The epidemiologically important Mycobacterium tuberculosis Beijing genotype strains, highly endemic in East Asia, have become an emerging infection in certain geographic areas, including Russia, because of its increasing prevalence and association with multidrug resistance (MDR). The aim was to verify whether MDR Beijing strains circulating in the emerging regions present some biological particularities that could contribute to their success in causing disease in comparison with the sporadic strains from locations with low prevalence of the Beijing genotype. We evaluated virulence-associated characteristics of the MDR Beijing strains isolated in Russia and compared them with those of the drug-resistant and susceptible Beijing strains from Brazil and reference H37Rv strain. We found that Russian MDR strains demonstrated an increased bacterial fitness and growth in THP-1 macrophage-like cells, as well as a higher capacity to induce non-protective cytokine synthesis and necrotic macrophage death. By contrast, the biological properties of the strains isolated in Brazil largely resembled those of the H37Rv strain, with the exception of the drug-resistant isolates that presented significantly reduced fitness. The data demonstrate that the emerging MDR strains of the Beijing genotype circulating in Russia do express a pattern of properties associated with the enhanced virulence favouring its clonal dissemination in this region.

Pulmonary tuberculosis (PTB) is associated with chronic inflammation and anemia. How anemia impacts systemic inflammation in PTB patients undergoing antitubercular therapy (ATT) is not fully understood. In the present study, data on several blood biochemical parameters were retrospectively analyzed from 118 PTB patients during the first 60 days of ATT. Multidimensional statistical analyses were employed to perform detailed inflammatory profiling of patients stratified by anemia status prior to treatment. Anemia was defined as hemoglobin levels <12.5 g/dL for female and <13.5 g/dL for male individuals. The findings revealed that most of anemia cases were likely caused by chronic inflammation. A distinct biosignature related to anemia was detected, defined by increased values of uric acid, C-reactive protein, and erythrocyte sedimentation rate. Importantly, anemic patients sustained increased levels of several biochemical markers at day 60 of therapy. Preliminary analysis failed to demonstrate association between persistent inflammation during ATT with frequency of positive sputum cultures at day 60. Thus, TB patients with anemia exhibit a distinct inflammatory profile, which is only partially reverted at day 60 of ATT.

BackgroundClinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT).MethodsProspective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested.ResultsCirculating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point.ConclusionsCRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT.

Although many studies have assessed factors affecting culture conversion during tuberculosis treatment, few have looked into the effect of tobacco smoking. This study included 89 active pulmonary tuberculosis patients with positive sputum culture upon presentation and collected information regarding smoking history and culture conversion after 60 days of therapy. Current smokers had a higher risk (OR 5.6; 95%CI 1.7-18.7) of non-conversion after two months of therapy when compared to never and ex-smokers. Cavities on chest X-ray and alcohol abuse were shown to confound this association. After adjustment for cavities on the chest X-ray and alcohol abuse current smoking compared to current non-smoking remained significantly associated with culture non-conversion at 60 days of treatment (adjusted OR 6.9; 95%CI 1.8-26.7, p = 0.002) with a significant (p = 0.004) trend in adjusted OR with the number of cigarettes smoked daily to 11.6 (1.8-73.4) among those smoking more than 20 cigarettes per day. In conclusion tobacco smoking was found to delay culture conversion during treatment for pulmonary tuberculosis in a dose-dependent manner. More research is needed to elucidate the effects of smoking on tuberculosis treatment response, and of smoking cessation during tuberculosis treatment.