Orchestration of an effective T lymphocyte response at infection sites is critical for protection against Mycobacterium tuberculosis (Mtb) infection. However, the local T cell immunity landscape in human tuberculosis is poorly defined. Tuberculous pleural effusion (TPE), caused by Mtb, is characterized by an influx of leukocytes to the pleural space, providing a platform suitable for delineating complex tissue responses to Mtb infection. Using single-cell transcriptomics and T cell receptor sequencing, we analyzed mononuclear cell populations in paired pleural fluid and peripheral blood of TPE patients. While all major cell clusters were present in both tissues, their relative proportions varied significantly by anatomic location. Lineage tracking analysis revealed subsets of CD8 and CD4 T cell populations with distinct effector functions specifically expanded at pleural sites. Granzyme K–expressing CD8 T cells were preferentially enriched and clonally expanded in pleural fluid from TPE, suggesting that they are involved in the pathogenesis of the disease. The findings collectively reveal the landscape of local T cell immunity in tuberculosis.

Objective: Linezolid is one of the key drugs for the treatment of multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB). We aimed to describe the incorporation of the Michigan Neuropathy Screening Instrument (MNSI) and serum trough concentration as screening tools for neurotoxicity in the management of MDR/XDR-TB patients receiving a linezolid-based treatment regimen in Shenzhen, China. Methods: A total of 73 patients on a linezolid-containing anti–MDR/XDR-TB regimen were prospectively enrolled. The MNSI was used for peripheral neuropathy screening. Optic neuropathy was diagnosed by ophthalmologists. Serum trough concentration was recorded and its relationship with neuropathy analyzed. Results: Of all patients, neuropathy was observed in 40% (29) during anti-TB treatment. Of these, 20 (69%) had peripheral neuritis, seven (24%) optic neuritis, and two (7%) both. Serum trough concentration > 2 mg/L was observed in 17 (59%) patients with neuropathy and 13 (30%) patients without neuropathy. There was a significant statistical difference between the two groups (P=0.013). Time to onset of neuropathy from initiation of the linezolid-containing regimen was within 2 months for eight (28%) patients, 2– 6 months for 18 (62%) patients, and > 6 months for three (10%) patients. Sixteen (55%) patients were adjusted to a lower dose of 300 mg linezolid daily. Four (14%) patients had linezolid permanently removed from their regimen. Conclusion: Neuropathy is a commonly reported adverse event associated with long-term use of linezolid. MNSI and serum trough–concentration monitoring can be adopted as simple screening tools for early detection of neuropathy to balance linezolid efficacy and tolerability.

Background: Diagnostics for pulmonary tuberculosis (PTB) are usually inaccurate, expensive, or complicated. The breathomics-based method may be an attractive option for fast and noninvasive PTB detection. Method: Exhaled breath samples were collected from 518 PTB patients and 887 controls and tested on the real-time high-pressure photon ionization time-of-flight mass spectrometer. Machine learning algorithms were employed for breathomics analysis and PTB detection mode, whose performance was evaluated in 430 blinded clinical patients. Results: The breathomics-based PTB detection model achieved an accuracy of 92.6%, a sensitivity of 91.7%, a specificity of 93.0%, and an AUC of 0.975 in the blinded test set (n = 430). Age, sex, and anti-tuberculosis treatment does not significantly impact PTB detection performance. In distinguishing PTB from other pulmonary diseases (n = 182), the VOC modes also achieve good performance with an accuracy of 91.2%, a sensitivity of 91.7%, a specificity of 88.0%, and an AUC of 0.961. Conclusions: The simple and noninvasive breathomics-based PTB detection method was demonstrated with high sensitivity and specificity, potentially valuable for clinical PTB screening and diagnosis.

Background: PD-1 checkpoint inhibitors have shown a robust tumor response in the treatment of various cancers. Pembrolizumab is an anti-PD-1 checkpoint antibody approved for the treatment of unresectable or metastatic melanoma in more than 40 countries. Although autoimmune pneumonitis is considered a common immune-related adverse event of PD-1 inhibitors, only limited studies have assessed the development of opportunistic infections such as pulmonary tuberculosis (TB).
Case presentation: A patient with metastatic melanoma whose pulmonary TB was activated after administration of pembrolizumab for melanoma is reported. Anti-TB drugs were administered, followed by pembrolizumab (2 mg/kg, repeated every 28 days), which successfully cured the TB and achieved complete response for melanoma. Conclusion: Activated pulmonary TB was observed during the administration of pembrolizumab. It was safe and effective in the current patient to combine anti-TB drugs and PD-1 inhibitors. More importantly, screening pulmonary TB before administration of PD-1 inhibitors is recommended.

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.

Background: Early diagnosis and timely treatment of tuberculosis are critical for disease control and management. However, diagnostic delay remains severe around the world. We aim to evaluate the duration and factors associated with diagnostic delay of tuberculosis in Shenzhen, China. Methods: We conducted a face-to-face interview to collect the whole care-seeking process of patients diagnosed with active TB in Shenzhen, China, from April 1 to September 30, 2021. The duration from symptom onset to confirmed diagnosis was recorded. The risk factors of diagnostic delay were identified by binary stepwise logistic regression analysis. Results: Among 288 confirmed TB cases, 170 (59.0%) were delayed diagnosis. The median diagnostic delay was 39.5 days. Median patient delay was 23 days and health system delay was 7 days. Income ≤ 315USD/month (OR = 2.97 [95% CI: 1.15– 7.69]), cough (OR = 3.00 [95% CI: 1.16– 7.76]), weight loss (OR = 15.59 [95% CI: 1.85– 131.56]), use of traditional Chinese Medicine (OR = 5.03 [95% CI: 1.04– 24.31]) and over-the-counter cough syrup (OR = 2.73 [95% CI: 1.10– 6.76]) were significant risk factors for patient delay. Fever (OR = 0.13[95% CI: 0.04– 0.48]) and hemoptysis (OR = 0.06 [95% CI0.01– 0.30]) were protective factors for patient delay. Cough (OR = 2.85 [95% CI: 1.49– 5.49]) and availability of chest X-ray (OR = 0.21[CI: 0.11– 0.39]) were factors associated with health system delay. Conclusion: Delayed diagnosis of tuberculosis remains an unresolved problem. Patients with low income, self-treatment with over-the-counter medicine and accepting TCM suffered from a higher risk of patient delay. It is important to give more help to the vulnerable people and strengthen tuberculosis knowledge among primary health providers. Keeping all health providers alert to TB symptoms can facilitate earlier TB diagnosis and better disease control.