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Background & Objectives: Diabetes mellitus (DM) is an important risk factor for tuberculosis and has received increasing emphasis. However, the reverse association of tuberculosis impacting blood sugar levels has not been well studied. The present study was conducted to evaluate the prevalence of hyperglycemia in patients with tuberculosis and assess its resolution following successful treatment of tuberculosis., Methods: In this prospective study, a total of 582 patients with tuberculosis were evaluated for hyperglycaemia [DM or impaired glucose tolerance (IGT)] with random blood sugar (RBS) and all patients with RBS >100 mg/dl were subjected to a 75 g oral glucose tolerance test (OGTT). All patients received thrice weekly intermittent Directly Observed Treatment Short Course (DOTS) for tuberculosis. Patients with hyperglycaemia were re-evaluated at the end of anti-tuberculosis treatment with an OGTT and glycated hemoglobin (HbA 1c ) levels to assess for glycaemic status., Results: In the present study, 41 of the 582 patients were found to have DM [7%, 95% confidence interval (CI) (5.2, 9.4)] while 26 patients were found to have IGT [4.5%, 95% CI (3, 6.5)]. Three patients were lost to follow up. Of the 26 patients with IGT, 17 [65.4%, 95% CI (46.1, 80.7)] reverted to euglycaemic status following successful treatment of tuberculosis, while the blood sugar levels improved in all patients with DM following treatment of tuberculosis., Interpretation & Conclusions: Our study results show that tuberculosis adversely impacts glycaemic status with improvement in blood sugar levels at the end of successful treatment of tuberculosis. Longitudinal studies with large sample size are required to confirm these findings., Competing Interests: None

Background & Objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH)., Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs., Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2FNx015/FNx017 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006)., Interpretation & Conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

Background & objectivesAcute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS.MethodsSixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed.ResultsCommon causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 28-day mortality was 36/64 (56.2%).Independent predictors of mortality included non-pulmonary organ failure, [Hazard ratio (HR) 7.65; 95% CI 0.98-59.7, P=0.05], Simplified Acute Physiology Score (SAPS-II) [HR 2.36; 95% CI 1.14-4.85, P=0.02] and peak pressure (P peak ) [HR 1.13; 95% CI 1.00-1.30, P = 0.04] at admission.Interpretation & conclusionsBacterial and viral pneumonia, malaria and tuberculosis resulted in ARDS in a considerable number of patients. Independent predictors of mortality included non-pulmonary organ failure, SAPS II score and P peak at baseline. Elevated levels of biomarkers such as TNF-α, PCT and hsCRP at admission might help in identifying patients at a higher risk of mortality.

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]

Background: Early diagnosis and treatment of drug-resistant tuberculosis (TB) is crucial to halt the spread of drug resistance in the community. Aim: The aim of the study was to compare rapid diagnostic tests (GeneXpert and line probe assay, LPA) with conventional liquid culture for the diagnosis of drug-resistant TB and to assess the risk factors for it. Method: This cross-sectional study recruited 229 multidrug-resistant TB suspects who were sputum smear positive. They were evaluated by the rapid diagnostic tests and sensitivity, specificity, positive predictive value and negative predictive value were calculated for drug resistance detection as compared to liquid culture drug susceptibility testing. The risk factors for the development of drug resistance were also assessed and the P value of < 0.05 was considered significant. Results: In the final comparison, 193 samples were included. The sensitivity and specificity of GeneXpert for detection of drug resistance (rifampicin) was 100% (95% confidence interval, CI: 88.8–100%) and 99.4% (95% CI: 96.6–99.9%), respectively. Whereas sensitivity and specificity of LPA was 94.3% (95% CI: 80.8–99.3%) and 100% (95% CI: 97.7–100%), respectively. Only three discordant samples were observed. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease were found to be significant risk factors for the development of drug-resistant TB with high statistical significance (P value < 0.05). Conclusion: Both rapid diagnostic tests have very high sensitivity and specificity for detection of drug resistance in sputum smear positive with the advantage of short turn-around time. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease are significant risk factors for drug resistance. [ABSTRACT FROM AUTHOR]

Context: Sputum smear-negative and sputum-scarce pulmonary tuberculosis (PTB) is a diagnostic challenge. Xpert® Mycobacterium tuberculosis/rifampin (MTB/RIF) provides a rapid diagnosis on high-quality biological specimen obtained by bronchoscopy. Aims: The aim of this study is to evaluate Xpert® MTB/RIF on bronchoalveolar lavage (BAL) fluid in sputum smear-negative and sputum-scarce PTB patients. Settings: Tertiary care hospital in India. Design: This was prospective observational study. Materials and Methods: Between January 2015 and November 2016, we prospectively recruited sputum-smear negative and sputum-scarce patients under evaluation for PTB and performed BAL. Sensitivity, specificity, positive, and negative predictive values were calculated for the diagnosis of PTB on BAL fluid for acid-fast bacilli smear and Xpert® MTB/RIF using liquid culture as the reference standard and compared to the final diagnosis based on composite reference standard. Sensitivity, specificity, and predictive values were calculated with 95% class intervals. McNemar's test was used for comparison of sensitivities. Results: Of the 60 patients included, 52 (88.3%) had a final diagnosis of PTB and 16 (26.7%) were culture confirmed. Xpert® MTB/RIF had a sensitivity and specificity of 81% (54%-96%) and 73% (56%-85%) in culture confirmed cases; 46% (32%-60%) and 100% (63%-100%) for the final diagnosis; 32% (17%-51%) and 100% (54%-100%) in culture negative cases, respectively. Culture had a sensitivity of 32% (20%-47%) for the final diagnosis. Conclusions: In sputum smear-negative and sputum-scarce patients with clinico-radiological features of PTB Xpert® MTB/RIF has good sensitivity for diagnosis on BAL fluid. It is useful even when cultures are negative. [ABSTRACT FROM AUTHOR]

Background & objectives: There is a paucity of data from India on response to treatment of tuberculosis (TB) in patients with human immunodeficiency virus (HIV)-TB co-infection. This study was done to assess the frequency and pattern of TB, outcome of anti-tuberculosis treatment, and the factors related to poor outcome of TB treatment in adult patients with HIV infection. Methods: Retrospective review of case records of HIV-TB co-infected patients attending the antiretroviral therapy (ART) clinic in a tertiary care centre in north India was done. Results: Of the 1754 patients included in the study, 583 (33.2%) were diagnosed with active TB and 466 (79.9%) of them had CD4 count less than 200/µl at diagnosis. Extrapulmonary TB was diagnosed in 372 (63.8%) patients [76 (20.4%) had disseminated TB], and pulmonary TB in 211 (36.2%) patients. "Favourable outcome" (cure and completed treatment) was observed in 332 (77%) patients. Unfavourable outcome included default (8.1%), treatment failure (1.6%), and death (13.2%). At 1-year post-treatment follow up, 12 (3.6%) patients had disease relapse. CD4 count of less than 200/ µl at diagnosis [OR-2.32, CI (1.06-5.09)], and retreatment cases [OR-2.91, CI (1.22-6.89)] were independent predictors of unfavourable outcome. Interpretation & conclusions: There is an urgent need to strengthen the information, education, communication activities and expand the ART services to meet the requirement of early testing and treatment initiation in patients co-infected with HIV-TB. The findings highlight the need for performing drug susceptibility testing (DST) for patients starting retreatment regimen to improve treatment outcome. [ABSTRACT FROM AUTHOR]

Most studies have described worse outcomes with coronavirus disease 2019 (COVID-19) in patients with human immunodeficiency virus (HIV). This has been attributed to COVID-19 associated lymphopenia (resulting in lower CD4 count), higher prevalence of comorbidities (established risk factors for severity in COVID-19) and pre-existing lung damage. The problem has been further aggravated by the lack in the access to routine care in HIV patients due to diversion of resources. In this article, we discuss the impact of COVID-19 on patients with HIV infection. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of ART leads to the phenomenon of immune reconstitution inflammatory syndrome (IRIS). The hallmark of the syndrome is paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease process soon after initiation of therapy. The overall incidence of IRIS is unknown, but is dependent on the population studied and the burden of underlying opportunistic infections. The immunopathogenesis of the syndrome is unclear and appears to be result of unbalanced reconstitution of effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART. Biomarkers, including interferon-γ (INF-γ), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and interleukin (IL)-2, 6 and 7, are subject of intense investigation at present. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. Majority of patients with IRIS have a self-limiting disease course. ART is usually continued and treatment for the associated condition optimized. The overall mortality associated with IRIS is low; however, patients with central nervous system involvement with raised intracranial pressures in cryptococcal and tubercular meningitis, and respiratory failure due to acute respiratory distress syndrome (ARDS) have poor prognosis and require aggressive management including corticosteroids. Paradigm shifts in management of HIV with earlier initiation of ART is expected to decrease the burden of IRIS in developed countries; however, with enhanced rollout of ART in recent years and the enormous burden of opportunistic infections in developing countries like India, IRIS is likely to remain an area of major concern. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) is the leading cause of death as a single infectious agent worldwide. In 2017, there were an estimated 1.3 million TB deaths among HIV-negative people and 300,000 deaths among HIV-positive people. The rapid and accurate diagnosis of TB in lymphnode specimens remains a challenging task today. In 2016, World Health Organization endorsed a commercial molecular assay, the LoopAMP™ Mycobacterium tuberculosis complex (MTBC) detection kit (Eiken Chemical Company, Tokyo, Japan), which uses loop-mediated isothermal amplification (LAMP) for sputum samples only. No prospective studies on LAMP in diagnosis of Tubercular Lymphadenitis in adults have been done yet. Methods A prospective observational study with a total of 70 lymph-node aspirate specimens from suspected cases of Tubercular Lymphadenitis with age >18 years were selected and subjected to Ziehl–Neelsen staining, LAMP and culture in mycobacterial growth indicator tube (MGIT960). The immunochromatographic test was used to confirm MTB complex (MTBC) in culture positive samples and phenotypic drug susceptibility testing was done using MGIT-960. The composite reference standard (CRS) used in the study includes symptoms, radiological evidence and follow-up of 2 months. 2 × 2 tables were made and Sensitivity, Specificity, PPV, NPV of TB-LAMP were calculated with respect to AFB smear and composite reference standard (CRS). Results LAMP assay was able to detect MTBC in 34.3% (24/70) of lymph-node specimens. Sensitivity and specificity of the assay were 100% and 69.7%, respectively, considering smear as gold standard. On comparing with CRS, the assay showed 100% sensitivity and 100% specificity in the diagnosis of MTBC. Conclusion In our study, LAMP assay was found to be a promising tool for the diagnosis of Tubercular Lymphadenitis and could be used for rapid and cost-effective diagnosis of Tubercular Lymphadenitis in resource-limited settings. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Oligoarticular arthritis (inflammation of upto 4 joints) has a wide range of infectious and non-infectious etiologies. The aim of our study was to identify the features which could help in the differentiation of infectious from non-infectious arthritis. The study was prospective and observational, and included 100 patients with oligoarticular inflammatory arthritis. The final diagnosis was made using standard diagnostic criteria and the patients were categorized into infectious and non-infectious groups. Among the 100 patients who were recruited, the following final diagnosis were made: peripheral spondyloarthritis (n = 37), axial spondyloarthritis (n = 11), tuberculosis (n = 19), brucellosis (n = 6), septic arthritis (n = 6), gouty arthritis (n = 5), early rheumatoid arthritis (n = 5), non-tubercular mycobacteria (n = 2), SLE (n = 2), post-chikungunya arthritis (n = 2), acute lymphocytic leukaemia (n = 1), pachydermoperiostosis (n = 1), sarcoidosis (n = 1) and juvenile idiopathoic arthritis (n = 1). The patients were categorized into two groups: infectious (33) and non-infectious (60). The presence of monoarthritis, clinically-significant weight loss, hepatomegaly, splenomegaly and erosive arthritis were significantly more common in the infectious group as compared to the non-infectious group. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 17-year-old boy with actionomycosis, an unusual cause of fibrosing mediastinitis (FM) and superior vena cava syndrome. Soft tissue density in the anterior and middle mediastinum was shown in contrast-enhanced computed tomography (CECT) while hypointense mass in T2-weighed axial image was revealed by magnetic resonance imaging (MRI). FM has been associated with histoplasmosis and tuberculosis.

Lymph node tuberculosis is one of the most common forms of extrapulmonary tuberculosis worldwide. The study aimed to evaluate the role of positron emission tomography-computed tomography (PETCT) in determining post-treatment response in lymph node tuberculosis. A PET-CT was done in all treatment naïve tubercular lymphadenitis adults at baseline and after six months of therapy. The post-treatment clinical response was compared with the metabolic response on PET-CT. Of the 25 patients with tubercular lymphadenitis, 9/25 patients showed a complete metabolic response (CMR) at six months, while 16 patients had a partial metabolic response (PMR). All patients with CMR had a good clinical response. However, discordance between clinical and PET findings was noticed in those with PMR. The role of PET-CT in evaluating post-treatment response in patients with tubercular lymphadenitis needs further evaluation with a larger sample size. [ABSTRACT FROM AUTHOR]

Myelopathy in central nervous system tuberculosis is notorious for poor outcomes, determined by the severity of inflammation and cord level involved. Acute-onset quadriplegia or paraplegia in these cases represents a neuro-emergency. We report a young female with disseminated tuberculosis who presented with acute onset flaccid quadriparesis with loss of bladder and bowel function. Imaging helped identify the extensive involvement of the neuraxis. We propose that, in addition to anti-tubercular therapy, high-dose corticosteroids such as pulse methylprednisolone may result in a meaningful improvement and show greater rapidity of response in cases of severe central nervous system inflammation such as arachnoiditis or myelopathy. [ABSTRACT FROM AUTHOR]

To evaluate Gene Xpert for diagnosis of Female Genital Tuberculosis (FGTB) as compared to conventional methods.Study Design: It was a prospective study conducted over 167 cases of infertile female genital tuberculosis (FGTB) diagnosed on composite reference standard (CRS) (smear for AFB, histopathological evidence of epithelioid granuloma or definite or possible findings of tuberculosis on laparoscopy). All women underwent endometrial biopsy for AFB microscopy, culture, gene Xpert, PCR and histopathology) and laparoscopy and hysteroscopy for diagnosis and prognostication of disease. The results of Gene Xpert were compared with conventional methods in detection of FGTB. All patients were treated with 6 months course of rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E) (RHZE for 2 months, RHE for 4 months) using directly observed treatment short course strategy.Results: Mean age, parity, body mass index and history of contact was 28.3 years, 0.28, 22.9 Kg/m2 and 38.92% respectively. Primary infertility was seen in 87.42% cases with mean duration of 2.42 years. Menstrual dysfunctions, abdominal or pelvic pain and lump were seen in 38.92%, 14.37% and 10.77% cases. Abnormal vaginal discharge and adnexal mass were seen in 28.14% and 13.17 % cases. On diagnostic laparoscopy, definite findings of tuberculosis (beaded tubes, tuebrcles and caseous nodules) were seen in 96 (57.48%) women while probable findings of tuberculosis (pelvic or abdominal adhesions, hydrosaplinx, tubo-ovarian mass, pyosalpinx) were seen in 81 (48.50%) women. On laboratory investigations, positive AFB on microscopy or culture was seen in 2.99% casess, PCR was positive in 47.90% gene Xpert was positive in 18.56% cases while epitheloid granuloma was seen on histopathology in 16 (9.58%) cases. Gene Xpert had sensitivity of 35.63%, specificity of 100%, positive predictive value of 100% and negative predictive value of 58.82% and diagnostic accuracy of 66.47% in the present study.Conclusion: Gene Xpert is a very useful test to rule in tuberculosis whereas when it is negative it is not a good test to rule out tuberculosis. [ABSTRACT FROM AUTHOR]