The Effect of Pulse Vaccination on the Transmission Dynamics of Rotavirus Diarrhea

Diarrhea is the third most fatal disease in the developing countries. Approximately 611,000 children die each year due to effect of rotavirus infection. Rotavirus also causes gastroenteritis in adults and it is the main cases of travellers’ diarrhea. After initial contact, children are more susceptible to be affected with diarrhoeal illnesses of any kind, but the repeatition of infections with rotavirus tend to be less severe than the original infection. Rotavirus continues to persist, is attributed to the different modes of transmission among the pathogens. To fight against this problem, several rotavirus vaccines have been developed. Federal Drug Administration (FDA) approved drugs within the last two years are currently in use. These vaccines present a degree of protection from rotavirus infection. We formulate a model of the spread of rotavirus diarrhea based on a continuous time ordinary differential equations model. We further expand the model to investigate the effects of pulse vaccination. We use computer simulations to further analyze the effect of vaccination as a controlled method. We find the minimum levels of vaccination necessary in this model to eradicate severe rotavirus disease.


Introduction
Rotavirus is a virus for which babies and young children suffer from diarrhea. The common symptoms are vomiting and fever. Due to dehydration and its symptoms including vomiting and watery diarrhea usually last for 3 -8 days. Rotavirus is not the only cause of diarrhea, but it is one of the most common symptoms to diagnose the disease. Worldwide 95% of children are infected before their 5 years of age and between ages of 4 months to 36 months it reaches its extremity [3]. In developed countries there are fewer deaths associated with rotavirus. But the financial burden of the disease is considerable [2].
The dynamics of rotavirus infections are very complicated. The predominant mode of rotavirus transmission is fecal-oral [5]. The infection spreads through respiratory secretions and person-to-person contacts [6]. The period of incubation of rotavirus disease is near about for 2 days. Contaminated environment is the major cause for the endemic infections but high rates of infections among infants younger than three years old have been identified regardless of sanitary conditions [5].
Rotavirus vaccine is an oral (swallowed) vaccine.
Diarrhoea or vomiting which are caused by other germs will not be prevented by Rotavirus vaccine. But it is very good at preventing diarrhoea and vomiting caused by rotavirus. Most babies who get the vaccine will not get rotavirus diarrhea at all, and almost all of them will be protected from severe rotavirus diarrhea. The development of rotavirus vaccines is used for the control of diarrheal disease in children, and the impact of the introduction of these vaccines at the population-scale is uncertain [3].
A few mathematical studies about Rota virus till today have been addressed as the disease transmission, vaccine and drug options [4][5][6][7][8][9][10]. Atkinsa et al. [7] worked on the reduction in RVGE incidence. They observed that if vaccineinduced protection does not wane over three years, severe RVGE in children under five years of age could be eliminated within two years after the introduction of Rota virus vaccination. Skim et al. [8] worked on the role of breast feeding (maternal antibody) on rotavirus control, incorporating the seasonal variation in transmission rate factors. Zelata et al. [9] presented deterministic as well as stochastic models for the transmission of rotavirus in a pediatric hospital ward and draw on published data to compare the efficacy of several possible control measures in reducing the number of infections. Roldao et al [10], in their works studied the production of rotavirus virus-like particles (VLP) using the baculovirus expression vector system (BEVS). But control theoretic Mathematical modelling and effect of impulsive vaccination have been received relatively little attention.
This article has been arranged in the following manner.
The model without vaccination to examine various dynamics of the system is considered in the section 2. A mathematical model on the basis of perfect drug adherence is analyzed as well as numerical results of this model are discussed in Section 3 and 4 respectively. Implication of the results is discussed in Section 5.

The System Without Vaccination
In this section a mathematical model by the effect of rota virus has been propose by considering the three populationsusceptible population (S), Infected population (I) and Vaccinated population (V)respectively. Here the system of ordinary differential equations have been obtained by assuming the population mix homogeneously. Thus, the equation of the model becomes: (1) where the system parameters are defined in the Table 1.
Existence condition and stability analysis of the basic model: Using the model (1) where ' & . To study the local stability of the model (1), linearising the system and obtained the following jacobian matrix.
For the disease free equilibrium , the Jacobian becomes The characteristic equation of the matrix is Eigen values are / 0 1 0, / ( 1 0, All eigen values are negative if the basic reproduction ration 3 % 1 1.
Hence it can be concluded that the disease free equilibrium stable if the basic reproduction number is less than unity. Other wise the system is unstable.

The System with Vaccination
Now emphasising the system with pulse vaccination given regular intervals of time say 7 , to a proportion of the susceptible human population 8 the impulsive system, in ordinary differential equation form is illustrated below: which implies that where Π 0 F = .

Numerical Simulation
In numerical simulation, the perfect drug adherence of rota virus vacccination have been described. All the parameters are taken from Table 1. The initial condition are assumed as 0 200, 0 80, 0 0 and the unit of the concentration is 8@;W:•/ 4ƒ.   Table 1 with these parametric conditions 3 1 1. Thus the disease free equilibrium exists.  Table 1 with these parametric conditions 3 6 1. Thus the disease free equilibrium exists.
It has been observed that for a high natural death rate ( 0.1 ), 3 1 1 , i.e. the disease free state is stable. However, for the low natural death rate ( 0.05), 3 6 1 and the system moves towards instability. Thus infected population increases and as a result the system moves from disease free to endemic state. The change of concentration with respect of time in the absence of impulsive vaccination reflects in Figure 3 for the conditions 3 2.5 6 1. Thus, the endemic equilibrium exists. Figure 4. shows the change of concentration for each model variables with respect of time in presence of perfect adherence. In this figure the dosing interval is fixed at 7 10. This means the vaccine is taken at ten days interval. From this figure we can easily conclude that after introducing the vaccination, the susceptible population as well as infected population reduces. Also during the treatment the vaccinated population enhance comparatively with the presence of perfect drug adherence.

Conclusion
A basic mathematical model has been formulated to study the infection for Rota Virus on human population. In this model, susceptible population, infected population and vaccinated population have been considered. It has been observed that the system has two equilibriums, one is disease free and another is endemic equilibrium. The disease free equilibrium is asymptotically stable if the basic reproduction number is below the unity. But if the basic reproduction number is more than unity, then the disease free equilibrium becomes unstable.
The impulsive differential equations have also been formulated as the vaccination period is not instantaneous. It has also been worked on the optimal interval of vaccination period and weightage of the dosage, by using the impulsive differential equation so that disease can be controlled.
In a nutshell, vaccination against Rota Virus can reduce the infectability of the disease, but is unable to eradicate the disease. The critical vaccination period suggests that careful follow-up must be taken. Hence optimal level of vaccination period as well as weightage of pulse vaccination affect the disease progression and disease replication.