TB PCR in BAL and EBUS-TBNA samples for the diagnosis of pulmonary and mediastinal lymph node TB: retrospective TRiBE study.

INTRODUCTION: The role of Xpert Ultra in bronchoalveolar lavage (BAL) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples for pulmonary and mediastinal lymph node tuberculosis (TB) remains unclear. METHODS: This was a retrospective observational service evaluation at a tertiary TB centre in a low-incidence setting. The diagnostic indices of Xpert Ultra, smear and culture (with cytology for EBUS-TBNA samples) were compared with culture positivity or a composite reference standard of clinical TB diagnosis. Trace readouts, a new category of results for Xpert Ultra indicating low bacillary load, were analysed in two ways as a true positive or true negative result. 282 BAL and 139 EBUS-TBNA samples were included in the analysis. RESULTS: BAL: sensitivity with 95% CI against culture-confirmed pulmonary TB from BAL samples for Xpert Ultra (trace as positive) was 0.91 (0.82 to 0.98), Xpert Ultra (trace as negative) was 0.76 (0.69 to 0.83), smear was 0.38 (p=0.0009) and culture was 1.00 (0.91 to 1.00). Specificities for all the tests were ≥0.99 (0.98 to 1.00). The addition of smear to Xpert Ultra did not improve the diagnostic accuracy.EBUS-TBNA: sensitivity against culture-confirmed TB from EBUS-TBNA samples for Xpert Ultra (trace as positive) was 0.71 (0.63 to 0.78), Xpert Ultra (trace as negative) was 0.59 (0.54 to 0.63), smear was 0.12 (p=0.002), culture was 1.00 (0.89 to 1.00), cytology was 0.87 (0.76 to 0.98) and rapid on-site evaluation of cytology (ROSE) was 0.92 (0.78 to 1.00). Specificities were 0.99 (0.97 to 1.00), 0.99 (0.97 to 1.00), 1.00 (0.98 to 1.00), 1.00 (0.98 to 1.00), 0.67 (0.67 to 0.68) and 0.42, respectively. CONCLUSION: Xpert Ultra had a significantly higher sensitivity compared with smear in both BAL and EBUS-TBNA samples. Xpert Ultra had a lower sensitivity compared with culture but comparable specificity with results being available within <24 hours. Trace readings in our low-incidence setting were associated with culture positivity in all BAL samples.

The value of histopathologic examination and Xpert (MTB/RIF) assay in diagnosis of cervical lymph node tuberculosis after coarse needle biopsy guided by CEUS: a retrospective analysis of 612 cases.

OBJECTIVE: To investigate the value of histopathological examination (HPE) and Xpert Mycobacterium tuberculosis bacilli/rifampicin (MTB/RIF) assay in diagnosis of cervical lymph node tuberculosis (LN TB) after coarse needle biopsy (CNB). METHODS: We retrospectively analyzed 612 samples obtained from October 2017 to August 2023 from patients suspected cervical LN TB with surgically pathological, microbial culture confirmed, and clinically confirmed cervical lymph node enlargement who received ultrasound-guided CNB assisted by contrast-enhanced ultrasound (CEUS) at our hospital. All specimens were assessed by HPE and the Xpert (MTB/RIF) assay. We analyzed the results to determine the diagnostic value of HPE and Xpert (MTB/RIF) assay in samples taken after CEUS-assisted CNB of LN TB, and to evaluate the safety of CNB. RESULTS: Based on the comprehensive reference standard established in this study, 532 of 612 patients were diagnosed with cervical LN TB, of which 476 were CNB positive cases, the positive rate of diagnosis was 89.5%。The sensitivity, specificity, positive predictive value, negative and predictive value of HPE were 80.4%, 91.2%, 98.4%, 41.2% respectively, while those of the Xpert MTB/RIF assay were 75.7%, 98.7%, 99.7%, 38.0% respectively. No postoperative complications were noted, and the Clavien-Dindo grade was 2. CONCLUSION: CEUS-assisted CNB has high diagnostic value and is safe for cervical LN TB. The sensitivity of HPE is slightly higher than that of Xpert (MTB/RIF) assay, and the specificity of Xpert (MTB/RIF) assay is higher than that of HPE, so Xpert (MTB/RIF) assay can correct the cervical lymph node tuberculosis with negative HPE.

Post-tuberculosis treatment paradoxical reactions.

Paradoxical reactions (PR) to tuberculosis (TB) treatment are common during treatment, but have also been described after treatment. A presentation with recurrent signs or symptoms of TB after cure or completion of prior treatment needs to be differentiated between microbiological relapse and a paradoxical reaction. We searched all published literature on post-treatment PR, and present a synthesis of 30 studies, focusing on the epidemiology, diagnosis and management of this phenomenon. We report an additional case vignette. The majority of studies were of lymph node TB (LN-TB), followed by central nervous system TB (CNS-TB). A total of 112 confirmed and 42 possible post-treatment PR cases were reported. The incidence ranged between 3 and 14% in LN-TB and was more frequent than relapses, and between 0 and 2% in all TB. We found four reports of pulmonary or pleural TB post-treatment PR cases. The incidence did not differ by length of treatment, but was associated with younger age at initial diagnosis, and having had a PR (later) during treatment. Post-treatment PR developed mainly within the first 6 months after the end of TB treatment but has been reported many years later (longest report 10 years). The mainstays of diagnosis and management are negative mycobacterial cultures and anti-inflammatory treatment, respectively. Due to the favourable prognosis in LN-TB recurrent symptoms, a short period of observation is warranted to assess for spontaneous regression. In CNS-TB with recurrent symptoms, immediate investigation and anti-inflammatory treatment with the possibility of TB retreatment should be undertaken.

Cytomorphological patterns and clinical features of presumptive tubercular lymphadenitis patients and their comparison with bacteriological detection methods: a cross-sectional study.

INTRODUCTION: Tuberculous lymphadenitis (TBLN) is an infection of the lymph node caused by Mycobacterium tuberculosis. Histological diagnoses of presumptive patients are often accompanied by cytomorphological features. However, the sensitivities of these features are often precluded by the variable degrees of narrative similarities compared to other diagnostic modalities. OBJECTIVE: The aim of this study was to investigate and compare the cytomorphological and clinical features of presumptive TBLN patients with bacteriological detection methods. METHODS: A similar cohort of TBLN patients from our previous study who were enrolled prospectively from the ALERT Specialized Hospital, Addis Ababa, Ethiopia, was considered for this analysis. SPSS version 26 was used for data analysis. Descriptive analysis was conducted to characterize the study population using the independent variable and presented with frequency tables. The chi-square test was used to measure the association. A P-value of < 0.05 was considered statistically significant. RESULTS: Using FNAC, 60/126 (47.6%) of the participants were reported to have features consistent with TB. Of the total FNAC-positive cases, many (30/60 and 27/60) showed pattern B (caseous necrosis only) and pattern C (epithelioid granuloma with caseous necrosis), respectively. Strong concordance was observed in Pattern A (abundant caseous necrosis with few epithelioid macrophages) followed by patterns B and C with GeneXpert and MGIT culture (P value < 0.001). Night sweats and alcohol intake were shown to correlate with positive cases as reported by FNAC (P value = 0.008 respectively), GeneXpert (P value = 0.02 & 0.001), and culture methods (P-value = < 0.001 & 0.002). CONCLUSION: Cytomorphological features, particularly patterns A, B, and C, could be considered in the diagnosis of TBLN given their comparable outcomes with bacteriological detection methods. On another note, we recommend that due care and attention be given when treating TBLN patients based solely on clinical presentation, as these diagnostics may be prone to false results, leading to inappropriate administration of anti-TB drugs and other consequences.

Performance of fine needle aspiration cytology and Ziehl-Neelsen staining technique in the diagnosis of tuberculosis lymphadenitis.

INTRODUCTION: Proper diagnosis of tuberculosis (TB) lymphadenitis is critical for its treatment and prevention. Fine needle aspirate cytology (FNAC) is the mainstay method for the diagnosis of TB lymphadenitis in Ethiopia; however, the performance of FNAC has not been evaluated in the Eastern Region of Ethiopia. This study aimed to evaluate the performance of FNAC and Ziehl-Neelsen (ZN) staining compared with that of GeneXpert for the diagnosis of TB lymphadenitis. METHODS: Fine needle aspiration (FNA) specimens collected from 291 patients suspected of having TB lymphadenitis were examined using FNAC, ZN, and GeneXpert to diagnose TB lymphadenitis. Gene-Xpert was considered the reference standard method for comparison. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa coefficient were determined using SPSS version 25. RESULTS: The sensitivity, specificity, PPV, and NPV of ZN for diagnosing TB lymphadenitis were 73.2%, 97.4%, 96.2%, and 80.1% respectively. There was poor agreement between ZN and GeneXpert (Kappa=-0.253). The sensitivity, specificity, PPV, and NPV of FNAC were 83.3%, 94.8%, 93.5%, and 86.3% respectively. There was moderate agreement between the FNAC and GeneXpert (Kappa = 0.785). CONCLUSION: The fine needle aspiration cytology (FNAC) is a more sensitive test for the diagnosis of TB lymphadenitis than ZN. The FNAC showed a moderate agreement with the GeneXpert assay. This study recommends the FNA GeneXpert MTB/RIF test in preference to FNAC for the diagnosis of TB lymphadenitis to avoid a missed diagnosis of smear-negative TB lymphadenitis.

Evaluation of molecular and bacteriological detection methods performed on the formalin-fixed paraffin-embedded biopsy samples collected from endometrial and lymph node tuberculosis suspected patients.

BACKGROUND: Endometrial Tuberculosis is one of the most common gynecological problems known to have serious implications for the quality of life like infertility. The commonly practiced histopathology solely relies on the suggestive feature of Tuberculosis (TB) with low specificity. Regarding the alternative bacteriological and molecular detection tools, little evidence was generated on their utility in the diagnosis of endometrial tuberculosis in Ethiopia. Therefore, we aim to investigate the detection rate of molecular and bacteriological detection methods on formalin-fixed paraffin-embedded biopsy samples for the diagnosis of endometrial and lymph node TB. METHODS: A retrospective cross-sectional study was conducted on 90 formalin fixed paraffin embedded biopsy samples from patients with gynecologic and lymph problems collected between 2018 and 2022 at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. SPSS version 26 was used for statistical analysis. The diagnostic performance was calculated using the histopathology method as the reference standard. Cohen's Kappa value was used to measure the level of agreement. A test with a P-value of < 0.05 was considered statistically significant. RESULTS: A total of 90 samples were analyzed in the current study. Auramine O, GeneXpert MTB/RIF assay, and Real-Time PCR tests have shown a detection rate of 32/90 (36%), 43/90 (47.8%), and 54/90 (60%) respectively (P ≤ 0.01). The sensitivity and specificity of AO were 38.1% and 95% respectively. RT PCR showed superior sensitivity followed by GeneXpert MTB/RIF assay, 70% and 58.6%. AO and molecular methods have shown a similarly low level of agreement with histopathology (Kappa value = 0.2). CONCLUSIONS: In a resource-limited setting, the selection of diagnostic tools needs careful attention. Putting the patients on anti-TB treatments based solely on histopathological findings may lead to undesired and adverse complications. Therefore, applying molecular and bacteriological detection methods along with histopathology, could help minimize inappropriate antimicrobial use.

The diagnosis of nontuberculous cervicofacial lymphadenitis: A systematic review.

BACKGROUND: Nontuberculous mycobacterial cervicofacial lymphadenitis (NTMCL) is an uncommon condition detected in young immunocompetent children who typically present with a nontender neck mass. Various tests have been proposed to assist in the work-up of suspected NTMCL, with varying diagnostic utility. This systematic review investigates the sensitivity of the various diagnostic methods used in the work-up of pediatric NTMCL. METHODS: A systematic review in accordance with PRISMA guidelines was performed using the Pubmed, EMBASE, and Web of Science databases. Searches were filtered for English language studies published prior to 05/10/22. Studies meeting criteria included studies featuring 15+ pediatric patients with confirmed or suspected NTMCL. Studies with any reported diagnostic methodology used in the workup of NTMCL were included. RESULTS: Of 836 abstracts/articles reviewed, 21 studies met inclusion criteria. Diagnostic methods included culture(n = 11 studies), PPD-Tb(Tuberculin)(n = 12), PPD-Scrofulaceum, -Avium, or -Kansasii(n = 6), staining techniques(n = 4), IGRA(n = 3), and ultrasound(n = 2). All studies had an overall low risk of bias. Among patients confirmed to have NTMCL based on PCR and/or culture, the most sensitive tests were PPD-A(0.94, 95 % CI 0.91 to 0.97; n = 210 patients) and PPD-S(0.75, 95 % CI 0.68 to 0.81; n = 171). Auramine and Ziehl-Neelsen staining techniques had moderately high sensitivity(0.85 and 0.60 respectively), though were limited by low patient numbers(n = 20). PPD-Tb(0.45, 95 % CI 0.39 to 0.50; n = 300) and IGRA(0.02; 95 % CI 0 to 0.06; n = 48) demonstrated poor sensitivity. Among patients suspected to have NTM lymphadenitis based on global assessment, the most sensitive tests included combined PPD-S + A + K(0.92, 95 % CI 0.86 to 0.98; n = 85), PCR(0.82, 95 % CI 0.75 to 0.88; n = 136), and PPD-A(0.72, 95 % CI 0.62 to 0.81; n = 84). Culture showed a sensitivity of 0.54(95 % CI 0.50 to 0.58; n = 494). PPD-K, PPD-S, IGRA, and staining techniques demonstrated lower sensitivity. CONCLUSIONS: This systematic review is the largest study investigating the sensitivity of the various diagnostic methods used in the work-up of pediatric NTMCL. Patients with clinical suspicion for NTMCL and a positive PPD-Tb should first have tuberculous lymphadenitis ruled out with IGRA. Patients with a positive PPD-Tb and negative IGRA and high clinical suspicion for NTMCL can undergo presumptive surgical intervention. Patients with a negative PPD-Tb can undergo NTM antigen skin testing if available, or if high clinical suspicion exists, surgical intervention to reduce tissue burden and elicit additional tissue data.

The spectrum of cytological findings in patients with BCG lymphadenitis: A series of 13 cases.

CONTEXT: Bacillus Calmette-Guérin (BCG) vaccine has been used to prevent tuberculosis and/or its severe complications for long. BCG lymphadenitis is a common complication of the vaccine, which is sometimes subjected to cytological examination. The aim of the study is to describe the cytological findings of BCG lymphadenitis. SETTINGS: The study was conducted in a tertiary care hospital in the western part of India from January 2021 to December 2022. DESIGN: The study was performed on archived material of all patients who were referred to the fine needle aspiration clinic for cytology examination. Clinical and pathological data of cases were retrieved, and cases of BCG lymphadenitis were selected in the study based on these data. Slides of cases were retrieved, and cytological findings were studied. MATERIALS AND METHODS: Papanicolaou, Giemsa, and Hematoxylin & eosin-stained smears, as well as Ziehl-Neelson stain (Z.N. stain) smears of all BCG lymphadenitis cases, were retrieved. Cases were reviewed for individual cytological features and overall cytological diagnostic categories. Z.N. stain smears were evaluated for acid-fast bacilli. RESULTS AND CONCLUSIONS: Diagnostic categories observed in BCG lymphadenitis include suppurative lymphadenitis/abscess (15 %), necrotizing lymphadenitis (23 %), necrotizing granulomatous lymphadenitis (46 %), suppurative granulomatous lymphadenitis (8 %), non-necrotizing granulomatous lymphadenitis (8 %). Acid-fast bacilli were detected by Z.N. stain in 8 cases (62 %). The cytological findings of BCG lymphadenitis closely overlap with those of tuberculous lymphadenitis. So, clinical context is very important while reporting isolated axillary lymphadenopathy, specifically in recently vaccinated infants, to avoid misdiagnosis as tuberculous lymphadenitis.

Study of Diagnostic Yield of Nucleic Acid Amplification Test among Tuberculous Cervical Lymphadenitis in Immunocompetent Patients.

BACKGROUND: The most common form of extrapulmonary tuberculosis (TB) is tuberculous lymphadenitis, which constitutes about 30-40% of all extrapulmonary TB cases. A new diagnostic method like the nucleic acid amplification test (NAAT) is a very sensitive and rapid test for diagnosing tuberculous cervical lymphadenopathy. It also detects rifampicin sensitivity among positive patients. OBJECTIVES: (1) To evaluate the diagnostic yield of TrueNAT for detecting Mycobacterium tuberculosis bacteria in the fine-needle aspirated samples of cervical lymph nodes compared with Ziehl-Neelsen (ZN) staining; (2) to evaluate the diagnostic yield of TrueNAT for diagnosis of tuberculosis through comparison with the cytology report of fine-needle aspiration (FNA) sample of cervical lymph node and with necrotic cervical lymph node on ultrasonography (USG) neck. MATERIALS AND METHODS: A total of 50 patients enrolled in this prospective study from January to December 2022. Demographic profile and clinical history were noted. Fine-needle aspirate samples were sent for TrueNAT assay, cytological examination, and ZN staining. USG neck was done for necrotic findings in the cervical lymph nodes. RESULTS: The TrueNAT positivity rate was 70%. TrueNAT sensitivity and specificity were assessed according to the cytology report, acid-fast bacilli (AFB) positivity on ZN stain, and the finding of necrosis in the cervical lymph node on the USG neck. The sensitivity and specificity of the TrueNAT assay were 80.49 and 77.78%, respectively, in accordance with necrosis on FNA cytology; 17.14 and 93.33%, respectively, in accordance with AFB positivity on ZN stain; and 74.29 and 33.33%, respectively, in accordance with lymph node necrosis on USG neck. CONCLUSION: The TrueNAT assay should be used as an adjunctive test in addition to the conventional cytological examination of the FNA sample of lymph nodes for the rapid diagnosis of tuberculosis. It also detects rifampicin resistance simultaneously.

[Diagnostic value and influencing factors of endobronchial ultrasound-guided transbronchial needle aspiration combined with Xpert MTB/RIF for intrathoracic lymph node tuberculosis].

Objective: To evaluate the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) puncture to obtain intrathoracic lymph node samples combined with Xpert MTB/RIF (Xpert) detection for the diagnosis of intrathoracic lymph node tuberculosis. Methods: From March 2018 to June 2021, 106 patients [55 males and 51 females, age (45.1±18.6) years] with suspected intrathoracic lymph node tuberculosis and EBUS-TBNA were collected in Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, including 64 patients with subsequent diagnosis of intrathoracic lymph node tuberculosis and 42 patients without tuberculosis. Xpert test and traditional etiology test were performed on the patients' intrathoracic lymph node puncture specimens. The positive results of different detection methods and different methods were analyzed, and the influencing factors of Xpert independent detection positive were analyzed by univariate and multivariate logistic regression. Results: The sensitivity of Xpert was 65.6% (95%CI: 52.7%-77.1%), the specificity was 97.6% (95%CI: 87.4%-99.9%), the positive predictive value was 97.7% (95%CI: 85.7%-99.7%), the negative predictive value was 65.1% (95%CI: 57.0%-72.4%). The positive rate of Xpert alone (65.6%, 42/64) was not significantly different from that of MGIT960, histopathology and Xpert combined detection (70.3%, 45/64) (P<0.05). Multivariate logistic regression analysis showed that the location of the diseased lymph nodes in the mediastinum (OR=5.84, 95%CI: 1.112-30.704, P=0.037), necrosis in the lymph nodes (OR=6.32, 95%CI: 1.460-27.384, P=0.014), and the axial depth of the lymph nodes≥17 mm (OR=6.61, 95%CI: 1.408-30.969, P=0.017) were the promoting factors for the positive Xpert test. Conclusions: EBUS-TBNA combined with Xpert detection has a high clinical diagnostic value for intrathoracic lymph node tuberculosis. When the number of puncture samples is small, Xpert detection can be preferred. The positive rate of Xpert detection can be improved by selecting lymph nodes with mediastinal lesions, lymph nodes necrosis, and axial lymph nodes depth≥17 mm for puncture.

Lymphoma and Other Lymph Node Pathologies Among Adult Patients with Lymphadenopathy in Abakaliki, Nigeria.

INTRODUCTION: Lymphadenopathy is usually due to benign or malignant conditions. It can also be local or systemic in distribution and can involve peripheral or deep-seated lymph nodes. This study aimed to determine the prevalence of lymphoma and the distribution pattern of lymph node pathologies among adult patients who presented with lymphadenopathy and its relationship with age and sex. METHODS: A retrospective study was conducted, and a record of all cases of lymphadenopathy with histological diagnosis over 5-year period (January 2017 to December 2021) was extracted from Departments of Anatomical Pathology of Alex Ekwueme Federal University Teaching Hospital, Abakaliki. The data generated were analyzed using Statistical Package for Social Sciences (SPSS) software, version 26. RESULTS: One hundred and ninety results were extracted with an age range of 18 to 94 years and a mean age of 41 ± 16 years. They were made up of 75 (39.5%) males and 115 (60.5%) females, with a male-to-female ratio of 1:1.5. The prevalence of lymphoma was 50.0% (95/190). Thirty-five (18.4%) were Hodgkin's lymphoma (HL), while 60 (31.6%) were non-Hodgkin's lymphoma (NHL). Other pathologies manifested by cases of lymphadenopathy include metastatic tumor deposits (38 (20%)), reactive lymphoid hyperplasia (29 (15.3%)), and tuberculous lymphadenitis (18 (9.5%)). Others include sinus histiocytosis (4 (2.1%)), dermatopathic lymphadenitis (5 (2.6%)), and Castleman's disease (1 (0.5%)). CONCLUSION: About half of all patients who presented with lymphadenopathy were lymphoma with a high prevalence of 50%, and the majority were NHL. Other major causes of lymphadenopathy were metastatic tumor deposits, reactive lymphoid hyperplasia, and tuberculous lymphadenitis. Any case of lymphadenopathy should be properly investigated early for effective management.

Esophageal anthracosis occurred after treatment of esophageal tuberculosis secondary to mediastinal tuberculous lymphadenitis: a rare case report.

BACKGROUND: Anthracosis is a disease generally considered to be in the lungs resulting from exposure to industrial dust in the workplace. Esophageal anthracosis is a fairly rare phenomenon and shows a strong correlation with tuberculosis. Moreover, esophageal involvement in tuberculosis is also rare. We here present an extremely rare case in which follow-up gastroesophageal endoscopy revealed a mass with a sunken, black area in the center and raised ring-like pattern in the surrounding mucosa resembling malignant melanoma. Uncovering the patient's tuberculosis history finally avoided a misdiagnosis or overtreatment. CASE PRESENTATION: A 67-year-old male patient was admitted to the hospital due to "repeated chest pain for 1 month". Endoscopic ultrasonography and contrast-enhanced CT scans revealed a mass adjacent to the esophageal wall with unclear boundaries. Aspiration biopsy confirmed that esophageal tuberculosis was caused by nearby mediastinal tuberculous lymphadenitis. After a standard anti-tuberculosis treatment regimen, the patient achieved a favorable prognosis. The follow-up gastroesophageal endoscopy showed a sunken black lesion with elevated peripheral mucosa replacing the original tuberculous mass, which was thought to be anthracosis, a disease that rarely occurs in the esophagus. CONCLUSION: The diagnosis of tuberculosis should be taken into consideration when a submucosal mass appears in the middle part of the esophagus. Endoscopic ultrasonography can effectively contribute to a definite diagnosis. Moreover, this is the first case of esophageal anthracosis observed only 1 year after the treatment of tuberculosis, indicating esophageal anthracosis can be a short-term disease. The traction of the reduction of tubercular mediastinal lymph nodes after anti-tuberculosis treatment may create a circumstance for pigmentation or dust deposition.

Xpert MTB/RIF in the Diagnosis of Mediastinal Tuberculous Lymphadenitis by Endoscopic Ultrasound-Guided Needle Aspiration Techniques: A Systematic Review and Meta-Analysis.

BACKGROUND: Lymphadenopathy is one of the most prevalent clinical manifestations of extrapulmonary tuberculosis. Endosonography is the recommended technique in the diagnostic work-up of mediastinal lymphadenopathies. Xpert MTB/RIF assay is a self-contained cartridge-based fully automated DNA testing platform which can accurately detect both tuberculosis and mycobacterial resistance to rifampicin. A few studies assessed its accuracy for mediastinal lymph node aspirates collected using endosonography. A systematic review of observational studies was performed to provide a pooled estimate of sensitivity and specificity of Xpert MTB/RIF in the diagnosis of mediastinal tuberculous lymphadenitis using endoscopic ultrasound-guided needle aspiration techniques. METHODS: A search of the scientific evidence was carried out using PubMed, Embase, and Scopus. Articles describing observational studies on Xpert MTB/RIF in the diagnosis of mediastinal tuberculous lymphadenitis using endoscopic ultrasound-guided needle aspiration techniques were selected. RESULTS: Eight studies met the inclusion criteria. The overall pooled sensitivity was 61% (95% CI = 55-68%; I2 = 66.3%; p = 0.004), overall pooled specificity was 89% (95% CI = 85-91%; I2 = 90.1%; p < 0.0001). Area under the sROC curve was 0.68. Only one study reported data on rifampin resistance detection and showed a sensitivity of 83.3% and a specificity of 16%. CONCLUSIONS: Xpert MTB/RIF shows a good accuracy in the diagnosis of mediastinal mycobacterial lymphadenitis by endosonographic needle aspiration techniques. It should be always recommended for suspected mediastinal tuberculosis.

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

A Case of Mediastinal Tuberculous Lymphadenitis in a Chronic Dialysis Patient Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA).

A 54-year-old woman on dialysis due to chronic renal failure had a fever lasting 2 weeks and was referred to a hospital. Non-enhanced CT and blood tests showed no remarkable findings. She was hospitalized and received an antibacterial drug. Although she was discharged after the fever subsided, she was hospitalized again due to a fever a few days later. A contrast-enhanced CT revealed mediastinal lymphadenopathy, and she was transferred to our hospital for a bronchoscopy. Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) for subcarinal lymph nodes was performed in our hospital. The Polymerase Chain Reaction (PCR) test of the obtained specimen was positive for mycobacterium tuberculosis, and histologically, caseous granulomas were found in the specimen. She was diagnosed with mediastinal tuberculous lymphadenitis, and HREZ (isoniazid, rifampicin, ethambutol, and pyrazinamide) treatment was started. The fever subsided immediately, and she was discharged from our hospital 2 weeks after the initiation of treatment. Thereafter, she received treatment as an outpatient. Since the use of a contrast medium was complicated by dialysis, a non-enhanced CT was performed at first, and it was difficult to make a diagnosis from this. We report this as an informative case that could be diagnosed with EBUS-TBNA, which was easily performed on a patient weakened by prolonged fever and dialysis.

Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of tuberculosis in children and adolescents. OBJECTIVES: To assess the diagnostic accuracy of Xpert Ultra for detecting: pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance, in children with presumed tuberculosis. Secondary objectives To investigate potential sources of heterogeneity in accuracy estimates. For detection of tuberculosis, we considered age, comorbidity (HIV, severe pneumonia, and severe malnutrition), and specimen type as potential sources. To summarize the frequency of Xpert Ultra trace results. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 9 March 2021. SELECTION CRITERIA: Cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children under 15 years of age. We included ongoing studies that helped us address the review objectives. We included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). For detecting tuberculosis, reference standards were microbiological (culture) or composite reference standard; for stool, we also included Xpert Ultra performed on a routine respiratory specimen. For detecting rifampicin resistance, reference standards were drug susceptibility testing or MTBDRplus. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and, using QUADAS-2, assessed methodological quality judging risk of bias separately for each target condition and reference standard. For each target condition, we used the bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We summarized the frequency of Xpert Ultra trace results; trace represents detection of a very low quantity of Mycobacterium tuberculosis DNA. We assessed certainty of evidence using GRADE. MAIN RESULTS: We identified 14 studies (11 new studies since the previous review). For detection of pulmonary tuberculosis, 335 data sets (25,937 participants) were available for analysis. We did not identify any studies that evaluated Xpert Ultra accuracy for tuberculous meningitis or lymph node tuberculosis. Three studies evaluated Xpert Ultra for detection of rifampicin resistance. Ten studies (71%) took place in countries with a high tuberculosis burden based on WHO classification. Overall, risk of bias was low. Detection of pulmonary tuberculosis Sputum, 5 studies Xpert Ultra summary sensitivity verified by culture was 75.3% (95% CI 64.3 to 83.8; 127 participants; high-certainty evidence), and specificity was 97.1% (95% CI 94.7 to 98.5; 1054 participants; high-certainty evidence). Gastric aspirate, 7 studies Xpert Ultra summary sensitivity verified by culture was 70.4% (95% CI 53.9 to 82.9; 120 participants; moderate-certainty evidence), and specificity was 94.1% (95% CI 84.8 to 97.8; 870 participants; moderate-certainty evidence). Stool, 6 studies Xpert Ultra summary sensitivity verified by culture was 56.1% (95% CI 39.1 to 71.7; 200 participants; moderate-certainty evidence), and specificity was 98.0% (95% CI 93.3 to 99.4; 1232 participants; high certainty-evidence). Nasopharyngeal aspirate, 4 studies Xpert Ultra summary sensitivity verified by culture was 43.7% (95% CI 26.7 to 62.2; 46 participants; very low-certainty evidence), and specificity was 97.5% (95% CI 93.6 to 99.0; 489 participants; high-certainty evidence). Xpert Ultra sensitivity was lower against a composite than a culture reference standard for all specimen types other than nasopharyngeal aspirate, while specificity was similar against both reference standards. Interpretation of results In theory, for a population of 1000 children: • where 100 have pulmonary tuberculosis in sputum (by culture): - 101 would be Xpert Ultra-positive, and of these, 26 (26%) would not have pulmonary tuberculosis (false positive); and - 899 would be Xpert Ultra-negative, and of these, 25 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in gastric aspirate (by culture): - 123 would be Xpert Ultra-positive, and of these, 53 (43%) would not have pulmonary tuberculosis (false positive); and - 877 would be Xpert Ultra-negative, and of these, 30 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in stool (by culture): - 74 would be Xpert Ultra-positive, and of these, 18 (24%) would not have pulmonary tuberculosis (false positive); and - 926 would be Xpert Ultra-negative, and of these, 44 (5%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in nasopharyngeal aspirate (by culture): - 66 would be Xpert Ultra-positive, and of these, 22 (33%) would not have pulmonary tuberculosis (false positive); and - 934 would be Xpert Ultra-negative, and of these, 56 (6%) would have tuberculosis (false negative). Detection of rifampicin resistance Xpert Ultra sensitivity was 100% (3 studies, 3 participants; very low-certainty evidence), and specificity range was 97% to 100% (3 studies, 128 participants; low-certainty evidence). Trace results Xpert Ultra trace results, regarded as positive in children by WHO standards, were common. Xpert Ultra specificity remained high in children, despite the frequency of trace results. AUTHORS' CONCLUSIONS: We found Xpert Ultra sensitivity to vary by specimen type, with sputum having the highest sensitivity, followed by gastric aspirate and stool. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both microbiological and composite reference standards. However, the evidence base is still limited, and findings may be imprecise and vary by study setting. Although we found Xpert Ultra accurate for detection of rifampicin resistance, results were based on a very small number of studies that included only three children with rifampicin resistance. Therefore, findings should be interpreted with caution. Our findings provide support for the use of Xpert Ultra as an initial rapid molecular diagnostic in children being evaluated for tuberculosis.

Xpert MTB/XDR for detection of pulmonary tuberculosis and resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin.

BACKGROUND: The World Health Organization (WHO) End TB Strategy stresses universal access to drug susceptibility testing (DST). DST determines whether Mycobacterium tuberculosis bacteria are susceptible or resistant to drugs. Xpert MTB/XDR is a rapid nucleic acid amplification test for detection of tuberculosis and drug resistance in one test suitable for use in peripheral and intermediate level laboratories. In specimens where tuberculosis is detected by Xpert MTB/XDR, Xpert MTB/XDR can also detect resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin. OBJECTIVES: To assess the diagnostic accuracy of Xpert MTB/XDR for pulmonary tuberculosis in people with presumptive pulmonary tuberculosis (having signs and symptoms suggestive of tuberculosis, including cough, fever, weight loss, night sweats). To assess the diagnostic accuracy of Xpert MTB/XDR for resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin in people with tuberculosis detected by Xpert MTB/XDR, irrespective of rifampicin resistance (whether or not rifampicin resistance status was known) and with known rifampicin resistance. SEARCH METHODS: We searched multiple databases to 23 September 2021. We limited searches to 2015 onwards as Xpert MTB/XDR was launched in 2020. SELECTION CRITERIA: Diagnostic accuracy studies using sputum in adults with presumptive or confirmed pulmonary tuberculosis. Reference standards were culture (pulmonary tuberculosis detection); phenotypic DST (pDST), genotypic DST (gDST),composite (pDST and gDST) (drug resistance detection). DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed reports for eligibility and extracted data using a standardized form. For multicentre studies, we anticipated variability in the type and frequency of mutations associated with resistance to a given drug at the different centres and considered each centre as an independent study cohort for quality assessment and analysis. We assessed methodological quality with QUADAS-2, judging risk of bias separately for each target condition and reference standard. For pulmonary tuberculosis detection, owing to heterogeneity in participant characteristics and observed specificity estimates, we reported a range of sensitivity and specificity estimates and did not perform a meta-analysis. For drug resistance detection, we performed meta-analyses by reference standard using bivariate random-effects models. Using GRADE, we assessed certainty of evidence of Xpert MTB/XDR accuracy for detection of resistance to isoniazid and fluoroquinolones in people irrespective of rifampicin resistance and to ethionamide and amikacin in people with known rifampicin resistance, reflecting real-world situations. We used pDST, except for ethionamide resistance where we considered gDST a better reference standard. MAIN RESULTS: We included two multicentre studies from high multidrug-resistant/rifampicin-resistant tuberculosis burden countries, reporting on six independent study cohorts, involving 1228 participants for pulmonary tuberculosis detection and 1141 participants for drug resistance detection. The proportion of participants with rifampicin resistance in the two studies was 47.9% and 80.9%. For tuberculosis detection, we judged high risk of bias for patient selection owing to selective recruitment. For ethionamide resistance detection, we judged high risk of bias for the reference standard, both pDST and gDST, though we considered gDST a better reference standard. Pulmonary tuberculosis detection - Xpert MTB/XDR sensitivity range, 98.3% (96.1 to 99.5) to 98.9% (96.2 to 99.9) and specificity range, 22.5% (14.3 to 32.6) to 100.0% (86.3 to 100.0); median prevalence of pulmonary tuberculosis 91.3%, (interquartile range, 89.3% to 91.8%), (2 studies; 1 study reported on 2 cohorts, 1228 participants; very low-certainty evidence, sensitivity and specificity). Drug resistance detection People irrespective of rifampicin resistance - Isoniazid resistance: Xpert MTB/XDR summary sensitivity and specificity (95% confidence interval (CI)) were 94.2% (87.5 to 97.4) and 98.5% (92.6 to 99.7) against pDST, (6 cohorts, 1083 participants, moderate-certainty evidence, sensitivity and specificity). - Fluoroquinolone resistance: Xpert MTB/XDR summary sensitivity and specificity were 93.2% (88.1 to 96.2) and 98.0% (90.8 to 99.6) against pDST, (6 cohorts, 1021 participants; high-certainty evidence, sensitivity; moderate-certainty evidence, specificity). People with known rifampicin resistance - Ethionamide resistance: Xpert MTB/XDR summary sensitivity and specificity were 98.0% (74.2 to 99.9) and 99.7% (83.5 to 100.0) against gDST, (4 cohorts, 434 participants; very low-certainty evidence, sensitivity and specificity). - Amikacin resistance: Xpert MTB/XDR summary sensitivity and specificity were 86.1% (75.0 to 92.7) and 98.9% (93.0 to 99.8) against pDST, (4 cohorts, 490 participants; low-certainty evidence, sensitivity; high-certainty evidence, specificity). Of 1000 people with pulmonary tuberculosis, detected as tuberculosis by Xpert MTB/XDR: - where 50 have isoniazid resistance, 61 would have an Xpert MTB/XDR result indicating isoniazid resistance: of these, 14/61 (23%) would not have isoniazid resistance (FP); 939 (of 1000 people) would have a result indicating the absence of isoniazid resistance: of these, 3/939 (0%) would have isoniazid resistance (FN). - where 50 have fluoroquinolone resistance, 66 would have an Xpert MTB/XDR result indicating fluoroquinolone resistance: of these, 19/66 (29%) would not have fluoroquinolone resistance (FP); 934 would have a result indicating the absence of fluoroquinolone resistance: of these, 3/934 (0%) would have fluoroquinolone resistance (FN). - where 300 have ethionamide resistance, 296 would have an Xpert MTB/XDR result indicating ethionamide resistance: of these, 2/296 (1%) would not have ethionamide resistance (FP); 704 would have a result indicating the absence of ethionamide resistance: of these, 6/704 (1%) would have ethionamide resistance (FN). - where 135 have amikacin resistance, 126 would have an Xpert MTB/XDR result indicating amikacin resistance: of these, 10/126 (8%) would not have amikacin resistance (FP); 874 would have a result indicating the absence of amikacin resistance: of these, 19/874 (2%) would have amikacin resistance (FN). AUTHORS' CONCLUSIONS: Review findings suggest that, in people determined by Xpert MTB/XDR to be tuberculosis-positive, Xpert MTB/XDR provides accurate results for detection of isoniazid and fluoroquinolone resistance and can assist with selection of an optimised treatment regimen. Given that Xpert MTB/XDR targets a limited number of resistance variants in specific genes, the test may perform differently in different settings. Findings in this review should be interpreted with caution. Sensitivity for detection of ethionamide resistance was based only on Xpert MTB/XDR detection of mutations in the inhA promoter region, a known limitation. High risk of bias limits our confidence in Xpert MTB/XDR accuracy for pulmonary tuberculosis. Xpert MTB/XDR's impact will depend on its ability to detect tuberculosis (required for DST), prevalence of resistance to a given drug, health care infrastructure, and access to other tests.

Lymph Node Tuberculosis in Otolaryngological Practice: A Study of 68 Cases at the Sourô Sanou University Hospital of Bobo Dioulasso, Burkina Faso.

INTRODUCTION: Lymph node tuberculosis (LNTB) frequently affects peripheral cervical lymph node body sites. We aimed to study epidemiology and diagnostic and therapeutic characteristics of LNTB patients in ENT routine practice. METHODS: We conducted a cross-sectional prospective study in the ENT and cervicofacial surgery department at the Sourô Sanou University Hospital of Bobo Dioulasso, Burkina Faso, for a period of 36 months. RESULTS: There were 68 cases with LNTB, of which 54.4% were mostly men. The mean age and the median age were calculated at 37 ± 6.8 and 42 years, respectively. The patient's age ranged between 3 and 81 years, and the most represented age group was from 30 to 60 years (62%). According to geographical origin, most patients (79%) originated from rural areas. In 6 cases (9%), patients reported diabetes and 12 patients were HIV positives (18%). Most clinical features leading to the ENT consultation were cervical lymph nodes (82%) and cervical scrofuloderma (18%). For the multiple locations, the lymphadenopathies involved mostly the transversal cervical chain (56%) and spinal chain (50%). Histopathology examination was the mostly diagnosed methods used in 68%. A 6-month anti-tuberculous treatment was given with a follow-up of 6 months without any relapse in 62 cases (97%). CONCLUSION: The frequency of 68 cases of LNTB in 3 years is underappreciated. Among all lymph node sites, transversal cervical chain and cervical spinal chain were mostly affected. Further advanced studies are recommended to determine the prevalence and contributing factors of LNTB in the study area.

Clinical features and diagnostic approaches for abdominal tuberculosis: five-year experience from a non-tuberculosis-designated hospital in China.

BACKGROUND AND PURPOSE: abdominal tuberculosis (TB) is a common form of extrapulmonary TB but it is still a diagnostic dilemma in clinical practice. This study aimed to highlight the clinical features and diagnostic approaches for abdominal TB. METHODS: seventy cases of diagnosed abdominal TB were retrospectively collected between August 1st, 2015 and June 30th, 2020. They were classified as peritoneal TB, lymph node TB, gastrointestinal TB, visceral TB or mixed TB. RESULTS: eighteen patients were diagnosed with peritoneal TB, nine with lymph node TB, five with gastrointestinal TB, two with visceral TB and 36 with mixed TB. More than 65 % of the patients had tuberculosis of other sites except the abdomen. The median diagnosis time was 60 days. Ascites (58.6 %), abdominal distension (48.6 %), weight loss (44.3 %) and fever (42.9 %) were the most common symptoms. The overall microbiological and histological detection rates were 70.0 % and 38.6 %, respectively. The non-ascite samples yielded a higher microbiological confirmation rate (63.6 %) than the total samples (40.8 %). Diagnosis was confirmed histologically in 18 patients (69.2 %). Forty-five cases (64.3 %) were clinically diagnosed. Invasive procedures such as surgery (6/7), percutaneous biopsy (7/7) and endoscopy in lymph node TB (4/5) had high confirmation rates. CONCLUSIONS: the diagnosis of abdominal TB should be reached by a combination of clinical, laboratory, radiological, microbiological and pathological findings.

Retrospective observational study to compare Xpert MTB/RIF assay with other diagnostic tests in lymph node tuberculosis.

Background: Lymph node tuberculosis (TB) is the most common form of extrapulmonary TB in India. Standards for TB care in India recommend microscopy/culture/CBNAAT/molecular test/histopathology examination and drug sensitivity testing on appropriate specimens from the presumed sites of involvement for all patients with presumptive extrapulmonary TB. Objectives: To analyze the utility of Xpert MTB/Rif assay in lymph node TB. Methods: All patients who underwent lymph node sampling between July 2014 and June 2017 and for whom Xpert MTB/Rif assay was done were included. Demographic profile, Xpert MTB/Rif assay result, histopathology/cytology findings, smear acid-fast bacillus (AFB), and AFB culture results were noted. A composite reference score (CRS) was made. Results: Xpert MTB/Rif assay was positive in 63 of the 81 patients. Xpert had a sensitivity of 82.14% and specificity of 86.18%when compared against AFB culture and 75.61% and 98.97% when compared against CRS. Conclusion: Xpert MTB/Rif assay is a valuable test for rapid diagnosis of lymph node TB.