Matching Items (9)

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Immune response in the study of infectious diseases (co-infection) in an endemic region

Description

Diseases have been part of human life for generations and evolve within the population, sometimes dying out while other times becoming endemic or the cause of recurrent outbreaks. The long

Diseases have been part of human life for generations and evolve within the population, sometimes dying out while other times becoming endemic or the cause of recurrent outbreaks. The long term influence of a disease stems from different dynamics within or between pathogen-host, that have been analyzed and studied by many researchers using mathematical models. Co-infection with different pathogens is common, yet little is known about how infection with one pathogen affects the host's immunological response to another. Moreover, no work has been found in the literature that considers the variability of the host immune health or that examines a disease at the population level and its corresponding interconnectedness with the host immune system. Knowing that the spread of the disease in the population starts at the individual level, this thesis explores how variability in immune system response within an endemic environment affects an individual's vulnerability, and how prone it is to co-infections. Immunology-based models of Malaria and Tuberculosis (TB) are constructed by extending and modifying existing mathematical models in the literature. The two are then combined to give a single nine-variable model of co-infection with Malaria and TB. Because these models are difficult to gain any insight analytically due to the large number of parameters, a phenomenological model of co-infection is proposed with subsystems corresponding to the individual immunology-based model of a single infection. Within this phenomenological model, the variability of the host immune health is also incorporated through three different pathogen response curves using nonlinear bounded Michaelis-Menten functions that describe the level or state of immune system (healthy, moderate and severely compromised). The immunology-based models of Malaria and TB give numerical results that agree with the biological observations. The Malaria--TB co-infection model gives reasonable results and these suggest that the order in which the two diseases are introduced have an impact on the behavior of both. The subsystems of the phenomenological models that correspond to a single infection (either of Malaria or TB) mimic much of the observed behavior of the immunology-based counterpart and can demonstrate different behavior depending on the chosen pathogen response curve. In addition, varying some of the parameters and initial conditions in the phenomenological model yields a range of topologically different mathematical behaviors, which suggests that this behavior may be able to be observed in the immunology-based models as well. The phenomenological models clearly replicate the qualitative behavior of primary and secondary infection as well as co-infection. The mathematical solutions of the models correspond to the fundamental states described by immunologists: virgin state, immune state and tolerance state. The phenomenological model of co-infection also demonstrates a range of parameter values and initial conditions in which the introduction of a second disease causes both diseases to grow without bound even though those same parameters and initial conditions did not yield unbounded growth in the corresponding subsystems. This results applies to all three states of the host immune system. In terms of the immunology-based system, this would suggest the following: there may be parameter values and initial conditions in which a person can clear Malaria or TB (separately) from their system but in which the presence of both can result in the person dying of one of the diseases. Finally, this thesis studies links between epidemiology (population level) and immunology in an effort to assess the impact of pathogen's spread within the population on the immune response of individuals. Models of Malaria and TB are proposed that incorporate the immune system of the host into a mathematical model of an epidemic at the population level.

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Date Created
  • 2011

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Biodiversity, dispersal, and risk: species spread in ecological and social-ecological systems

Description

The closer integration of the world economy has yielded many positive benefits including the worldwide diffusion of innovative technologies and efficiency gains following the widening of international markets. However,

The closer integration of the world economy has yielded many positive benefits including the worldwide diffusion of innovative technologies and efficiency gains following the widening of international markets. However, closer integration also has negative consequences. Specifically, I focus on the ecology and economics of the spread of species and pathogens. I approach the problem using theoretical and applied models in ecology and economics. First, I use a multi-species theoretical network model to evaluate the ability of dispersal to maintain system-level biodiversity and productivity. I then extend this analysis to consider the effects of dispersal in a coupled social-ecological system where people derive benefits from species. Finally, I estimate an empirical model of the foot and mouth disease risks of trade. By combining outbreak and trade data I estimate the disease risks associated with the international trade in live animals while controlling for the biosecurity measures in place in importing countries and the presence of wild reservoirs. I find that the risks associated with the spread and dispersal of species may be positive or negative, but that this relationship depends on the ecological and economic components of the system and the interactions between them.

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  • 2016

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Understanding the impact of social factors on the transmission dynamics of infectious diseases across highly heterogeneous risk environments

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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

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.

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  • 2018

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Potential emergence of dengue in the Phoenix Metropolitan Area: a micro-climatic and demographic analysis

Description

The spread of dengue worldwide currently places half of the world’s population at risk. In the absence of a dengue vaccine, control of the disease requires control of the mosquito

The spread of dengue worldwide currently places half of the world’s population at risk. In the absence of a dengue vaccine, control of the disease requires control of the mosquito species that transmit the virus. The most important of these is. Advances in research detailing the responsiveness of Aedes aegypti to small changes in climate enable the production of more sophisticated remote sensing and surveillance techniques for monitoring these populations. Close monitoring of global dengue activity and outbreaks likewise enables a greater specificity when determining to which human populations the virus is most likely to spread. There have been no locally acquired cases in Arizona to date, but the high abundance of Aedes aegypti in the Phoenix Metropolitan area raises concern within the Arizona Department of Health Services over the potential transmission of dengue in the city. This study develops a model that combines mosquito abundance, micro-climatic and demographic information to delineate regions in Phoenix that are most support transmission of dengue. The first chapter focuses on the impact that daytime high and low temperatures have on Aedes aegypti’s ability to become infectious with dengue. It argues that NDVI (normal difference vegetative index) imaging of the Phoenix area can be used to plot areas where mosquitoes are most likely to become competent vectors. The second chapter focuses on the areas in the city where mosquitoes are most likely to be exposed to the virus. Based on proximity to Phoenix and the high volume of traffic across the Arizona-Mexico border, I treat the Mexican state of Sonora as the source of infection. I combine these two analyses, micro-climatic and demographic, to produce maps of Phoenix that show the locations with the highest likelihood of transmission overall.

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Date Created
  • 2016

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Cultural transmission and the disease ecology of tuberculosis in indigenous communities of the Paraguayan Chaco

Description

The health situation of indigenous peoples is comparable to that of the world's poorest populations, but with the additional burdens of social and cultural marginalization, geographic and cultural barriers to

The health situation of indigenous peoples is comparable to that of the world's poorest populations, but with the additional burdens of social and cultural marginalization, geographic and cultural barriers to accessing health services, and, in some areas, appropriation of land and natural resources. Cultural transmission (the transfer of beliefs, ideas, and behaviors from one culture to another) from outsider health institutions should presumably aid in closing this health gap by transferring knowledge, practices, and infrastructure to prevent and treat disease. This study examines the biosocial construction of the disease ecology of tuberculosis (TB) in indigenous communities of the Paraguayan Chaco with varying degrees of cultural transmission from outside institutions (government, religious, and NGOs), to determine the influence of cultural transmission on local disease ecologies. Using a biocultural epidemiological framework for the analysis of human infectious disease ecology, this study employed an interdisciplinary, mixed methods approach to examine the interactions of host, pathogen, and the environment in the Paraguayan Chaco. Three case studies examining aspects of TB disease ecology in indigenous communities are presented: (1) The effective cultural transmission of biomedical knowledge to isolated communities, (2) Public health infrastructure, hygiene, and the prevalence of intestinal parasites: co-morbidities that promote the progression to active TB disease, and (3) Community-level risk factors for TB and indigenous TB burden. Findings from the case studies suggest that greater influence from outside institutions was not associated with greater adoption of biomedical knowledge of TB. The prevalence of helminthiasis was unexpectedly low, but infection with giardia was common, even in a community with cleaner water sources. Communities with a health post were more likely to report active adult TB, while communities with more education were less likely to report active pediatric TB, suggesting that healthcare access is the major determinant of TB detection. More research is needed on the role of non-indigenous community residents and other measures of acculturation or integration in TB outcomes, especially at the household level. Indigenous TB burden in the Chaco is disproportionately high, and better understanding of the mechanisms that produce higher incidence and prevalence of the disease is needed.

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Date Created
  • 2014

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Spatial spread of rabies in wildlife

Description

Rabies disease remains enzootic among raccoons, skunks, foxes and bats in the United States. It is of primary concern for public-health agencies to control spatial spread of rabies in wildlife

Rabies disease remains enzootic among raccoons, skunks, foxes and bats in the United States. It is of primary concern for public-health agencies to control spatial spread of rabies in wildlife and its potential spillover infection of domestic animals and humans. Rabies is invariably fatal in wildlife if untreated, with a non-negligible incubation period. Understanding how this latency affects spatial spread of rabies in wildlife is the concern of chapter 2 and 3. Chapter 1 deals with the background of mathematical models for rabies and lists main objectives. In chapter 2, a reaction-diffusion susceptible-exposed-infected (SEI) model and a delayed diffusive susceptible-infected (SI) model are constructed to describe the same epidemic process -- rabies spread in foxes. For the delayed diffusive model a non-local infection term with delay is resulted from modeling the dispersal during incubation stage. Comparison is made regarding minimum traveling wave speeds of the two models, which are verified using numerical experiments. In chapter 3, starting with two Kermack and McKendrick's models where infectivity, death rate and diffusion rate of infected individuals can depend on the age of infection, the asymptotic speed of spread $c^\ast$ for the cumulated force of infection can be analyzed. For the special case of fixed incubation period, the asymptotic speed of spread is governed by the same integral equation for both models. Although explicit solutions for $c^\ast$ are difficult to obtain, assuming that diffusion coefficient of incubating animals is small, $c^\ast$ can be estimated in terms of model parameter values. Chapter 4 considers the implementation of realistic landscape in simulation of rabies spread in skunks and bats in northeast Texas. The Finite Element Method (FEM) is adopted because the irregular shapes of realistic landscape naturally lead to unstructured grids in the spatial domain. This implementation leads to a more accurate description of skunk rabies cases distributions.

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Created

Date Created
  • 2013

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Applications of nonlinear systems of ordinary differential equations and Volterra integral equations to infectious disease epidemiology

Description

In the field of infectious disease epidemiology, the assessment of model robustness outcomes plays a significant role in the identification, reformulation, and evaluation of preparedness strategies aimed at limiting the

In the field of infectious disease epidemiology, the assessment of model robustness outcomes plays a significant role in the identification, reformulation, and evaluation of preparedness strategies aimed at limiting the impact of catastrophic events (pandemics or the deliberate release of biological agents) or used in the management of disease prevention strategies, or employed in the identification and evaluation of control or mitigation measures. The research work in this dissertation focuses on: The comparison and assessment of the role of exponentially distributed waiting times versus the use of generalized non-exponential parametric distributed waiting times of infectious periods on the quantitative and qualitative outcomes generated by Susceptible-Infectious-Removed (SIR) models. Specifically, Gamma distributed infectious periods are considered in the three research projects developed following the applications found in (Bailey 1964, Anderson 1980, Wearing 2005, Feng 2007, Feng 2007, Yan 2008, lloyd 2009, Vergu 2010). i) The first project focuses on the influence of input model parameters, such as the transmission rate, mean and variance of Gamma distributed infectious periods, on disease prevalence, the peak epidemic size and its timing, final epidemic size, epidemic duration and basic reproduction number. Global uncertainty and sensitivity analyses are carried out using a deterministic Susceptible-Infectious-Recovered (SIR) model. The quantitative effect and qualitative relation between input model parameters and outcome variables are established using Latin Hypercube Sampling (LHS) and Partial rank correlation coefficient (PRCC) and Spearman rank correlation coefficient (RCC) sensitivity indices. We learnt that: For relatively low (R0 close to one) to high (mean of R0 equals 15) transmissibility, the variance of the Gamma distribution for the infectious period, input parameter of the deterministic age-of-infection SIR model, is key (statistically significant) on the predictability of the epidemiological variables such as the epidemic duration and the peak size and timing of the prevalence of infectious individuals and therefore, for the predictability these variables, it is preferable to utilize a nonlinear system of Volterra integral equations, rather than a nonlinear system of ordinary differential equations. The predictability of epidemiological variables such as the final epidemic size and the basic reproduction number are unaffected by (or independent of) the variance of the Gamma distribution for the infectious period and therefore for the choice on which type of nonlinear system for the description of the SIR model (VIE's or ODE's) is irrelevant. Although, for practical proposes, with the aim of lowering the complexity and number operations in the numerical methods, a nonlinear system of ordinary differential equations is preferred. The main contribution lies in the development of a model based decision-tool that helps determine when SIR models given in terms of Volterra integral equations are equivalent or better suited than SIR models that only consider exponentially distributed infectious periods. ii) The second project addresses the question of whether or not there is sufficient evidence to conclude that two empirical distributions for a single epidemiological outcome, one generated using a stochastic SIR model under exponentially distributed infectious periods and the other under the non-exponentially distributed infectious period, are statistically dissimilar. The stochastic formulations are modeled via a continuous time Markov chain model. The statistical hypothesis test is conducted using the non-parametric Kolmogorov-Smirnov test. We found evidence that shows that for low to moderate transmissibility, all empirical distribution pairs (generated from exponential and non-exponential distributions) for each of the epidemiological quantities considered are statistically dissimilar. The research in this project helps determine whether the weakening exponential distribution assumption must be considered in the estimation of probability of events defined from the empirical distribution of specific random variables. iii) The third project involves the assessment of the effect of exponentially distributed infectious periods on estimates of input parameter and the associated outcome variable predictions. Quantities unaffected by the use of exponentially distributed infectious period within low transmissibility scenarios include, the prevalence peak time, final epidemic size, epidemic duration and basic reproduction number and for high transmissibility scenarios only the prevalence peak time and final epidemic size. An application designed to determine from incidence data whether there is sufficient statistical evidence to conclude that the infectious period distribution should not be modeled by an exponential distribution is developed. A method for estimating explicitly specified non-exponential parametric probability density functions for the infectious period from epidemiological data is developed. The methodologies presented in this dissertation may be applicable to models where waiting times are used to model transitions between stages, a process that is common in the study of life-history dynamics of many ecological systems.

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Date Created
  • 2014

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On the dynamics of infectious diseases in modern landscapes: urban settings and drug resistance

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

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.

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Created

Date Created
  • 2014

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Cities in ecology: settlement patterns and diseases

Description

A sequence of models is developed to describe urban population growth in the context of the embedded physical, social and economic environments and an urban disease are developed. This set

A sequence of models is developed to describe urban population growth in the context of the embedded physical, social and economic environments and an urban disease are developed. This set of models is focused on urban growth and the relationship between the desire to move and the utility derived from city life. This utility is measured in terms of the economic opportunities in the city, the level of human constructed amenity, and the level of amenity caused by the natural environment. The set of urban disease models is focused on examining prospects of eliminating a disease for which a vaccine does not exist. It is inspired by an outbreak of the vector-borne disease dengue fever in Peru, during 2000-2001.

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Date Created
  • 2012