Estimating the prevalence rate of a disease is crucial for controlling its spread, and for planning of healthcare services. Due to limited testing budgets and resources, prevalence estimation typically entails pooled, or group, testing where specimens (e.g., blood, urine, tissue swabs) from a number of subjects are combined into a testing pool, which is then tested via a single test. Testing outcomes from multiple pools are analyzed so as to assess the prevalence of the disease. The accuracy of prevalence estimation relies on the testing pool design, i.e., the number of pools to test and the pool sizes (the number of specimens to combine in a pool). Determining an optimal pool design for prevalence estimation can be challenging, as it requires prior information on the current status of the disease, which can be highly unreliable, or simply unavailable, especially for emerging and/or seasonal diseases. We develop and study frameworks for prevalence estimation, under highly unreliable prior information on the disease and limited testing budgets. Embedded into each estimation framework is an optimization model that determines the optimal testing pool design, considering the trade-off between testing cost and estimation accuracy. We establish important structural properties of optimal testing pool designs in various settings, and develop efficient and exact algorithms. Our numerous case studies, ranging from prevalence estimation of the human immunodeficiency virus (HIV) in various parts of Africa, to prevalence estimation of diseases in plants and insects, including the Tomato Spotted Wilt virus in thrips and West Nile virus in mosquitoes, indicate that the proposed estimation methods substantially outperform current approaches developed in the literature, and produce robust testing pool designs that can hedge against the uncertainty in model inputs.Our research findings indicate that the proposed prevalence estimation frameworks are capable of producing accurate prevalence estimates, and are highly desirable, especially for emerging and/or seasonal diseases under limited testing budgets. / Doctor of Philosophy / Accurately estimating the proportion of a population that has a disease, i.e., the disease prevalence rate, is crucial for controlling its spread, and for planning of healthcare services, such as disease prevention, screening, and treatment. Due to limited testing budgets and resources, prevalence estimation typically entails pooled, or group, testing where biological specimens (e.g., blood, urine, tissue swabs) from a number of subjects are combined into a testing pool, which is then tested via a single test. Testing results from the testing pools are analyzed so as to assess the prevalence of the disease. The accuracy of prevalence estimation relies on the testing pool design, i.e., the number of pools to test and the pool sizes (the number of specimens to combine in a pool). Determining an optimal pool design for prevalence estimation, e.g., the pool design that minimizes the estimation error, can be challenging, as it requires information on the current status of the disease prior to testing, which can be highly unreliable, or simply unavailable, especially for emerging and/or seasonal diseases. Examples of such diseases include, but are not limited to, Zika virus, West Nile virus, and Lyme disease. We develop and study frameworks for prevalence estimation, under highly unreliable prior information on the disease and limited testing budgets. Embedded into each estimation framework is an optimization model that determines the optimal testing pool design, considering the trade-off between testing cost and estimation accuracy. We establish important structural properties of optimal testing pool designs in various settings, and develop efficient and exact optimization algorithms. Our numerous case studies, ranging from prevalence estimation of the human immunodeficiency virus (HIV) in various parts of Africa, to prevalence estimation of diseases in plants and insects, including the Tomato Spotted Wilt virus in thrips and West Nile virus in mosquitoes, indicate that the proposed estimation methods substantially outperform current approaches developed in the literature, and produce robust testing pool designs that can hedge against the uncertainty in model input parameters. Our research findings indicate that the proposed prevalence estimation frameworks are capable of producing accurate prevalence estimates, and are highly desirable, especially for emerging and/or seasonal diseases under limited testing budgets.

El objetivo de esta memoria se centra en primer lugar en la modelización del comportamiento de enfermedades estacionales mediante sistemas de ecuaciones diferenciales y en el estudio de las propiedades dinámicas tales como positividad, periocidad, estabilidad de las soluciones analíticas y la construcción de esquemas numéricos para las aproximaciones de las soluciones numéricas de sistemas de ecuaciones diferenciales de primer orden no lineales, los cuales modelan el comportamiento de enfermedades infecciosas estacionales tales como la transmisión del virus Respiratory Syncytial Virus (RSV). Se generalizan dos modelos matemáticos de enfermedades estacionales y se demuestran que tiene soluciones periódicas usando un Teorema de Coincidencia de Jean Mawhin. Para corroborar los resultados analíticos, se desarrollan esquemas numéricos usando las técnicas de diferencias finitas no estándar desarrolladas por Ronald Michens y el método de la transformada diferencial, los cuales permiten reproducir el comportamiento dinámico de las soluciones analíticas, tales como positividad y periocidad. Finalmente, las simulaciones numéricas se realizan usando los esquemas implementados y parámetros deducidos de datos clínicos De La Región de Valencia de personas infectadas con el virus RSV. Se confrontan con las que arrojan los métodos de Euler, Runge Kutta y la rutina de ODE45 de Matlab, verificándose mejores aproximaciones para tamaños de paso mayor a los que usan normalmente estos esquemas tradicionales. / Arenas Tawil, AJ. (2009). Mathematical modelling of virus RSV: qualitative properties, numerical solutions and validation for the case of the region of Valencia [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/8316