Browsing by Subject "Infectious Diseases"

Now showing 1 - 5 of 5
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    The Association of Social Disparity with Invasive Group A Streptococcus Infections in Minnesota Using Census Tract Level Socioeconomic Status, 1996-2016
    (2018-10) Kamal-Ahmed, Ishrat
    It has been difficult to determine the association, if any, between invasive Group A Streptococcus (iGAS) disease and social determinants of health (SDH) due to lack of data on an individual’s income, race, or living condition. While it is possible for a marginalized group to be genetically predisposed to specific infections, in most cases, socioeconomic factors such as poverty may be stronger determinants of disparities in infectious diseases. We used Census derived area-based information on SDH as a proxy for an individual’s data, and combined geocoding technology and proven statistical methods to investigate any association between iGAS cases with poverty, race, and living conditions. The Minnesota Department of Health Emerging Infections Program collected data on more than 3,600 iGAS cases from 1996 to 2016. The analysis was divided into three phases. For the first phase, iGAS cases from 1996 to 2016 were geocoded to their corresponding Census tract poverty levels and analyzed as outlined by the Harvard School of Public Health Disparities Geocoding Project method. Results demonstrated there would be 18% (population attributable fraction, or PAF, of 18%) reduction in iGAS if the exposure to poverty were reduced to zero. PAF was highest (29.4%) for 45-64 year-olds. The highest incidence rate ratio (IRR) of 2.26 (95% CI [2.02, 2.52]) was observed between the least impoverished (poverty level <=5%) and the most impoverished group (poverty level >=20%). RII (relative index of inequality) of 2.45 (95% CI [2.14, 2.77]) indicated that people in the most impoverished group were 2.45 times more likely to have iGAS than those in the least impoverished group. For the second phase, in addition to poverty, we appended area based racial diversity and overcrowded living condition from the U.S. Census and American Community Survey to each geocoded case. We divided the data into four groups of years (1996-2000), (2001-2005), (2006-2010) and (2011-2016) to observe any temporal pattern. A multilevel Poisson regression model was used to account for spatial similarity. While individual predictors -- poverty, racial diversity, and overcrowded living conditions -- were strongly associated with iGAS cases, multiple regression produced an inconsistent result due to moderate to high multicollinearity between these three measures. A principal component analysis used to reduce the correlated variables to a single latent variable and 73% of variance in the three SDH measures could be attributed to this variable. We created an index score by combining all three predictor variables using the first principal component of the correlation matrix. Every 10% increase in this combination of predictors is associated with an increase of the case count per 100,000 population in the first year-grouping (1996-2000) of 39% (p<.0001, 95% CI [31%-48%]), in the second grouping (2001-20015) of 21% (p<.0001, 95% CI [13%-29%]), in the third grouping (2006-2010) of 25% (p<.0001, 95% CI [17%-33%]), and in the fourth grouping (2011-2016) of 42% (p<.0001, 95% CI [33%-52%]). Finally, for the third phase of the analysis, over 2,000 cases were reported between 01/1/07 and 12/31/16. The residence of each case was geocoded to its corresponding Census tract allowing area-based measures of poverty from the American Community Survey to be appended to each case. We divided the data into two sets of 5 years each: (2007-2011) and (2012-2016) to observe any temporal pattern. A multilevel Poisson regression model was used to account for spatial similarity. For every 10% increase in CT poverty from 2007-2011, and from 2012-2016, the rate per 100,000 population for iGAS infection increased by 16% (p<.0001, 95% CI [8%-25%]), and 16% (p<.0001, 95% CI [8%-24%] respectively for whites. For every 10% increase in CT poverty from 2007-2011, and from 2012-2016, the rate for iGAS infection increased by 30% (p<.0001, 95% CI [16%-45%]), and 20% (p<.0001, 95% CI [8%-33%] respectively for non-whites. Since incidence rates are comparatively similar for both races, and racial diversity and poverty of a neighborhood are moderately correlated indicating more non-whites live in areas with higher poverty, the association of iGAS with race is mediated mostly by poverty. Invasive Group A Streptococcus infection disproportionately affects marginalized populations, likely due to factors associated with SDH and may be mitigated through proactive public health measures. Similar methods can be applied where an individual’s information on social determinants of health such as income, race, ethnicity, literacy, employment status, etc. is missing from the data. This may help accurately quantify any social disparity, and subsequently design targeted intervention for both chronic and infectious diseases. Since a long-term improvement of social infrastructure is warranted, vaccine development is an immediate and plausible solution.
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    Integration of Life Sciences and Engineering - Highly Infectious Diseases in Population : Control System Analysis and Synthesis
    (2020-07) Bhattacharjee, Srijita
    The research in this master's thesis focuses on the integration of engineering and biological sciences. The thesis starts with a literature survey to find out the model of a highly infectious disease such as smallpox among a certain metropolitan population. The chosen nonlinear model is simulated using MATLAB and Simulink to obtain input-output relations in the time domain. Next, the nonlinear model is linearized around an equilibrium point to demonstrate the analysis of the linear system exhibiting control system characteristics such as controllability, observability, and stability. Finally, from the control system synthesis (design) point of view, the theory of linear optimal control has been implemented on the linearized model. The problem of finite-horizon linear quadratic regulation has been investigated to provide the necessary optimal feedback to the smallpox model.
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    Investigating cytotoxic cell responses during Cryptococcal meningitis in patients with chronic advanced HIV co-infection
    (2024-11) Okafor, Elizabeth
    Due to underlying immunosuppression, persons with chronic advanced HIV are susceptible to infections from opportunistic pathogens. Cryptococcus neoformans is an opportunistic fungal pathogen which causes localized pulmonary disease in immunocompetent persons; however, persons who are immunosuppressed can develop disseminated disease into the central nervous system called Cryptococcal meningitis (CM). Patients with CM present with constitutional symptoms such as fever, vomiting and weight loss, and central nervous system specific symptoms such as headache, photophobia, and nuchal rigidity due to high fungal burden in the brain impairing the recycling of cerebrospinal fluid. Treatment with a ~12-month course of combination antifungal therapy, as well as beginning antiretrovirals four-six weeks after antifungal treatment has been established, is essential for fungal clearance. However, despite prompt treatment mortality remains high, especially in low-resourced countries in sub-Saharan Africa. The immune response during CM is dysregulated due to low quantities of and dysfunctional CD4+ T-cells, which are principal players in orchestrating inflammatory immune responses in infected tissues. On one end of the spectrum, poor inflammatory responses allow for rampant C. neoformans fungal growth. While on the other end, hyper-inflammatory response, as in immune reconstitution inflammatory syndrome, can damage fragile tissues such as the brain parenchyma. While understanding CD4+ T-cells are essential to cryptococcal pathogenesis, little is known regarding cytotoxic cells, specifically CD8+ T-cells and Natural killer cells, during CM. Cytotoxic cells have the capability to target extracellular and intracellular pathogens, such as C. neoformans, for destruction as well as produce key inflammatory mediators that induce differentiation of naïve CD4+ T-cells and monocyte populations. Thus, the aims of this thesis are to 1) investigate the immune environment in the CNS to define the role of cytotoxic cells in patient outcome from CM and 2) characterize the cytotoxic cell populations in the CNS and periphery during infection to determine cellular function and contribution to the antifungal response.
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    Membrane Serine Protease Protects Mycobacterium Avium Subsp. Paratuberculosis against Phagosomal Acid Stress
    (2011-01) Kugadas, Abi
    Pathogenic mycobacteria survive in the acidic environment of the phagosome. We hypothesize that a serine protease of Mycobacterium avium subspecies paratuberculosis (MAP), encoded by MAP0403, aids in the resistance to phagosomal acidification and is critical for survival in macrophages. The modulation of expression of MAP0403 within macrophages by MAP K-10 was studied. Bafilomycin treatment was used to block phagosomal acidification. Gene encoding the MAP serine protease was significantly up regulated in the acidified phagosomes. Highest levels of MAP0403 expression correlated with peak phagosome acidification in macrophages. Bioinformatically predicted genes that encode proteins interacting or are co-expressed with MAP0403 during phagosomal acidification were analyzed by microarray. Results show that the genes involved in DNA repair, protein synthesis and those located immediately up stream of MAP serine protease are up regulated in the acidified phagosome. Inasmuch as Mycobacterium smegmatis cannot resist and persist in the acidified phagosome, we cloned the open reading frame of MAP0403 into M. smegmatis mc2 155. Compared with controls, M. smegmatis mc2 155 transformants carrying the MAP serine protease show increased survival during in vitro acid stress and in monocyte derived macrophages. Further, we show that serine protease carrying M. smegmatis transformants are able to maintain intra-bacterial pH when exposed to an acidic media (pH~5), while controls failed to do so. Our studies suggest that MAP serine protease is critical in resisting the phagosomal acidification by MAP.
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    Uganda
    (2012-04-01) Birkenkamp, Kate