Acinetobacter baumannii est un pathogène nosocomial qui induit principalement des infections du système respiratoire ou urinaire, et des septicémies chez les patients immunodéprimés. L'émergence de souches multi résistantes aux antibiotiques et l'augmentation de nombreuses d'infections par A. baumannii fait de ce pathogène un enjeu majeur de santé publique. De plus aujourd'hui émerge des souches hypervirulentes. Nous nous sommes intéressés à différentes souches afin de caractériser le phénotype hypervirulent de ces souches. L'étude du système de sécrétion de type VI montre la complexité des mécanismes de virulence d'A. baumannii et sa régulation dépendante des souches. Dans un second temps l'étude des souches cliniques hypervirulentes et nous avons mis en évidence deux nouveaux potentiels mécanismes de virulence : une phase de réplication intracellulaire et une limitation de la réponse immunitaire. Ces mécanismes peuvent expliquer la virulence accrue de ces souches chez l'homme. L'étude nous montre également qu'A. baumannii est un pathogène complexe et qu'on son étude à l'heure actuelle nécessité l'emploi de souche représentative des souches infectant les patients / A. baumannii is an hospital acquired pathogen which causes mainly ventilator associated infection, urinary tract infection and bacteraemia. Last years Multi Drug Resistant strains increase and nosocomial infection cause by A. baumannii also which led him as a serious health care problem. We compare different strains in propose to find phenotype that can explain hypervirulent strain emergence. We studied type six secretion and showed that the complexity of A. baumannii virulence mechanism. Indeed type six secretion system regulation is strain dependant. Secondary we study hypervirulent strain and showed that intracellular stage exists and there is intracellular replication. Also hypervirulent strain induces less immune response. Those two mechanisms can explain A. baumannii hypervirulent phenotype

Lors des infections bactériennes, selon les tissus infectés, et selon la nature des pathogènes, l’organisme répond en mobilisant différents acteurs. Nous avons décidé d’utiliser le modèle du zebrafish ou Danio rério pour étudier la réponse immunitaire innée dans les situations d’infection bactérienne où les phagocytes professionnels ne peuvent pas venir au contact direct des bactéries. Pour cela, j’ai développé un modèle d’infection de la notochorde del’embryon de zebrafish. Lors de l’injection des bactéries dans ce compartiment, les bactéries se retrouvent protégées par une épaisse gaine de collagènes que les phagocytes ne peuvent pas pénétrer. Alors que les mycobactéries,protégées par la gaine de collagène ne sont pas détectées par les phagocytes, les bactéries E. coli sont immédiatement détectées ce qui déclenche une importante inflammation locale autour de la notochorde. Alors que les bactéries E. coli, bien qu’inaccessibles à la phagocytose sont éliminées dans les première 24 heures qui suivent l’injection, l’inflammation dure plusieurs jours.J’ai étudié les mécanismes qui conduisent à cette inflammation persistante et ses conséquences à long terme sur le développement du poisson. J’ai montré le rôle central de la cytokine IL1b dans ce processus, et j’ai développé une lignée transgénique qui permet d’étudier l’induction de cette cytokine in vivo chez le poisson.J’ai ensuite étudié le rôle des deux principales populations de phagocytes dans l’élimination des bactéries E coli. J’ai montré que les macrophages ne sont pas impliqués dans la disparition des bactéries alors que les neutrophiles, bien qu’incapable de pénétrer à l’intérieur de la gaine de collagène sont nécessaires à l’élimination des bactéries.J’ai ensuite montré que la myelopéroxidase et le monoxyde d’azote ne sont pas impliqués dans l’élimination des bactéries alors que les espèces réactives de l’oxygène produites par les neutrophiles sont nécessaires pour éradiquer l’infection. / In bacterial infections, according to the infected tissue and the nature of pathogens, the body responds by mobilizing various actors. I decided to use zebrafish or Danio rerio model to study the innate immune response to bacterial infection in the situations that professional phagocytes cannot come in direct contact with the bacteria. For this, I developed a model of infection in the notochord of zebrafish embryo. Upon injection of bacteria in this compartment, the microbes find themselves protected by the thick collagensheath where the phagocytes cannot penetrate. While mycobacteria are not detected by phagocytes; E. coli bacteria are sensed and a significant local inflammation around the notochord is mounted. The E. coli, although inaccessible to phagocytosis are eliminated within the first 24 hours after injection, the inflammation lasts several days.I studied the mechanisms that lead to this persistent inflammation and its long term consequences on the development of the fish. I showed the central role of the cytokine IL1B in this process, and I developed a transgenic line that allows studying in vivo the induction of this cytokine in fish.I then studied the roles of the two main populations of phagocytes in the elimination of E. coli. I revealed that macrophages are not involved in the removal of bacteria but neutrophils, although unable to penetrate inside the collagen casing, are necessary for the bacterial elimination. I also confirmed that myeloperoxidase and nitrogen monoxide are not involved in the removal of bacteria, rather the reactive oxygen species produced by neutrophils are needed to eradicate the infection.

Infections are a major source of morbidity and cause of mortality during the post-operative phase for patients. Wound infections are the second most commonly encountered type of nosocomial, hospital-acquired, infection in the United States (Nichols, 2007:8). Owing to the fact that wound infection may be induced, such as, by not applying infection control and sterile technique principles in the operating room complex, it is imperative to implement infection control principles and apply sterile technique principles. The researcher noticed that some of the sterile technique principles were not carried out in the operating room complex which lead to the necessity to assess the knowledge of registered nurses’ regarding the implementation of infection control and sterile technique principles. The main goal of the study was to explore and describe the knowledge of registered nurses’ in two private hospitals in the Nelson Mandela Metropole, related to infection control and sterile technique principles in the operating room complex. Following the analysis of the data, the researcher made recommendations for changes to be made to the existing infection control guidelines in the operating room complex. The research design was quantitative, explorative, descriptive and contextual in nature. The sample consisted of all the registered nurses known as scrub nurses, in the operating room complex. The unit managers were excluded from the study, because the researcher utilized their assistance with the handing out and collecting of the questionnaires because, not all scrub nurses were at work at the same time. Firstly a pilot study was conducted (in both private hospitals) to confirm the reliability of the data collection instrument. Data was collected by means of a questionnaire that was self-administered and consisted out of three sections: Section A – Biographical Data; Section B – Knowledge Base Related to Infection Control Principles and Section C – Knowledge Base Related to the Principles of Asepsis. The researcher consulted experts to ensure the reliability and validity of the questionnaires and to ensure that the iv questionnaires would measure what it is intended to measure and that it will remain consistent. The data obtained from the questionnaires was analyzed by means of statistical and inferential analysis and included descriptive statistics with the assistance of a statistician. Following the analysis of the data, recommendations for changes to be made to the existing infection control guidelines in the operating room complex was made. This was done with relevant literature and the guidelines were discussed with experts in the field. The researcher ensured that all the legal and ethical requirements, such as the participants’ right to privacy, were maintained throughout the study.

Class of 2017 Abstract / Objectives: To assess the cost-effectiveness of vancomycin, daptomycin, linezolid, oritavancin, and telavancin as empiric treatment for MRSA skin and soft tissue infections in an inpatient setting from a third party perspective. Methods: A decision analytic tree model was constructed using TreeAge Pro and utilizing efficacy data from published clinical trials and costs estimates using HCUPnet.gov and Micromedex’s RedBook. Sensitivity analyses were run on linezolid costs, as well as oritavancin’s costs and efficacy data. Results: Linezolid was the most cost effective medication, dominating all other therapies. In a sensitivity analysis, increasing linezolid’s cost to include 7 days of inpatient therapy did not result in other therapies no longer being dominated. In two other sensitivity analyses, oritavancin was no longer dominated at 91.8% efficacy, but was still dominated with only 3 days of inpatient therapy. Conclusions: Linezolid was the most cost effective therapy for empiric treatment of suspected MRSA skin and soft tissue infections requiring hospitalization from a third party perspective.

Magister Scientiae Dentium - MSc(Dent) / Over the last few decades, and throughout the world, there would seem to have been an increase in the number and severity of infections affecting the maxillofacial region. In the South African setting this seems to be especially evident in the state health system. Maxillofacial infection of odontogenic origin is largely preventable. If treated appropriately and early in the pathological process, the progression of the disease process is generally prevented and complications avoided. Management of maxillofacial infections once established has serious implications for patients and an already stressed health system. The reasons for this perceived increase in infections are likely multifactorial and it is hoped that this study may aid in understanding factors contributing to this burden.

Tuberculosis (TB) continues to be a worldwide health problem despite available effective chemotherapy. In the past 2 decades, distribution of new TB cases in the U.S. has shifted to persons over the age of 65, who account for 12% of the U.S. population but 27% of the total TB morbidity. Residents of long-term care facilities are at greater risk of developing TB than are elderly persons living in private homes or in the community at large. Because this older age group continues to be the largest repository for TB and because the geriatric population in this country is growing, TB is an important medical issue.

Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the United States. Its incidence has been increasing in the recent years despite preventative measures. CDI increases annual expenses by 1.5 billion dollars. Cancer patients are at higher risk to acquire CDI, as explained by their frequent exposure to risk factors. CDI in cancer patients is associated with higher mortality rates and prolonged hospitalization. Furthermore, CDI affects the course of the disease by delaying treatments such as chemotherapy. Chemotherapeutics drugs are considered independent risk factors for CDI. This review discusses Clostridium difficile infection in cancer patients, including those who are receiving chemotherapy. Herein, we summarize recent data regarding the epidemiology, risk factors, including chemotherapy regimens, pathogenesis, diagnostic techniques and treatment options, including newer agents. Method: A literature search was performed using the PubMed and Google Scholar databases. The MeSH terms utilized in different combinations were 'clostridium difficile', 'neoplasia/cancer/oncology', 'chemotherapy', 'diagnosis', and 'treatment', in addition to looking up each treatment option individually to generate a comprehensive search. The articles were initially screened by title alone, followed by screening through abstracts. Full texts of pertinent articles (including letters to editors, case reports, case series, cohort studies, and clinical trials) were included in this review.

Chez l’homme, la primo-infection par le vírus Herpès simplex de type 1 (HSV-1) a lieu au niveau de la muqueuse oro-pharyngée. Après une phase de réplication, les virions pénètrent les terminaisons axonales et migrent vers le ganglion trijumeau ipsilatéral (TG), puis vers le TG controlatéral. Le virus entre alors dans un état de latence dans les 2 TG. Les réactivations d’HSV-1 dans ces neurones sont responsables des kératites herpétiques (KH), unilatérales et survenant toujours du même côté chez un patient donné.En utilisant un modèle murin oro-oculaire, qui reproduit les aspects essentiels de la maladie chez l’homme, nous avons précédemment démontré que l’inoculation virale latéralisée d’un côté de la bouche entraine une réplication virale dans la lèvre, suivie d’une KH ipsilatérale à l’inoculation 6 jours plus tard. De manière concomitante, le virus se propage aux 2 TG, mais les réactivations ne surviennent que du côté ipsilatéral à l’inoculation. Nous avons également observé qu’après une primo-infection dans une lèvre avec une souche d’HSV-1 non-neurovirulente, les souris étaient protégées contre les signes de la maladie et contre la réactivation d’une souche sauvage pleinement virulente inoculée secondairement dans l’autre lèvre (souche ré-infectante). Afin de comprendre les mécanismes immunitaires en jeu dans cet état de protection, nous avons combiné une analyse en cytométrie en flux multiparamétrique à des tests immunologiques, pour quantifier et définir l’infiltrat immunitaire hématopoïétique et les chémokines inflammatoires au site d’inoculation et dans les TG. Nous avons démontré qu’après une inoculation unique avec la souche sauvage virulente, un infiltrat immun riche en cellules pro-inflammatoires, survenaient de manière retardée dans les lèvres inoculées, et persistaient dans les TG. A l’opposé, l’infiltrat immunitaire était plus précoce dans les tissus réinfectés (après une primo-infection par la souche non neurovirulente), plus riche en cellules de l’immunité adaptative, et associé à des concentrations moindres de chémokines inflammatoires. En outre, cet infiltrat s’estompait plus rapidement, avec une disparition concomitante des chémokines inflammatoires. Ces données permettent de mieux comprendre la nature et la cinétique de la réponse immunitaire anti-HSV-1, et pourront être utiles pour le développement futur de stratégies vaccinales anti-HSV-1. / In humans, Herpes simplex virus type 1 (HSV-1), primary infection occurs in the oral mucocutaneous tissues. Virions replicated here penetrate sensitive neuronal axons, migrate to both trigeminal ganglion (TG) where it established a lifelong latency. Reactivations of HSV-1 in the TG neurons induce clinical recurrences in the connected peripheral tissues. This process is involved in herpes simplex keratitis (HSK), a condition that, strikingly, occurs almost exclusively in the same eye for a given patient. Based on an experimental oro-ocular (OO) model of HSV-1 infection, that recapitulates most of these human clinical features, we previously demonstrated that a virus inoculation on one side of the mouth, leads to viral replication in the lip, followed by HSK. Virus concomitantly disseminates to both TG, but reactivation only occurs in the TG ipsilateral to the inoculation site. We also observed that after a primary inoculation with a non-neurovirulent strain of HSV-1 in one lip, mice are protected against both acute phase disease and reactivation after a superinfection with a fully virulent wild-type strain of HSV-1 in the contralateral lip.In order to understand the underlying mechanisms involved in this state of protection, we combined high resolution flow cytometry and bead-based immunoassays, to quantify hematopoietic subsets and inflammatory chemokines in the site of inoculation and in the TG. We demonstrated that after a single inoculation with the wild-type strain, a delayed immune infiltrate, boasting more proinflammatory subsets, occurred in the lip and persisted in the TG. In contrast, the immune infiltrate occurred earlier in the superinfected lip and ipsilateral TG, with less inflammatory chemokines but more adaptive immune subsets. Moreover, cellular infiltrate resolved faster, correlating with nullification of inflammatory chemokines locally. These data show that immune response kinetics influence the development of natural immunity to HSV-1, and can be harnessed to protect against disease and reactivations.

Cytokine profiles during cowpox virus (CPV) strain Brighton and vaccinia virus (VV) strain Western Reserve infections were characterized in intranasal (i.n.) and intraperitoneal (i .p.) models in BALB/c mice. The time-course of induction and effects of cidofovir treatment on interferon (IFN)-γ, IFN-γ inducible protein (IP)-10, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were determined. The four models have distinct patterns of cytokine induction. CPV i.p. and VV i.n. infections showed increased induction throughout the time studied. CPV i.n. infection resulted in delayed induction of IFN-γ and IP-10. Cytokine levels were fairly constant during VV i.p. infections. Cidofovir treatment (100 mg/kg/day i.p. for 2 days) significantly reduced certain cytokine levels in the four models. Treatment did not affect IP-10 in the CPV i.n. model; IFN-γ and IP-10 in the CPV i.p. model; or IL-6, IP- 10, and MCP-1 in the VV i.p. model. Characterization of cytokine responses has implications for understanding the immune responses and pathogeneses of viral infections in these models.

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