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Math Exploration

Mathematical modeling of infectious diseases

Daniel Gutiérrez Pavón A01420372


TABLE OF CONTENT
Mathematical modeling of infectious diseases ................................................ 1
Rationale................................................................................................... 1
Introduction .............................................................................................. 1
Epidemiology and mathematical models ................................................................................. 1
Measles ................................................................................................................................ 2
Epidemic Models .................................................................................................................. 2
The MSEIR Model ................................................................................... 3
Compartments and variables .................................................................................................. 3
Population Growth ............................................................................................................... 3
Passive Immune Infants ........................................................................................................ 4
Susceptible Individuals .......................................................................................................... 6
Exposed Population .............................................................................................................. 7
Infectives .............................................................................................................................. 8
Removed with immunization ............................................................................................... 10
Herd immunity................................................................................................................... 11

Conclusion ............................................................................................. 11
References .............................................................................................. 12

Math Exploration ii
Math Exploration
Mathematical modeling of infectious diseases

Rationale
For this project I have chosen to research and analyze the use of
mathematical models by applying it to epidemics. The reason of
my choice is simply because people usually think that mathematics
can only be used for scientific research, but in this paper I am going
to prove how math can also be used to explain a problem of public
concern that affects primarily the society; and also when I was
looking for possible topics I found this one which is really
interesting and uses one of my favorite mathematical tools,
calculus.

The aim of this exploration is to demonstrate at the end how math can give us an accurate
year to estimate the annihilation of the measles virus on a global scale.

Introduction
Epidemiology and mathematical models

Epidemiology is the study of the distribution and determinants of health related states or
events, enabling us to keep control of diseases and health problems we have been suffering
since the beginning of our times. And it is of common knowledge that throughout history
we have suffered from terrible diseases, such as the Black Plague in the XIV century, which
have taken millions of lives. Nowadays, even though we have developed more ways to
reduce the death rate on a global scale, infectious diseases account for almost thirty percent
of the deaths in developing countries. This is why throughout this exploration we will
review the process to make a mathematical model for an infectious disease.

It is really important first that we determine what is a mathematical model and why are they
so important for mankind today. Mathematical models, which describe systems using
mathematical concepts and language, started being used in epidemiology since the late 19th
and early 20th century due to the large public health concern for diseases that increased the

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mortality rates among children, such as measles. The use of mathematical models in this
field aims to understand the spreading mechanisms of a disease, gives an idea of what to
expect on the future course of the epidemic and allow us to figure out the best ways we may
control the spread of the epidemic.

In September 2000, during the Millennium Summit of the United Nations, all 191 Member
States agreed to try to achieve eight Millennium Development Goals by 2015. Two of these
are concerned with health problems, the shortening of child mortality rates and to combat
infectious diseases, and there is one particular disease that the WHO has been concerned for
several years that could help to accomplish these goals, measles.

Measles

Measles is one of the most infectious diseases and one of the leading causes of death among
children, before the implementation of the immunization programs, the outbreaks of the
disease caused millions of deaths each year. Coughing and sneezing, contact with infected
people or with nasal and throat secretions, are the main causes for the spread of the virus;
there is no specific antiviral treatment and most people recover from 2-3 weeks. Since 1963,
measles can be prevented through immunization vaccines, and in 2012, 84% of the world’s
children received one dose of measles vaccine by their first birthday. Thanks to this, the
number of cases has decreased dramatically from an estimated of 4 million cases in 1980 to
339, 845 cases in 2010. By the end of 2020 the WHO expects to eradicate measles in at least
five WHO regions, goal that could be achieved with a strategic implementation that would
keep high vaccination coverage, surveillance and rapid response of disease outbreaks, and to
build social awareness.

Epidemic Models

There are two types of models that are useful to study the behavior of infectious diseases,
stochastic and deterministic models. For the purpose of this exploration we will focus in the
later ones.

A deterministic system is a system that does not allow any randomness in the future
outcomes determined by known relationships among states and events. This type of model
categorizes the individuals of a population into subgroups, which represent each stage of the
epidemic, determining the size of each compartment as the transition rates tell us the
changes they suffer as the variable of time changes. There are several deterministic
compartmental models such as the SI, SIR, SIS, SIRS, SEIS, SEIR and the MSEIR model.
We will be using the latter one in order to build a more accurate epidemic model.

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The MSEIR Model
Compartments and variables

This specific model aims to classify a certain population into five categories, which its size
can be determined by a differential equation that represents the change suffered into each
compartment. The compartments are represented by the following variables, which should
always comply with the equation 𝑁! =   𝑀! + 𝑆! + 𝐸! + 𝐼! + 𝑅! :

• M(t)   Represents the number of infants that acquire passive immunity for a certain
period, and can be susceptible after the period has passed.
• S(t) Represents the number of individuals, who have not gotten diseased and can
become infected after exposure to the virus.
• E(t) Represents the individuals that got diseased, but they are still within the latent
period they cannot show any symptoms and infect other people.
• I(t) Represents the number of people that are infected, being able to pass the
disease to the susceptible subgroup.
• R(t)  Within this last subgroup, we can find all the people who have recovered
from the disease and cannot get the disease again and infect others.

Population Growth

Regularly, the epidemic models do not take into account a growing population, making
some assumptions that make them less real. Some of these assumptions include a
population that is large and constant, homogeneous mixing, infection rate proportional
to the number of infectives and a recovery rate that is constant. But throughout this
model we will leave aside the population as a constant and will make it be a growing
population, where the variable N will symbolize the population.

To do this we will use a simple differential equation that will allow us to get an estimate
of the increase suffered through time, the formula we are going to use is the next one:

𝑑𝑁!
= 𝛼 − 𝜇 𝑁!
𝑑𝑡

The equation above helps us to understand the rate at which the population increases,
being 𝛼 the birth rate at t = 0 in our model we will be starting in 2010, when the birth

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rate equaled 19.57 per thousand people, so 𝛼 will be 0.01957; and 𝜇 will be our death
rate at t = 0, which in our case is 8.05 per thousand people, being 𝜇 equal to 0.00805.
And finally N stands for the population; then the yield of the equation will be added to
the following year so that we can observe the increase of the population, this calculation
can be done with the use of a spreadsheet without forgetting to establish 𝛼 and 𝜇 as
constants.

𝒅𝑵
Nt Year Population = 𝜷 − 𝝁 𝑵𝒕
𝒅𝒕

N0 2010 6,916,183,482   79,  674,  434  


N10 2020 7,755,525,817   89,  343,  657  
N20 2030 8,696,730,048   100,  186,  330  
N30 2040 9,752,158,049   112,  344,  861  
N40 2050 10,935,671,924   125,  978,  941  

And the graph will look like this;

Population Growth
12
Population in billions

10
8
6
Fig. 1 4
2
0
2000 2010 2020 2030 2040 2050 2060
Year Population Growth

As we can see in Fig. 1 we were able to make a prediction of the population until 2050, and
if we compare this data to population expected by the UN in the same year, which is 10.9
billion, we can say that our prediction is really accurate.

Passive Immune Infants

When we talk about passive immune infants or M(t), as it was previous said, we are talking
about the number of babies born immunized for a certain period thanks to the passing of
antibodies from the mother to the child by breastfeeding. In the case of measles, the babies

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can only be immune for 6 months, but because only 82% of the population is immune to
this disease and only 30% of the mothers can breastfeed, it leaves us with only 24.6% of
newborns that have passive immunity. The next differential equation can be used to
determine the net increase of the M(t) subgroup:

𝑑𝑀!
=  𝛼 𝑁! − 𝑆! − (𝛿 − 𝜇)𝑀!
𝑑𝑡

This last equation refers to the change that the M(t) subgroup suffers through time, taking
into account that there will be an increase as there are more newborns in the population that
are immunized, without the ones that are susceptible from birth, enter this subgroup; and a
decrease as the children of the initial M(t) start losing its immunity at a rate 𝛿 or as they die
at a rate 𝜇. In this case 𝛿 will be 24.6%, which we had already established as the percent of
newborns that have passive immunity. Our initial values for N, S and M will be
6’916’183’482,  1’207’015’778  and  160’540’270  respectively.    

Our  table  will  look  like  this;  

𝒅𝑴𝒕
Mt Year Population =  𝜶 𝑵𝒕 − 𝑺𝒕 − (𝜹 − 𝝁)𝑴𝒕
𝒅𝒕

M0 2010 160,540,270   70,943,156  


M10 2020 480,054,850   11,653,528  
M20 2030 575,651,268   10,350,016  
M30 2040 680,190,  283   10,247,444  
M40 2050 784,882,776   9,765,886  
 

and  graphed  should  look  like  this  

 
Passive Immune Infants
1
Population in billions

0.8

0.6
Fig. 2 0.4

0.2

0
2000 2010 2020 2030 2040 2050 2060
Year Passive Immune Infants

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As we can see in Fig. 2 the graph shows an increase of the children with immunity,
highlighting that the change suffered at the beginning will be dramatic, but it can also be
observed that at t = 15 it stabilizes and then continues with the increase at a slower rate.
Also we have to remember that the population will also increase, so the fact that there are
more babies with immunity when they are born does not mean that we are making some
progress with the eradication of measles, we need to look at the other subgroups so that we
can really estimate our progress.

Susceptible individuals

The number of individuals who have not gotten the disease are put into this subgroup,
which changes as the immune children stop having passive immunity, causing an increase.
The decrease of the function will be caused by the contagious rate, the death rate of the
susceptible group, and a vaccination rate that we will assign. Our differential function will
be as the following:

𝑑𝑆 𝜎𝑆! 𝐼!
=  𝛼𝑆! + 𝛿𝑀! − 𝛽 − 𝜇𝑆! − 𝜗𝑁!
𝑑𝑡 𝑁!

First of all, we already know the values of 𝛼,  𝛿  and  𝜇, we just have to define our contact
!!! !!
rate, which will be solved by 𝛽 !!
. The 𝜎 equals to the number of contacts, in the case of
measles, our value will be 9; 𝛽  stands for the probability that you really get infected, which
in our case will be 85%. When I say that we will be taking into account the vaccination rate
assigned by us, I mean that every year we will be adding a new percentage of the population
to the R(t) group by making sure that they are vaccinated, in our case 𝜗= 0.01152. Our
table should give us the next values:

St Year Population 𝒅𝑺 𝝈𝑺𝒕 𝑰𝒕


=  𝜶𝑺𝒕 + 𝜹𝑴𝒕 − 𝜷 − 𝝁𝑺𝒕 − 𝝑𝑵𝒕
𝒅𝒕 𝑵𝒕
S0 2010 1,  207,  015,  778   -­‐696,  666,  864  
S10 2020 957,  481,  149   -­‐11,  030,  161  
S20 2030 725,  595,  592   -­‐37,  164,  731  
S30 2040 371,  111,  535   -­‐24,  913,  693  
S40 2050 227,  650,  841   -­‐5,  365,  147  

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Giving us the graph below,

Susceptible
1.4
Population in billions
1.2
Fig. 3 1
0.8
0.6
0.4
0.2
0
2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 2055
Year Susceptibles

After watching this graph we can see that there will be a decrease in the number of
susceptible, the rate at which it goes down will start being a really drastic change but will
stabilize through time. At the end of this exploration we will need to come back to this so
that we can make an accurate prediction for the year where the eradication will occur.

Exposed population

An individual within this subgroup have been infected by the virus, but they are still within
the latent period, having no symptoms and not being able to pass the disease to others. The
input of this subgroup happens when the virus infects the people in the susceptible group,
and the output occurs when the latent period o the disease passes and when the people
within this group start dying. In the case of measles the latent period lasts 7 days, but to
build our model we will need the part this value represents within our time lapse, which is 1
year; so we will divide 7 over 365 days, giving us as a result 0.01918. This last value is
going to be placed as 𝜀 , which represents our average latent period. The formula we will use
to build our model is;

𝑑𝐸 𝜎𝑆! 𝐼!
=  𝛽 − (𝜀 + 𝜇)𝐸!
𝑑𝑡 𝑁!

our table of values should give us the next results:

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𝒅𝒚 𝝈𝑺𝒕 𝑰𝒕
Et Year Population =  𝜷 − (𝜺 + 𝝁)𝑬𝒕
𝒅𝒙 𝑵𝒕

E0 2010 17,  500,  000   42,  913,  667  


E10 2020 372,  444,  012   40,  669,  243  
E20 2030 893,  830,  775   62,  610,  176  
E30 2040 1,  468,  619,  105   44,  183,165  
E40 2050 1,  806,  805,  421   25,  894,  061  

Allowing us to build the next graph;

Exposed
2
Population in billions

1.5
Fig. 4
1

0.5

0
2000 2010 2020 2030 2040 2050 2060
Year
Exposed

The graph in Fig. 4 gives us an increasing function with really small oscillations that tell us
that increase rate of the population within this subgroup will vary through time, which is a
really natural behavior because as your population grows the number of individuals getting
infected is always going to increase at different rates. Obviously there are many other factors
that could change the behavior of our graph, such as all the random variations that affect the
risks of exposure, where it is more likely to end up with more population getting diseased in
less time, because we would be doing a stochastic model instead of a deterministic one.

Infectives

Now is the time where we will be analyzing if the number of infectious people, which
means that they have the disease and are able to transmit it. The first thing we need to know
is that for measles, the disease is infectious for about 10 days. The differential equation to

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get this model is determined by the increase of infected people who have surpassed the
latent period of the disease and will decrease as the number of deaths within the subgroup
increases and as the infectious time is over, leaving us an equation that looks like this;

𝑑𝐼
=  𝜀𝐸! − (𝛾 + 𝜇)𝐼!
𝑑𝑡
!"
where 𝛾  represents the average infectious time, being the value for measles of 𝛾= !"#, below
we can see our table of values and the graph of the subgroup’s population.

𝒅𝑰
It Year Population =  𝜺𝑬𝒕 − (𝜸 + 𝝁)𝑰𝒕
𝒅𝒕

I0 2010 32,  500,  000   -­‐816,  419  


I10 2020 53,  798,  517   40,  669,  243  
I20 2030 133,  225,  023   62,  610,  176  
I30 2040 289,  132,  252   44,  183,165  
I40 2050 471,  515,  904   25,  894,  061  

Infected
0.5
Population in billions

0.4

Fig. 5 0.3

0.2

0.1

0
2000 2010 2020 2030 2040 2050 2060
Year Infected

As you may see in Fig.5, there is no deceleration in the number of people getting infected,
but initial amount of people infected is multiplied by a factor of 10. However, as we will
explain at the end this is a future that we will not have to bare, yes the number of infected
will increase but not to such high levels.

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Removed with immunization

Finally we have reached the last subgroup of our model, within this subgroup we can find
all the people who have already had the disease and are not able to get it again, and also all
the ones who have acquired immunity through vaccination campaigns; making the only
way to get out of this after dying. So our equation to know the number of people who have
already gotten immunized looks like this;

𝑑𝑅
=  𝛾𝐼! + 𝜗𝑁! − 𝜇𝑅!
𝑑𝑡

here are the results of our differential equation and how it should look like when graphed.

𝒅𝑹
Rt Year Population =  𝜸𝑰𝒕 + 𝝑𝑵𝒕 − 𝝁𝑹𝒕
𝒅𝒕

R0 2010 5,  498,  627,  434   36,300,  894  


R10 2020 5,  891,  747,  290   43,  389,  024  
R20 2030 6,  365,  427,  390   52,  676,  832  
R30 2040 6,  943,  104,  874   64,  374,  298  
R40 2050 7,  644,  816,  982   77,  356,  408  

Recovered
10
Population in billions

6
Fig. 6
4

0
2000 2010 2020 2030 2040 2050 2060
Year Recovered

In Fig.6, we can see more clearly that even though, as we had discussed before, the number
of infectives increases that does not mean that we are having more troubles dealing with
measles, because the number of immunized people continues increasing and if we could see

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a stagnation in this graph, then we would be in real troubles. Now, there is one factor that
we haven’t discussed that will allow us to see if we can eradicate measles before 2050, herd
immunity.

Herd immunity and vaccination

An outbreak does not necessarily has to take place, when the number of susceptible has
decreased significantly and the number of immunes is kept at a constant level through
actions such as vaccination, providing an indirect protection to the susceptible population,
this is called herd immunity. When we talk about measles, the susceptible population needs
to be less than 5% of the total population to eradicate the disease; coming back to Fig. 3, we
can see that in 2037 the number of susceptible has reached to a 4.91% of the total
population. So we can say that by 2037, we will have not to worry about this disease, but
this will just happen if we continue increasing the number of vaccinated by 1.15% percent
each year.

Conclusion

Epidemic models allow us to make predictions of how a disease will behave and allows us
to think for the best ways to avoid outbreaks. Math helps us to have a more realistic idea of
the future’s outcome, by taking into account patterns seen in history and putting them in
differential equations to observe the changes suffered within the population. Some people
think that calculus is not useful in real life, but as we have proven above, it is one of the
most reliable tools we have to predict the future.

Now that we made our epidemic model, we can conclude that measles’ eradication is
feasible if we continue with an increase of the vaccinated percentage population. Right now,
the WHO has only as a goal to eradicate it in only 5 regions by 2020, but if we continue
taking measures to avoid large outbreaks we can make measles the third disease eradicated
in man’s history, being the first smallpox and the future to be polio.

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