 80(2):268–278.
Kilpatrick, A.M., Daszak, P., et al., 2006. Proceedings of the Royal Society B: Biological Sciences,
273(1599):2327–2333. ISSN 0962-8452, 1471-2954. doi:10.1098/rspb.2006.3575.
Kilpatrick, A.M., Meola, M.A., et al., 2008. PLoS Pathog, 4(6):e1000092.
doi:10.1371/journal.ppat.1000092.
LaDeau, S.L., Kilpatrick, A.M., and Marra, P.P., 2007. Nature, 447(7145):710–713. ISSN 0028-0836.
doi:10.1038/nature05829.
Lanciotti, R.S., Ebel, G.D., et al., 2002. Virology, 298(1):96–105. ISSN 0042-6822.
doi:10.1006/viro.2002.1449.
Park, S.W., Dushoff, J., et al., 2018. PNAS, 115(34):E7892–E7893.
Rund, S.S., Braak, K., et al., 2019a. Scientific data, 6(1):40.
Rund, S.S., Moise, I.K., et al., 2019b. J Am Mosquito Control Assoc, 35(1):75–83.
Sedda, L., Lucas, E.R., et al., 2019. J Roy Soc Interface, 16(153):20180941.