T. Balamugesh

Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosis

To the Editor: Tuberculosis (TB) remains the second leading cause of death from an infectious disease in adults. Extrapulmonary TB (EPTB) accounts for about 25% of all cases of active TB. Pleural TB is the second most common manifestation of EPTB. Existing tests for the diagnosis of pleural TB have major limitations in terms of accuracy, time to diagnosis and drug resistance testing, and require special expertise for sample acquisition and interpretation of the results. Biopsy of the pleural tissue for combined histological examination and culture is considered the diagnostic gold standard, albeit imperfect [1, 2]. The Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA) is a rapid, World Health Organization (WHO) endorsed, automated PCR test optimised for respiratory specimens that can detect both Mycobacterium tuberculosis (MTB) and rifampicin resistance [3, 4]. Given the limitations of available tests for the diagnosis of pleural TB, several studies have evaluated the performance of Xpert using pleural fluid as a sample type. Overall, these studies show limited accuracy with sensitivity averaging around 44% [5–7]. However, the preferred specimen for the diagnosis of pleural TB is pleural tissue. To date, the evaluation of Xpert performed on pleural tissue has been limited to isolated samples within larger studies [4, 6, 7]. We enrolled consecutive adult patients that were evaluated for pleural TB in the pulmonary clinic and inpatient ward at the Christian Medical College, Vellore, India. Pleural TB was suspected based on clinical symptoms and radiographic evidence of a pleural effusion. Information on demographics, comorbidities, presenting symptoms and results of diagnostic evaluation were collected prospectively. The institutional review boards of the Christian Medical College …

Clinico-pathologic study of pulmonary carcinoid tumours – A retrospective analysis and review of literature

OBJECTIVE To determine the characteristic clinico-pathologic features of pulmonary carcinoid tumours in India. METHODS Retrospective analysis of the clinico-pathologic and radiologic data of patients with pulmonary carcinoid tumours from the department of Pulmonary Medicine of the Christian Medical College, a tertiary care teaching hospital in Southern India, over a study period of 3 years (2001-2004). RESULTS There were 25 cases of pulmonary carcinoid tumours: typical 22 (88%) and atypical 3 (12%). The ratio of female to male was 0.8:1. There were 3 smokers (all of whom were males) in the typical carcinoid group and none in the atypical carcinoid group. Haemoptysis and cough were the commonest presenting symptoms. The common radiologic findings were post-obstructive pneumonitis or atelectasis, and mass lesion. Carcinoid syndrome was not present in any patient. Most of the tumours were central (n=23; 92%) and in the main bronchi (n=13; 52%). The most common site was the right main bronchus (n=9; 36%). Diagnosis was made by flexible bronchoscopy and bronchial biopsy in 23 patients (92%). The tumour bled significantly following biopsy in most patients; however, there was no mortality, and only 1 patient required blood transfusion. Surgical option was offered to most; 13 patients (52%) had pneumonectomy and 4 patients (16%) had lobectomy. A review of large series from the literature is also presented. CONCLUSION The clinico-pathologic and radiologic features of pulmonary carcinoid tumours are presented. We report the first series of pulmonary carcinoid tumours from India.

Challenges in the development of an immunochromatographic interferon-gamma test for diagnosis of pleural tuberculosis.

Existing diagnostic tests for pleural tuberculosis (TB) have inadequate accuracy and/or turnaround time. Interferon-gamma (IFNg) has been identified in many studies as a biomarker for pleural TB. Our objective was to develop a lateral flow, immunochromatographic test (ICT) based on this biomarker and to evaluate the test in a clinical cohort. Because IFNg is commonly present in non-TB pleural effusions in low amounts, a diagnostic IFNg-threshold was first defined with an enzyme-linked immunosorbent assay (ELISA) for IFNg in samples from 38 patients with a confirmed clinical diagnosis (cut-off of 300pg/ml; 94% sensitivity and 93% specificity). The ICT was then designed; however, its achievable limit of detection (5000pg/ml) was over 10-fold higher than that of the ELISA. After several iterations in development, the prototype ICT assay for IFNg had a sensitivity of 69% (95% confidence interval (CI): 50-83) and a specificity of 94% (95% CI: 81-99%) compared to ELISA on frozen samples. Evaluation of the prototype in a prospective clinical cohort (72 patients) on fresh pleural fluid samples, in comparison to a composite reference standard (including histopathological and microbiologic test results), showed that the prototype had 65% sensitivity (95% CI: 44-83) and 89% specificity (95% CI: 74-97). Discordant results were observed in 15% of samples if testing was repeated after one freezing and thawing step. Inter-rater variability was limited (3%; 1out of 32). In conclusion, despite an iterative development and optimization process, the performance of the IFNg ICT remained lower than what could be expected from the published literature on IFNg as a biomarker in pleural fluid. Further improvements in the limit of detection of an ICT for IFNg, and possibly combination of IFNg with other biomarkers such as adenosine deaminase, are necessary for such a test to be of value in the evaluation of pleural tuberculosis.

Rare cause of paradoxical worsening of pleural effusion in a patient with tuberculosis

A 33-year-old patient, Known case of chronic kidney disease on maintenance dialysis presented with complaints of low-grade fever and weight loss of 2 months duration. Computed tomography (CT) revealed bilateral mild pleural effusion with significant mediastinal and abdominal adenopathy. CT-guided fine-needle aspiration cytology of abdominal lymph nodes and bone marrow culture was suggestive of tuberculosis. The patient was started on four drug anti-tubercular therapy, post 6 weeks of initiation he developed new onset fever and chest X-ray revealed moderate right pleural effusion. Diagnostic thoracocentesis was suggestive of chylothorax. To the best of our knowledge, this is the first case report of chylothorax due to the paradoxical reaction in the HIV-negative tuberculous patient.

Prevalence of Hepatotoxicity From Antituberculosis Therapy: A Five-Year Experience From South India.

Background: Antituberculosis (ATT) drug-induced liver injury (DILI) is a common and serious adverse effect of tuberculosis (TB) treatment. This retrospective study was carried out to study the prevalence of DILI among patients who had received anti-TB medications and to study some of the known risk factors responsible for causing DILI. Materials and Methods: This longitudinal descriptive study was performed to evaluate cases of DILI with predefined criteria. Patients of all ages, diagnosed and treated for smear positive pulmonary TB from January 1, 2008 to December 31, 2012 and those who came for regular follow-up were included in the study. Multiple logistic regression analysis was performed to determine the association of different risk factors and DILI. The confounders considered were age, sex, weight, body mass index, doses of drugs (fixed or per kg), ATT regimens (daily or intermittent), and treatment categories. Results: Of the 253 patients analyzed, 24 (9.48%) developed DILI. Associations of different risk factors were insignificant; including chronic alcohol consumption, hepatitis B infection, hepatitis C infection, HIV infection, and existing chronic TB. Conclusion: DILI was not significantly associated with known risk factors in our settings.

Chylous ascites and chylothorax: a case study

A40-year-old male patient was admitted with the symptoms of progressive dyspnea, orthopnea, and abdominal distension of 2 months duration. On examination, vitals were as follows: BP 100/80 mmHg, pulse rate 120/min, and respiratory rate 36/min. He had small bilaterally supraclavicular nodes, a large right axillary lymph node, and the jugular venous pressure was elevated. On auscultation, breath sounds were decreased over both lung bases and heart sounds were only faintly audible. The clinical signs suggestive of free fluid were present in the abdomen. (Published: 7 September 2010) Citation: Libyan J Med 2010, 5: 5298 - DOI: 10.3402/ljm.v5i0.5298