Pseudomonas aeruginosa (PA) infections in Cystic Fibrosis (CF) patients are not easily cleared due to the conversion from a nonmucoid to a mucoid phenotype. Alginate is an acetylated exopolysaccharide produced by mucoid PA that is responsible for increased resistance to antibiotics, host phagocytic killing, and propagating biofilm formation. Understanding the interaction between PA and host cells is critical to understanding chronic infection and inflammation in CF. In order to investigate this, we used A549 pulmonary epithelial cells and murine alveolar macrophages (MH-S) to examine host response to nonmucoid versus mucoid PA infection. Adhesion assays in A549 pulmonary epithelial cells revealed that mucoid PA mutants adhere poorly compared to their nonmucoid counterparts. Similarly, phagocytosis assays using MH-S infected with PA revealed that mucoid PA are increasingly resistant to phagocytosis. The alginate acetylation mutant FRD1175 is more susceptible to phagocytic killing than alginate+ FRD1. Adherence and phagocytosis of mucoid FRD1 was increased by increasing the multiplicity of infection (MOI) from 50:1 to 500:1. Furthermore, confocal microscopy revealed that mucoid PA are inherently less inflammatory than nonmucoid strains in both A549 and MH-S. Increasing the MOI of mucoid FRD1 from 50:1 to 500:1 significantly increased caspase-1 activation in MH-S but not in A549, revealing that intensity of inflammatory signaling by epithelial cells is likely independent of increased adherence. FRD1175 infection in both A549 and MH-S revealed that alginate acetylation plays a significant role in reducing inflammasome activation. Western analysis revealed that PA does not actively induce TGF-β secretion by A549 epithelial cells. Similarly, NF-κB expression was reduced in both A549 and MH-S when infected with mucoid FRD strains, but not PA from the PAO background, suggesting FRD strains have accumulated additional mutations facilitating escape of inflammation. MH-S treated with cytochalasin D to block phagocytosis were still able to activate NF-κB signaling, suggesting NF-κB activation is adherence but not phagocytosis dependent. These data increase our understanding of the various mechanisms in which mucoid PA is able to evade host immune defenses and provides insight into potential therapies to treat PA infections.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Master of Science / Department of Clinical Sciences / Greg Grauer / A urinary tract infection (UTI) is defined as a temporary or permanent breach in host defense mechanisms that allows microbes to adhere, multiply, and persist within the urinary tract. Development of a UTI is multi-factorial with bacterial number and virulence and the health status of the patient (normal urogenital tract anatomy and physiology and systemic immunocompetence) playing important roles in determining the outcome. A UTI can involve a single site, such as the renal pelvis, ureter, bladder, urethra, prostate or vagina, or can include multiple sites. Infection of any portion of the urinary tract may increase the likelihood of infection in other locations. Diagnosis of a UTI incorporates findings from the history, physical examination, complete urinalysis, and urine culture. Proper classification and localization of the UTI are important when formulating a treatment regime as well as evaluating treatment success and failure. Most UTI can be successfully managed with appropriate antibiotic treatment; however, bacterial resistance and compromised host defense mechanisms can result in persistent or recurrent infections. In patients with recurrent UTI, identification of underlying predisposing conditions will often improve treatment success. In patients where underlying causes cannot be identified or treated, therapies designed to prevent recurrent UTI may be employed. Proanthrocyanidins found in cranberry juice inhibit E. coli attachment to human uroepithelial cells, impairing bacterial adherence and colonization. These characteristics have encouraged widespread usage of cranberry extract as a prevention strategy for woman predisposed to urinary tract infections. E. coli is a common cause of canine urinary tract infection. Current treatment emphasizes eradication of established infection rather than infection prevention, but increased antibiotic resistance necessitates strategies to prevent infection. We hypothesized that purified cranberry extract (CE) inhibits bacterial adhesion to canine uroepithelial cells. The results of our study show that CE supplementation can reduce adhesion of uropathogenic E. coli to canine uroepithelium and suggests one mechanism by which CE might improve urinary tract health.

Recent events have thrown the spotlight on infectious disease outbreak response. We developed a data-driven method, EpiGro, which can be applied to cumulative case reports to estimate the order of magnitude of the duration, peak and ultimate size of an ongoing outbreak. It is based on a surprisingly simple mathematical property of many epidemiological data sets, does not require knowledge or estimation of disease transmission parameters, is robust to noise and to small data sets, and runs quickly due to its mathematical simplicity. Using data from historic and ongoing epidemics, we present the model. We also provide modeling considerations that justify this approach and discuss its limitations. In the absence of other information or in conjunction with other models, EpiGro may be useful to public health responders. (C) 2016 The Authors. Published by Elsevier B.V.

Aortic infections are rare, life-threatening and constitute a major challenge in surgical management. This thesis aims to evaluate short – and long-term outcome of endovascular aortic repair (EVAR) for mycotic aortic aneurysms (MAA) and the subsequent risk of recurrent infections, changes in surgical practice over time for abdominal MAAs in Sweden and outcome for different treatment modalities, as well as the risk of secondary vascular infection after treatment with Open abdomen after aortic surgery. Paper I, a retrospective single centre study of patients with MAA treated with EVAR, demonstrated a good short-term outcome, 91% survival at 30-days, and acceptable mid-term survival, 73% at 1-year. Paper II, a retrospective international multicentre study of patients treated with EVAR for MAA, confirmed the results in paper I, and showed that EVAR is feasible and for most MAA patients a durable treatment option, 5-year survival was 55% and 10-year 41%. A total of 19% died from an infection-related complication, mostly during the first postoperative year. Non-Salmonella-positive culture was a predictor for late infection–related death. Paper III, a population-based cohort study on all abdominal MAAs operated on between 1994-2014 in Sweden. Overall survival was 86% at 3-months, 79% at 1-year and 59% at 5-years. The survival was significantly better after endovascular compared to open repair up to 1-year without increasing recurrence of infection or reoperation, thereafter there was no difference. After 2001 EVAR constituted 60 % of all repairs, thus indicating a paradigm shift in treatment for abdominal MAAs in Sweden. Paper IV, a prospective multicentre study of patients treated with open abdomen after aortic surgery. Infectious complications, such as graft infections, occurred after intestinal ischaemia and prolonged OA-treatment, and were often fatal.

L’infection par le virus de l’hépatite C est fréquente chez les patients infectés par le VIH. Chez les patients co-infectés VIH-VHC, les lésions hépatiques sont plus sévères et évoluent plus rapidement vers la cirrhose et ses complications. Cette thèse est consacrée à la description des patients co-infectés pris en charge, en France (2006-2008), à l’évaluation de la prévalence et des facteurs de stéatose hépatique chez ces patients, et à la question de l’évaluation non invasive de la fibrose hépatique. La prise en charge des patients co-infectés VIH-VHC devrait inclure un dépistage systématique de la stéatose hépatique. L’évaluation de la fibrose hépatique par l’utilisation de deux scores non invasifs (Fibroscan-Apri, Fibroscan-Fibrotest, par exemple) pourrait être envisagée. En cas de discordance entre les résultats de ces scores, une biopsie hépatique doit être réalisée. / Chronic hepatitis C virus (HCV) infection is common in patients with human immunodeficiency virus (HIV). HIV-HCV Co-infection is associated with more severe and more rapid progression of HCV, leading to increased incidence of fibrosis, cirrhosis, and end-stage liver disease. Our work is devoted to the description of HIV-HCV co-infected patients (2006-2008). We also evaluated the prevalence and factors associated with liver steatosis in these patients. Lastly, we addressed the issue of the non-invasive assessment of liver fibrosis. The management of HIV-HCV co-infected patients should comprise a systematic screening of liver steatosis. The assessment of liver fibrosis using two non-invasive tests (eg Fibroscan-Apri, Fibroscan-Fibrotest) should be considered. In case of discordance between the results of these tests, a liver biopsy must be performed.

Master of Public Health - MPH / Background: Globally, it is estimated that about 1.8 million adolescents (aged 10–19 years) were living with HIV in 2015. In Kenya an estimated 133,455 adolescents were living with HIV in 2015, of which 75% (105,679) were in need of antiretroviral therapy (ART). Among adolescents on ART in 2016, 63% reported viral suppression; which is far below the UNAIDS targets of 90%. Viral suppression (having less than 1000 copies of viral RNA/ml of blood) is a key indicator of HIV treatment success, and is associated with better quality of life and reductions in HIV incidence at a population level. Homabay County recorded the highest HIV prevalence (26%) and the highest number of adolescents living with HIV in Kenya (15,323) in 2015. By the end of June 2017 5,709 adolescents were initiated on ART in Homabay County. Despite the successes in initiating HIV positive adolescents on ART, little is known about the factors that are associated with viral suppression. The current study investigated the factors associated with viral suppression among adolescents initiated on ART before November 30, 2017 in Homabay County, Kenya. Methods: A descriptive cross-sectional study was conducted among 925 adolescents registered on ART for at least 6 months and with at least one documented viral load in the last 12 months, in six health facilities in Homabay County. Data was extracted from the electronic medical records and exported into an excel spreadsheet. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to viral suppression using Stata 12.0.

Magister Curationis - MCur / As South Africa continues to experience the highest prevalence of HIV/AIDS globally, co-occurring mental illness poses challenges for public health. Mental illness has increased among people living with HIV/AIDS (PLWHA), as infected individuals succumb to the psychological stress and trauma of the disease. Key research issues, not yet well established, relate to whether professional nurses, working in psychiatric hospitals in South Africa, are equipped with the necessary knowledge and skills to be able to provide effective mental healthcare services, given the increase in mental illness of PLWHA. An increase in mental illness translates into an increase in demand for psychiatric services by PLWHA. There is a paucity of research on HIV/AIDS knowledge of professional nurses working in psychiatric hospitals in South Africa, despite the established acknowledgement of the increase of mental illness amongst PLWHA. The aim of this study was to assess the HIV/AIDS knowledge, attitude and perceived risks of professional nurses working in a psychiatric hospital in the Western Cape, South Africa. A quantitative, descriptive survey design, using an all-inclusive sampling method, was used to select 121 professional nurses employed at a psychiatric hospital in Western Cape to participate in the study. The objectives of the study were to: describe professional nurses’ knowledge of HIV/AIDS; describe the attitudes of professional nurses towards PLWHA and mental illness; and determine professional nurses’ perceived HIV risks in a psychiatric hospital.