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Evaluating the viability of a DNA-based chip targeted for C. trachomatis, N. gonorrhoeae, and other pathogens of interest

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Sexually transmitted diseases like gonorrhea and chlamydia, standardly treated with antibiotics, produce over 1.2 million cases annually in the emergency department (Jenkins et al., 2013). To determine a need for antibiotics, hospital labs utilize bacterial cultures to isolate and identify

Sexually transmitted diseases like gonorrhea and chlamydia, standardly treated with antibiotics, produce over 1.2 million cases annually in the emergency department (Jenkins et al., 2013). To determine a need for antibiotics, hospital labs utilize bacterial cultures to isolate and identify possible pathogens. Unfortunately, this technique can take up to 72 hours, leading to several physicians presumptively treating patients based solely on history and physical presentation. With vague standards for diagnosis and a high percentage of asymptomatic carriers, several patients undergo two scenarios; over- or under-treatment. These two scenarios can lead to consequences like unnecessary exposure to antibiotics and development of secondary conditions (for example: pelvic inflammatory disease, infertility, etc.). This presents a need for a laboratory technique that can provide reliable results in an efficient matter. The viability of DNA-based chip targeted for C. trachomatis, N. gonorrhoeae, and other pathogens of interest were evaluated. The DNA-based chip presented several advantages as it can be easily integrated as a routine test given the process is already well-known, is customizable and able to target multiple pathogens within a single test and has the potential to return results within a few hours as opposed to days. As such, implementation of a DNA-based chip as a diagnostic tool is a timely and potentially impactful investigation.

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2016-12

Tracing the Evolutionary Histories of Leprosy and Tuberculosis using Ancient DNA and Phylogenomics Methods

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Leprosy and tuberculosis are age-old diseases that have tormented mankind and left behind a legacy of fear, mutilation, and social stigmatization. Today, leprosy is considered a Neglected Tropical Disease due to its high prevalence in developing countries, while tuberculosis is

Leprosy and tuberculosis are age-old diseases that have tormented mankind and left behind a legacy of fear, mutilation, and social stigmatization. Today, leprosy is considered a Neglected Tropical Disease due to its high prevalence in developing countries, while tuberculosis is highly endemic in developing countries and rapidly re-emerging in several developed countries. In order to eradicate these diseases effectively, it is necessary to understand how they first originated in humans and whether they are prevalent in nonhuman hosts which can serve as a source of zoonotic transmission. This dissertation uses a phylogenomics approach to elucidate the evolutionary histories of the pathogens that cause leprosy and tuberculosis, Mycobacterium leprae and the M. tuberculosis complex, respectively, through three related studies. In the first study, genomes of M. leprae strains that infect nonhuman primates were sequenced and compared to human M. leprae strains to determine their genetic relationships. This study assesses whether nonhuman primates serve as a reservoir for M. leprae and whether there is potential for transmission of M. leprae between humans and nonhuman primates. In the second study, the genome of M. lepraemurium (which causes leprosy in mice, rats, and cats) was sequenced to clarify its genetic relationship to M. leprae and other mycobacterial species. This study is the first to sequence the M. lepraemurium genome and also describes genes that may be important for virulence in this pathogen. In the third study, an ancient DNA approach was used to recover M. tuberculosis genomes from human skeletal remains from the North American archaeological record. This study informs us about the types of M. tuberculosis strains present in post-contact era North America. Overall, this dissertation informs us about the evolutionary histories of these pathogens and their prevalence in nonhuman hosts, which is not only important in an anthropological context but also has significant implications for disease eradication and wildlife conservation.

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2017