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Mathematical modeling
Hans-Peter Duerr & Martin Eichner
Institut für Medizinische Biometrie
Universität Tübingen
Topic Slide
AddOn InfluSim 56
• Infectious Disease Epidemiology: Theory and Practice. Neil Graham. Jones and Bartlett Publishers, Inc.
• Mathematical Epidemiology of Infectious Diseases: Model Building, Analysis and Interpretation (Wiley
Series in Mathematical and Computational Biology), O. Diekmann and J. A. P. Heesterbeek.
• Epidemic Models: Their Structure and Relation to Data (Publications of the Newton Institute). Denis Mollison
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling Folie 3 / 56
Program
Lesson 1
SARS 2002/2003:
why modeling, and what
is a mathematical model?
(the example of bacterial
growth)
Logarithmic
Linear
Draw into each graph the bacterial growth curve you would expect if
• … the generation
time of the bacterium
was not 0.5h but 1h
• … the before-
Exercise 1
mentioned changes
occur simultaneously
1. Parameter:
=A2*tGen =Bakt0
"Bakt0"
2. Parameter:
"tGen"
3. Parameter
=A2*tGen =C2*multFaktor "multFaktor"
dB(t ) ~
= l B(t )
Integration dt Derivative
B(t ) = const × e
~
lt
Linear
æ B(t ) ö
ç1 - ÷
è K ø
B(t ) =
approaches zero when B0 K
the bacterial culture ~
-l t
approaches the value of B0 + ( K - B0 )e
the capacity (B(t)=K)."
lower bounds of
each axis into the
• Draw a qualitative
curve for the per 1
capita-reproduction
rate l and the num-
ber of bacteria over
time, B(t). Where is
the inflection point
of B(t)? Time
Extensions of
the SIR-model:
SIRS
SEIR
SEIRS
S dS(t) / dt = m [ S(t)+I(t)+R(t) ]
I =1
R
S Proportion susceptibles m per capita birth rate
new Infections
1
0.8
S*S
0.6
P 2(S*I)
0.4 I*I
Sum
0.2
0
0 0.2 0.4 0.6 0.8 1
Susceptible Infectious Proportion susceptible
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling Folie 24 / 56
Dynamic description: Infection
new infections
Loss of infectiousity
Mortality
Infizierten
Zahl der
dI(t) / dt = bc I(t) S(t) - g I(t) - m I(t)
dR(t) / dt = g I(t) - m R(t) Zeit
Exercise 3
Draw your qualitative prediction into the graph on how the course of the
epidemic would change (higher, faster, slower, etc) if
the contact rate between patients recover more b and g increase at the
people increases? (b ↑) rapidly? (g ↑) same time
No. of infectous people
infectious diseases –
learning by doing Program here, using
the parameters listed
• Complete file beyond
"10_SIR.txt" with the {--- Parameters ---}
equations of the SIR-
model (save your work),
and specify the initial
values (INIT S, I, R).
• Click "Run"
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling Folie 30 / 56
Aim: Performing a
Exercise 3: sensitivity analysis
Parameters|Define Sliders...
Exercise 3 (File "10_SIR.txt")
Wichtig!
Wichtig!
Definition: R0 = b c D
• R0>1: Infection can persist;
an endemic state ist possible
• R0<1: Infection cannot persist; goes extinct
D = 1 / (g+m) average duration of the infectious period
Average Critical
age at vaccination
Disease R0
infection coverage
[years] pcrit [%]
Measles 5.0 15.6 94
Pertussis 4.5 17.5 94
Mumps 7.0 11.5 91
Rubella 10.2 7.2 86
Polio 10.4 6.1 84
Diphteria 10.4 6.1 84
S¥
1
- log (S¥) = R0 (1 - S¥)
0.8
Proportion susceptible
0.6
0.4
0.2
0
1 2 3 4 5
Basic reproduction number R0
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling Folie 37 / 56
Exercise 4: Aim: Understanding the
endemic infection influence of demography
Exercise 4 (File "11_SIRreparameterized.txt")
DT 0 0.1 1
DTOUT 0 1 10
iniInfected 0 0.0001 1
lifeExpectYears 0 50 100
durationInfected 0 10 20
R0 0 15 20
0.8
Proportions
0.6 suszeptible
infizierte
0.4
immune
0.2
0
0 1000 2000 3000
Time [days]
S dS(t) / dt = m ........
(1-p) - bc I(t) S(t) - m S(t)
I dI(t) / dt = bc I(t) S(t) - g I(t) - m I(t)
m p + g I(t) - m R(t)
R dR(t) / dt = .......
S Proportion susceptible m Per capita birth rate c P (infection | contact)
I Proportion infectious b Contact rate p Proportion vaccinated
R Proportion immune g rate of loss of infectiousity
2.
S 0 = m (1-p) - bc I S - m S I=...
I 0 = bc I S - g I - m I S=...
R 0 =mp+gI-mR R=...
S S = (g + m) / (bc) = 1 / R0
I I = (1 - 1/R0 - p) m / (g + m)
R R = 1-S-I
S Proportion susceptible m Per capita birth rate c P (infection | contact)
I Proportion infectious b Contact rate p Proportion vaccinated
R Proportion immune g rate of loss of infectiousity
S
I I = (1 - 1/R0 - p) m / (g + m)
R
I Proportion infectious m Per capita birth rate = death rate p Proportion vaccinated
Basic reproduction number: g rate of loss of infectiousity
R0 = bc / (g+m)
S
0 = (1 - 1/R0 - pcrit) m / (g + m)
I
R Û pcrit = 1 - 1 / R0 =1-S
0.8
0.6
Persistence
0.4
0.2
0
0 2 4 6 8 10 12 14 16 18 20
Basic reproduction number R0
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling Folie 52 / 56
Summary
• The proportion of susceptibles in the endemic
equilibrium does not depend on the proportion p of
vaccinated children
• Transmission stops if p ³ pcrit
• The critical vaccination coverage is pcrit = 1 - 1/R0
• The model can be used for sensitivity analyses into the
effects of different vaccination strategies:
- What is the critical vaccination coverage?
- How does vaccination impact on the prevalence and incidence of the
infection?
- what is the best vaccination strategy (e. g. ring vaccination vs. mass
vaccination)?
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling Folie 53 / 56
Estimation of model parameters
m Per capita birth rate = death rate
1 / m is the life expectancy
g Loss-of-infection rate
1 / (g+m) is the average duration of the infectious period