Human enteric pathogen Salmonella contaminates raw produce and triggers significant economic loss and illness. Under a natural environment, Salmonella resides in soil and enters the interior of plants without causing disease or eliciting symbiotic growth. Upon being consumed by humans, complex virulence mechanisms are elicited by the specific intestine conditions, such as high temperature and humidity and lead to profound infection. The lack of effective prevention and drug treatment are largely attributed to the unclear mechanistic understanding on Salmonella association with environmental media, and in vivo host and pathogen factors required for persistent infection. We have explored the potential of deploying the model plant organism Arabidopsis thaliana to tackle this fundamental yet clinically challenging question, as Arabidopsis possesses many advantages as a model system, including enriched genomic resources, powerful genetic tools, low maintenance cost and a large collection of individual gene deletion mutants. Our preliminary data demonstrated Arabidopsis seedlings under liquid culture conditions mimicking the intestine environment were infected and killed by salmonella within 2 days upon inoculation. The Arabidopsis system possesses well-developed genetic information and the resources to study host factors required for infection on very short time scales, thus complementing traditional animal genetic studies. We aim to define the pathogen factors required for this infection. By merging the fields of extremely powerful Arabidopsis genetics and bacterial genetics/genomics, we hope to provide insight into possible new paradigms for addressing salmonella-mediated food born infection.

Thesis--Ph. D., University of Hong Kong. / Typewritten.

The existence, probability and control measures of airborne infections have been widely discussed for centuries. Although public belief regarding airborne infection kept on altering throughout the entire history of medicine and is still controversial, many airborne transmission experiments and airborne infection outbreak analyses have been carried out. Different airborne transmission models have been built and various airborne control measures have been evaluated. One of the major knowledge gaps obstructing applications of some airborne control measures in clinical practices and public applications is that there is a lack of evidence in proving the effectiveness of such measures. Ventilation as an important airborne infection control method can be achieved by opening windows, or increasing the outdoor air supply rate in mechanical ventilation systems or indirectly by using filters and ultraviolet equipments. However the applications of ventilation in infection control were largely restricted to isolation rooms rather than regarded as a public control measure. In this study we focus on evaluating the effectiveness of ventilation as a community measure. Results, therefore, can provide evidence for using ventilation as a public health measure for controlling respiratory diseases transmitted by the airborne route or multi-routes. Two mathematical modeling approaches (deterministic model and social network model) are adopted to estimate different airborne diseases outbreaks with a focus on ventilation and a corresponding analysis of their relative effectiveness compared with other public health measures. A comprehensive understanding of detailed control strategies (including both engineering and public health control) will be achieved through gradually complicated and realistic models. It’s commonly believed that many respiratory infections are transmitted through multiple routes including airborne, droplet-borne and contact routes. Hence the effectiveness of airborne control measures was doubted when the airborne route was not dominant. Therefore, we developed a model to simulate partially airborne transmitted diseases outbreaks and evaluated the relative effectiveness of ventilation when the role of airborne transmission altered. Knowing the complex transmission mechanisms of respiratory transmission and the role of the airborne route in the transmission process is essential in determining the effectiveness of airborne control measures. Hence in this study we also tested the virus exposures dose to infectious patients at different distances when patients were carrying out different respiratory activities. A complex model considering transmission mechanisms of respiratory infections was also built to evaluate the influence of the transmission route in large scale outbreak simulations. The results showed that increasing ventilation rate especially in homes, offices and classrooms is an effective control method for controlling airborne and partially airborne transmitted infections. Combining isolation and increasing ventilation rate can reach similar or even better control effect compared with other general public health interventions such as vaccination. This finding suggested the important role of ventilation in airborne infectious disease prevention and intervention. The ventilation rate required by existing ventilation standards such as ASHRAE 62 might be too low for the purpose of controlling possible airborne outbreaks. / published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

Background: End Stage Renal Disease (ESRD) is one of the commonest diseases in Hong Kong. Patient with ESRD needs to start dialysis for life maintenance. Peritoneal dialysis (PD) is the predominant dialysis modality for home dialysis patients. More than 80% of dialysis patients in Hong Kong receive PD. However, it also brings out some PD-related infectious complication such as tenckhoff exit-site infection, tenckhoff tunnel infection and PD peritonitis. These complications markedly contribute to treatment failure in PD patients. Especially PD peritonitis, it remains a leading complication of PD. Also it is a main cause of patients switch to haemodialysis (HD)and discontinue PD. Nevertheless, if the primary prevention of PD education do better, research evidences have shown that peritonitis infection rate of PD patients can be effectively reduced. It can be achieve by the utilization of effective education strategies and advanced training skills to enhance patients’ knowledge and skills of peritoneal dialysis. Purpose: This written proposal aims to identify the best evidence of PD education and to develop a guideline for this health education programme. The goal of the programme is to reduce the rate of PD-related infection for patients who started PD treatment at home after first CAPD training and education. Method: A total of 12 studies which focused on PD education and strategies for reducing PD-related infections were searched from electronic databases. Data extraction and critical appraisal were performed on these 12 studies. After the integrative review, the implementation potential was assessed. The results shown that the transferability of finding is high and it is feasible to conduct the proposed innovation. Then, the evidence-based guideline for PD education programme were developed and based on the high and medium level of evidence with grades of recommendation stated. Before implementing the proposed innovation, a communication plan was developed and targeted the various stakeholders (the administrators, nurses, patients and their relatives). The proposer would initiate the change and the programme leading group would guide and sustain the proposed innovation. The next process was planning a pilot study to examine the feasibility of the proposed innovation before implementation. Finally, different outcomes of the programme has been identified and evaluated in the evaluation plan. The methods for data analysis were formulated. Conclusion: The proposed peritoneal dialysis education programme with best evidences support is worthy to be adopted in the clinical setting for the beneficial of PD patients to reduce their PD-related infectious complications. / published_or_final_version / Nursing Studies / Master / Master of Nursing

Abstract We investigated the relationship between prevalence and severity of clinical signs of Demodex cafferi infection in freeranging African buffalo (Syncerus caffer) and other factors such as age, sex, pregnancy status, and concomitant infections with bovine tuberculosis (BTB), Rift Valley fever (RVF), and brucellosis (BA). Approximately half of 203 buffalo examined in this study had clinical signs of demodicosis (cutaneous nodules); younger age classes had the highest prevalence and severity of lesions (x2521.4, df56, P50.0015). Nodules were generally limited to the head and neck region, but in severe cases were present over the entire animal. We found no significant association between clinical severity of the Demodex infection and gender, pregnancy status, or infection with BTB, RVF, or BA.

This thesis investigates the distribution of legionellae in water systems in the Royal Liverpool University Hospital (RLUH) and examines some of the factors that affect colonisation by these organisms. The effect of persistent contamination of the domestic water system on immunocompromised patients was monitored, and the envirorunental control of legionellae by various methods was assessed. A fluorescent monoclonal antibody (DFA) was evaluated for its ability to detect L. pneumophila in domestic and cooling water, and was highly sensitive and specific for this purpose. DFA detected non-culturable L. pneumophila in the cold water system (CWS) that were not recovered following heat shock procedures. Legionellae were not isolated from air conditioning humidifiers, and were rarely detected in cooling towers despite treatment with inadequate concentrations of biocide. A high pH assisted in preventing legionella colonisation. Calorifier sediment contained legionellae and high levels of insoluble copper oxides. Culture media and a low pH, released Cuions from sediment which were markedly inhibitory to legionellae. Low concentrations of Cuions were detected in domestic hot water. At temperatures below 60°C legionellae were detected in the hot water supply to the wards, and calorifiers were regularly re-seeded by legionellae returning from contaminated peripheral parts of the system. Legionellae were not detected in the HWS when 60°C was achieved. L. pneumophila sgps 6, 12 and L. bozemanii predominated in domestic water. L. pneumophila sgp 1 was detected on one occasion only in a cold water storage tank and a calorifier, and did not colonise any of the water systems. L. pneumophila sgps 6 and 12 were isolated from three nosocomial cases of Legionnaires' disease. Endemic legionellae prepared as yolk sac antigens, detected significant titres of legionella antibodies (~ 1 :64) in samples from six subjects which did not react ( < 1: 16) with the PHLS L. pneumophUa sgp 1 yolk sac antigen. Most raised titres were to L. pneumophila sgp 12, and the highest titre in heterologous responses identified the infecting serogroup of L. pneumophila. Routine culture of respiratory samples from susceptible patients. detected only one undiagnosed case of Legionnaires' disease. Legionellae were not detected in water from showers that were regularly flushed or irradiated with UV light. Re-colonisation of showers by legionellae was closely associated with the reappearance of amoebae. A trace heating element was effective at maintaining dead-legs at 50°C (± 1.5) and reduced legionellae in these sites. Legionellae proliferated where pipes and heating element were not adequately insulated. Re-circulating the HWS through dead-legs eradicated legionellae from this site but resulted in heavy colonisation of adjacent mixer valves. Automatic drain valves failed to prevent legionellae from colonising shower hoses and mixer valves, and hyperchlorination of shower hoses and water strainers had only a short term effect. Showers heated electrically at point of use were not colonised by legionellae entering in the CWS, or by wild strains of legionellae introduced with calorifier sediment. This appeared to be due to rapid throughput of water, extensive use of copper, and pasteurisation of calorifier contents following discharge of heat from the heating elements, after the shower ceased operating.

No description available.

No description available.

Using a multiple stage age of infection model, we derive an expression for the basic reproduction number, Ro. We apply this method to find Ro in analogous treatment models. We find, in the model without treatment, Ro depends only on the mean infective period, and not on the infective distribution. In treatment models, Ro depends on the mean infective and mean treatment period, as well as the distribution of the infective period, but not on the distribution of the treatment period. With an explicit formula for Ro and the final size relation, we provide a practical alternative to evaluating the effect of treatment and other control measures. We compare our models to previous models of SARS and TB.

Strong clinical and experimental evidence has suggested the involvement of Chlamydia pneumoniae (C. pneumoniae) in the development of atherosclerosis. However, the direct role of C. pneumoniae infection in vascular remodelling processes in the absence of a host immune response remains undetermined. To study the direct effect of this pathogen within the arterial wall, we developed a novel ex vivo porcine coronary artery model that supported bacterial growth for up to two weeks in culture. Employing this approach, we demonstrated that C. pneumoniae infection could alter vascular functions parameters, including endothelial-dependent relaxation responses. This impairment was associated with a decrease in eNOS expression and increased oxidative stress, changes that are also noted in atherosclerotic plaques. We further demonstrated that C. pneumoniae infection initiates medial thickening via vascular smooth muscle cell (VSMC) proliferation. This proliferative response was associated with an increase in expression of endogenous heat shock protein 60 (Hsp60) and alterations in nuclear protein import machinery. Additionally, C. pneumoniae infection and Hsp60 overexpression in primary VSMCs resulted in alteration in nuclear protein import parameters leading to the cell proliferation. Using a rabbit atherosclerotic model, we demonstrated that Hsp60 is induced during atherosclerotic lesion growth and correlated with both the proliferative status and the expression of protein involved in nuclear protein import within the atherosclerotic vessel. In summary, our work has demonstrated the feasibility of studying the molecular mechanisms of infection-induced atherosclerosis using an ex vivo coronary culture system. Importantly, our data has provided the first direct evidence that an active C. pneumoniae infection alone, without contributions from a host immune system, can mediate endothelial dysfunction and stimulate arterial thickening, two key remodelling processes present during atherosclerotic progression. Our findings further suggest the involvement of Hsp60 as a key contributor in growth-based pathologies like C. pneumoniae-mediated atherosclerosis possibility through modulation of nuclear protein import.