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OF INFECTIOUS DISEASES
Pej Rohani & John Drake
Total mortality
Infant mortality
MULTIFACETED APPROACH TO
UNDERSTANDING INFECTIOUS DISEASES
Medicine But these approaches don’t
address important questions at
population level ...
Microbiology
Genomics Immunology
Vaccines & Drugs
EMERGING
PATHOGENS
SCHOOL
OUTBREAK
• agent?
• Is it novel?
Is a vaccine available?
MODELING QUESTIONS
I. BASICS
Why does
epidemic
What does turn over?
growth rate
# Boys confined to bed
tell us?
Why did it
What go
determines extinct?
0 2 4 6 8 10 12
invasion? Day
MODELING QUESTIONS II.
CONTROL IMPLICATIONS
How to Random or
prevent aimed at age/
spatial When is it core group?
spread? best to
implement
controls? Drugs, Vaccines
Is it or other control
evolving? measures?
How
drastic
?
Probability of
How to prevent
invasion or
invasion/
extinction
reinvasion?
WHAT IS A
MODEL?
Different types of models:
A mathematical/computational model is an abstract
model that uses mathematical language to describe the
behaviour of a system
A Statistical model attempts to describe relationships between
observed quantities and independent variables
Reality Conceptualization
Abstraction
Interpretation
Transparency
Ability to understand model components
Decreases with model complexity
Flexibility
How easily can model be adapted to new scenarios?
Decreases with model complexity
REALISM VS
TRANSPARENCY
Transparency
Multi-Scale
Network
Resolution
Agent-Based
“Realism”
Structured
Homogeneous
Solution tools
‘HOW’ DO YOU
MODEL?
Analytical Models
Concentrate on problems that can be expressed and
analysed fully using analytical approaches.
Problem-‐based Models
Construct most “appropriate” model and use
whatever combination of methods for analysis and
prediction.
Ready-‐Made
Software
ModelMaker
www.modelkinetix.co
m/modelmaker/model
maker.html
GLOBAL
SIMULATORS
RESOURCE
MATERIALS
Keeling & Rohani (2008)
Dynamic equations
Computer code
THE SIMPLEST
MODELS
Let’s develop a model for Boarding School influenza outbreak
Some important choices need to be made at outset
1. What do we want to keep track of?
Amount of virus in population?
Antibody titre of everyone in population (school)?
Cities in which infected people have been found?
CATEGORISING
INDIVIDUALS
Healthy Incubating Diseased Clinical status
Susceptible
Infectious
Recovered/Immune
These are our
“system variables”
THE SIMPLEST
MODELS
2. What model structure?
-- Determined by pathogen biology
Carrier
Transmission Recovery
Deterministic 50 independent
stochastic
realizations
Network
Resolution
Agent-Based
Structured
Homogeneous
Solution tools
THE SIMPLEST
MODELS
We’ve settled on a deterministic SIR model – now what?
Then,
W(t+ δt) = W(t) + Inflow rate × elapsed time - Outflow rate × elapsed time
BATH TUB
EXAMPLE
Water inflow rate,
I(t)
W (t + 6t) = W (t) + I ⇥ 6t — O
⇥ 6t
Rearrange
W (t + 6t) — W
=I —
(t) Water outflow
O rate, O(t)
6t
Left hand side is a difference quotient for derivative of W with
respect to time
Let δt → 0 dW
=I —
dt
O
MANY BATHTUBS =
COMPARTMENT
MODELS
MODEL
EQUATIONS
If we knew X t and Yt, could we predict Xt+ t and Yt+t, where t is
some (very short) time later?
And
Z t+t = Z t + ( t) Yt
X t+t = X t – ( t) X t Yt /N
Yt+t = Yt + ( t) X t Yt /N - ( t)
Yt Z t+t = Z t + ( t) Yt
1
=
ц
Z 1
x fmean
For a random variable x, with probability density function f(x), the (x)dx is given
by 0
AN ODE
MODEL
Consider the equation describing Susceptible dynamics
Xt+ t = X t – ( t) X t Yt/N
Re-write as
Xt+ t - X t = - ( t) X t Yt/N
(X t+t – X t )/ t = X t Yt /N
o цY rates
dt
AN ODE SIR
MODEL dX Y
dt = —βX N
dY Y
= βX —
dt цY N
dZ
=
dt
цY
Important to notice: transmission rate is assumed to depend on frequency
of infecteds in population (Y/N). Hence, this is frequency-
dependent transmission
SIMULATING
EPIDEMICS Transmission rate,
β = 10 yr-1
Transmission rate,
β = 50 yr-1
Transmission rate,
β = 100 yr-1
1
Transmission rate,
β = 200 yr-1
Infected
Susceptible
0.1
0 0
0 0.5 1 0 0.05 0.1 0.15 0.2 0 0.05 0.1 0.15 0.2 0 0.05 0.1 0.15 0.2
= 10; 1/ = 10d = 50; 1/ = 10d = 1e+02; 1/ = 10d = 2e+02; 1/ = 10d
1 1 1 0.8
0.9
0.8 0.8 0.8
0.6
0.7
Infected
Susceptible
= 10; 1/ = 20d = 50; 1/ = 20d = 1e+02; 1/ = 20d = 2e+02; 1/ = 20d
1 1 1
Infected
Susceptible
0.5 0.5
Infectious period (1/γ) = 20 days 0.5 0.4 0.5 0.5
0.2
0 0 0 0 0 0
0 0.5 1 0 0.05 0.1 0.15 0.2 0 0.05 0.1 0.15 0.2 0 0.05 0.1 0.15 0.2
= 10; 1/ = 30d = 50; 1/ = 30d = 1e+02; 1/ = 30d = 2e+02; 1/ = 30d
1 1 1
0.8
Infected
Susceptible
R₀ < 1 R₀ =4
No invasion Successful invasion
R0 AND MODEL
PARAMETERS
Transmission Rate (β, yr⁻¹)
R0 < 1
1918 Influenza
Ebola
SARS
Phocine Distemper
HIV (MSM)
HIV (FSW)
Mumps
Pertussis
THE DEATH OF AN
EPIDEMIC
In SIR equations, let’s divide equation for dX/dt by dZ/dt:
dX/dZ = - ( X Y/N)/(Y)
= - R0 X/N
N
Contact Rate
Population Size
DOES IT
MATTER?
Again, pathogen invasion if dY/dt > 0
If initially everyone susceptible (X=N),
NY – Y>0 Y(N - ) > 0
In this case, we define R0 N so
need R0>1
dY
= . . . — цY —
dt
↵Y
TRANSMISSION &
Rβ=0.0426,
Density
0 Dependent
γ=24, α=18, μ=0.02
Frequency
β=426, γ=24, α=18, μ=0.02
D ependent
NT = 1000 No invasion threshold
= 0.0426; 1/ = 15d = 426; 1/ = 15d
= 426; 1/ = 15d
10000 10000
10000
11
Size
Population Size
10 10
Size 9
0
5000
Populati
5000
R
R
5000 0
on
5000 0
Infected
NT detcefnI
1 Population
0
0 0 0 100 200 300 400 500 600 700 800 900 1000
0 100 200 300 400 500 600 700 800 900 1000
Time (years) Time (years)
0
00 100100 200200 300300 400400 500500 600600 700700 800800 900900 FD
0
00
transmission → pathogen can wipe out
100100 200200 300300 400400 500500 600600 700700 800800
10001000
Time (years)
900900 10001000
Time host(years)
WHAT SHOULD WE
DO?
If population size doesn’t change, FD & DD equivalent (βFD = N x
βDD)
Otherwise:
Frequency-dependence generally more appropriate in large
populations with heterogenous mixing, STDs, vector-borne
pathogens
Density-dependence representative of wildlife & livestock
diseases (especially with smaller population sizes)