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Mathematical modeling of infectious diseases can help public health officials to make decisions related to the mitigation of epidemic outbreaks. However, over or under estimations of the morbidity of any infectious disease can be problematic. Therefore, public health officials can always make use of better models to study the potential

Mathematical modeling of infectious diseases can help public health officials to make decisions related to the mitigation of epidemic outbreaks. However, over or under estimations of the morbidity of any infectious disease can be problematic. Therefore, public health officials can always make use of better models to study the potential implication of their decisions and strategies prior to their implementation. Previous work focuses on the mechanisms underlying the different epidemic waves observed in Mexico during the novel swine origin influenza H1N1 pandemic of 2009 and showed extensions of classical models in epidemiology by adding temporal variations in different parameters that are likely to change during the time course of an epidemic, such as, the influence of media, social distancing, school closures, and how vaccination policies may affect different aspects of the dynamics of an epidemic. This current work further examines the influence of different factors considering the randomness of events by adding stochastic processes to meta-population models. I present three different approaches to compare different stochastic methods by considering discrete and continuous time. For the continuous time stochastic modeling approach I consider the continuous-time Markov chain process using forward Kolmogorov equations, for the discrete time stochastic modeling I consider stochastic differential equations using Wiener's increment and Poisson point increments, and also I consider the discrete-time Markov chain process. These first two stochastic modeling approaches will be presented in a one city and two city epidemic models using, as a base, our deterministic model. The last one will be discussed briefly on a one city SIS and SIR-type model.
ContributorsCruz-Aponte, Maytee (Author) / Wirkus, Stephen A. (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Camacho, Erika T. (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2014
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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

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
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Description
In the United States, seasonal influenza is responsible for enormous medical costs and lost earnings as well as thousands of deaths. Medical masks are effective non-pharmaceutical preventions for minimizing the spread of illness in the event of an influenza outbreak. However, people in the United States rarely wear face masks

In the United States, seasonal influenza is responsible for enormous medical costs and lost earnings as well as thousands of deaths. Medical masks are effective non-pharmaceutical preventions for minimizing the spread of illness in the event of an influenza outbreak. However, people in the United States rarely wear face masks the way many people in Asian countries do.

In a previous study of public response to the 2009 influenza A H1N1 pandemic, 71% of United States respondents supported the recommendation to wear a mask during the flu outbreak, while only 8% of respondents reported they wore a mask in public to protect themselves from getting sick. What are the factors that cause this gap? The purpose of this exploratory study is to identify barriers to the wearing of masks among adults in the United States.

The research was conducted through an online survey of 84 American residents via the Survey Monkey Audience service to collect their opinions on influenza, mask-wearing, and the perceived barriers to wearing face masks for flu prevention. The results are presented in the descriptive analysis and the non-parametric analysis.

The results showed a barrier against social interaction is a significant factor (p=0.003) regarding the impact between flu experience and the perceived barriers. The participants believed mask-wearing may lead other people difficult to perceiving their feelings. Regarding the relationship between mask-wearing experience and the perceived barriers, there were significant differences in perceived benefits (p=0.028), perceived risks (p= 0.003), and social value (p=0.021). Participants who have had worn masks had perceived higher benefits of mask-wearing, higher risks of catching the flu, and a higher agreement of importance to protect other people from getting the flu from them. The most common perceived barrier among the participants is product satisfaction. 85.71% of the participants agreed that wearing face masks is uncomfortable. 80.95% of the participants agreed with the importance to wear face masks as it protects other people from getting the flu from them, but only 37.5% of the participants with flu history had worn face masks.

By examining barriers to the wearing of masks for influenza prevention, this study can assess public willingness to adopt personal prevention behaviors and provide information for related policies in the future.
ContributorsHung, Yu-Wen (Author) / Herring, Donald (Thesis advisor) / Velasquez, Joseph (Committee member) / Lamb, Gerri (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Influenza has shown its potential to affect and even kill millions of people within an extremely short time frame, yet studies and surveys show that the general public is not well educated about the facts about influenza, including prevention and treatment. For this reason, public perception of influenza is extremely

Influenza has shown its potential to affect and even kill millions of people within an extremely short time frame, yet studies and surveys show that the general public is not well educated about the facts about influenza, including prevention and treatment. For this reason, public perception of influenza is extremely skewed, with people generally not taking the disease as seriously as they should given its severity. To investigate the inconsistencies between action and awareness of best available knowledge regarding influenza, this study conducted literature review and a survey of university students about their knowledge, perceptions, and action taken in relationship to influenza. Due to their dense living quarters, constant daily interactions, and mindset that they are "immune" to fairly common diseases like influenza, university students are a representative sample of urban populations. According to the World Health Organization (WHO), 54% of the world's population lived in cities as of 2014 (Urban population growth). Between 2015 and 2020, the global urban population is expected to grow 1.84% per year, 1.63% between 2020 and 2025, and 1.44% between 2025 and 2030 (Urban population growth). Similar projections estimate that by 2017, an overwhelming majority of the world's population, even in less developed countries, will be living in cities (Urban population growth). Results of this study suggest possible reasons for the large gap between best available knowledge and the perceptions and actions of individuals on the other hand. This may lead to better-oriented influenza education initiatives, more effective prevention and treatment plans, and generally raise excitement and awareness surrounding public health and scientific communication.
ContributorsGur-Arie, Rachel Ellen Haviva (Author) / Maienschein, Jane (Thesis director) / Laubichler, Manfred (Committee member) / Creath, Richard (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-12
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Description
Background: While research has quantified the mortality burden of the 1957 H2N2 influenza pandemic in the United States, little is known about how the virus spread locally in Arizona, an area where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.
Methods: Using archival

Background: While research has quantified the mortality burden of the 1957 H2N2 influenza pandemic in the United States, little is known about how the virus spread locally in Arizona, an area where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.
Methods: Using archival death certificates from 1954 to 1961, this study quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and generation intervals of 3 and 4 days. Local newspaper articles from The Arizona Republic were analyzed from 1957-1958.
Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 17.85 in the elderly (≥65 years). All other age groups had extremely low excess-mortality and the typical U-shaped age-pattern was absent. However, relative risk was greatest (3.61) among children and young adolescents (5-14 years) from October 1957-March 1958, based on incidence rates of respiratory deaths. Transmissibility was greatest during the same 1957-1958 period, when the mean reproduction number was 1.08-1.11, assuming 3 or 4 day generation intervals and exponential or fixed distributions.
Conclusions: Maricopa County largely avoided pandemic influenza from 1957-1961. Understanding this historical pandemic and the absence of high excess-mortality rates and transmissibility in Maricopa County may help public health officials prepare for and mitigate future outbreaks of influenza.
ContributorsCobos, April J (Author) / Jehn, Megan (Thesis director) / Chowell-Puente, Gerardo (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
The 2017-2018 Influenza season was marked by the death of 80,000 Americans: the highest flu-related death toll in a decade. Further, the yearly economic toll to the US healthcare system and society is on the order of tens of billions of dollars. It is vital that we gain a better

The 2017-2018 Influenza season was marked by the death of 80,000 Americans: the highest flu-related death toll in a decade. Further, the yearly economic toll to the US healthcare system and society is on the order of tens of billions of dollars. It is vital that we gain a better understanding of the dynamics of influenza transmission in order to prevent its spread. Viral DNA sequences examined using bioinformatics methods offer a rich framework with which to monitor the evolution and spread of influenza for public health surveillance. To better understand the influenza epidemic during the severe 2017-2018 season, we established a passive surveillance system at Arizona State University’s Tempe Campus Health Services beginning in January 2018. From this system, nasopharyngeal samples screening positive for influenza were collected. Using these samples, molecular DNA sequences will be generated using a combined multiplex RT-PCR and NGS approach. Phylogenetic analysis will be used to infer the severity and temporal course of the 2017-2018 influenza outbreak on campus as well as the 2018-2019 flu season. Through this surveillance system, we will gain knowledge of the dynamics of influenza spread in a university setting and will use this information to inform public health strategies.
ContributorsMendoza, Lydia Marie (Author) / Scotch, Matthew (Thesis director) / Hogue, Brenda (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Description
Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high

Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high levels of conservation. On its own it is poorly immunogenic and offers little protection against influenza infections, but by combining it with a potent adjuvant, this limitation may be overcome. Recombinant immune complexes, or antigens fused to antibodies that have been engineered to form incredibly immunogenic complexes with one another, were previously shown to be useful, immunogenic platforms for the presentation of various antigens and could provide the boost in immunogenicity that M2e needs to become a powerful universal influenza A vaccine. In this thesis, genetic constructs containing geminiviral replication proteins and coding for a consensus sequence of dimeric M2e fused to antibodies featuring complimentary epitopes and epitope tags were generated and used to transform Agrobacterium tumefaciens. The transformed bacteria was then used to cause Nicotiana benthamiana to transiently express M2e-RICs at very high levels, with enough RICs being gathered to evaluate their potency in future mouse trials. Future directions and areas for further research are discussed.
ContributorsFavre, Brandon Chetan (Author) / Mason, Hugh (Thesis director) / Mor, Tsafrir (Committee member) / Diamos, Andrew (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The influenza virus is the main cause of thousands of deaths each year in the United States, and far more hospitalizations. Immunization has helped in protecting people from this virus and there are a number of therapeutics which have proven effective in aiding people infected with the virus. However, these

The influenza virus is the main cause of thousands of deaths each year in the United States, and far more hospitalizations. Immunization has helped in protecting people from this virus and there are a number of therapeutics which have proven effective in aiding people infected with the virus. However, these therapeutics are subject to various limitations including increased resistance, limited supply, and significant side effects. A new therapeutic is needed which addresses these problems and protects people from the influenza virus. Synbodies, synthetic antibodies, may provide a means to achieve this goal. Our group has produced a synbody, the 5-5 synbody, which has been shown to bind to and inhibit the influenza virus. The direct pull down and western blot techniques were utilized to investigate how the synbody bound to the influenza virus. Our research showed that the 5-5 synbody bound to the influenza nucleoprotein (NP) with a KD of 102.9 ± 74.48 nM. It also showed that the synbody bound strongly to influenza viral extract from two different strains of the virus, the Puerto Rico (H1N1) and Sydney (H3N2) strains. This research demonstrated that the 5-5 synbody binds with high affinity to NP, which is important because influenza NP is highly conserved between various strains of the virus and plays an important role in the replication of the viral genome. It also demonstrated that this binding is conserved between various strains of the virus, indicating that the 5-5 synbody potentially could bind many different influenza strains. This synbody may have potential as a therapeutic in the future if it is able to demonstrate similar binding in vivo.
ContributorsKombe, Albert E. (Author) / Diehnelt, Chris (Thesis director) / Woodbury, Neal (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of International Letters and Cultures (Contributor)
Created2014-05
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Description
The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as

The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as a possible Influenza therapeutic. Specifically, at CIM, we have attempted to design these initial synbodies to target the entire Influenza virus and preliminary data leads us to believe that these synbodies target Nucleoprotein (NP). Given that the synbody targets NP, the penetration of cells via synbody should also occur. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. The focus of my honors thesis is to explore how synthetic antibodies can potentially inhibit replication of the Influenza (H1N1) A/Puerto Rico/8/34 strain so that a therapeutic can be developed. A high affinity synbody for Influenza can be utilized to test for inhibition of Influenza as shown by preliminary data. The 5-5-3819 synthetic antibody's internalization in live cells was visualized with Madin-Darby Kidney Cells under a Confocal Microscope. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. Expression of NP over 8 hours time was analyzed via Western Blot Analysis, which showed NP accumulation was retarded in synbody treated cells. The data obtained from my honors thesis and preliminary data provided suggest that the synthetic antibody penetrates live cells and targets NP. The results of my thesis presents valuable information that can be utilized by other researchers so that future experiments can be performed, eventually leading to the creation of a more effective therapeutic for influenza.
ContributorsHayden, Joel James (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
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Mortality of 1918 influenza virus was high, partly due to bacteria coinfections. We characterize pandemic mortality in Arizona, which had high prevalence of tuberculosis. We applied regressions to over 35,000 data points to estimate the basic reproduction number and excess mortality. Age-specific mortality curves show elevated mortality for all age

Mortality of 1918 influenza virus was high, partly due to bacteria coinfections. We characterize pandemic mortality in Arizona, which had high prevalence of tuberculosis. We applied regressions to over 35,000 data points to estimate the basic reproduction number and excess mortality. Age-specific mortality curves show elevated mortality for all age groups, especially the young, and senior sparing effects. The low value for reproduction number indicates that transmissibility was moderately low.
ContributorsJenner, Melinda Eva (Author) / Chowell-Puente, Gerardo (Thesis director) / Kostelich, Eric (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-05