* Valores obtidos por soma. Há dupla contagem, tendo em vista que o pesquisador que participa de dois ou mais grupos classificados em grandes áreas predominantes diferentes foi computado uma vez em cada grande área.

Tuberculosis (TB) is an important public health problem and remains one of the most threatening curable infectious diseases, despite improvements in diagnostic and drug susceptibility tests. The effective control of TB is based on the immediate detection of Mycobacterium tuberculosis, followed by the prompt implementation of adequate antituberculous therapy (29).The emergence of strains resistant to the major anti-TB drugs speeds up the need for rapid methods for the identification of resistant M. tuberculosis strains in order to treat the disease effectively and, at the same time, prevent the spread of resistant strains (6,8,9,16). Multidrug-resistant (MDR) M. tuberculosis strains, which are resistant at least to rifampin (RIF) and isoniazid (INH), have emerged worldwide and seriously threaten TB control and prevention programs (30).The main mutations that confer RIF resistance are located in the rpoB gene, specifically, in the well-defined 81-bp core region (22,24). About 95% of RIF-resistant strains have a mutation in this region, which facilitates the rapid development of approaches for the detection of resistance to this drug (23,24,26). However, the molecular basis of resistance to

Abstract

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

BackgroundSmoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs).ObjectiveIn the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs.MethodsA total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer’s instructions.ResultsIn smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs’ false-negative results (aOR: 3.35; 95%CI:1.47–7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02–3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97–22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related.ConclusionsSmoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke.