Mathematical Modeling of Infectious Diseases

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Mathematical Modeling of Infectious Diseases

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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

Math Exploration 1

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.

Math Exploration 2

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

Math Exploration 3

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

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

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.

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

Math Exploration 4

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.

𝒅𝑴𝒕

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

𝒅𝒕

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

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

Math Exploration 5

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:

= 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

Math Exploration 6

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!

Math Exploration 7

𝒅𝒚 𝝈𝑺𝒕 𝑰𝒕

Et Year Population = 𝜷 − (𝜺 + 𝝁)𝑬𝒕

𝒅𝒙 𝑵𝒕

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

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

Math Exploration 8

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

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.

Math Exploration 9

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

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

Math Exploration 10

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.

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.

Math Exploration 11

References

• Glaser, A. (2007, April 9). Dynamics and Control of Infectious Diseases. Princeton

University. Retrieved March 11, 2014, from

http://www.princeton.edu/~aglaser/lecture2007_diseases.pdf

• Earn, D. J. (n.d.). A Light Introduction to Modelling Recurrent Epidemics.

University of Ottawa. Retrieved March 11, 2014, from

http://mysite.science.uottawa.ca/rsmith43/MAT4996/earn.pdf

• Encyclopedia of Medicine.. (n.d.). Measles. TheFreeDictionary.com. Retrieved March

11, 2014, from http://medical-dictionary.thefreedictionary.com/measles

• Gupta, S. (2012, April 23). Measles death rate drops; still a major public health

concern. The Chart RSS. Retrieved March 11, 2014, from

http://thechart.blogs.cnn.com/2012/04/23/global-measles-deaths-drop-still-a-

major-public-health-concern/

• Herrera, L. (2012, March 20). Modelo MSEIR. prezi.com. Retrieved March 11, 2014,

from http://prezi.com/enufoc0orpvy/modelo-mseir/

• Hethcote, H. W. (n.d.). The Mathematics of Infectious Diseases—. Society for

Industrial and Applied Mathematics. Retrieved March 11, 2014, from

http://web.abo.fi/fak/mnf/mate/kurser/dynsyst/2009/uke44/hethcote2000.pdf

• Introduction to Epidemic Modelling. (n.d.). University of Columbia. Retrieved March

11, 2014, from http://www.stat.columbia.edu/~regina/research/notes123.pdf

• Machira, M. (n.d.). Reduced measles and varicella passive immunity and susceptible

infants in the 21ST century. Myth or reality?. Australian Journal of Biomedical Science.

Retrieved March 11, 2014, from

http://www.sciencej.com/ajhb/maria_1_1_2011_8_12.pdf

• Medlock, J. (2002, May 24). University of Washington Applied Mathematics

Department. Math Cornell. Retrieved March 11, 2014, from

Math Exploration 12

http://www.math.cornell.edu/~vlad/math4250/various/epidemiology_intro_talk.p

df

• Orenstein, W. A., Heinman, A. R., & Strebel, P. M. (n.d.). Eradicating measles: a

feasible goal?. Measles-Rubella Initiative. Retrieved March 11, 2014, from

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Goal.pdf

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EPIDEMIOLOGY. Utrecht University. Retrieved March 11, 2014, from

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months). Data. Retrieved March 11, 2014, from

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axzz2vhzEvHcT

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2014, from

Math Exploration 13

http://homepage.math.uiowa.edu/~stroyan/CTLC3rdEd/3rdCTLCText/Chapters

/Ch2.pdf

• Health Organization. (n.d.). Measles. WHO. Retrieved March 8, 2014, from

http://www.who.int/mediacentre/factsheets/fs286/en/

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veragemcv.html

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Math Exploration 14

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