Process algebra for epidemiology: evaluating and enhancing the ability of PEPA to describe biological systems

Modelling is a powerful method for understanding complex systems, which works by simplifying them to their most essential components. The choice of the components is driven by the aspects studied. The tool chosen to perform this task will determine what can be modelled, the maximum number of components which can be represented, as well as the analyses which can be performed on the system. Performance Evaluation Process Algebra (PEPA) was initially developed to tackle computer systems issues. Nevertheless, it possesses some interesting properties which could be exploited for the study of epidemiological systems. PEPA's main advantage resides in its capacity to change scale: the assumptions and parameter values describe the behaviour of a single individual, while the resulting model provides information on the population behaviour. Additionally, stochasticity and continuous time have already proven to be useful features in epidemiology. While each of these features is already available in other tools, to find all three combined in a single tool is novel, and PEPA is proposed as a useful addition to the epidemiologist's toolbox. Moreover, an algorithm has been developed which allows converting a PEPA model into a system of Ordinary Differential Equations (ODEs). This provides access to countless additional software and theoretical analysis methods which enable the epidemiologist to gain further insight into the model. Finally, most existing tools require a deep understanding of the logic they are based on and the resulting model can be difficult to read and modify. PEPA's grammar, on the other hand, is easy to understand since it is based on few, yet powerful concepts. This makes it a very accessible formalism for any epidemiologist. The objective of this thesis is to determine precisely PEPA's ability to describe epidemiological systems, as well as extend the formalism when required. This involved modelling two systems: the bubonic plague in prairie dogs, and measles in England and Wales. These models were chosen as they exhibit a good range of typical features, allowing to thoroughly test PEPA. All features required in each of these models have been analysed in detail, and a solution has been provided for representing each of these features. While some of them could be expressed in a straightforward manner, PEPA did not provide the tools to express others. In those cases, we determined methods to approach the desired behaviour, and the limitations of said methods were carefully analysed. In the case of models with a structured population, PEPA was extended to simplify their expression and facilitate the writing process of the PEPA model. The work also required the development of an algorithm to derive ODEs adapted to the type of models encountered. Finally, the PEPAdum software was developed to assist the modeller in the generation and analysis of PEPA models, by simplifying the process of writing a PEPA model with compartments, performing the average of stochastic simulations and deriving and explicitly providing the ODEs using the Stirling Amendment

Improved Continuous Approximation of PEPA Models through Epidemiological Examples

We present two individual based models of disease systems using PEPA (Performance Evaluation Process Algebra). The models explore contrasting mechanisms of disease transmission: direct transmission (e.g. measles) and indirect transmission (e.g. malaria, via mosquitos). We extract ordinary differential equations (ODEs) as a continuous approximation to the PEPA models using the Hillston method and compare these with the traditionally used ODE disease models and with the results of stochastic simulation. Improvements to the Hillston method of ODE extraction for this context are proposed, and the new results compare favourably with stochastic simulation results and to ODEs derived for equivalent models in WSCCS (Weighted Synchronous Calculus of Communicating Systems)

Measles epidemics and PEPA: An exploration of historic disease dynamics using process algebra

We demonstrate the use of the process algebra PEPA for realistic models of epidemiology. The results of stochastic simulation of the model are shown, and ease of modelling is compared to that of Bio-PEPA. PEPA is shown to be capable of capturing the complex disease dynamics of the historic data for measles epidemics in the UK from 1944--1964, including persistent fluctuations due to seasonal effects