Beruflich Dokumente
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&
Mathematical modeling
Hans-Peter Duerr & Martin Eichner
Institut fr Medizinische Biometrie
Universitt Tbingen
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Program
Topic
Slide
Lesson 1
Exercise 1
11
Exercise 2
17
Lesson 2
19
Exercise 3
29
Exercise 4
38
Lesson 3
41
Exercise 5
44
InfluSim
56
AddOn
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Literature selection
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
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Lesson 1
Program
SARS 2002/2003:
why modeling, and what
is a mathematical model?
(the example of bacterial
growth)
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Country
China
Hong Kong
Taiwan
Kanada
Singapur
Vietnam
USA
Philippinen
Deutschland
906
[%]
7
17
27
16
14
8
0
14
0
10.8%
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Hotel Metropole
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e.g. between
Chicago and New
York 25.000
Passengers per day
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Prediction
Logarithmic
Linear
l = 1/ D
Bi = 2 Bi -1
B(t ) = B0 2l t
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Exercise 1:
preliminary considerations
Draw into each graph the bacterial growth curve you would expect if
the culture was
started with 10000
bacteria, rather than
1 bacteria
Exercise 1
the generation
time of the bacterium
was not 0.5h but 1h
the beforementioned changes
occur simultaneously
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling
Folie 11 / 56
=Bakt0
1. Parameter:
"Bakt0"
2. Parameter:
"tGen"
=A2*tGen
=C2*multFaktor
3. Parameter
"multFaktor"
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Exercise 1
results
l = 1/ D
Integration
"is proportional
to the individual
rate of division l
"
"and proportional
to the number of
bacteria reproducing
at time t "
dB(t ) ~
= l B(t )
dt
~
lt
B(t ) = const e
Total number of bacteria at time t
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Derivative
B(t )
1 K
Linear
B(t ) =
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B0 K
B0 + ( K - B0 )e
~
-l t
Summary
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Exercise 2:
preliminary considerations
Draw a qualitative
curve for the per
capita-reproduction
rate l and the number of bacteria over
time, B(t). Where is
the inflection point
of B(t)?
Exercise 2
Time
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Exercise 2 ("00_bacterialGrowth.txt")
Exercise 2:
First steps
Aim: first steps with modeling
software
Complete file
"00_bactGrowth.txt" with the
equations of the bacterial growth
curve (save your work), and specify
the initial value B(0).
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Lesson 2
Program
Deterministic models:
SIR-model, theory, basic
reproduction number R0,
epidemic vs. endemic
case
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SIR-Model
Extensions of
the SIR-model:
SIRS
SEIR
SEIRS
Common way of
representing a model:
Compartiments
& Transititions
Susceptible
Infectious
immune
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Information needed
Durations:
Rates:
contact rate(s)
Probabilities:
P(infection | transmission)
Demography:
Disease:
....
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling
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S dS(t) / dt = m
[ S(t)+I(t)+R(t) ]
=1
R
S Proportion susceptibles
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R
S Proportion susceptible
I Proportion infectious
b Contact rate
R Proportion immune
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling
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P (infection | contact)
1
0.8
P
S*S
2(S*I)
I*I
Sum
0.6
0.4
0.2
0
Susceptible
Infectious
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R
S Proportion susceptible
I Proportion infectious
b Contact rate
R Proportion immune
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling
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P (infection | contact)
R dR(t) / dt = g I(t)
S Proportion susceptible
I Proportion infectious
b Contact rate
R Proportion immune
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P (infection | contact)
I Proportion infectious
b Contact rate
R Proportion immune
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P (infection | contact)
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www.uni-tuebingen.de/modeling/Mod_Pub_Software_SIR_en.html
Initialisation
Exercise 3:
preliminary considerations
Zeit
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
people increases? (b )
Time
Exercise 3
Zahl der
Infizierten
Time
Time
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Exercise 3:
Aim: Performing a
sensitivity analysis
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Wichtig!
Wichtig!
Wichtig!
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Disease
Measles
Pertussis
Mumps
Rubella
Polio
Diphteria
Average
age at
infection
[years]
5.0
4.5
7.0
10.2
10.4
10.4
R0
15.6
17.5
11.5
7.2
6.1
6.1
Critical
vaccination
coverage
pcrit [%]
94
94
91
86
84
84
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Epidemic
SIR Model; without births and deaths
bc = 0,5/day, g = 0,1/day, m = 0/day R0 = 5
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Epidemic
SIR Model; without births and deaths
bc = 0,2/Tag, g = 0,1/Tag, m = 0/Tag R0 = 2
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Susceptible
Infectious
Resistent
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Proportion susceptible
- log (S) = R0 (1 - S)
0.8
0.6
0.4
0.2
0
1
2
3
4
Basic reproduction number R0
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Exercise 4:
endemic infection
Minimum
Use
Maximum
STOPTIME
100
5000
DT
0.1
DTOUT
10
iniInfected
0.0001
lifeExpectYears
50
100
durationInfected
10
20
R0
15
20
For R0=15 (Measles-like) simulate an extended period of time by increasing STOPTIME from 100 to 5000 days (=13.7 years)
Simulate a population with a lower life expectancy (developing countries) by decreasing lifeExpectYears from 50 to 30 years.
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Endemic case
SIR Modell with demography
bc = 0,5/day, g = 0,1day, m = 0,0005/day R0 = 5
Proportions
1
0.8
suszeptible
infizierte
immune
0.6
0.4
0.2
0
0
1000
2000
Time [days]
3000
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Summary
Neglecting births and deaths,
we model an epidemic scenario;
after the epidemic, a proportion of susceptibles,
which depends on R0, remains
logKurve
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Lesson 3
Program
Vaccination:
final size of an epidemic,
critical vaccination coverage
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I Proportion infectious
b Contact rate
R Proportion immune
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P (infection | contact)
S dS(t) / dt = m ........
(1-p) - bc I(t) S(t) - m S(t)
I
m p + g I(t) - m R(t)
R dR(t) / dt = .......
S Proportion susceptible
I Proportion infectious
b Contact rate
p Proportion vaccinated
R Proportion immune
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P (infection | contact)
Exercise 5: Vaccination
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Exercise 5: Vaccination
Technical remark:
1.
2.
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Exercise 5: Vaccination
For R0=15, increase
p up to a value when
there is no epidemic
anymore. This is the
ciritical vaccination
coverage p*. Repeat
the procedure for
R0=10, 5 and 2, and
plot your results in
the graph to the right.
What is the critical
vaccination coverage
when the basic reproduction number tends
to values of R01
p*
1
0.8
0.6
0.4
0.2
0
R0
0
10
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15
Endemic equilibrium
no change of model variables in the endemic equilibrium
0 = m p + g I(t) - m R(t)
S Proportion susceptible
I Proportion infectious
b Contact rate
p Proportion vaccinated
R Proportion immune
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P (infection | contact)
Endemic equilibrium
no change of model variables in the endemic equilibrium
0 = m (1-p) - bc I S - m S
0 = bc I S - g I - m I
0 =mp+gI-mR
I=...
S=...
R=...
S Proportion susceptible
I Proportion infectious
b Contact rate
p Proportion vaccinated
R Proportion immune
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P (infection | contact)
Endemic equilibrium
Estimate R0 from the
proportion of
susceptibles in the
endemic equilibrium
R0 = bc / (g+m)
S = (g + m) / (bc) = 1 / R0
R = 1-S-I
= (1 - 1/R0 - p) m / (g + m)
S Proportion susceptible
I Proportion infectious
b Contact rate
p Proportion vaccinated
R Proportion immune
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P (infection | contact)
S
I
= (1 - 1/R0 - p) m / (g + m)
R
I Proportion infectious
p Proportion vaccinated
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S
I
R
0 = (1 - 1/R0 - pcrit) m / (g + m)
pcrit = 1 - 1 / R0 =1-S
To eliminate a disease, it is not necessary to
vaccinate the whole population
Hans-Peter Duerr, University of Tuebingen, www.uni-tuebingen.de/modeling
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Proportion vaccinated
Elimination
0.8
0.6
Persistence
0.4
0.2
0
0
10
12
14
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16
18
20
Summary
The proportion of susceptibles in the endemic
equilibrium does not depend on the proportion p of
vaccinated children
Transmission stops if p pcrit
The critical vaccination coverage is
pcrit = 1 - 1/R0
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Loss-of-infection rate
1 / (g+m) is the average duration of the infectious period
R0
pcrit
bc
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Vergleich:
deterministische vs. stochastische Modelle
Wichtig!
Wichtig!
Wichtig!
Deterministische Modelle
stochastische Modelle
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AddOn: InfluSim
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