Tuberculosis
-
This paper describes the development of a microscope array capable of imaging separate fields of view without the need for opto-mechanical scanning components. This microscope array can be integrated with array illuminating optics, a full frame digital single lens reflex (DSLR) camera, and automated algorithms for the detection of Mycobacterium tuberculosis (MTB). The entire array will fit within the area of a typical sputum smear. ⋯ A single prototype miniature objective of this design has been built, and images are presented demonstrating its imaging performance. Images are sufficiently high quality for diagnostic use. When fully integrated, this device has the potential to significantly improve performance compared to conventional microscopy systems and to enable more effective diagnosis of tuberculosis at the point of care.
-
In this study we demonstrate that it is possible to shift the immune system during a chronic infection with Mycobacterium tuberculosis. TGFβ and IL10 cytokines inhibit the Th1 response during chronic pulmonary infection with M. tuberculosis. We show that intrapulmonary delivery of siRNA targeting TGFβ1 is able to reduce the pulmonary bacillary load in mice chronically infected with M. tuberculosis: an effect that appears to be partly dependent on IL10 expression. ⋯ Five days after the last treatment with siRNA, the levels of tgfb1 transcripts and TGFβ1 protein were reduced when compared with control groups treated with RNase-free water or non-targeting siRNA. Mice treated with siRNA also had increased expression of the antimicrobial mediators (NO and iNOS) which effectively reduced the bacterial load by 0.17 and 0.47 log(10) in C57BL/6 and IL-10 KO mice respectively when compared with their respective control mice. More importantly, the bacterial load in siRNA treated IL-10 KO mice four weeks after the last treatment remained 0.32 log(10) lower than in control mice.
-
Patients with pulmonary tuberculosis (PTB) frequently have reduced IFN-γ production in response to mycobacterial antigens, compared to individuals with latent Mycobacterium tuberculosis infection (LTBi). However, it is not clear whether this reduced responsiveness is restricted to a particular T cell subset. Herein, PBMCs from 26 PTB patients, 30 household contacts (HHCs) of PTB, and 30 tuberculin positive (TST+) healthy subjects not recently exposed to PTB, were stained with CFSE and stimulated non-specific (PPD) for 120 h, and specific (CFP-10/ESAT-6) and latency (HSpX) mycobacterial antigens for 144 h and the percentage of CD4(+) and CD8(+)IFN-γ(+) T cells responding determined by flow cytometry, in addition to their memory phenotype by the CD45RO and CD27 expression. ⋯ CD4(+)IFN-γ(+) and CD8(+)IFN-γ(+) cells exhibited a central memory phenotype (CD45RO(+)CD27(+)), irrespective of the group of subjects and the antigen used for stimulation. In conclusion, PTB patients had a decreased percentage of CD4(+) and CD8(+) precursor cells and CD4(+)IFN-γ(+). HHCs exhibited the highest frequency of CD4(+) and CD8(+) precursors and CD4(+)IFN-γ(+)-producing cells.
-
Tuberculosis (TB) is a leading cause of death globally. TB had been considered conquered in Europe but has re-emerged as a significant problem, partly because of poor TB control programs and the link with HIV infection, migrants and other vulnerable populations, but also because a mood of complacency led to declining investment in research and public health infrastructure. In the European Union (EU), efforts initiated by the European Academies Science Advisory Council (EASAC) now assess how research can better inform policy development and indicate the gaps and uncertainties in the scientific evidence base. ⋯ The academies conclude that, overall, the EU has failed so far to respond sufficiently to the global TB threat but can still draw on considerable strengths in its science. The EU also has a humanitarian responsibility to support TB control in developing countries. It remains very important for the EC that neither biomedical research nor investment in health services should become a casualty of the current economic recession.
-
Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. ⋯ One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community.