- Research
- Open Access
Modeling the effect of quarantine and vaccination on Ebola disease
- Thomas Wetere Tulu^{1, 3}Email author,
- Boping Tian^{1}Email author and
- Zunyou Wu^{2}
https://doi.org/10.1186/s13662-017-1225-z
© The Author(s) 2017
- Received: 9 January 2017
- Accepted: 1 June 2017
- Published: 23 June 2017
Abstract
Ebola virus infection is a severe infectious disease with the highest case fatality rate which has become the global public health treat now. What makes the disease the worst of all is no specific effective treatment available, its dynamics is not much researched and understood. In this article a new mathematical model incorporating both vaccination and quarantine to study the dynamics of Ebola epidemic has been developed and comprehensively analyzed using fractional derivative in the sense of the Caputo derivative of order \(\alpha \in(0,1]\). The existence as well as nonnegativity of the solution to the model is also verified and the basic reproduction number is calculated. Besides, stability conditions are also checked and finally simulation is done using both the Euler method and one of the top ten most influential algorithms known as Markov Chain Monte Carlo (MCMC) method. Different rates of vaccination to predict the effect of vaccination on the infected individual over time and that of quarantine are discussed. The results show that quarantine and vaccination are very effective ways to control Ebola epidemic. From our study it was also seen that there is less possibility of an individual for getting Ebola virus for the second time if they survived his/her first infection. Last but not least, real data has been fitted to the model, showing that it can be used to predict the dynamic of Ebola epidemic.
Keywords
- mathematical modeling
- Caputo derivative
- stability
- epidemic model
- numerical simulation
MSC
- 37N25
- 92D30
1 Introduction
Ebola is a severe and often deadly illness killing between 50% and 90% of those infected with the virus [1–3] named after a river in the Democratic Republic of Congo (formerly Zaire) where it was first identified in 1976 with a high case fatality rate. The disease first came into the lime light in 1976 in Zaire and Sudan. It is a disease of humans and other primates caused by an Ebola virus. Symptoms start two days to three weeks after contacting the virus with a fever, sore throat, muscle pain and headaches [4–8]. Typically, vomiting, diarrhea and rash flow, along with decreased functioning of the liver and kidneys. Around this time, the affected people may begin to bleed within the body and externally. The virus may be acquired upon contact with blood or bodily fluids of an infected people or animal. Spreading through the air has not been documented in the natural environment. Fruit bats are believed to be a carrier and may spread the virus without being affected [9–15]. Once human infection occurs, the disease may spread among people, as well. Male survivors may be able to transmit the disease via semen for nearly two months. To make the diagnosis, typically other diseases with similar symptoms such as malaria, cholera and other viral hemorrhagic fevers are first excluded. To confirm the diagnosis, blood samples are tested for viral antibodies, viral RNA, or the virus itself. What makes the disease the worst of all is the absence of specific effective treatment. Efforts to help those who are infected are supportive and include giving either oral rehydration therapy (slightly sweet and salty water to drink) or intravenous. As the effective measures for controlling Ebola epidemic still lack, it needs more attention by medical staff, epidemiologists, mathematicians and other stakeholders.
Mathematical modeling is one of the most important tools in analyzing the epidemiological characteristics of an infectious disease and can provide some useful insights into the dynamics of the disease. Various models have been used to study different aspects of Ebola epidemic.
Chowell et al. constructed a mathematical model for Ebola virus disease transmission (Congo 1995 and Uganda 2000) and fitted it to historical data in estimation of \(R_{o}\) [16]. Althaus presented a SEIR mathematical model and fitted the model to the reported data of infected cases and deaths for Ebola virus disease in Guinea, Sierra Leone and Liberia [17]. The latest study by Rachah and Torres recommends inclusion of intervention factors like quarantine procedure in the mathematical model to treat the infected individuals and investigate the effect of vaccination on Ebola virus disease [18].
Besides, according to the World Health Organization (WHO) report 2016, an experimental Ebola vaccine and quarantine was highly protective against the deadly Ebola virus in a major trial [19].
In this work, our goal is to develop a new mathematical model to study the effect of both vaccination and quarantine on the spread of Ebola virus as per the recommendation from World Health Organization (WHO) using both classical and fractional-order SIRD Ebola epidemic models. Our model differs from other mathematical models that have been used to study the Ebola epidemics [9, 16–18, 20, 21] in that it incorporates both vaccination and quarantine interventions. In addition, our work differs in that it uses one of the top ten most influential algorithms known as Markov Chain Monte Carlo algorithm to simulate the process as the spread of Ebola virus is a random process. To the best of our knowledge, this is the first integrated simulation method used beside the Euler method for this kind of infectious disease of humans. In the Euler method, the parameters are regarded constant, which may not be true in the practical case. To eliminate such defects, we used the Monte Carlo method which enabled to observe the reality in a better way and see how the Ebola virus is transmitted in crowd more accurately. In other words, the states (susceptible, infected, recovered/removed, death) at time \(t+1\) depend only on the state at time t (that means our physical state is Markov process). Hence, the Monte Carlo method is more sensible way to reflect the reality.
The text is organized as follows. In this section we have provided background information about Ebola disease; in Section 2, we give the definition of the Caputo fractional derivative of order α; in Section 3, we develop a basic mathematical model to describe the dynamics of the Ebola virus and its extension using Caputo fractional order; in Section 4, we find parameters with statistical data based on WHO; Section 5 deals with the basic properties of the model; in Section 6 we show the existence of the disease-free equilibrium for the model, derive the basic reproduction number and prove stability conditions. The parameters in Section 4 are used to simulate the basic model in Section 7 using both the Euler method and the Monte Carlo method. Finally, a conclusion and future work are presented.
2 Fractional-order model
In this section we discuss the definition of Caputo derivative and present the fractional-order SIRD model with vaccination and quarantine interventions in the sense of the Caputo derivative of order \(\alpha \in (0,1]\) in the next section.
Definition 2.1
The fractional integral of order \(\alpha > 0\) of a function \(g: R^{+} \rightarrow R\) is defined by \(I^{\alpha}g(t)= \frac{1}{\Gamma(\alpha)}\int_{0}^{t} (t-x)^{\alpha-1} g(x) \,dx\), where \(\Gamma(\cdot)\) is a gamma function.
Definition 2.2
The Caputo fractional derivative of order α> 0, \(n-1<\alpha<n\), \(n\in\mathbb{N}\) is defined as \(D^{\alpha}g(t)= \frac{1}{\Gamma(n-\alpha)}\int_{0}^{t} \frac {g(x)^{(n)}}{(t-x)^{\alpha+n-1}} g(x) \,dx\), where the function \(g(t)\) has absolutely continuous derivatives up to order \((n-1)\).
3 Mathematical model formulation and description
A compartmental model with a constant population was used to describe the natural history and epidemiology of Ebola. Briefly, the population is divided into four compartments: susceptible individuals (S) may become infected (I) after the contact with Ebola-infected individuals who are capable of infecting others including nurses, doctors etc. at hospitals and with a chance of infecting others before being recovered/removed from the disease (R) or die of Ebola and then join (D).
The susceptible population is increased by the susceptibility of individuals (rate of loss of infection acquired immunity) into the population at the rate γ. This population will be decreased if it acquires infection after the contact with an infected non-quarantined individual at the rate \(\beta=pc\), where p is the probability of successfully getting Ebola after the contact with an Ebola-infected individual and c is the per-capita contact rate. As there is a proved possibility of treatment of Ebola by vaccination [19, 22, 23], the susceptible individuals are further decreased at the rate v because of vaccination.
The population of infected individuals is generated by the infection of susceptible individuals at the rate β. This population is decreased by recovering from Ebola disease at the rate of \(\alpha_{1}\) and \(\alpha_{2}\), where \(\alpha_{1}\) is the recovery rate of an infected quarantined individual and \(\alpha_{2}\) is the recovery rate of an infected non-quarantined individual. This population is further decreased by death due to Ebola at a rate \(\delta _{1}\) and \(\delta_{2}\), where \(\delta_{1}\) is the death rate of an infected quarantined individual and \(\delta_{2}\) is the death rate of an infected non-quarantined individual due to Ebola. Here it is assumed that \(\alpha_{1}\) is greater than \(\alpha_{2}\) and \(\delta_{1}\) is less than \(\delta_{2}\), which is biologically reasonable.
The population of recovered infected individuals is generated by those recovered from Ebola and those individuals from susceptible because of vaccination at the rate of v and decreased by individuals that lost immunity and rejoined the susceptible group at the rate of γ.
4 Model parameters
Model parameters for simulation
Parameter | Average value |
---|---|
Total number of population (N) | 10,000 people/day |
Contact rate (β) | variable day^{−1} |
Rate of quarantining (q) | 0.3 day^{−1} |
Rate of loss of infection acquired immunity (γ) | 0.25 day^{−1} |
Rate from S to R (vaccination rate) (v) | 0.15 day^{−1} |
Recovery rate, quarantined individual (\(\alpha_{1}\)) | 0.4 day^{−1} |
Recovery rate, non-quarantined individual (\(\alpha_{2}\)) | 0.25 day^{−1} |
Death rate by Ebola, quarantined individual (\(\delta_{1}\)) | 0.3 day^{−1} |
Death rate by Ebola, non-quarantined individual (\(\delta_{2}\)) | 0.75 day^{−1} |
5 Basic properties
Since the model monitors changes in the human population, all the variables and parameters are assumed to be positive for all t≥0.
The model is therefore analyzed in a suitable feasible region \(D = \{S(t), I(t), R(t), D(t) \in R_{+}^{4}\}\), which is positively invariant for system (3.11) to (3.14) above.
Proof
Assume the initial conditions \(S(0)\ge 0\), \(I(0)\ge 0\), \(R(0)\ge 0\) and \(D(0)\ge 0\).
6 Analysis of the model
6.1 Existence and stability of disease-free equilibrium point
At the disease-free equilibrium state, we have absence of infection. Thus, all the Ebola-infected classes will be zero, and the entire population will comprise of only Ebola-free, susceptible individuals. A disease-free equilibrium state of the model above is given by \(E_{0}=(S^{*}, I^{*}, R^{*}, D^{*})\). Equating the model to zero and solving, we get \(E_{0}=(S^{*}, I^{*}, R^{*}, D^{*})=(S_{0}, 0, \frac{v}{\gamma}S_{0}, N-S_{0}-\frac{v}{\gamma}S_{0})\).
Theorem 6.1
Proof
Theorem 6.2
For system (3.11) to (3.14), the disease-free equilibrium is globally asymptotically stable if \(R_{0}<1\).
Proof
7 Numerical simulation
7.1 Numerical simulation using the Euler method
7.1.1 Experiment 1
From Figure 2 we see that the population of susceptible individuals immediately begins to drop because of the high degree of how infectious the Ebola virus is. Consequently, the population of the dead people starts rising.
7.1.2 Experiment 2
7.1.3 Experiment 3
7.2 Simulation using the Monte Carlo method
7.2.1 Experiment 4
From Figure 5 we clearly see that the number of Ebola-infected individuals increases and then decreases. At the same time the population of those who die by Ebola rises swiftly and reaches the peak showing the biological reality that Ebola is fatal. The model is more realistic to show the situation. Therefore, the medical, health departments and other stakeholders should focus on this moment. Moreover, the population of the susceptible also decrease at this time as more people get infected showing that the spread of Ebola is high unless controlled.
7.2.2 Experiment 5
Here the experiment deals with the relation between quarantine and the population of Ebola-infected individuals.
7.2.3 Experiment 6
7.2.4 Experiment 7
7.2.5 Experiment 8
From Figures 7, 8 and 9, we see the effect of the rate of vaccination on the Ebola-infected population for \(v=0\), \(v=0.25\) and \(v=0.45\). When v changes from 0 to 0.45, the number of Ebola-infected individuals reduces from 1,150 to 779. It is clearly seen that when the rate of vaccination increases, the population of Ebola-infected individuals decreases.
7.2.6 Experiment 9
8 Conclusion
Overall, the dynamical behavior of the formulated Ebola epidemic model is investigated, which plays a vital role in controlling the spread of Ebola virus. The classical SIRD model with vaccination and quarantine interventions is extended to a system of fractional-order derivatives in the sense of the Caputo derivative of order \(\alpha \in(0,1]\) because of its accuracy in solutions of real world problems. Our new model has the details about all compartments, and we found it fits well the data of confirmed cases provided by WHO for the Ebola outbreak in West Africa. The parameter values used are all the latest values. To secure more realistic approach, we used two different simulation methods, i.e., the Euler and Monte Carlo methods. As the spread of Ebola virus is a random process, the Monte Carlo algorithm is used to simulate the Markov Chain process of which the transfer matrix changes over time. From the point of view of our result of Markov Chain Monte Carlo simulation, we claim that there is less possibility of an individual getting Ebola virus for the second time if they survived the first infection. None of the previous research discovered weather a person can re-catch Ebola or not if they survived the first case. Moreover, from our experimental results, we also see that Ebola is really fatal and spreads swiftly, which means a regulation that reflects the reality very well is obtained and the model works better and more efficiently for the Ebola outbreak in West Africa.
Once again, from our experimental results we see that though Ebola spreads swiftly, it can be controlled upon increasing vaccination. Vaccination is a very efficient method in reducing the number of Ebola-infected individuals in a short period of time and increases the number of recovered individuals. Increasing the rate of infected quarantine is also another efficient method to control the Ebola epidemic as seen from our study. Hence, vaccination and isolation of the Ebola patient and providing great treatment are crucial measures to control the Ebola epidemics. Besides, as the cost of vaccination might be high for Ebola-infected countries, we recommend an optimal control to reduce the cost and number of infected individuals. Moreover, in order to prevent Ebola epidemics, through the analysis of the model, the government must strictly manage the policy on Ebola and carry it out. This in turn helps health campaigning and raising health literacy, which plays a vital role in controlling a quick spread of the disease. We finally strongly believe that our study will play its own role in the current effort of controlling Ebola.
Declarations
Acknowledgements
This research was partly supported by the National Natural Science Foundation of China (NSFC) grant number 91646106 and the National Social Science Foundation of China grant number 13&ZD166. Besides, the authors thank the journal editors and anonymous reviewers for their comments and recommendations which greatly improved our manuscript and made it more suitable for the readers of the journal.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Authors’ Affiliations
References
- Clarke, K: Fast vaccine offers hope in battle with Ebola. Nature 424, 681-684 (2003) View ArticleGoogle Scholar
- Smith, R, Blower, S: Could disease modifying vaccine cause population-level perversity? Lancet Infect. Dis. 4, 636-639 (2004) View ArticleGoogle Scholar
- WHO: Glimmers of hope on the Ebola front. Bull. World Health Organ. 92(10), 704-705 (2014) View ArticleGoogle Scholar
- Anonymous: Ebola haemorrhagic fever in Sudan. Bull. World Health Organ. 56(2), 247-270 (1978) Google Scholar
- Anonymous: Ebola haemorrhagic fever in Zaire. Bull. World Health Organ. 56(2), 271-293 (1978) Google Scholar
- Bray, M, Defense against filoviruses used as biological weapons. Antivir. Res. 57, 53-60 (2003) View ArticleGoogle Scholar
- Legrand, J, Grais, R, Boelle, P: Understanding the dynamics of Ebola epidemics. Epidemiol. Infect. 135(4), 610-621 (2007) View ArticleGoogle Scholar
- Okware, SI, An outbreak of Ebola in Uganda. Trop. Med. Int. Health 7(12), 1068-1075 (2002) View ArticleGoogle Scholar
- Rivers, CM, Lofgren, ET, Marathe, M, Eubank, S, Lewis, BL: Modeling the impact of interventions on an epidemic of Ebola in Sierra Leone and Liberia. PLoS Curr. Outbreak (2014) Google Scholar
- Fauquet, C: Virus Taxonomy Classification and Nomenclature. Academic Press, Oxford (2005) Google Scholar
- Jones, S: Live attenuated recombinant vaccine protects non human primates against Ebola and Marburg viruses. Nat. Med. 11(7), 786-790 (2005) View ArticleGoogle Scholar
- Leroy, E: Fruit bats are reservoirs of Ebola virus. Nature 438(1), 575-576 (2005) View ArticleGoogle Scholar
- Rouquet, P: Wild animal mortality monitoring and human Ebola outbreaks in Gabon and republic of Congo. Emerg. Infect. Dis. 11(2), 283-290 (2005) View ArticleGoogle Scholar
- Sullivan, NJ, Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature 424, 681-684 (2003) View ArticleGoogle Scholar
- Walsh, PD, Biek, R, Real, LA: Wave-like spread of Ebola Zaire. PLoS Biol. 3(11), 1-18 (2005) View ArticleGoogle Scholar
- Chowell, G, Hengartner, NW, Castillo-Chavez, C, The basic reproductive number of Ebola and the effects of public health measures: the cases of Congo and Uganda. J. Theor. Biol. 229, 119-126 (2004) MathSciNetView ArticleGoogle Scholar
- Althaus: Estimating the reproduction number of Ebola virus during the 2014 outbreak in West Africa. PLoS Curr. (2014) Google Scholar
- Torres, D, Rachah, A: Mathematical Modeling, Simulation and Optimal Control of the 2014 Ebola Outbreak in West Africa (2015) Google Scholar
- WHO: World Health organization report (2016). Available at: http://www.who.int/csr/disease/ebola/en
- Legrand, J, Grais, R, Boelle, R, Valleron, A, Flahault, A: Understanding the dynamics of Ebola epidemics. Epidemiol. Infect. 135, 610-621 (2007) View ArticleGoogle Scholar
- Torres, D, Rachah, A: Predicting and controlling Ebola infection. Math. Methods Appl. (2015) Google Scholar
- Valleron, AJ, Schwartz, D, Goldberg, M, Salamon, RC: L’épidemiologie Humaine, Conditions de Son Développement en France, et Rôle des Mathématiques. Inst. Fr. Acad. Sci. 462 (2006) Google Scholar
- www.pastemagazine.com/articles/2016/12/successful-ebola-vaccine-fast-tracked-for-use.html
- Ahmed, A, El-Sayed, AMA, El-Saka, HAA: Equilibrium points, stability and numerical solutions of fractional-order predator-prey and rabies models. J. Math. Anal. Appl. 325, 542-553 (2007) MathSciNetView ArticleMATHGoogle Scholar
- Area, I, Batarfu, H, Losada, J, Nieto, JJ, Shammakh, M, Torres, A: On a fractional order Ebola epidemic model. Adv. Differ. Equ. 2015, 278 (2015) MathSciNetView ArticleMATHGoogle Scholar
- Ozalp, N, Demirci, EV: Nonlinear dynamics and chaos in a fractional-order HIV model. Math. Comput. Model. 54(1-2), 1-6 (2011) View ArticleMATHGoogle Scholar
- Rostamy, D, Mottaghi, E: Stability analysis of a fractional-order epidemic model with multiple equilibriums. Adv. Differ. Equ. 2016, 170 (2016) MathSciNetView ArticleGoogle Scholar
- Diethlem, K: A fractional calculus based model for the simulation of an outbreak of dengue fever. Nonlinear Dyn. 71(4), 613-619 (2011) MathSciNetView ArticleGoogle Scholar
- Smith, H: Monotone Dynamical Systems, an Introduction to the Theory of Competitive and Cooperative Systems. Math. Surveys and Monographs, vol. 41 (1995) MATHGoogle Scholar
- Huo, H-F, Feng, L-X: Global stability for an HIV/AIDS epidemic model with different latent stages and treatment. Appl. Math. Model. 37, 1480-1489 (2013) MathSciNetView ArticleMATHGoogle Scholar
- Van den Driessche, P, Watmough, J: Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission. Math. Biosci. 180, 29-48 (2002) MathSciNetView ArticleMATHGoogle Scholar
- Lakshimikantham, V, Leela, S, Matynyuk, A: Stability analysis of non-linear systems. J. Soc. Ind. Appl. Math. 31(41), 152-154 (1989) Google Scholar