Thesis (doctoral)--Turku, 1983.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Thesis (doctoral)--Universiteit van Amsterdam, 1897.

Inaug.-diss.-Bern. / Benützte literatur : p. [63]-64.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1958. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 132-143).

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 90-96).

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

kocfachung@gmail.com / soniaguillenb@gmail.com / armrons@gmail.com / Artículo de revista que fue aceptada para publicación en la Revista PLOS ONE el 03 de Febrero de 2015. / Background: An increase in multidrug-resistant tuberculosis (MDR-TB) cases is evident worldwide. Its management implies a complex treatment, high costs, more toxic anti-tuberculosis drug use, longer treatment time and increased treatment failure and mortality. The aims of this study were to compare mortality between MDR and drug-susceptible cases of tuberculosis, and to determine risk factors associated with mortality among MDR-TB cases. Methods and Results: A retrospective cohort study was performed using data from clinical records of the National Strategy for Prevention and Control of Tuberculosis in Lima, Peru. In the first objective, MDR-TB, compared to drug-susceptible cases, was the main exposure variable and time to death, censored at 180 days, the outcome of interest. For the second objective, different variables obtained from clinical records were assessed as potential risk factors for death among MDR-TB cases. Cox regression analysis was used to determine hazard ratios (HR) and 95% confidence intervals (95%CI). A total of 1,232 patients were analyzed: mean age 30.9 ±14.0 years, 60.0% were males. 61 patients (5.0%) died during treatment, whereas the MDR-TB prevalence was 19.2%. MDR-TB increased the risk of death during treatment (HR=7.5; IC95%: 4.1–13.4) when compared to presumed drug-susceptible cases after controlling for potential confounders. Education level (p=0.01), previous TB episodes (p<0.001), diabetes history (p<0.001) and HIV infection (p=0.04) were factors associated with mortality among MDR-TB cases. Conclusions: MDR-TB is associated with an increased risk of death during treatment. Lower education, greater number of previous TB episodes, diabetes history, and HIV infection were independently associated with mortality among MDR-TB cases. New strategies for appropriate MDR-TB detection and management should be implemented, including drug sensitivity tests, diabetes and HIV screening, as well as guarantee for a complete adherence to therapy.

M. Tech. / Internationally, 9.2 million new cases and 1.7 million deaths occurred from tuberculosis (TB) in 2006. The vast majority of TB deaths occurred in the developing world, that is, Asia and Africa (WHO, 2008). The risk of infection is worsened by overcrowding of healthcare facilities which share re-circulated air without high efficiency particulate arrestance (HEPA) filtration or effective decontamination devices. With emerging and re-emerging infectious agents, the importance of the microbial influence on indoor air quality is gaining momentum around the world. The transmission of Mycobacterium tuberculosis (MTB) is a recognized occupational hazard and the mode of airborne transmission in risk settings needs to be investigated. The current study examined the efficacy of Polymerase Chain Reaction (PCR) for the early detection of airborne MTB using three types of filters: Polytetrafluoroethylene (PTFE), Polycarbonate (PC) and Gelatine, and a sedimentation gel (impaction method). A total of 520 samples, 68 internal positive controls and 68 internal negative controls were tested using two different PCR detection methods. The four different sampling types were each exposed to samples containing an avirulent strain of MTB (H37Ra) and negative controls exposed to aerosolized distilled water in an uncontrolled environment. The air was filtered at a flow rate of 2.5 L/min for a specified time. The filter membranes and sedimentation gel were removed from their respective holders, washed and analysed using conventional and real time (RT) PCR. An additional step using magnetic bead separation was used to assess its performance in overcoming inhibition. The sampling methods used included an in - house preparation of sedimentation gel. This sampling method was used in a study by Vadrot and colleagues in 2004 for detection of airborne MTB using the PCR method. Commercially available filters that were used as sampling methods included PTFE, PC and Gelatine. The detection methods included conventional PCR which detected the MTB complex in three hours, RT-PCR which detected MTB species in 70 minutes and RT-PCR coupled to magnetic bead separation (RT-PCR M) which detected MTB species in 90 minutes. The magnetic bead separation method purified the nucleic acids in the sample by eliminating the inhibitors that were present. The current study showed that by using the magnetic bead capture assay in conjunction with RT-PCR, gave excellent results of 100% sensitivity and 100% specificity when using PTFE, PC and Gelatine sampling methods. The sedimentation gel showed results of 90% sensitivity and 90% specificity. The Gelatine sampling method results showed 100% inhibition with conventional PCR. In conclusion, the use of conventional PCR is limiting for the detection of airborne MTB, possibly due to inhibition factors. In addition, the PTFE filter demonstrated excellent results for all detection methods used. The sedimentation gel did not perform well with PCR and RT-PCR, however gave excellent results with RT-PCR M. The PC filter can be considered the second sampling method of choice after PTFE filter, showing superior results for all diagnostic parameters using RT-PCR M, followed by RT-PCR and then PCR. The greatest application of using this validated method will be in the area of infection control. Environmental practitioners and occupational hygienists would be able to use this method to evaluate environmental control measures and monitor the air quality in healthcare facilities and other workplaces.

Mycobacterium tuberculosis exploits various molecules on host cells to gain entry and establish a niche for survival and replication. We characterized the role of the glycoprotein CD43 in the pathogenesis of M. tuberculosis. Using gene-deleted mice (CD43-/-), we assessed association of the bacterium with macrophages and found that CD43 was required for optimal binding of M. tuberculosis strain Erdman by splenic, peritoneal, alveolar, and bone marrow-derived macrophages. Macrophages from heterozygote (CD43+/-) mice, which express 50% less CD43 than wild type (CD43+/+) mice, bound more bacteria than CD43-/- but less than CD43+/+ indicating that the surface expression of CD43 correlates with binding of M. tuberculosis. The role of CD43 in binding bacteria may be restricted to mycobacterial species as CD43-/- macrophages also bound less Mycobacterium avium and Mycobacterium tuberculosis H37Rv, but there was no observed role in the binding of Salmonella typhimurium or Listeria monocytogenes. Although absence of CD43 resulted in decreased binding of M. tuberculosis, the subsequent growth of the bacterium within CD43-/- macrophages was enhanced as illustrated by increased bacterial numbers and decreased doubling times, indicating that that the mechanism of entry may influence subsequent. To elucidate mechanisms by which CD43 controls of growth of M. tuberculosis, we examined the induction of antimycobacterial activities. In response to M. tuberculosis, CD43-/- macrophages were deficient in the production of nitric oxide, TNF-⍺, and IL-12. Furthermore, M. tuberculosis induced less apoptosis, but more necrosis, in CD43-/- macrophages compared to CD43+/+. The enhanced growth of M. tuberculosis was abrogated by IFN-Ɣ-stimulation with whereas addition of TNF-⍺ restored both the intracellular growth rates and amounts of apoptosis to wild type levels. To investigate the role of CD43 in vivo, we infected CD43-/- and CD43+/+ mice with M. tuberculosis and assessed bacterial loads and organ pathology. Absence of CD43 resulted in increased bacterial loads in lungs and spleens during both acute and chronic stages of infection, and formation of granulomas occurred more quickly in CD43-/- mice. These data point to a dual role for CD43 in the uptake and subsequent growth of M. tuberculosis in macrophages and mice. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate