Dynamics of Infectious Diseases

A module in Phys 7654 (Spring 2010):

Basic Training in Condensed Matter Physics
Feb 24 - Mar 19

Chris Myers
crm17@cornell.edu
Clark 517 / Rhodes 626 / Plant Sci 321

Wednesday, February 24, 2010

 Overview of module

• Introduction to models of infectious disease dynamics

- some basic biology of infectious diseases (not much)
- standard classes of models
‣ compartmental (fully-mixed)
‣ spatial (metapopulations & network-based)
- phenomenology of disease dynamics & control
‣ epidemic thresholds, herd immunity, critical component
size, percolation, role of contact network structure,
stochastic vs. deterministic models, control strategies, etc.
‣ case studies (FMD, SARS, measles, H1N1?)

Wednesday, February 24, 2010

 Tentative schedule
• Wed 2/24 : Lecture
• Fri 2/26✧: Lecture
• Wed 3/3 : Lecture; Homework #1 due (see website)
• Fri 3/5 : No Class (Physics Prospective Grad Visit Day)
• Wed 3/10 : Myers away - possibly a guest lecture
• Fri 3/12✧: Lecture
• Wed 3/17*: Lecture
• Fri 3/19*: Lecture
• 3/20-3/28: Spring break; module finished

*APS March Meeting (Myers here. Who is away?)

✧Overlap with CAM colloquium (Fri 3:30)

Wednesday, February 24, 2010

 Resources
• Course website
- www.physics.cornell.edu/~myers/InfectiousDiseases
- also accessible via Basic Training website:
‣ people.ccmr.cornell.edu/~emueller/
Basic_Training_Spring_2010/Infectious_Diseases.html
- contains links to relevant reading materials (some requiring
institutional subscription*), lecture slides, class schedule,
homeworks, etc. (continually updated)

* use Passkey from CIT:

https://confluence.cornell.edu/display/CULLABS/Passkey+Bookmarklet

Wednesday, February 24, 2010

Wednesday, February 24, 2010
 Resources

• Books
- M. Keeling & P. Rohmani, Modeling Infectious Diseases in Humans and
Animals [K&R]; programs online at www.modelinginfectiousdiseases.org
- O. Diekmann & J.A.P. Heesterbeek, Mathematical Epidemiology of Infectious
Diseases [D&H]
- R.M. Anderson & R.M. May, Infectious Diseases of Humans [A&M]
- D.J. Daley & J. Gani, Epidemic Modeling: An Introduction [D&G]
- S. Ellner & J. Guckenheimer, Dynamic Models in Biology (Ch. 6) [E&G]

• Local activity
- EEID - Ecology and Evolution of Infections and Disease at Cornell
‣ website at www.eeid.cornell.edu, mailing list: EEID-L@cornell.edu
- 8th annual EEID conference: http://www.eeidconference.org/
‣ to be held at Cornell in early June 2010

Wednesday, February 24, 2010

 Simulations: Milling about at a conference
• Individuals executing
random walk on a 2D
square lattice
• Two individuals in
“contact” if they occupy
the same lattice site
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)
• Infectious individuals
can infect susceptibles
with probability β
• Infectious individuals
can recover with
probability γ

Wednesday, February 24, 2010

 Simulations: Milling about at a conference
• Individuals executing
random walk on a 2D
square lattice
• Two individuals in
“contact” if they occupy
the same lattice site
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)
• Infectious individuals
can infect susceptibles
with probability β
• Infectious individuals
can recover with
probability γ

Wednesday, February 24, 2010

 Dynamics

Wednesday, February 24, 2010

 Tracing
distribution of
infectious contacts

network of infectious spread

Wednesday, February 24, 2010

 Increased infectiousness

• Same as before,
except two individuals
in “contact” if they
occupy the same
lattice site or are on
neighboring sites
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)

Wednesday, February 24, 2010

 Increased infectiousness

• Same as before,
except two individuals
in “contact” if they
occupy the same
lattice site or are on
neighboring sites
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)

Wednesday, February 24, 2010

 Dynamics

Wednesday, February 24, 2010

 Vaccination

• Same as original
simulation, except 40%
of the population has
been vaccinated
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)
• CYAN = vaccinated
(and immune)

Wednesday, February 24, 2010

 Vaccination

• Same as original
simulation, except 40%
of the population has
been vaccinated
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)
• CYAN = vaccinated
(and immune)

Wednesday, February 24, 2010

 Dynamics

Wednesday, February 24, 2010

 Culling
• Same as original
simulation, except
instead of recovery,
infecteds - and their
nearest neighbors - are
culled at rate c
- ORIGIN Middle English : from
Old French coillier, based on
Latin colligere (see collect).

• RED = susceptible (not

infectious)
• YELLOW = infectious
• GREY = culled (and
dead)
• Finding an “optimal”
culling strategy is a
politically and
economically sensitive
issue

Wednesday, February 24, 2010

 Culling
• Same as original
simulation, except
instead of recovery,
infecteds - and their
nearest neighbors - are
culled at rate c
- ORIGIN Middle English : from
Old French coillier, based on
Latin colligere (see collect).

• RED = susceptible (not

infectious)
• YELLOW = infectious
• GREY = culled (and
dead)
• Finding an “optimal”
culling strategy is a
politically and
economically sensitive
issue

Wednesday, February 24, 2010

 Culling (take 2)

• Same as last
simulation, with a
higher cull rate
• RED = susceptible (not
infectious)
• YELLOW = infectious
• GREY = culled (and
dead)

Wednesday, February 24, 2010

 Culling (take 2)

• Same as last
simulation, with a
higher cull rate
• RED = susceptible (not
infectious)
• YELLOW = infectious
• GREY = culled (and
dead)

Wednesday, February 24, 2010

 Inhomogeneous mixing

• Two segregated
subpopulations, with a
small percentage of
mixers who flow freely
back and forth
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)

Wednesday, February 24, 2010

 Inhomogeneous mixing

• Two segregated
subpopulations, with a
small percentage of
mixers who flow freely
back and forth
• RED = susceptible (not
infectious)
• YELLOW = infectious
• BLUE = recovered
(and immune)

Wednesday, February 24, 2010

 Dynamics

Wednesday, February 24, 2010

 Scales, foci & the multidisciplinary nature of
infectious disease modeling & control

- control strategies
- epidemiology
response
- public health & logistics
- economic impacts

- disease ecology
- demography
between hosts - vectors, water, etc.
- zoonoses
- weather & climate

transmission

- virology, bacteriology, mycology, etc.

within-host
- immunology

Wednesday, February 24, 2010

 Scales, foci & the multidisciplinary nature of
infectious disease modeling & control

Wednesday, February 24, 2010

 Scales, foci & the multidisciplinary nature of
infectious disease modeling & control

Wednesday, February 24, 2010

 Infection Timeline

K&R, Fig. 1.2

Wednesday, February 24, 2010

 Compartmental models
• Assumptions:
- population is well-mixed: all contacts equally likely
- only need to keep track of number (or concentration) of hosts in different states
or compartments
• Typical states
- Susceptible: not exposed, not sick, can become infected
- Infectious: capable of spreading disease
- Recovered (or Removed): immune (or dead), not capable of spreading disease
- Exposed: “infected”, but not infectious
- Carrier: “infected” (although perhaps asymptomatic), and capable of spreading
disease, but with a different probability

Wednesday, February 24, 2010

 Compartmental models
SIR: lifelong immunity S I R

SIS: no immunity S I

SEIR: SIR with latent (exposed) period S E I R

SIR with waning immunity S I R

C
SIR with carrier state S I
R
adapted from K&R
Wednesday, February 24, 2010
 An aside on graphical notations
state transitions
S I R influence

adapted from K&R

S I R A&M, Fig. 2.1

infection recovery

Petri Net: bipartite graph of places

(states) and transitions (reactions)

Wednesday, February 24, 2010

 Susceptible-Infected-Recovered (SIR)
• Dates back to Kermack & McKendrick (1927), if
not earlier
S I R
• Assume initially no demography
infection recovery
- disease moving quickly through population of
fixed size N
• Let:
dS/dt = −βSI
- X = # of susceptibles; proportion S = X/N dI/dt = βSI − γI
- Y = # of infectives; proportion I = Y/N
dR/dt = γI
- Z = # of recovereds; proportion R = Z/N
- note X+Y+Z = N, S+I+R=1
• average infectious period = 1/γ
• force of infection λ
- per capita rate at which susceptibles become
infected

Wednesday, February 24, 2010

 Transmission & mixing
• Must make assumption regarding form of transmission rate
- N = population size, Y = number of infectives, and β = product of contact
rates and transmission probability
• mass action (frequency dependent, or proportional mixing)
- force of infection λ = βY/N; # contacts is independent of the population size
• pseudo mass action (density dependent)
- force of infection λ = βY; # contacts is proportional to the population size
mass action:
κ = # contacts / unit time; c = prob. of transmission upon contact;
1-δq = prob. that a susceptible escapes infection in time δt

1 − δq = (1 − c) (κY /N )δt

δq = 1 − e−βY δt/N where β = −κlog(1 − c)

lim δq/δt = dq/dt = βY /N

δt→0

Wednesday, February 24, 2010

 SIR dynamics

S I R

infection recovery

dS/dt = −βSI
γ= 1.0
dI/dt = βSI − γI
dR/dt = γI

• Outbreak dies out if transmission

rate is sufficiently low
• Outbreak takes off if transmission
rate is sufficiently high

Wednesday, February 24, 2010

 R0 and the epidemic threshold
Introduction into fully susceptible population S I R

infection recovery

dI/dt = I(β − γ)
dS/dt = −βSI
> 0 if β/γ > 1 (grows)
dI/dt = βSI − γI
< 0 if β/γ < 1 (dies out)
dR/dt = γI

dS/dτ = −R0 SI
• define basic reproductive ratio:
dI/dτ = R0 SI − I
R0 = β/γ dR/dτ = I
τ = γt
= average number of secondary cases
arising from an average primary case
in an entirely susceptible population
• epidemic threshold at R0 = 1

Wednesday, February 24, 2010

 R0 and the epidemic threshold

R0 = β/γ
= average number of secondary cases arising from an average primary
case in an entirely susceptible population
≈ transmission rate / recovery rate

• epidemic threshold at R0 = 1
- fraction of susceptibles must exceed γ/β
- R0-1 [relative removal (recovery) rate] must be small enough
to allow disease to spread

• estimating R0 from incidence data is a major goal when

confronted with new outbreak

Wednesday, February 24, 2010

 Epidemic burnout

dS/dR = −βS/γ = −R0 S S I R

infection recovery

• integrate with respect to R:

dS/dt = −βSI
S(t) = S(0)e −R(t)R0
dI/dt = βSI − γI
R ≤ 1 =⇒ S(t) ≥ e−R0 > 0 dR/dt = γI

• there will always be some susceptibles who escape infection

• the chain of transmission eventually breaks due to the decline in
infectives, not due to the lack of susceptibles

Wednesday, February 24, 2010

 Fraction of population infected
S(t) = S(0)e−R(t)R0
S(∞) = 1 − R(∞) = S(0)e −R(∞)R0

• solve this equation (numerically) for R(∞) = total proportion of population infected

initial slope
= R0

R0 = 2

• outbreak: any sudden onset of infectious disease

• epidemic: outbreak involving non-zero fraction of population (in limit N→∞), or
which is limited by the population size

Wednesday, February 24, 2010

 SIR with demography
birth

• Allow for births and deaths

- assume each happen at a
constant rate µ
S I R
- R0 reduced to account for both
recovery and mortality infection recovery

β
R0 = death death death

γ+µ
dS/dt = µ − βSI − µS
dI/dt = βSI − γI − µI
dR/dt = γI − µR

Wednesday, February 24, 2010

 Equilibria
birth

dS/dt = dI/dt = dR/dt = 0

S I R

infection recovery

I (βS − (γ + µ)) = 0 =⇒ death death death

I = 0 or dS/dt = µ − βSI − µS
S = (γ + µ)/β = 1/R0 dI/dt = βSI − γI − µI
dR/dt = γI − µR
• Disease-free equilibrium

(S ∗ , I ∗ , R∗ ) = (1, 0, 0)
• Endemic equilibrium (only possible for R0>1):

1 µ 1 µ
(S , I , R ) = ( , (R0 − 1), 1 −
∗ ∗ ∗
− (R0 − 1))
R0 β R0 β

Wednesday, February 24, 2010

 Endemic equilibrium
1 µ 1 µ
(S , I , R ) = ( , (R0 − 1), 1 −
∗ ∗ ∗
− (R0 − 1))
R0 β R0 β

• Pool of fresh susceptibles

enables infection to be
sustained
• To establish equilibrium, must
have each infective productive
one new infective to replace
itself
• S = 1/R0

R0 = 5

Wednesday, February 24, 2010

 Vaccination
• minimum size of susceptible population needed to sustain epidemic
ST = γ/β =⇒ R0 = S/ST
• vaccination reduces the size of the susceptible population
• immunizing a fraction p reduces R0 to:
(1 − p)S
i
R0 = = (1 − p)R0
ST
• critical vaccination fraction is that required to reduce R0 < 1
1
pc = 1 − “herd immunity”
R0
alternatively, pc needed to drive endemic equilibrium to I*=0:

1 µ 1 µ K&R, Fig. 8.1

(S , I , R ) = ( , (R0 − 1), 1 −
∗ ∗ ∗
− (R0 − 1))
R0 β R0 β

Wednesday, February 24, 2010