Matching Items (5)
Filtering by
- All Subjects: Drug Resistance
- All Subjects: Optimal Control
- All Subjects: public health
Description
Infectious diseases are a leading cause of death worldwide. With the development of drugs, vaccines and antibiotics, it was believed that for the first time in human history diseases would no longer be a major cause of mortality. Newly emerging diseases, re-emerging diseases and the emergence of microorganisms resistant to existing treatment have forced us to re-evaluate our optimistic perspective. In this study, a simple mathematical framework for super-infection is considered in order to explore the transmission dynamics of drug-resistance. Through its theoretical analysis, we identify the conditions necessary for the coexistence between sensitive strains and drug-resistant strains. Farther, in order to investigate the effectiveness of control measures, the model is extended so as to include vaccination and treatment. The impact that these preventive and control measures may have on its disease dynamics is evaluated. Theoretical results being confirmed via numerical simulations. Our theoretical results on two-strain drug-resistance models are applied in the context of Malaria, antimalarial drugs, and the administration of a possible partially effective vaccine. The objective is to develop a monitoring epidemiological framework that help evaluate the impact of antimalarial drugs and partially-effective vaccine in reducing the disease burden at the population level. Optimal control theory is applied in the context of this framework in order to assess the impact of time dependent cost-effective treatment efforts. It is shown that cost-effective combinations of treatment efforts depend on the population size, cost of implementing treatment controls, and the parameters of the model. We use these results to identify optimal control strategies for several scenarios.
ContributorsUrdapilleta, Alicia (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Wang, Xiaohong (Thesis advisor) / Wirkus, Stephen (Committee member) / Camacho, Erika (Committee member) / Arizona State University (Publisher)
Created2011
Description
The 2009-10 influenza and the 2014-15 Ebola pandemics brought once again urgency to an old question: What are the limits on prediction and what can be proposed that is useful in the face of an epidemic outbreak?
This thesis looks first at the impact that limited access to vaccine stockpiles may have on a single influenza outbreak. The purpose is to highlight the challenges faced by populations embedded in inadequate health systems and to identify and assess ways of ameliorating the impact of resource limitations on public health policy.
Age-specific per capita constraint rates play an important role on the dynamics of communicable diseases and, influenza is, of course, no exception. Yet the challenges associated with estimating age-specific contact rates have not been decisively met. And so, this thesis attempts to connect contact theory with age-specific contact data in the context of influenza outbreaks in practical ways. In mathematical epidemiology, proportionate mixing is used as the preferred theoretical mixing structure and so, the frame of discussion of this dissertation follows this specific theoretical framework. The questions that drive this dissertation, in the context of influenza dynamics, proportionate mixing, and control, are:
I. What is the role of age-aggregation on the dynamics of a single outbreak? Or simply speaking, does the number and length of the age-classes used to model a population make a significant difference on quantitative predictions?
II. What would the age-specific optimal influenza vaccination policies be? Or, what are the age-specific vaccination policies needed to control an outbreak in the presence of limited or unlimited vaccine stockpiles?
Intertwined with the above questions are issues of resilience and uncertainty including, whether or not data collected on mixing (by social scientists) can be used effectively to address both questions in the context of influenza and proportionate mixing. The objective is to provide answers to these questions by assessing the role of aggregation (number and length of age classes) and model robustness (does the aggregation scheme selected makes a difference on influenza dynamics and control) via comparisons between purely data-driven model and proportionate mixing models.
This thesis looks first at the impact that limited access to vaccine stockpiles may have on a single influenza outbreak. The purpose is to highlight the challenges faced by populations embedded in inadequate health systems and to identify and assess ways of ameliorating the impact of resource limitations on public health policy.
Age-specific per capita constraint rates play an important role on the dynamics of communicable diseases and, influenza is, of course, no exception. Yet the challenges associated with estimating age-specific contact rates have not been decisively met. And so, this thesis attempts to connect contact theory with age-specific contact data in the context of influenza outbreaks in practical ways. In mathematical epidemiology, proportionate mixing is used as the preferred theoretical mixing structure and so, the frame of discussion of this dissertation follows this specific theoretical framework. The questions that drive this dissertation, in the context of influenza dynamics, proportionate mixing, and control, are:
I. What is the role of age-aggregation on the dynamics of a single outbreak? Or simply speaking, does the number and length of the age-classes used to model a population make a significant difference on quantitative predictions?
II. What would the age-specific optimal influenza vaccination policies be? Or, what are the age-specific vaccination policies needed to control an outbreak in the presence of limited or unlimited vaccine stockpiles?
Intertwined with the above questions are issues of resilience and uncertainty including, whether or not data collected on mixing (by social scientists) can be used effectively to address both questions in the context of influenza and proportionate mixing. The objective is to provide answers to these questions by assessing the role of aggregation (number and length of age classes) and model robustness (does the aggregation scheme selected makes a difference on influenza dynamics and control) via comparisons between purely data-driven model and proportionate mixing models.
ContributorsMorales, Romarie (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Mubayi, Anuj (Thesis advisor) / Towers, Sherry (Committee member) / Arizona State University (Publisher)
Created2016
Description
Statistical Methods have been widely used in understanding factors for clinical and public health data. Statistical hypotheses are procedures for testing pre-stated hypotheses. The development and properties of these procedures as well as their performance are based upon certain assumptions. Desirable properties of statistical tests are to maintain validity and to perform well even if these assumptions are not met. A statistical test that maintains such desirable properties is called robust. Mathematical models are typically mechanistic framework, used to study dynamic interactions between components (mechanisms) of a system, and how these interactions give rise to the changes in behavior (patterns) of the system as a whole over time.
In this thesis, I have developed a study that uses novel techniques to link robust statistical tests and mathematical modeling methods guided by limited data from developed and developing regions in order to address pressing clinical and epidemiological questions of interest. The procedure in this study consists of three primary steps, namely, data collection, uncertainty quantification in data, and linking dynamic model to collected data.
The first part of the study focuses on designing, collecting, and summarizing empirical data from the only national survey of hospitals ever conducted regarding patient controlled analgesia (PCA) practices among 168 hospitals across 40 states, in order to assess risks before putting patients on PCA. I used statistical relational models and exploratory data analysis to address the question. Risk factors assessed indicate a great concern for the safety of patients from one healthcare institution to other.
In the second part, I quantify uncertainty associated with data obtained from James A Lovell Federal Healthcare Center to primarily study the effect of Benign Prostatic Hypertrophy (BPH) on sleep architecture in patients with Obstructive Sleep Apnea (OSA). Patients with OSA and BPH demonstrated significant difference in their sleep architecture in comparison to patients without BPH. One of the ways to validate these differences in sleep architecture between the two groups may be to carry out a similar study that evaluates the effect of some other chronic disease on sleep architecture in patients with OSA.
Additionally, I also address theoretical statistical questions such as (1) how to estimate the distribution of a variable in order to retest null hypothesis when the sample size is limited, and (2) how changes on assumptions (like monotonicity and nonlinearity) translate into the effect of the independent variable on the outcome variable. To address these questions we use multiple techniques such as Partial Rank Correlation Coefficients (PRCC) based sensitivity analysis, Fractional Polynomials, and statistical relational models.
In the third part, my goal was to identify socio-economic-environment-related risk factors for Visceral Leishmaniasis (VL) and use the identified critical factors to develop a mathematical model to understand VL transmission dynamics when data is highly underreported. I primarily studied the role of age-specific- susceptibility and epidemiological quantities on the dynamics of VL in the Indian state of Bihar. Statistical results provided ideas on the choice of the modeling framework and estimates of model parameters.
In the conclusion, this study addressed three primary theoretical modeling-related questions (1) how to analyze collected data when sample size limited, and how modeling assumptions varies results of data analysis? (2) Is it possible to identify hidden associations and nonlinearity of these associations using such underpowered data and (3) how statistical models provide more reasonable structure to mathematical modeling framework that can be used in turn to understand dynamics of the system.
In this thesis, I have developed a study that uses novel techniques to link robust statistical tests and mathematical modeling methods guided by limited data from developed and developing regions in order to address pressing clinical and epidemiological questions of interest. The procedure in this study consists of three primary steps, namely, data collection, uncertainty quantification in data, and linking dynamic model to collected data.
The first part of the study focuses on designing, collecting, and summarizing empirical data from the only national survey of hospitals ever conducted regarding patient controlled analgesia (PCA) practices among 168 hospitals across 40 states, in order to assess risks before putting patients on PCA. I used statistical relational models and exploratory data analysis to address the question. Risk factors assessed indicate a great concern for the safety of patients from one healthcare institution to other.
In the second part, I quantify uncertainty associated with data obtained from James A Lovell Federal Healthcare Center to primarily study the effect of Benign Prostatic Hypertrophy (BPH) on sleep architecture in patients with Obstructive Sleep Apnea (OSA). Patients with OSA and BPH demonstrated significant difference in their sleep architecture in comparison to patients without BPH. One of the ways to validate these differences in sleep architecture between the two groups may be to carry out a similar study that evaluates the effect of some other chronic disease on sleep architecture in patients with OSA.
Additionally, I also address theoretical statistical questions such as (1) how to estimate the distribution of a variable in order to retest null hypothesis when the sample size is limited, and (2) how changes on assumptions (like monotonicity and nonlinearity) translate into the effect of the independent variable on the outcome variable. To address these questions we use multiple techniques such as Partial Rank Correlation Coefficients (PRCC) based sensitivity analysis, Fractional Polynomials, and statistical relational models.
In the third part, my goal was to identify socio-economic-environment-related risk factors for Visceral Leishmaniasis (VL) and use the identified critical factors to develop a mathematical model to understand VL transmission dynamics when data is highly underreported. I primarily studied the role of age-specific- susceptibility and epidemiological quantities on the dynamics of VL in the Indian state of Bihar. Statistical results provided ideas on the choice of the modeling framework and estimates of model parameters.
In the conclusion, this study addressed three primary theoretical modeling-related questions (1) how to analyze collected data when sample size limited, and how modeling assumptions varies results of data analysis? (2) Is it possible to identify hidden associations and nonlinearity of these associations using such underpowered data and (3) how statistical models provide more reasonable structure to mathematical modeling framework that can be used in turn to understand dynamics of the system.
ContributorsGonzalez, Beverly, 1980- (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Mubayi, Anuj (Thesis advisor) / Nuno, Miriam (Committee member) / Arizona State University (Publisher)
Created2015
Description
Extraordinary medical advances have led to significant reductions in the burden of infectious diseases in humans. However, infectious diseases still account for more than 13 million annual deaths. This large burden is partly due to some pathogens having found suitable conditions to emerge and spread in denser and more connected host populations, and others having evolved to escape the pressures imposed by the rampant use of antimicrobials. It is then critical to improve our understanding of how diseases spread in these modern landscapes, characterized by new host population structures and socio-economic environments, as well as containment measures such as the deployment of drugs. Thus, the motivation of this dissertation is two-fold. First, we study, using both data-driven and modeling approaches, the the spread of infectious diseases in urban areas. As a case study, we use confirmed-cases data on sexually transmitted diseases (STDs) in the United States to assess the conduciveness of population size of urban areas and their socio-economic characteristics as predictors of STD incidence. We find that the scaling of STD incidence in cities is superlinear, and that the percent of African-Americans residing in cities largely determines these statistical patterns. Since disparities in access to health care are often exacerbated in urban areas, within this project we also develop two modeling frameworks to study the effect of health care disparities on epidemic outcomes. Discrepant results between the two approaches indicate that knowledge of the shape of the recovery period distribution, not just its mean and variance, is key for assessing the epidemiological impact of inequalities. The second project proposes to study, from a modeling perspective, the spread of drug resistance in human populations featuring vital dynamics, stochasticity and contact structure. We derive effective treatment regimes that minimize both the overall disease burden and the spread of resistance. Additionally, targeted treatment in structured host populations may lead to higher levels of drug resistance, and if drug-resistant strains are compensated, they can spread widely even when the wild-type strain is below its epidemic threshold.
ContributorsPatterson-Lomba, Oscar (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Towers, Sherry (Thesis advisor) / Chowell-Puente, Gerardo (Committee member) / Arizona State University (Publisher)
Created2014
Description
This dissertation explores the impact of environmental dependent risk on disease dynamics within a Lagrangian modeling perspective; where the identity (defined by place of residency) of individuals is preserved throughout the epidemic process. In Chapter Three, the impact of individuals who refuse to be vaccinated is explored. MMR vaccination and birth rate data from the State of California are used to determine the impact of the anti-vaccine movement on the dynamics of growth of the anti-vaccine sub-population. Dissertation results suggest that under realistic California social dynamics scenarios, it is not possible to revert the influence of anti-vaccine
contagion. In Chapter Four, the dynamics of Zika virus are explored in two highly distinct idealized environments defined by a parameter that models highly distinctive levels of risk, the result of vector and host density and vector control measures. The underlying assumption is that these two communities are intimately connected due to economics with the impact of various patterns of mobility being incorporated via
the use of residency times. In short, a highly heterogeneous community is defined by its risk of acquiring a Zika infection within one of two "spaces," one lacking access to health services or effective vector control policies (lack of resources or ignored due to high levels of crime, or poverty, or both). Low risk regions are defined as those with access to solid health facilities and where vector control measures are implemented routinely. It was found that the better connected these communities are, the existence of communities where mobility between risk regions is not hampered, lower the overall, two patch Zika prevalence. Chapter Five focuses on the dynamics of tuberculosis (TB), a communicable disease, also on an idealized high-low risk set up. The impact of mobility within these two highly distinct TB-risk environments on the dynamics and control of this disease is systematically explored. It is found that collaboration and mobility, under some circumstances, can reduce the overall TB burden.
contagion. In Chapter Four, the dynamics of Zika virus are explored in two highly distinct idealized environments defined by a parameter that models highly distinctive levels of risk, the result of vector and host density and vector control measures. The underlying assumption is that these two communities are intimately connected due to economics with the impact of various patterns of mobility being incorporated via
the use of residency times. In short, a highly heterogeneous community is defined by its risk of acquiring a Zika infection within one of two "spaces," one lacking access to health services or effective vector control policies (lack of resources or ignored due to high levels of crime, or poverty, or both). Low risk regions are defined as those with access to solid health facilities and where vector control measures are implemented routinely. It was found that the better connected these communities are, the existence of communities where mobility between risk regions is not hampered, lower the overall, two patch Zika prevalence. Chapter Five focuses on the dynamics of tuberculosis (TB), a communicable disease, also on an idealized high-low risk set up. The impact of mobility within these two highly distinct TB-risk environments on the dynamics and control of this disease is systematically explored. It is found that collaboration and mobility, under some circumstances, can reduce the overall TB burden.
ContributorsMoreno Martínez, Victor Manuel (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Kang, Yun (Committee member) / Mubayi, Anuj (Committee member) / Arizona State University (Publisher)
Created2018