GeneXpert MTB/RIF for rapid diagnosis and rifampin resistance detection of endobronchial tuberculosis.

BACKGROUND AND OBJECTIVE: Delayed diagnosis and treatment of tuberculosis (TB) contribute to poor outcomes, especially for endobronchial TB (EBTB), which typically leads to tracheobronchial stenosis. Finding rapid and accurate diagnostic tools for EBTB is crucial. GeneXpert Mycobacterium tuberculosis (MTB)/rifampin (RIF) was recommended by the World Health Organization (WHO) as a standard molecular biological diagnostic technique for MTB. The aim of this study was to evaluate the efficacy of GeneXpert MTB/RIF for diagnosing EBTB and for evaluating RIF resistance. METHODS: Biopsy tissue and bronchial brushings from EBTB patients were prospectively assessed with GeneXpert MTB/RIF. The diagnostic yields of auramine O-stained sputum smears and bronchial brush smears were obtained, and the results were compared with the cultures of sputum and biopsy tissues for MTB. RESULTS: In 61 confirmed cases of EBTB, the sensitivities of sputum smear, bronchial brush smear, sputum culture and tissue culture to diagnose EBTB were 13.1%, 32.8%, 36.1% and 68.9%, respectively. For bronchial brushings and biopsies, our data showed sensitivities of 57.4% and 63.9%, respectively, and a specificity of 100% for GeneXpert MTB/RIF, and these results were superior to those of sputum smears, bronchial brush smears and sputum culture. GeneXpert MTB/RIF for bronchial brushings and biopsies showed complementarity in its diagnostic performance. Resistance to RIF was identified in 17.4% (8/46) of GeneXpert MTB-positive cases. CONCLUSION: GeneXpert MTB/RIF may enable more rapid EBTB diagnosis and determination of RIF resistance, which are crucial for timely treatment.

Unifocal Tubercular Osteomyelitis of Ulna Diaphysis in a Child: A Case Report.

Introduction: Osteoarticular tuberculosis (OATB) contributes to around 10% of extrapulmonary tuberculosis of which the spine is the most common site. Isolated involvement of ulna diaphysis is extremely rare. We present a case of unifocal tuberculous osteomyelitis of ulna diaphysis in a 3 -year-old male child and highlight its resemblance with musculoskeletal tumors and stress the importance of GeneXpert mycobacterium tuberculosis (MTB)/resistance to rifampicin (RIF) in the diagnosis of OATB. Case Report: A mother of a 2-year-old male child incidentally noticed that her son complained of left forearm pain. She was not sure of any fall or trauma to the forearm. No history of fever or other constitutional symptoms was present. Clinical examination was uneventful except for local tenderness in over the dorsomedial aspect of the left mid forearm. A plain radiograph revealed an oval solitary lytic lesion over distal one-third ulna diaphysis. A needle biopsy was done after clinical, hematological, and radiological evaluation, and finally, GeneXpert detected tuberculosis without RIF. No further tests were required and the child was started on antitubercular therapy (ATT) which resulted in complete healing without any symptoms. Conclusion: The authors conclude that it is therefore essential to consider tuberculosis in the differential diagnosis while evaluating a lytic bone lesion. Where possible, all patients should have a biopsy of the lesion and provide a specimen for GeneXpert MTB/RIF to confirm the diagnosis and drug susceptibility testing.

Tuberculosis of Talonavicular Joint Without Pulmonary Involvement in an Indian Child: A Report of a Rare Case.

Osteoarticular tuberculosis is a rare entity, even in endemic countries. Isolated cases of tuberculosis of the talonavicular joint are sparse. Primary involvement of the talonavicular joint without pulmonary infection with Mycobacterium tuberculosis is rarest of rare. Here, we report a case of primary talonavicular joint tuberculosis without pulmonary involvement in an Indian child. To the best knowledge of the authors, it is the third such case ever reported in a child in the world. The patient presented with complaints of pain and swelling of the right foot. Detailed laboratory work-up backed by radiological investigations helped in establishing the diagnosis. He was managed conservatively with antitubercular chemotherapy with improvement in his symptoms and was transferred out to his native village.

Utility of a Clinical Scoring System (Bandim TB Score and Karnofsky Performance Score) to Assess Mycobacterial Burden in Terms of Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) Cycle Threshold Values Among Pulmonary TB Patients.

AIM: Tuberculosis (TB) continues to be a global public health problem. Physicians fail to clearly interpret cycle threshold (Ct) values as a measure of mycobacterial burden due to the paucity of literature correlating Ct values with the clinical scoring. This study aims to correlate the clinical scoring parameters (Bandim TB score and Karnofsky Performance score (KPS)) with Ct values obtained by Cartridge-Based Nucleic Acid Amplification Test (CBNAAT). MATERIALS AND METHODS: The study spanned from November 2019 to October 2021, during which a total of 40 cases were recruited. These cases were identified as pulmonary TB patients based on Ziehl-Neelsen staining for acid-fast bacilli and/or the GeneXpert MTB/RIF assay. Bandim TB scores and KPSs were recorded using standardized questionnaires. RESULTS: There was a strong negative correlation between Bandim TB score and Ct value (mean), and this correlation was statistically significant (rho = -0.82, p < 0.001). There was a moderate positive correlation between KPS and Ct value (mean), and this correlation was statistically significant (rho = 0.57, p < 0.001). CONCLUSION: No literature has compared Bandim TB score and KPS with the Ct values obtained by CBNAAT for pulmonary TB. Thus, the knowledge on the proper utilization of CBNAAT cycle threshold values and its correlation with clinical scoring parameters will help clinicians in the early identification and prompt initiation of appropriate treatment.

GeneXpert: A Rapid and Supplementary Diagnostic Tool for Tuberculous Meningitis, Experience from Tertiary Neurocenter.

Background Tuberculous meningitis (TBM) is a highly lethal form of central nervous system tuberculosis (CNS TB) that causes high mortality and morbidity in children and adults. Nonspecific clinical presentation and fewer TB bacilli challenge clinicians resulting in delays in diagnosis and treatment. Aim This study aimed to evaluate the utility of GeneXpert alone and in combination with culture using 1 mL of cerebrospinal fluid (CSF) in a volume constraint situation. Methods A total of 125 clinically confirmed TBM and 110 non-TBM cases, comprised of both infectious and noninfectious diseases. were included in the study. Patient details including clinical signs and symptoms, CSF, and imaging data were collected from the case records. CSF samples were obtained from all the patients and were tested by the mycobacterial culture method and GeneXpert test. The performance of both the tests was statistically calculated and reported in the form of sensitivity and specificity. Results Out of 125 TBM cases, 40 were detected positive by culture and 26 by GeneXpert. All 110 non-TBM cases were identified negative by both methods. The sensitivity and specificity of GeneXpert in comparison with culture were 27 and 100%, respectively. The culture was found to be more sensitive (32%) than GeneXpert. But the assay was able to detect a considerable number of clinically confirmed culture-negative TBM cases. Conclusion GeneXpert is a rapid test and including this as an adjunctive test along with the culture in routine clinical practice can improve the diagnosis of TBM in volume constraint scenario.

Drug-Resistant (DR) Tubercular Pleural Effusion: A Rare Case.

Tuberculosis (TB) is one of the most common infectious diseases in developing countries throughout the world. According to the WHO, there has been a rise in the number of cases of drug-resistant (DR) TB in recent times. Tubercular pleural effusion is challenging to diagnose given the low bacillary load and frequently negative stains for acid-fast bacilli (AFB) on Ziehl-Neelsen (ZN) staining. We present a case of successful diagnosis and management of primary extra-pulmonary multidrug-resistant (MDR) tubercular pleural effusion after being misdiagnosed from outside as drug-sensitive extra-pulmonary TB. Initial tests revealed exudative effusion with raised adenosine deaminase (ADA) levels, therefore the patient was started on conventional anti-tubercular therapy with isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E), but the patient did not improve in spite of regular treatment for two months, which warranted further investigations. Therefore Xpert® MTB/R assay (Cepheid Inc., Sunnyvale, USA), line probe assay (LPA), and drug sensitivity testing (DST) of the pleural fluid were sent, which were suggestive of R- and H-resistant tubercular effusion. The patient was started on an oral bedaquiline-containing regimen as per the WHO guidelines and the patient showed considerable improvement on follow up.

Tubercular lymphadenitis in the 21st century: A 5-Year single-center retrospective study from South India.

Background: Tubercular lymphadenitis (TBLN) remains the most frequent manifestation for extrapulmonary TB despite advancements in diagnostics and management over the years. Our study intends to explore five-year trend of TBLN in a tertiary care centre from south India, and aims to study clinico-demographic and diagnostic factors in the management of TBLN. Methods: All the adult patients (≥18 years) diagnosed and confirmed for TB lymphadenitis between January 2015 to December 2019 were retrospectively evaluated. Demographic factors, clinical manifestations, and different diagnostic approaches used in the management of TBLN were analysed using SPSS ver. 16. Results: A total of 164 patients with confirmed TBLN were included. Patients aged 18-45 years were the most affected (63.41%) with female dominancy. The most affected lymph nodes were cervical lymph nodes (84.1%) presenting with single palpable enlarged lymph node (80.5%). Majority (78.7%) of the lymph nodes were non-matted and 68.9% of enlarged lymph nodes were >3cm size. Excisional biopsy was performed for the majority of the patients 99 (60.4%) and 60.4% of the cases were managed with a combination of surgical excision and anti-tubercular treatment (ATT). Conclusions: The declining trend of TBLN observed in this study highlights the outcome of good public health policies; however, young females and high-risk groups like HIV infected or AIDS (affected more in the study) demand further attention. Overall, the advanced diagnostic tools along with surgical management and ATT can lead us to earlier diagnosis and successful treatment outcomes.

Utility of the GeneXpert Mycobacterium tuberculosis/Rifampin (MTB/RIF) Assay on Paraffin-Embedded Biopsy Tissue Samples for Detecting Tuberculosis: Comparison With Histopathology.

Introduction The Xpert Mycobacterium tuberculosis/Rifampin (MTB/RIF) assay is a qualitative nested real-time polymerase chain reaction (PCR) performed on the GeneXpert instrument system. Although, the utility of this technique for detecting tuberculosis (TB) in sputum and pus samples is well established, however, the usefulness of GeneXpert on biopsy samples is still a matter of debate. Therefore, in this study, we evaluated the utility of GeneXpert for detecting MTB in biopsy specimens diagnosed with TB. Methods A retrospective observational study was conducted at the Department of Pathology, Liaquat National Hospital and Medical College. The data collection period was between January 2016 and December 2018 over a period of three years. Specimens included trucut/incisional biopsies and lymph node excisions. Cases with a favoured histopathological diagnosis of TB were included in the study. The Xpert MTB/RIF assay was performed on the samples obtained from paraffin-embedded biopsy tissue material, and comparison of histological features with Xpert MTB/RIF assay was performed. Results A total of 114 cases were included in the study. The mean age of the patients was 40.53±16.83 years, and 57.9% of patients were male. 68.4% of cases were extra-nodal with the lung being the most common extra-nodal site. On histopathological analysis, caseation necrosis, epithelioid granulomas and Langhan's giant cells were present in 64.9%, 70.2%, and 59.6% cases, respectively. On GeneXpert PCR assay, MTB was detected in 26.3% cases. A significant association of MTB detection on Xpert PCR assay was noted with the presence of necrosis on histopathology. Conclusion In our study, we noted that the MTB detection rate by GeneXpert assay on histopathologically diagnosed cases of TB was only 26.3%, and the detection rate was significantly increased in the presence of caseation necrosis on a biopsy tissue sample. Despite the low detection rate due to rapid turnover time, GeneXpert assay is an excellent adjunctive tool for detecting MTB in paraffin-embedded tissue samples.

Evaluation of GeneXpert Mycobacterium tuberculosis/Rifampin for the detection of Mycobacterium tuberculosis complex and rifampicin resistance in nonrespiratory clinical specimens.

Background: The objective of this study is to assess the performance of Xpert Mycobacterium tuberculosis (MTB)/rifampin (RIF), an automated molecular test for MTB and resistance to RIF, against smear microscopy and culture method for the diagnosis of MTB infection. Methods: This is a retrospective analysis of 168 nonrespiratory patient specimens suspected of tuberculosis (TB) at TB Laboratory of Dubai Health Authority in the United Arab Emirates between September 2016 and November 2018. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test. Results: Of 168 nonrespiratory samples, 52 samples were positive by both culture and Xpert MTB/RIF, 9 samples were detected positive only by culture. Sensitivity, specificity, positive predictive value, and negative value of the Xpert MTB/RIF test were 82.69%, 100%, 100%, and 92.80%, respectively. No false positive was yielded by the Xpert MTB/RIF, and all 116 samples were true negative by Xpert MTB/RIF. The sensitivity of the Xpert MTB/RIF was 76.92% in lymph node tissue and aspirates, 66.67% in cerebrospinal fluid, 100% in gastric lavage and aspirate, 81.25% in other body fluids, 100% in pus, 85.71% in urine, and 66.67% in other tissue samples. Of 168 strains, five strains were rifampicin resistant by phenotypic and Xpert MTB/RIF and 163 were susceptible to rifampicin with culture and Xpert MTB/RIF. Conclusion: The performance of Xpert MTB/RIF assay was comparable to the gold standard culture method for identification of MTB in nonrespiratory clinical specimens. It does not replace the gold standard culture method, but it helps to achieve better sensitivity and obtain rapid results within 2 h.