Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1β, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPβ and PU.1 transcription factors and controls Mtb-induced IL-1β production. The high-IL-1β expressing genotype was associated with the development of active tuberculosis, the severity of pulmonary disease and poor treatment outcome in TB patients. Higher IL-1β expression did not suppress the activity of IFN-γ-producing T cells, but instead correlated with neutrophil accumulation in the lung. These observations support a specific role for IL-1β and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis.

Tuberculosis has become a great global public health threat. Compared with drug-susceptible tuberculosis (TB), the treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) involve more severe adverse events and poorer treatment outcomes. Linezolid (LZD) is the first oxazolidinones used for TB. Thanks to its potent activity against Mycobacterium tuberculosis, LZD has become one of the key agents in the regimens against MDR/XDR-TB. However, this drug may cause intolerability and other adverse events. Contezolid, another novel oxazolidinone, can also inhibit M. tuberculosis, still with fewer adverse effects compared with LZD. This paper is to prospect the potentials of contezolid in the treatment of MDR/XDR-TB, with focus on its efficacy and possible adverse effects.

Background: Diabetes mellitus (DM) is believed to affect tuberculosis (TB) at multiple levels in disease control and treatment efficacy, but clinical and radiological presentation resulting from interaction of the two diseases is not known. Methods: A cross-sectional study was conducted on data obtained from medical records of 438 patients confirmed with TB-DM comorbidity at the Third people's hospital of Shenzhen from May 01, 2014, to April 30, 2019. Their CT images were reviewed, and patients were divided into subgroups according to lung cavitation: with and without cavities, and number of segments showing pulmonary infiltration: <4 segment, 4-8 segment, >8 segment infiltrates. We then compared clinical parameters between these groups. Results: The median age of the patients was 50.0 years (IQR 43.3-56.0) and 86% (n=375) of them were male. Pulmonary cavities were found in 80.8% patients. About 42.7% and 27.2% patients were seen to have infiltration involving 4-8 and >8 lung segments, respectively. Patients presented with cavitation and infiltration involving a greater number of lung segments had significantly higher values of WBC, MONO%, GRA%, CRP, lower LYN% level and higher bacterial burden in sputum (P<0.001). Higher HbA1c and FBG were only observed in patients with lung cavities (P<0.001). There was no difference in positive ELISPOT.TB and PCT level between the groups regardless of presence or absence of lung cavity (P>0.9 and P=0.1 respectively). Lower HGB, ALB and higher PCT were observed in patients with infiltration involving more lung segments. Conclusion: Hyper-inflammation in peripheral blood was significantly associated with cavity and the number of lung lesions. Hyperglycemia was significantly associated with the development of lung cavity. Glycemic control and inflammation influenced radiographic manifestations in patients with TB-DM.

The aim of this study was to assess active tuberculosis-related deaths in Shenzhen city of China to identify major causes of mortality in different age groups. Patients and Methods: Medical records of mortality cases of patients with active TB diagnosed during 2013-2018 were reviewed. All TB deaths were classified into two broad age groups (the young group: 18-65 years old and the elderly group: >65 years old). Causes of death were analyzed based on medical records. Results: A total of 279 mortality cases of active TB were reviewed during the study period. Among them, mean age was 54.0±20.5 years old; 80.6% (225/279) were male. There were 5.7% and 4.6% MDR/XDRTB patients in the young and elderly group. Newly treated TB accounted for 89.6% in the young group and 85.1% in the elderly group. Pulmonary TB was a major infection type in both groups (65.1% vs 77.0%). Advanced TB (23.4%) and HIV coinfection (20.8%) were the leading causes of deaths in the young group, but deaths in the elderly group were mostly associated with underlying diseases, including cardiovascular disease (52.9%), diabetes (33.3%), COPD (16.1%) and cancer (11.5%). Malnutrition was a significant condition in both groups (43.2% vs 35.6%). In terms of respiratory complications, bacterial infection was the leading comorbidity in both groups (27.1% vs 18.4%), followed by septic shock (18.2% vs 12.6%) and respiratory failure (12.0% vs 11.5%). There were no significant statistical differences between the two groups. Conclusion: Our findings suggest that screening for HIV co-infection and early diagnosis of TB is vital in lowering TB-related deaths in young patients. Most deaths in elderly TB patients were caused by underlying health conditions or complications other than TB.