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The Ebola Medical Express

Comap paper 2015

Abstract

I could not possibly overstate the need for an urgent response. These were the words of Dr.
Tom Frieden, Director of the Centers for disease Control and prevention with regard to the 2014
Ebola outbreak. This statement by Dr. Frieden epitomizes the need for an efficient and rapid
delivery system to provide diseased ravaged areas with appropriate interventions in order to
control an epidemic outbreak. The objective of this paper is to introduce models to optimize the
eradication of Ebola by delivery of a new hypothetical medication developed by the World
Medical association. It is assumed that this medication can cure patients whose disease is not
advanced. In light of this, strategies to eradicate the disease will be centered on optimizing the
production and delivery of the medication which will meet the demands of the affected
population. In addition, the rate of spread of the disease will be modeled in order to inform us on
how to optimize the medical parameters and get the outbreak under control, ultimately
eradicating the disease within a population. We consider two major compartmental epidemic
diffusion models to accomplish this task, the SEIR model and modification of this model into the
SEIHFR by Legrand. In addition, modifications will be made to the SEIR model to include
parameters that are characteristic of the medical intervention and simulations will be performed
using the Runge-Kutta method in Sage to numerically solve systems of differential equations
which govern these models. These simulations will show that optimizing medical delivery and
production will result in a decrease in the spread of Ebola.

1 Introduction
The 2014 Ebola outbreak has been the largest ever since the various outbreaks after 1976 when it
was first discovered. The disease has its origins in West Africa and it is believed that the virus is
animal borne, particularly from the fruit fly bats. Four of the five virus strains occur in animal
hosts which are native to the region. There are various interventions which could be undertaken
in the eradication of the disease. Interventions include elimination of the animal host, isolation of
infected individuals and treatment with medication. At present medications for treating the
disease are being developed but at present there is no medically confirmed cure for Ebola.
However, we consider the application of various mathematical models in optimizing the
eradication of Ebola should such a medication be produced. In creating mathematical models for

this situation various parameters will be considered, namely: the quantity of medicine required,
possible feasible delivery systems, locations of delivery, speed of manufacturing of the drug, and
spread of the disease. In addition, this medication is assumed to cure patients who are not in the
advanced stages of the disease. Therefore, we assume that the medication will cure individuals
who are in the incubation stages of the disease. In devising the model for this we first consider
other epidemiological models and their limitations as a motivation for why our model is most
ideal for the proposed problem.

2 Mapping the Outbreak

Fig. 1 Map of the distribution of the 2014 Ebola outbreak in West Africa

Fig 2 Map of the reported cases of Ebola outbreak in 2014 (The purple line is indicative of the
range of the Pteropodidae fruit bat and the blue stars sho the outbreak found in humans) (Source:
WHO)
, n=22460

Fig 3 Graph of the 2014 confirmed Ebola cases for the countries of Graph Guinea, Liberia, and
Sierra Leone (WHO situation reports)

3 The Models
The models chosen were compartmental models. These models were used to show the spread of
the disease and were equipped with parameters that dealt with optimizing the eradication of the
disease by optimizing parameters that dealt with the distribution, productivity and quantity of
the medicine. In addition, seeing that our model is centered around optimizing Ebola eradication
based on optimizing parameters involved in medicine production and delivery, the only means of
transmission considered is that of human interaction. This is because the effect of the medication
is seen in humans and has no bearing on the animal hosts.

3.1 SEIR (Susceptible Exposed - Infected Recovered) model


SEIR models are compartmental epidemic diffusion models that have been used in modeling
multiple infectious diseases such as Malaria. The Ebola virus is transmitted by animal vectors
particularly fruit bats of the Pteropodidae family. The incubation period for the virus is 2 to 1
days. Therefore, victims are not infectious until after this period has elapsed. Therefore since
there is a period in which victims are infected but not infectious, to map the spread of the disease
we consider the classic, epidemiology SEIR model. This will inform us of how to optimize the
rate of manufacturing and delivery of the medication

Purpose of using SEIR model:


Because the medicine targets individuals at the latent stage in which they have not advanced into
the infected stage, we decided to use the SEIR model (Susceptible, Exposed, Infected,
Recovered) that specifically includes the exposed class E instead of the classic SIR model.
Flow chart for SEIR model:

Denotation:
S(t): the number of susceptible individuals at time t
E(t): the number of exposed individuals or individuals in the incubation period at time t

I(t): the number of infectious individuals at time t


R(t): number of individuals who have been infected and then removed from the possibility of
being infected again or of spreading the infection at time t
Total population size N(t) = S + E + I + R
Assumption:
Initial conditions:
S(0) =

And

S0

R0=

; E(0) =

E0

; I(0) =

I0

S 0 N
+
(the basic reproduction number) .

Explanation of

R0 :

The first term in the equation is the number of secondary infections

caused by an individual during infectious stage, and the second term is the number of secondary
infections incurred during the exposed stage. If
R0 <1, there is no epidemicif R 0 >1 ,ther e' s an epidemic .
** Our mission is to find a model that optimizes medicine manufacturing and delivering we
so that R 0 is kept control.
discuss later targets to minimize
Again, the model assumes infectivity that is reduced by a factor during the exposed period.
Thus the model has the following differential equations1:
S = -S(I+E)
E = S(I+E)-E
I = E-I
In which

1
SI is therate of susceptible people being infected ; is the meanexposed period ;

1
is the meanlength of infectious period .

1 Brauer, F., & Vez, C. (2013). Mathematical models for communicable diseases.
Philadelphia: Society for Industrial and Applied Mathematics.

3. 2 Medical Modeling based on epidemic diffusion modeling

During an epidemic outbreak health care providers are tasked with effectively delivering
medication to the affected regions as quickly as possible and meeting the demands of the affected
areas. In addition, these medical distributions are time sensitive so as to control the spread of the
disease, diminishing the spread and ultimately eradicating the disease. The rate of delivery of
medication to the affected regions is going to depend on the rate of production of the medication
and dynamics of the delivery routes. The SEIR model previously described therefore needs to be
modified to take these things into consideration. Liu and Xiao reconcile this issue by issue by
introducing a model for optimizing medical resource allocation by employing the use of genetic
algorithms. In addition an epidemic diffusion SEIRS model is used as an indication of the extent
to which medical allocation and distribution should be updated based on the proposed model.
The SEIR model can then be updated to show the decrease the spread of the disease. Liu and
Xiao propose a time-space model for optimizing medical allocation during epidemic outbreaks.
The spatial component is realized in the transfer of the medication from ADC - area distribution
centers (ADC) for the particular pharmaceutical product to district distribution centers (DDC)
and ultimately to emergency designated hospitals (EDH). Liu and Xiao propose a time-space
model for optimizing medical allocation during epidemic outbreaks. Their dynamic system for
the SEIRS diffusion model is governed by the following differential equations:
dS
kS (t ) I (t ) R(t )
dt
dE
kS(t ) I (t ) kS(t ) I (t )
dt
dI
kS (t ) I (t ) ( ) I (t )
dt
dR
I (t ) R (t )
dt

Where k is the average degree of distribution;


is the propagation coefficient of the epidemic;

is the rate of recovered people who do not have immunity; is the recovery rate;
is the

death rate; represents the incubation period of the disease, and k, , , , , > 0
3.3 Legrands SEIHFR Model

This model takes into account the spread of the disease from bodies that have not been properly
disinfected or buried properly.

Fig. 4: Table showing the transitions between compartments of Legrands SEIHFR model
(Legrand et al)
Denotations:
S - susceptible individuals
E - number of exposed individuals
I, - number of infectious cases in the community
H - number of hospitalized cases
F - number of cases who are dead but not yet buried
R - number of individuals removed from the chain of transmission
I, - transmission coefficient in the community
H - transmission coefficient at the hospital
F - transmission coefficient during funerals.
The formula for R0 is the spectral radius of the next generation matrix of the following system:


( 1 SI + H SH + F SF )
dS 1
=

dt N
dE
1
=
E
dt N ( 1 SI + H SH + F SF )
dI
=E( h 1 + i ( 11 ) ( 1 1 ) + d ( 1 1) 1 ) I
dt
dH
= h 1 I ( d h 2 + i h ( 1 2) ) H
dt
dF
= d ( 11 ) 1 I + d h 2 H f F
dt

dR
= i ( 11 ) ( 1 1 ) I + i h ( 1 2 ) H + f F
dt

F
=R 0 H + R0 I + R 0 F
f

R0= 1 + h 1 H

[ d h 2+ i h(1 2) ]/ +

Where
1

= h 1+ d ( 11 ) ( 1 1 )

is the mean duration of the infectious period for patients who survived the illness

3.3 Simulating the SEIR model with medical intervention


Given the importance of medical treatment to control and prevent the spread of
infectious diseases, the treatment rate of the infection is assumed to be
proportional to the number of infective individuals in classic SIR epidemic models

[1]. In order to describe the effect of limited medical treatment, Zhang and Liu [1]
introduced a continually differentiable treatment function:

h( I )

rI
1 I

(1)

where I denotes the number of susceptible individuals and r/ models the

1 I

maximum supply of medical resources per unit time and 1/(


reverse effect of delayed treatment in the infected individuals.

) describes the

Since the transmission of infectious disease also depends on the efficiency of the
supply of available medical resources (which depends on factors like speed of the
production of drugs, control strategies, speed of delivery), Zhou and Fan [2]
modified (1) as follows:

h * (I )

where

I
I

(2)

represents the maximum medical resources supplied per unit time and

> 0 is the efficiency of the medical resource supply. Thus, and have their own
significance in the epidemic model. To explore the dynamics of SIR model with
limited medical resources, Zhou and Fan [2] constructed the SIR as follows:

dS
SI

dS
dt
1 kI
dI
SI
I

(d )
dt 1 kI
I
dR
I
I
dR
dt
I

(3)

In (3) S(t),I(t) and R(t) represents the numbers of susceptible, infective and
recovered individuals at time t, respectively.

is the recruitment rate of the

population, d is the natural death rate of the population,

is the natural recovery

rate, and is the disease-related mortality. The incidence rate


inhibition effect due to psychological factors [2].

SI
1 kI

reflects the

Following a SEIR model proposed by Astacio, Biere et.al [3] for ebola, we include
Zhou and Fans continually differentiable treatment function to understand the
effect of the limitedness of the medical resources and the efficiency of the supply of
medicine on the transmission of Ebola.

dS
S ( I qE ) / N
dt
dE
E
S ( I qE ) / N E
dt
E
dI
E I
dt
dR
E
I
dt
E

(4)

In this model, S(t),E(t),I(t) and R(t) represents the numbers of susceptible, latent,
infective and recovered individuals at time t, respectively and N = S(t) + E(t) + I(t)

+ R(t). 1/ is the average time for a latent individual to become infectious, 1/ is


the average time it takes for an individual die after entering the infectious stage, q
is a weight factor (0 q 1), as the suspected individual has a lower chance of
getting infected from an latent individual [3], and
medical resources supplied per unit time and
resource supply [2].

represents the maximum

> 0 is the efficiency of the medical

Model assumptions:
1. The population studied will be constant during the epidemic. Thus, there will
not be deaths from any other outside factors. Also, the number of births
during the time period is assumed to be negligible as Ebola epidemics usually
last from three to four months [3].
2. The individuals in the recovered class will not return to the susceptible class
since there has not been a case in which a person who survived Ebola has
contracted the disease again [3].
3. The individuals in the latent class cannot infect other individuals in the same
class.
4. The model also assumes that individuals in infectious class can be recovered,
although our medicine specifically targets the individuals in the latent class.

Also, the death and recovery rate of an infectious individual are taken to be
the same [3].
In order to understand the effect of the medical intervention in the transmission of
infectious diseases like Ebola, we formatted the SEIR model and ran a simulation in
Sage using the Runge-Kutta method to solve the following system of differential
equation:
Simulation without medical intervention:

dS (t )
S (t ) I (t )
dt
dE (t )
S (t ) I (t ) E (t )
t
dI (t )
E (t ) I (t )
dt
dR (t )
I (t )
dt
Here we have normalized the total population and assumed that it is constant in the
entire time period.

After running the simulation, with t= 300,


= (2/10^6), = 1/14, = 1/10 (the
parameters were derived from real-time data in Ebola) and susceptible population =
42000, exposed population = 7000, infected population = 4100, recovered
population = 2000 we obtained the following population vs time graph:

Graph I. Simulation results without intervention


Legend:
Black color = susceptible population
Red = exposed population
Blue = infected population
Green = recovered population
Simulation with medical intervention:
In order to understand the effect of the medical intervention, a parameter that
includes the effect of intervention was added to the SEIR model:

dS (t )
S (t )( I (t ) dE (t ))
dt
dE (t )
S (t )( I (t ) dE (t )) E (t )
t
dI (t )
E (t ) I (t )
dt
dR(t )
I (t )
dt
With constant parameters from part I, we included d = 5 and ran a simulation:

Graph II. Simulation results with intervention with parameter d= 25

Legend:
Black color = susceptible population
Red = exposed population
Blue = infected population
Green = recovered population

Graph III. Simulation results with intervention parameter d= 50


Legend:
Black color = susceptible population
Red = exposed population
Blue = infected population
Green = recovered population

4 Conclusion
After comparing Graph I, Graph II and Graph III, we observe that medical
intervention significantly reduces the susceptible population, infectious and exposed
population. In addition, after the intervention parameter reaches an optimum value,
the graph becomes saturated. This means that interventions after a particular point
will not generate any appreciable decreases in the spread of Ebola.

5 References

[1] Jinhong Zhang, Jianwen Jia, and Xinyu Song, Analysis of an SEIR Epidemic Model with
Saturated Incidence and Saturated Treatment Function, The Scientific World Journal, vol. 2014,
Article ID 910421, 11 pages, 2014. doi:10.1155/2014/910421
[2] Linhua Zho and Meng Fan, Dynamics of an SIR epidemic model with limited medical
resources revisited, Nonlinear Analysis: Real World Applications(2011),
doi:10.1016/jnonrwa.2011.07.036
[3] Jaime Astacio, DelMar Breire et.al, Mathematical Models to study the outbreaks of Ebola,
Retrieved from https://ecommons.library.cornell.edu/bitstream/1813/31962/1/BU-1365-M.pdf
[4] Ming Liu and Yihong Xiao, Optimal Scheduling of Logistical Support for Medical Resource
with Demand Information Updating, Mathematical Problems in Engineering, Article ID
765098, in press.
[5] Legrand J, Grais Rf,Boelle PY, Valleron AJ, Flahault AJ. Understanding the dynamics of
Ebola epidemics. Epidemiology and Infection 2007;135(4):610-621.
doi:10.1017/S0950268806007217.

Retrieved : http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/distribution-map.html
Retrieved from: http://i100.independent.co.uk/article/how-worried-should-we-be-about-thespread-of-ebola--g1RbWHRfGl
WHO situation reports beginning on March 25, 2014 through the most recent situation report on
February 4, 2015.

Graph 2: Total suspected, probable, and confirmed cases and deaths of Ebola virus disease in
Guinea, March 25, 2014 February 1, 2015, by date of WHO Situation Report, n=2975
Graph 3: Total suspected, probable, and confirmed cases and deaths of Ebola virus disease
in Liberia, March 25, 2014 February 1, 2015, by date of WHO Situation Report, n=8745
Graph 4: Total suspected, probable, and confirmed cases and deaths of Ebola virus disease
in Sierra Leone, March 25, 2014 February 1, 2015, by date of WHO Situation Report,
n=10740

Gra2: Total suspected, probable, and confirmed cases and deaths of Ebola virus disease in
Guinea, March 25, 2014 February 1, 2015, by date of WHO Situation Report, n=2975

Graph 3: Total suspected, probable, and confirmed cases and deaths of Ebola virus disease
in 4 February 1, 2015, by date of WHO Situation Report, n=8745one, March 25, 2014
February 1, 2015, by date of WHO Situation Report, n0

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