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Background: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. Methods: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15–60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. Results: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. Conclusions: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. Trial registration: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India). [ABSTRACT FROM AUTHOR]

Background & objectives: Despite advances in diagnostics and therapeutics, tuberculosis (TB) is widely prevalent and contributes to a significant burden of illness in both developing and developed nations. The present study was aimed to assess the role of coronin in TB patients and healthy controls. Coronin is a leucocyte-specific protein that is actively recruited in mycobacterial phagolysosomes, where it inhibits lysosomal delivery of Mycobacterium by activating a calcium-dependent phosphatase-calcineurin. Methods: In the study, 100 newly diagnosed cases of TB (pulmonary and extra-pulmonary) and healthy controls were prospectively enrolled over one year and the levels of coronin-1a in these patients and controls were measured by quantitative PCR (qPCR). Results: A total of 100 TB patients and 100 healthy individuals as controls were assessed. There were 59 patients with extra-pulmonary TB (EPTB) and 41 of pulmonary TB (PTB). In 47 per cent of patients, corroborative histopathological evidence of TB was also available. Significantly higher values of coronin-1a were observed in TB patients (19.94±2.61) than in healthy controls (16.09±1.91) (P<0.001). Interpretation & conclusions: Coronin 1a appears to play an important role in the TB disease pathophysiology and agents developed against coronin may have a role in the treatment of TB. Further studies are required to assess if coronin-1a levels are elevated in non-tubercular infective a etiologies and whether these can be a potential drug target in patients with TB. [ABSTRACT FROM AUTHOR]

Background: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post‐tubercular lung disease. However, some evidence suggests that CPA might co‐exist in patients with newly‐diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end‐of‐TB‐therapy. Materials and Methods: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end‐of‐TB‐therapy with symptom assessment, anti‐Aspergillus IgG antibody and imaging of chest for diagnosing CPA. Results: We recruited 255 patients at baseline out of which 158 (62%) completed their follow‐up. Anti‐Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end‐of‐TB‐therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end‐of‐TB‐therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end‐of‐TB‐therapy. Conclusions: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti‐tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of CPA relies on the detection of the IgG Aspergillus antibody, which is not freely available, especially in resource-poor settings. Point-of-care tests like LDBio Aspergillus ICT lateral flow assay, evaluated in only a few studies, have shown promising results for the diagnosis of CPA. However, no study has compared the diagnostic performances of LDBio LFA in setting of tuberculosis endemic countries and have compared it with that of IgG Aspergillus. Objectives: This study aimed to evaluate the diagnostic performances of LDBio LFA in CPA and compare it with existing the diagnostic algorithm utilising ImmunoCAP IgG Aspergillus. Methods: Serial patients presenting with respiratory symptoms (cough, haemoptysis, fever, etc.) for >4 weeks were screened for eligibility. Relevant investigations, including direct microscopy and culture of respiratory secretions, IgG Aspergillus, chest imaging, etc., were done according to existing algorithm. Serums of all patients were tested by LDBio LFA and IgG Aspergillus (ImmunoCAP Asp IgG) and their diagnostic performances were compared. Results: A total of 174 patients were included in the study with ~66.7% patients having past history of tuberculosis. A diagnosis of CPA was made in 74 (42.5%) of patients. The estimated sensitivity and specificity of LDBio LFA was 67.6% (95% CI: 55.7–78%) and 81% (95% CI: 71.9–88.2%), respectively, which increased to 73.3% (95% CI: 60.3–83.9%) and 83.9% (95% CI: 71.7–92.4%), respectively, in patients with a past history of tuberculosis. The sensitivity and specificity of IgG Aspergillus was 82.4% (95% CI: 71.8–90.3%) and 82% (95% CI: 73.1–89%); 86.7% (95% CI: 75.4–94.1%) and 80.4% (95% CI: 67.6–89.8%), in the whole group and those with past history of tuberculosis, respectively. Conclusions: LDBio LFA is a point-of-care test with reasonable sensitivity and specificity. However, further tests may have to be done to rule-in or rule-out the diagnosis of CPA in the appropriate setting. [ABSTRACT FROM AUTHOR]

Objective: The objective was to study the sensitivity, specificity, and diagnostic accuracy of various computed tomography (CT) chest findings in diagnosing recurrence among pulmonary tuberculosis (PTB) suspects. Materials and Methods: A prospective observational study was conducted in a tertiary care hospital in New Delhi. A total of 130 suspects with a past history of treatment for PTB, who presented with any of the symptoms suggestive of recurrence were included. Sputum-positive, HIV-positive patients, pregnant females, and patients aged <18 years were excluded. Patients underwent CT chest followed by bronchoalveolar lavage (BAL). Results: A total of 62 patients were there in the final analysis. The median age of the patients with recurrent PTB was 27.5 years. Cough was the universal symptom in all these patients (>90%). Hemoptysis was the predominant symptom among patients with chronic pulmonary aspergillosis (66.6%). Necrotic mediastinal lymph nodes had good diagnostic accuracy of 88.71% with area under the curve of 0.806, P < 0.001 in diagnosing recurrent TB. BAL GeneXpert and mycobacteria growth indicator tube had good sensitivity (83.33% and 84.62%, respectively), specificity (100% for both), and excellent diagnostic accuracy (95.16% and 96.36%, respectively) for diagnosing recurrence in sputum negative and sputum scarce patient, (P < 0.001) when compared with composite reference standard. For culture-positive cases, BAL GeneXpert MTB/RIF had 100% sensitivity and 97.73% specificity in diagnosing recurrent PTB patients. Conclusion: The presence of mediastinal necrotic lymph node is the most accurate CT finding that can differentiate recurrent TB from post-TB sequelae. No other single chest CT scan finding had reliable diagnostic accuracy in comparison to microbiological tools in diagnosing recurrence among sputum negative or scarce previously treated PTB suspects. [ABSTRACT FROM AUTHOR]

Background: Pulmonary aspergilloma (PA) is a common complication seen in patients with pulmonary tuberculosis sequelae. Antifungal therapy, including oral azoles, is commonly used though only surgical resection offers curative benefit. Local administration of amphotericin B, like intracavitary instillation, has been effective in aspergilloma patients though nebulised amphotericin B (nAB) has never been formally assessed. Objective: The aim of this prospective, non‐inferior, open‐label, randomised control trial is to evaluate the efficacy and safety of nebulised amphotericin B compared to oral itraconazole therapy in the treatment of PA. Patients/Methods: Diagnosed cases of PA (n=33) were randomised into the control group receiving oral itraconazole (n=18) and intervention group receiving nebulised amphotericin B (n = 15). Response to treatment was assessed both clinically and radiologically at the end 6 months. Results and Conclusion: The number of patients showing overall improvement at the end of 6 months in the control arm(oral itraconazole) vs intervention arm(nebulised amphotericin B) was 65% (95% CI 38.3–85.8) and 67%(95% CI 38.4%–88.2%), respectively, in the intention‐to‐treat and 79% (95% CI 49.2%–95.3%), and 65% (95% CI 38.4%–88.2%), respectively, in the per‐protocol analysis. While there was no statistically significant difference between the intervention and control arm in both the analyses, non‐inferiority was shown in the per‐protocol but not in the intention‐to‐treat analysis. No major adverse events were noted in either group; however, a significant proportion of patients receiving nAB reported minor cough (40%), which, however, did not lead to discontinuation of therapy in any patients. Nebulised amphotericin B can be an effective therapeutic option for pulmonary aspergilloma patients. [ABSTRACT FROM AUTHOR]