Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?

Tuberculosis vaccine candidates are entering clinical studies in areas where BCG fails. This is a high-risk strategy. We suggest that geographical variation in the efficacy of BCG is related to the presence in developing countries of a cross-reactive background Th2-like response, probably attributable to exposure of mother and infant to helminths and environmental mycobacteria. Such Th2-like activity can stop Mycobacterium tuberculosis from being pushed into a latent state by the Th1 response, impair bactericidal functions and cause toxicity of TNF-alpha and pulmonary fibrosis. A successful vaccine, rather than driving a Th1 response, might need to suppress this pre-existing subversive Th2-like component. (c) 2005 Elsevier Ltd. All rights reserved

The quantification of water usage in a South African platinum refinery using various water accounting methods

A dissertation submitted to the Faculty of Engineering and Built Environment, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science in Engineering, Johannesburg 2018South Africa is the darling of the platinum world with majority of the global platinum reserves being located in its backyard. Despite boasting extensive platinum mining activity, South Africa contrastingly has limited water resources. Additional pressure is placed on existing water resources due to climate change, poor water infrastructure and greater urbanisation. Hence water management in the mining sector, particularly the platinum mining sector is of great significance. Platinum precious metal refineries are often neglected in terms of water related studies as they are comparatively smaller than other components involved in platinum production, such as platinum mines, hence the significance of this study as a means to increase awareness about platinum PMRs. Accurate accounting of water usage in mining operations is necessary if water is to be effectively managed and minimised. Two water accounting methods were employed to evaluate water usage in a South African platinum precious metal refinery, namely the Water Accounting Framework and Water Footprint Network method. Flowrates and rainfall data were provided by the refinery, whilst evaporation data was obtained from the South African Department of Water and Sanitation. This information along with the appropriate assumptions was used to generate a comprehensive water account for the refinery. The Water Accounting Framework found the volume of the total water inputs into the refinery to be 48.51 ML/year and the total volume of water outputs from the refinery is about 0.99 of the volume of the total inputs. The Water Footprint Network method found the total water footprint to be 49086.07 m3 /year or 49.09 ML /year, comparable to the results of the Water Accounting Framework. The total water footprint was equivalent to the blue water footprint. The total product water footprint of the refinery being valued at 1.20 m3/kg PGM was found to be greater than that of base metal refineries. After viable recommendations were taken into consideration the total product water footprint was reduced by 25%.XL201

Efavirenz and neuropsychiatric effects

No Abstrac

The expression and role of IL-4 and IL-4(delta)2 in tuberculosis with and without HIV co-infection.

Background: Tuberculosis progresses despite potent Thl responses. A putative explanation is the presence of a subversive Th2 response. However interpretation is confounded by a novel cytokine, IL-452, a splice variant and inhibitor of IL-4. Methods: The expression of Thl cytokines (IFN-y), IL-452, Th2 cytokines (IL-4) and sCD30 was investigated in whole blood, lung lavage and mononuclear cell cultures from donors with TB, TB-HIV co-infection, and matched controls. Results: After validation of a fluorogenic real-time RT-PCR assay, the half-life of IL- 4 mRNA, but not IL-452, was found to be prolonged in TB vs controls (P<0.002). mRNAs for IL-4 and IL-452 were elevated in unstimulated cells from blood and lung lavage of patients vs controls (p<0.005). Patients with TB expressed significantly greater mRNA levels of both cytokines in T-cells (p<0.05 compared to controls where expression was predominantly in non-T cells). Radiological disease correlated with the IL-4/IFN-y ratio and sCD30 (p<0.005). Tuberculosis antigen upregulated expression of IL-4 relative to IL-462 in mononuclear cell cultures from tuberculosis patients (P<0.05). By contrast, though HIV-TB co-infected donors had increased IL-4 in blood and lung lavage, in lung the predominant form was IL-452. After chemotherapy, in tuberculosis and in HIV-TB co-infection, IL-4 mRNA levels remained unchanged whilst IL-462 increased (p<0.05). Conclusions: A Th2-like response, prominent in T cells, and driven by TB antigen, is present in TB and is modulated by treatment suggesting a role for IL-4 and its antagonist, IL-452 in the pathogenesis of TB and their ratio as a possible marker of disease activity. Furthermore, enhancement of IL-4 mRNA stability, a hitherto undescribed regulatory mechanism in human TB, may facilitate the immunopathological effect of IL-4. The specific antigens inducing the IL-4 response require identification to facilitate future vaccine development strategies. Further studies are required to determine whether IL-4 facilitates systemic HIV progression in co-infected patients

Recommendations for the use of endoscopic lung volume reduction in South Africa: Role in the treatment of emphysema

Emphysema is a very common cause of morbidity and mortality in South Africa (SA). Therapeutic options in severe emphysema are limited. Endoscopic lung volume reduction (ELVR) is increasingly being used internationally for the treatment of advanced emphysema in a subset of patients with advanced disease, aiming to obtain the same functional advantages as surgical lung volume reduction while reducing risks and costs. In addition to endobronchial valves, ELVR using endobronchial coils is now available in SA. The high cost of these interventions underscores the need for careful patient selection to best identify those who may or may not benefit from ELVR-related procedures. The Assembly on Interventional Pulmonology of the South African Thoracic Society appointed a committee comprising both local and international experts to extensively review all relevant evidence and provide advice on the use of ELVR in SA based on published evidence, expert opinion and local access to the various devices

The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis

Background: NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-alpha synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB).Methods: We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells.Results: No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro.Conclusion: There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations

South African Thoracic Society Congress 2023

South African Thoracic Society Congress 202