Glucans are fungal cell wall glucose polymers that are released into the blood of infected patients. The role of glucans in infection is unknown. We examined serum glucan and cytokine levels in intensive care unit (ICU) patients with infections. There was an inverse correlation (p<0.001) between serum glucan levels and interleukin (IL)-2), IL-4, tumor necrosis factorα (TNFα) and granulocyte macrophage-colony stimulating factor (GM-CSF) levels in infected ICU patients. The correlation between serum cytokines and serum glucan was only observed at glucan concentrations <40 pg/ml. No change was observed at serum glucan levels of >40 pg/ml. There was no correlation between serum glucan levels and systemic levels of IL-1β, IL-5, IL-6, IL-8, IL-10 or IFNγ. Interestingly, blood borne glucans did not suppress systemic cytokine levels in infected ICU patients, instead they were maintained at control levels. We conclude that circulating glucans may prevent cytokine upregulation in response to infection. This may represent an adaptive response to septic injury.

Microsporidia are obligate intracellular, spore-forming, fungal-related pathogens that employ a unique organelle, the polar tube, to transfer infectious spore contents into host cells to initiate infection. Spore adherence to host cells may provide the proximity required for polar tube/host cell interaction during in vivo infection. In previous in vitro studies, host sulfated glycosaminoglycans (GAGs) or recombinant microsporidia endospore protein (EnP1) was implicated in the pathogen adherence and infection process; however, complete ablation of spore adherence and infection could not be achieved, suggesting that additional or alternative spore and host cell determinants of adherence and infection may exist. Analysis of the Encephalitozoon intestinalis genome revealed about 100 predicted proteins containing the canonical integrin-binding motif arginine-glycine-aspartic acid (RGD); and, many pathogens have been shown to engage integrin molecules on cell surfaces. We hypothesized that host cell integrins play a role in microsporidia adherence and infection. In this study, we demonstrated that addition of exogenous integrin ligands or recombinant alpha 3 beta 1 integrin or alpha 5 beta 1 integrin to assays of E. intestinalis adherence and infection significantly reduced spore adherence and infection of host cells, supporting our hypothesis and implicating these specific integrins as putative host cell receptors for E. intestinalis spores.

Surgical site infections (SSIs) are a leading cause of morbidity and mortality in the United States. Researchers have demonstrated the impact that SSIs have on the healthcare system and the need to improve patient outcomes. The purpose of this project was to develop an educational program for the 8-member nursing staff of an outpatient vascular surgical office to help reduce the occurrence of SSI rates for patients seen pre and postoperatively after a noted increase in SSI rates at this clinical setting. Guided by the Fitzpatrick model, a group of 6 health care providers comprising 3 surgeons and 3 nurse practitioners served as content experts to conduct formative evaluation during development of the educational program. Members of the surgical office nursing staff completed a questionnaire; results were analyzed using descriptive analysis. Findings indicated that 100% of nursing staff had no on-site work training on basic signs and symptoms of infection and infection control; 100% of staff were not confident in assessment of the surgical site and addressing patient issues; and at least 50% reported that they lacked knowledge of proper wound care including bathing, dressing changes, and expected symptoms for healing and/or complications postoperatively. Educational materials were designed to address these gaps. This project might benefit the surgical center nursing staff by providing education to help reduce surgical site infection in vascular patients, and bring about positive social change by improving quality of life and patient outcomes for the vascular surgery patient through a reduction in the occurrence of SSIs.

Indiana University-Purdue University Indianapolis (IUPUI) / Chlamydia is the most frequently reported bacterial sexually transmitted infection in the world. Most urogenital chlamydia infections in men and women are asymptomatic, but these infections can lead to irreparable damage in the reproductive system and other tissues. Apart from the urogenital chlamydial infections, we know that chlamydia infects the gastrointestinal tract (GIT) in humans and can colonize the GIT for extended intervals without eliciting pathology. We are interested in investigating tissue tropism determinants in Chlamydia spp. because these could be targeted to development live-attenuated vaccines. Recently, we generated mutagenized isolates of the mouse pathogen Chlamydia muridarum, a close relative of the human pathogen Chlamydia trachomatis which causes chlamydia. One mutant that we isolated is significantly attenuated in murine gastrointestinal tissues compared to wild type, but retains its pathogenicity in the murine urogenital tract. Using novel genetic techniques, whole-genome sequencing, and complementation using newly developed vector systems we identified a chromosomal factor, tc0600, that we believe mediates the altered tissue tropism phenotype of this mutant in mice. Notably, the Chlamydia trachomatis ortholog of tc0600 has been linked to chlamydial GIT tropism in humans.

No description available.

No description available.

Occidiofungin is a novel glycolipopeptide, synthesized and secreted by Burkholderia contaminans MS14, demonstrating broad-spectrum antifungal activity and potential for successful clinical applications. Its mechanism of action has not yet been determined but is known to exhibit fungicidal activity via the induction of apoptosis in a manner unique from that of currently approved antifungals. As an early investigation into occidiofungin’s mechanism of action, we aimed to identify environmental and cellular factors that significantly alter the susceptibility of the model organism, Saccharomyces cerevisiae. To that end, we have demonstrated that occidiofungin’s bioactivity requires active cellular growth, that new protein synthesis is necessary to adequately respond to occidiofungin exposure, and that alterations in transcriptional regulation in response to glucose and phosphate deprivation have synergistic and antagonist consequences, respectively, on occidiofungin’s effectiveness. Together, this data provides a foundation on which occidiofungin’s mechanism of action can be illuminated.

Hepatitis is an infectious disease that affects millions of people worldwide. The current project seeks to achieve two objectives: 1) To understand how hepatitis policies affect hepatitis prevalence in prison, and 2) To understand how hepatitis prevalence in prison affects the general population. Using a content analysis of correctional policies available through each state Department of Corrections (DOC) and secondary data from the 2010 Census, Centers for Disease Control and Prevention, and Corrections Compendium; hepatitis prevalence and policies are analyzed. The content analysis employed for this study revealed that some states have more comprehensive policies than others. However, all states may benefit from modifying their policies to meet recommendations constructed by the Federal Bureau of Prisons. Findings from descriptive statistics also suggest changes in HIV prevalence and policies positively affect hepatitis C prevalence. Future research should be dedicated to examining how personal interactions in prison also affect prevalence rates.

Healthcare-associated infections (HAIs) are used as a measure for federal value-based payment programs. Using data for 2015, the Centers for Disease Control and Prevention (CDC) developed newer risk adjustment models to calculate the standardized infection ratio (SIR) for various infections occurring in hospitals. New national baselines were set to compare performance among medical facilities and states. Despite adjustments for various facility-level factors that contribute to HAI risk, there are ongoing concerns that SIR calculations do not adequately account for non-hospital risk factors that have been linked to clinical outcomes. This explanatory study evaluates state-level data using simple linear regression to determine relationships between the standardized infection ratio (SIR) for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and several socioeconomic and geographic factors. Bivariate analysis produced significant correlation between SIR and high school education, with states exhibiting lower SIR relative to the percent of adults who completed high school. Higher SIRs were found relative to the percent of state populations subjected to poverty, obesity, and diagnosis of diabetes. Percent of nonprofit hospitals, adults with bachelor’s degrees, and rural residents were not significantly correlated with state measures of MRSA bacteremia. These findings can help guide efforts to reduce HAIs, improve safety of care, and advance population health efforts. The results from this study reinforce the notion that non-hospital factors may have significant effects on the incidence of MRSA bacteremia events occurring in hospitalized patients. Current risk adjustment models that predict MRSA bacteremia events for quality reporting purposes may not adequately account for these risk factors. The present study highlights some ways that hospitals, patients, and policymakers can work together to address social risk factors as a strategy for promoting better and safer care, and healthier communities. This study investigates aspects of the bigger picture of health care quality, performance measurement, and population health. This “feel for the whole” underscores the implications on state performance in infection prevention in the context of socioeconomic and medical vulnerabilities. The study emphasizes the need for greater multidisciplinary collaboration to address community health needs and reduce social and medical disparities.

Background: C. difficile is one of the primary infectious causes of morbidity and mortality in Canada. Colonized patients can pose a risk to others as a factor in the transmission and development of hospital-associated C. difficile infections. Despite immense efforts and resources invested in the reduction in C. difficile transmission within Canada and Hamilton Health Sciences – further reduction in these rates are unlikely, and novel screening strategies are imperative in this field of study. Methods: This project was a retrospective cohort study of adult in-patients admitted to either The Juravinski, Hamilton General, or St. Joseph’s Healthcare Hamilton Hospitals from January to April 2018 and September 2018 to August 2019. MSRA/VRE swabs were collected during admission or through universal point prevalence screening and subsequently tested for colonization. Results: From the 1056 patients in the data sample, 72 were colonized with asymptomatic C. difficile resulting in a prevalence rate of 6.81%. In-patient point prevalence screening strategies identified more carriers than admission swabs alone (p < 0.001). Risk factors for colonization on admission were being female (OR 2.66, 95% CI 1.02-8.33) and previous CDI (OR 4.76, 95% CI 1.49 – 13.86). During hospitalization, risk factors for colonization were previous CDI (OR 4.75 95% CI 2.14-9.94) and recent hospitalization within the last 12 months (OR 2.35, 95% CI 1.30-4.42). The multi-level Cox PH model identified those with a recent hospitalization (OR 2.21, 95% CI 1.32 – 3.73) and those with previous CDI (OR 2.40, 1.34 – 4.30) were twice as likely to develop asymptomatic C. difficile colonization throughout hospitalization. Conclusion: The addition of universal point prevalence screening in addition to admission screening helped identify more than double the amount of carriers in the population. Moreover, a previous hospitalization, previous CDI, and being female may indicate patients at the highest risk of colonization. / Thesis / Master of Science (MSc) / C. difficile infection (CDI) is a severe infectious disease. Patients with asymptomatic C. difficile present a risk to others as they can contribute to the spread and development of hospital-associated CDI. We are currently unsure of the proportion of adult in-patients colonized with asymptomatic C. difficile. Identifying these carriers early on in their hospital stay is imperative to reduce CDI rates in health care settings. Our study objectives were to determine the best screening strategies to identify asymptomatic carriers, identify risk factors for carriage, and understand the transition from asymptomatic C. difficile to symptomatic CDI. We demonstrated that being female, being recently hospitalized or previously having CDI may increase a patient's risk of being an asymptomatic carrier. Also, timely screening throughout a hospital stay in addition to admission screening helped identify more colonized in-patients. Lastly, we determined that 1 in 5 carriers would go on to develop symptomatic CDI infection.