The work in this thesis describes the approaches taken to advance the field of pulmonary optical molecular imaging for the diagnosis of unexplained pulmonary opacities in the critically ill patient where bacterial causes are suspected and the investigation of pulmonary nodules and masses where lung cancer is suspected. The bacterial work includes the development and assessment of a multivalent fluorescently labelled antimicrobial peptide fragment that allows for the in vivo in situ detection of bacteria in the distal lung. This Smartprobe (chapter 3), called NBD-UBIdend remains specific for bacteria and pathogenic pulmonary fungi (Aspergillus fumigatus) over mammalian cells, and has a clinically relevant limit of detection when it is imaged in an ex vivo whole lung ovine ventilated model using fibered confocal fluorescence microscopy (FCFM). Furthermore, NBD-UBIdend detects all bacteria assessed, including a panel that accounts for 70% of ventilator associated pneumonia causing organisms. Chapter 4, develops this further and describes the in vitro and ex vivo evaluation of another Smartprobe utilising a fluorescently labelled modified polymyxin B moiety, called NBD-PMX. This compound detects gram-negative but not gram-positive bacteria and is compatible with pulmonary FCFM. This combination of Smartprobes and FCFM could allow the immediate stratification of patient therapy in the assessment of pulmonary opacities where bacterial causes are suspected. The lung cancer work includes the use of label free FCFM in a clinical cohort to determine if autofluorescence patterns can differentiate benign and malignant pulmonary nodules. This work (chapter 5) demonstrates here there is no differentiation using FCFM alone and therefore, for this technology to be used in lung cancer diagnostics a Smartprobe strategy may be beneficial. Finally, chapter 6 demonstrates a Smartprobe based approach for interrogating lung cancer and discusses a matrix metalloproteinase (MMP) compound that detects MMPs in a whole ventilated lung utilising a modified spontaneous ovine pulmonary adenocarcinoma model.

Les infections ostéo-auriculaires (IOA), principalement causées par les staphylocoques, sont des infections graves, responsables d'un taux élevé de mortalité et de morbidité suite à l'inflammation et l'importante destruction osseuse. Nous avons étudié si les interactions hôtes-pathogènes pouvaient influer sur la présentation clinique (aiguë, chronique…) des IOA. Nous avons d'abord développé un modèle in vitro d'infection intracellulaire d'ostéoblastes humains permettant de quantifier l'adhésion, l'invasion, la survie intracellulaire des staphylocoques et les dommages subis par les cellules infectées. Grâce à ce modèle, nous avons ensuite montré que les souches de S. aureus (SA) communautaires résistants à la méticilline (CA-MRSA), un groupe polyphylétique de souches hypervirulents associées à des formes aiguës et sévères d'IOA, induisent une cytotoxicité supérieure à celle des MRSA hospitaliers (HA-MRSA) associés à des IOA plus souvent chroniques. Ces résultats nous ont amené à décrire un nouveau mécanisme de virulence des CA-MRSA basé sur l'invasion des ostéoblastes et l'activité intracellulaire d'une toxine staphylococcique, les phénol-soluble modulins (PSM). Par la suite, en utilisant une large collection de souches cliniques de SA sensibles à la méticilline (MMSA) de fond génétique très divers, et en utilisant comme seul critère de corrélation la durée d'évolution réellement observée chez les patients, nous avons obtenu les premiers résultats validant l'hypothèse du rôle de l'internalisation de S. aureus dans les ostéoblastes dans la chronicité des IOA. Ces travaux nous ont également permis de démontrer la corrélation entre la dysfonction d'un des principaux systèmes de régulation de la virulence chez SA, le système agr, et le caractère chronique des IOA. La fonctionnalité du système agr, qui se traduit par la secrétion de la delta-hémolysine, est facilement détectable par spectrométrie de masse par la nouvelle technologie MALDI-TOF-MS, utilisée en laboratoire de routine pour l'identification bactérienne. Ainsi, nos résultats suggèrent que cette technique pourrait représenter la première méthode objective d'évaluation du degré de chronicité d'une IOA au moment du diagnostic, permettant ainsi d'améliorer la prise en charge initiale des patients. En parallèle, nous avons démontré que l'interaction entre SA et les ostéoclastes, seules cellules capables de résorber la matrice osseuse, était responsable de la destruction osseuse observée chez les patients atteints d'IOA par deux mécanismes complémentaires : i) SA inhibe l'ostéoclastogenèse des précurseurs myéloïdes qui se différencient alors en macrophages. Ces macrophages secrètent une multitude de signaux pro-inflammatoires facilitant ainsi le recrutement d'ostéoclastes matures sur le site de l'infection et l'ostéoclastogenèse des précurseurs non infectés ; ii) l'infection des ostéoclastes matures par SA triplent leur capacité de résorption. Ainsi nous avons démontré que les ostéoclastes jouaient un rôle central de la destruction osseuse observée lors des IOA. Nos travaux ouvrent de nouvelles perspectives dans la compréhension et l'amélioration de la prise en charge des IOA à SA / Pas de résumé anglais

In any host population, individuals may be infected with multiple pathogens concurrently or in sequence. The direction and strength of pathogen-pathogen interactions are often unknown and dependent on the mechanism of interaction. This thesis is concerned with the epidemiology of infections and coinfections in zebu cattle during their first year of life, and the consequences they have for hosts’ survival probabilities and growth rates. Specifically, the study aims to: a) identify the many different pathogen infections occurring in zebu cattle under one year old, b) identify the main causes of mortality and reduced growth rates, c) test for evidence of effects of pathogen-pathogen interactions on mortality and growth, and d) determine the risk factors for infections with pathogens associated with increased mortality and reduced growth rates in zebu calves. To achieve these aims data collected from an epidemiological follow-up study of a cohort of 548 indigenous zebu cattle, recruited at birth and followed for the entire first year of life was used. Growth rates were enormously variable (52 to 704% of birth-weight) and 88 (16%) of the calves died during the first year, most from infectious disease. In total, 25,104 calf weeks of observation and data from 5,337 individual calf visits were analysed. Over 50 different pathogens were identified in the cohort. The thesis begins by providing an overview of zebu cattle and the importance of cattle diseases relevant to Sub-Saharan Africa, emphasising the importance of epidemiological studies taking into account co-infections, which are common in the natural populations, as opposed to a single-pathogen focus. A detailed description of the study design, data collection and descriptive analysis of non-infectious factors, including management and environmental factors, and a descriptive analysis of all pathogens screened for in the study are provided. Using Cox proportional models with frailty terms, the study then identifies infectious and non-infectious risk factors associated with mortality. Further, the role co-infections play in decreasing survival probabilities are investigated, revealing that the hazard for death from East Coast Fever (ECF) - the single most important disease associated with 40% of all deaths - increases 10 times in animals co-infected with Trypanosoma species, and 1.3 times for every 1000 eggs per gram faeces increase in strongyle egg count. Mixed-effect models are used to study growth rates and the impact of coinfections, revealing both synergistic interactions (lower host growth rates) of T. parva and A. marginale co-infections, and antagonistic interactions (relatively higher host growth rates) of T. parva and T. mutans co-infections compared to single infections with T. parva. Further, this work shows that helminth infections can have a strong negative effect on the growth rates but this is burden-dependent. These findings provide baseline epidemiological data on the diseases with greatest impact on health and performance of young zebu cattle, information that is valuable in the prioritisation and control of diseases. Additionally, they provide evidence of co-infections affecting host growth and survival, and have important implications on disease control strategies, suggesting benefits of aan integrated approach to control of worm, tick and tsetse-borne diseases.

A Research Report submitted to the Faculty of Medicine of the University of the Witwatersrand Johannesburg in partial fulfilment of the requirements for the degree of Master of Medicine in the discipline of surgery 1991 / Severe intra-abdominal infection (IAI) carries a high mortality. Methods of treatment such as radical peritonaal debridement, continuos post-operative lavage and local intra-peritonaal instillation of anti-biotics have not improved. [Abbreviated Abstract. Open document to view full version] / MT2016

Thesis (M Med.(Family Medicine))--University of Limpopo, 2010. / Aim: To understand the help seeking behaviour of parents having children with minor illnesses such as fungal skin infection and to respond appropriately to such behaviours. Design: A descriptive qualitative study using the free attitude interview technique Method: The study was conducted in Francistown City Council Clinics. Eight participants were interviewed. Using purposeful sampling chose the participants. Each respondent was asked the same exploratory question “How much do you know about this skin infection?” Exploratory question (Setswana) is “O itse go le kae ka bolwetsi jone jo jwa letlalo?” The probe follow up questions were used to encourage elaboration on the topic. The discussions were held in Setswana language. The interviews were audio – taped. The recordings were transcribed, and the ideas that emerged were developed into themes. Results: Most of the respondents believed that Skin fungal infection was common in the community and it was generally called skin rash. It was believed to be infectious that it may be associated with HIV infection. Some however believe that its cause was known and it was treatable The help seeking behaviour of parents having children with minor illness like skin fungal infection falls within these reasons: Availability of alternative treatment, Concern of the child especially if the child complains about the problem, 6 Concern of the parents when the parents consider such minor health concern as a health problem for the child, issues around difficult in management of the problem, If problem is tolerable. Conclusion: Residents of Francistown city council, which was where the study was carried out perceived skin fungal infection as a common infectious skin problem, that is treatable. There is adequate knowledge of the symptoms of skin fungal infection among the participants. Some of the participants believed that skin fungal infection is common in children because they see the skin lesion as a normal change in colour for children before adult life. It was believe that as they get older the change in colour will then disappear. Many of them believe that they do not know the cause and even the few that felt that they knew the cause could not give a good account of the exact cause of the skin fungal infection, only one said that it is caused by a germ. Most of the participants were aware that it is treatable but yet they were not keen seeking for help when they come to the clinics because of one or two of the following reasons: Availability of alternative treatment; Concern of the child especially if the child complains about the problem; Concern of the parents when the parents consider such minor health concern as a health on the child; Issues around difficult in management of the problem; Health problem being tolerable

No description available.

Abstract not available

Thesis (B.A.)--Haverford College, Dept. of Economics, 2007. / Includes bibliographical references.

Chlamydiae are obligate intracellular pathogens that cause several serious conditions within the human host. Many of the symptoms associated with infection are thought to stem from the development of aberrant, or persistent, chlamydiae. Factors leading to chlamydial persistence include deprivation of amino acids, the release of certain cellular factors, or the addition of inhibitors of bacterial cell wall or DNA synthesis. Such changes within the chlamydial environment often lead to modifications in cell morphology, gene expression, chlamydial development, and antigen localization. In this report, I examine changes in antigen production and localization in Chlamydia-infected cells cultured in the presence of environmental stressors. There are three major areas of chlamydial biology examined: 1) how do the chlamydiae divide in the absence of FtsZ, 2) what is the importance of the predicted peptidoglycan hydrolase, PapQ; 3) what changes occur in antigen production and localization during the development of chlamydial persistence. One significant nonproteinacious factor apparently involved in chlamydial division is the SEP (septum) antigen, which localizes to the midcell of dividing chlamydiae. Non-dividing forms, such as persistent chlamydiae and EB, lack the septal placement of SEP, further suggesting the involvement of SEP in RB division. The production of the predicted hydrolase, PapQ, localizes to the cytosol of RB and, to a limited extent, within the EB. PapQ begins to accumulate as early as 12 hours after infection and during the time of RB-EB transition, an additional, smaller PapQ product accumulates. Ampicillin and tetracycline treatment inhibits accumulation of the smaller product suggesting that PapQ may be processed by a late expressed protease. This may have significance in RB-EB transition. The IncA-laden fibers protruding from the inclusion and into the host cytosol colocalize with a variety of different antigens that are generally restricted to the chlamydial outer membrane. Changes in culture conditions leads to changes in the amount and type of antigens localizing within the fibers. Chlamydial persistence dramatically influences the production and localization of several chlamydial antigens, creating significant changes in chlamydial cell biology that may enhance survival within the host. / Graduation date: 2003

Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2005. / "A dissertation in pharmaceutical science and chemistry." Advisor: Ashim K. Mitra. Typescript. Vita. Description based on contents viewed Mar. 12, 2007; title from "catalog record" of the print edition. Includes bibliographical references (leaves 138-147). Online version of the print edition.