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Studies comparing NAAT with reference standard for diagnosis of tuberculosis lymphadenitis

Studies comparing NAAT with reference standard for diagnosis of tuberculosis lymphadenitis

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Lymphadenitis is the most common extra-pulmonary manifestation of tuberculosis (TB). Conventional diagnostic methods such as smear microscopy and culture are not very accurate for TB lymphadenitis. Nucleic acid amplification tests (NAAT) may offer additional diagnostic benefit. To assess, in a systematic review, the performance of NAAT for the diag...

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... contained a mean of 56 samples (standard de- viation [SD] 7, range 10-286). Tables 1 and 2 provide detailed information on each of the included studies. ...

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... Hence, they have been widely used in the early diagnosis of TB [29,30]. Moreover, they have an extremely good diagnostic performance in paucibacillary EPTB [31]. However, these methods have limitations. ...
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Background Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die. The current study aimed to assess the accuracy of metagenomic next generation sequencing (mNGS) for TBM, and to identify a new test for the early diagnosis of TBM. Methods We searched for articles published in Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data up to June 30, 2020 for studies that assessed the efficacy of mNGS for the diagnosis of TBM. Then, the accuracy between mNGS and a composite reference standard (CRS) in these articles was compared using the meta-analysis approach. Results Four independent studies with 342 samples comparing mNGS and a CRS were included in this study. The sensitivity of mNGS for TBM diagnosis ranged from 27% to 84%. The combined sensitivity of mNGS was 61%, and the I ² value was 92%. Moreover, the specificity of mNGS for TBM diagnosis ranged from 96% to 100%. The combined specificity of mNGS was 98%, and the I ² value was 74%. The heterogeneity between studies in terms of sensitivity and specificity was significant. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for TBM was 0.98. Conclusions The sensitivity of mNGS for TBM diagnosis was moderate. Furthermore, the specificity was extremely high, and the AUC of the SROC indicated a very good diagnostic efficacy. mNGS could be used as an early diagnostic method for TBM, however, the results should be treated with caution for the heterogeneity between studies was extremely significant. Systematic review registration INPLASY202070100.
... However studies on NAAT for TBLN produce high variable of sensitivity (2-100%) and specificity (28-100%), precluding the determination of clinically meaningful estimates of accuracy. (Daley et al., 2007); (5) Ultrasound (USG) and CT scan are known to be effective for detecting enlarged lymph nodes and widely used to obtain information about the size of lymph nodes, localization and accessing their relation wiseventhh major structure in the neck. They are also useful in guidance for biopsy aspiration (Gupta, et al., 2007;Anmari, et.al., 2009). ...
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Tuberculous Lymphadenitis (TBLN) is most common extrapulmonary tuberculosis. The common symptom of TBLN is cervical lymphadenopathy which is known to mimic numerous pathological conditions like NHL. Coexistency TBLN and lymphoma is a rare. A woman, 56 years old, had chief complaint of cervical masses since 2 months ago. She had history of weight loss, fever and night sweats but no history of chronic cough. From physical examination and supporting examination, the patient was diagnosed with TBLN coexists with NHL. She got antituberculosis drug (ATD) for 2 weeks before chemotherapy. The patient died of septic shock 9 days later after chemotherapy. From HPE examination, TBLN and NHL may show simillar feature so Zhiel-Neelsen staining and Immunohistochemical are important to confirm each disease. ATD was given to supress the mycobacterium activity before chemotherapy. However the patient had febrile neutropenia after chemotherapy and died of septic shock. Both TBLN and NHL may occur with simillar sign and symptom and HPE. Further examinations have to be done to confirm the diagnosis of both disesases. Although ATD had given to prevent Tb infection progresivity. On 7 days after chemotherapy she had febrile neutropenia and lead to death due to septic shock.
... With the advance of molecular techniques, various polymerase chain reaction (PCR) methods have been introduced to identify M. tuberculosis more easily and quickly 7 . Due to shortcomings of conventional diagnostic tests,cartridge-based nucleic acid amplification test(CBNAAT) have emerged to enable clinicians for early recognition of M.tuberculosis from a variety of extrapulmonary clinical samples, with very good positive predictive value (PPV) (around 99%) and comparatively lesser negative predictive value 8,9 . Extra-pulmonary tuberculosis is far more complex because of the diversity of clinical sample types, difficulties in obtaining adequate tissue for analysis and in the extraction of M. tuberculosis DNA (MTB DNA) from the samples 10 . ...
... Tüberküloz lenfadenitte nükleik asit amplifikasyon testi de kullanılmaktadır. Fakat bununla ilgili çalışmalara bakıldığında hem yanlış pozitif hem de yanlış negatif sonuçlar mümkün olduğu için, geleneksel yöntemlerle birlikte ve klinik şüphe durumunda uygulanabilirliği vurgulanmaktadır (18). ...
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Çalışmamızda benign mediastinal/hiler lenfadenopati saptanan hastalar takip edilerek lenfadenopatiye neden olan hastalıkların dağılımı incelenmiştir. Çalışmamız, Mayıs 2015 ile Haziran 2016 tarihleri arasında prospektif olarak yürütüldü. Çalışmaya mediastinal/hiler lenfadenopati nedeni ile EBUS/ Mediastinoskopi/ Torakoskopi yapılan olgular alındı ve başlangıçta biyopside malignite saptanan hastalar çalışmadan çıkarıldı. Çalışmaya dahil edilen benign mediastinal/hiler LAP saptanan 93 hastanın %59.1 (55)’i kadın, %40.9 (38)’u erkek, yaş ortalaması 55.1 (±12.6) idi. Seksen üç hastaya Endobronşiyal Ultrason Eşliğinde Transbronşiyal İğne Aspirasyonu (EBUS TBİA), 7 hastaya mediastinoskopi, 2 hastaya Video-asiste torakoskopi (VATS) ve 1 hastaya torakotomi yapıldı. Hastaların son tanıları %53.8 (50) sarkoidoz, %12.9 (12) antrakoz, %5.1 (5) tüberküloz, %4.3 (4) silikozis, %1.1 (1) churg strauss sendromu, %1.1 (1) hipersensitivite pnömonisi, %1.1 (1) enfeksiyon, %1.1 (1) kanser, %19.4 (18) nedeni bilinmeyen olarak kabul edildi. Çalışmamızdaki esas bulgu benign mediastinal/hiler lenfadenopatinin en yaygın nedeninin sarkoidoz olarak bulunmasıdır. Enfeksiyöz nedenlerden tüberküloz ise 3. sıklıkta LAP nedeni olarak bulunmuştur. Ayrıca granülomatöz lenfadenitin benign mediastinal/hiler lenfadenopatilerin yarısından fazlasını oluşturduğu görülmüştür. Mediastinel/hiler LAP’lerin büyük oranda EBUS TBİA yöntemiyle örneklenebildiği saptanmıştır. Ayırıcı tanının yapılamadığı olgularda takip ile tanıya gidilebileceği de anlaşılmaktadır.
... 3,11,12,14,25 In addition, molecular testing and histopathological examination are necessary for an accurate diagnosis of tuberculous lymphadenitis. 35,36 Acquiring additional tissue core for AFB culture and MTB PCR is more difficult than acquiring rinse fluid from the EBUS-TBNA needle which is easy and quick, especially in prolonged procedural cases with multiple lymph node stations. 15,26 This study had several limitations. ...
Article
Background and objective We evaluated the usefulness of acid‐fast bacilli (AFB) culture and Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) needle rinse fluid for diagnosing tuberculous lymphadenitis. Methods EBUS‐TBNA needle rinse fluid was routinely used for AFB culture and MTB PCR. The patients were categorized according to the pre‐procedural diagnosis (Group A, suspected/histology‐confirmed lung cancer; Group B, extrapulmonary malignancy; and Group C, other benign diseases). Results Of the 4672 subjects, 104 (2.2%) were diagnosed with tuberculous lymphadenitis; 1.0%, 4.6% and 12.7% of Group A, B and C, respectively. Tuberculous lymphadenitis was diagnosed in 0.2%, 1.0% and 4.5% Group A, B and C patients, respectively, by histopathology. On addition of AFB culture to histopathology, tuberculous lymphadenitis was diagnosed in 1.0%, 4.4% and 10.3% of Group A, B and C patients, respectively (P < 0.001, P = 0.001 and P = 0.005, respectively). On addition of MTB PCR to histopathology, tuberculous lymphadenitis was diagnosed in 0.4%, 1.9% and 8.8%, respectively (Group C; P = 0.029). Conclusion Routine AFB culture of needle rinse fluid was useful to increase the diagnostic yield of tuberculous lymphadenitis for all subjects who underwent EBUS‐TBNA regardless of pre‐procedural diagnosis in an intermediate tuberculosis (TB)‐burden country. However, MTB PCR was only useful in subjects with pre‐procedural diagnosis of benign pulmonary diseases.
... Tüberküloz lenfadenitte nükleik asit amplifikasyon testi de kullanılmaktadır. Fakat bununla ilgili çalışmalara bakıldığında hem yanlış pozitif hem de yanlış negatif sonuçlar mümkün olduğu için, geleneksel yöntemlerle birlikte ve klinik şüphe durumunda uygulanabilirliği vurgulanmaktadır (18). ...
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Introduction: Granulomatous lung disease (GLD) is caused by a wide range of conditions and it is challenge for pulmonologist. A detailed history of exposures is fundamental in GDL and has been found pivotal to reach a precise diagnosis. Materials and methods: Between September 2014 and December 2016, the distribution of patients diagnosed with granulomatous lymphadenitis in the mediastinal/hilar lymph nodes by endobronchial ultrasound (EBUS) or mediastinoscopy was analyzed. To be listed as 'confident', a diagnosis of sarcoidosis required compatible histological, radiological and clinical findings in conjunction with negative cultures. Infectious entities listed as 'confident' had either microorganisms in tissue section, positive culture, positive serology or positive antigen detection in a consistent clinical pathological setting. Result: Granulomatous lymphadenitis was detected in 110 patients. The included 110 cases consisted of 70.9% women and median age of 53 (range 44-61) years. The final diagnosis of the patients was accepted to be sarcoidosis in 79 (71.8%), sarcoid like granulomas in 7 (6.4%), tuberculosis in 4 (3.6%), silicosis in 4 (3.6%), drug-associated granuloma in 2 (1.8%), hypersensitivity pneumonitis in 1 (0.9%), Chron disease in 1 (0.9%), unspecified in 12 (10.9%). Three patients were classified as tuberculosis based on culture. Conclusions: In this study, we found that the most common cause of granulomatous lymphadenitis was sarcoidosis. Contrary to expectations, the number of patients diagnosed with tuberculosis was very low.
... Histology can be used in the diagnosis of EPTB, but lacks specificity as several other conditions may present similar histological features [6]. Most nucleic acid amplification tests show better sensitivity, but are complex, expensive, technically demanding and prone to contamination, limiting their use in low-resource diagnostic settings [7][8][9][10]. The development of the GeneXpert1 MTB/RIF (Xpert) assay is a landmark in TB diagnostics, but reported sensitivities of the assay for EPTB samples are highly heterogeneous and vary widely across different sample types [11][12][13][14]. ...
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Background Extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting. Methods Patients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases. Results Patients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%). Conclusions We show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.
... NAATs are more sensitive than AFB and faster than cultures. In published studies, PCR has a sensitivity of 17%-100% and specificity of 67%-100% in the diagnosis of tuberculous lymphadenitis (23). For EBUS-TBNA-obtained material NAAT positivity was between 18.2% and 56.7% (11,(15)(16)(17). ...
Article
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Background/aim: Mediastinal lymph nodes are the second most commonly affected lymph nodes in tuberculous lymphadenitis. It is often difficult to diagnose tuberculosis in patients with lymphadenopathy without parenchymal lesions. The aim of this study was to describe the diagnostic utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with isolated mediastinal tuberculous lymphadenitis (MTLA). Materials and methods: This study included 527 patients who had undergone EBUS-TBNA between December 2012 and December 2014. Patients with the final diagnosis of MTLA were evaluated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of EBUS-TBNA were calculated.Results: The prevalence of MTLA in all patients who had undergone EBUS-TBNA for mediastinal lymphadenopathy of unknown etiology was 5.2% (28/527). EBUS-TBNA was diagnostic in 21/28 (75%) patients, and the remaining 7 patients required additional procedures for confirmation of diagnosis. Sensitivity, specificity, PPV, NPV, and accuracy of combined cytopathological and microbiological examinations of EBUS-TBNA in the diagnosis of MTLA were 87.5%, 98.5%, 91.4%, 98%, and 94.4%, respectively. There were no major complications.Conclusion: EBUS-TBNA is a safe and effective procedure for the diagnosis of MTLA. When microbiological and cytopathological examinations of samples are combined, EBUS-TBNA demonstrates good diagnostic accuracy and NPV for the diagnosis of MTLA.
... Due to the low performance of conventional bacteriological methods, the use of molecular diagnostic techniques, which have shown heterogeneous results, has increased; in this work, 5 cases were confirmed by molecular biology. In a systematic review carried out in 2007 by Daley et al., [16] sensitivity ranging between 2% and 100% was reported, depending on the type of molecular test used. No recent systematic reviews that included modalities such as Xpert MTB/RIF were found; however, evidence suggests its usefulness, particularly in cases where cultures are negative. ...
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Background: The pediatric population is at increased risk of disseminated and extrapulmonary tuberculosis (TB). There is little information on children affected by this entity. The demographic, clinical, and outcome characteristics of the treatment of children with extrapulmonary TB, treated at a national reference institution between January 1, 2008, and December 31, 2016, are described and analyzed in this work. Materials and methods: This was a retrospective observational study. Cases of extrapulmonary TB were identified, and variables were collected based on each criterion used for diagnosis and treatment outcomes. A descriptive analysis of the variables collected was performed. Results: Ninety-three cases were identified, of which 32 (34.4%) met the criteria for extrapulmonary TB. The mean age was 10.2 years (range 0.8-17 years), and the most frequent site of extrapulmonary TB was lymph node 40.6%, meningeal 21.9%, and ocular 18.8%. Bacteriological confirmation was obtained in 8 cases (25%) while the remaining 24 cases (75%) were classified as cases of clinically diagnosed TB. Two patients (6.2%) died during treatment although their decease was not attributable to TB. Conclusion: The clinical criterion was fundamental to establish the diagnosis. The microbiological isolation rate was low. Molecular biology tools increase bacteriological performance although their extended use is limited by cost. Regional multicenter studies are required to identify the target population and the tools necessary for timely management and treatment.
... Detection of TB lymphadenitis is a major challenge because its nonspecific clinical findings may overlap with other diseases. Various methods (PCR-based methods and DNA extraction protocols) have been widely used for TB diagnosis, however limited information about the usage of these techniques in the diagnosis of TB lymphadenitis has been published (2,3).Culture remains the gold standard for confirmation of TB disease (4). However, it takes at least two weeks and have low sensitivity for the diagnosis of extra- pulmonary TB. ...
Article
Introduction: Lymphadenopathy is a common clinical problem in pediatric age group. Tuberculous lymphadenopathy is a prominent cause of peripheral adenopathy amongst children in the developing countries. Tuberculous lymphadenitis is among the most frequent presentations of extrapulmonary tuberculosis. In this article, we presented five pediatric cases with mycobacterial infection detected in cervical lymph nodes. Case Presentation: First case admitted with a painless swelling in cervical and axillar regions and pathologic examination of the extirpated lymph node showed necrotizing granulomatous lymphadenitis. Second case presented with two months history of abdominal pain and painless swelling of right cervical region and Mycobacterium tuberculosis (MTB) was grown in culture from the lymph node. Third case admitted with a painless cervical mass, her sputum was found positive for MTB. Fourth case was admitted with one year history of swelling that became fistulized in 6 months and lymph node culture was found positive for MTB. Fifth case, admitted with a painful swelling in left upper gingival mucosa and extirpated lymph node showed chronic granulomatous inflammation. Conclusion: Pathological and microbiological examination of tissues such as cervical enlarged lymph nodes should be evaluated for diagnosis of tuberculous infections.