Sensitivity Of Xpert Research Articles

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.

Xpert MTB/RIF assay in the diagnosis of pulmonary tuberculosis in children in tertiary care setting in South India.

Xpert MTB/RIF is recommended for the diagnosis of tuberculosis (TB) in children. We determined the performance of Xpert MTB/RIF in the diagnosis of pulmonary TB in children. The characteristics of children influencing Xpert MTB/RIF positivity were explored. Children aged <15 years with symptoms suggestive of pulmonary TB were prospectively enrolled from 2013 to 2019. Two sputum/early morning gastric aspirate specimens were collected for examination by smear (fluorescence microscopy), Xpert MTB/RIF, and culture [Mycobacteria growth indicator tube (MGIT)/Lowenstein-Jensen (LJ) medium]. Diagnostic performance of Xpert MTB/RIF was evaluated using LJ and or MGIT culture positivity as the reference standard. Sensitivity, specificity with 95% confidence interval (CI) were calculated. Stratified analysis was done; P < .05 was considered statistically significant. Of the total 1727 enrolled children, 1674 (97%) with complete results for at least one sputum/gastric aspirate sample were analyzed. The sensitivity of Xpert MTB/RIF was 68.5% in sputum and 53.6% in gastric aspirate while the specificity was 99% for both. The sensitivity compared to smear was 68.5% vs. 33.7% (P < .001) and 53.6% vs. 14.5%; (P < .001) in sputum and gastric aspirate, respectively. The sensitivity of Xpert MTB/RIF was 23.9% with decision to treat as reference standard. Xpert MTB/RIF positivity was significantly influenced by sex, age, nutritional status, chest X-ray abnormality, TB infection status, and symptoms suggestive of TB. Xpert MTB/RIF as an upfront test compared to smear improves diagnosis of pulmonary TB in children yet the sensitivity is suboptimal. Newer TB diagnostic tools with improved sensitivity is warranted in children.

Diagnostic performance analysis of Xpert MTB/RIF in lymph node tuberculosis: A retrospective study

AimsTo retrospectively analyze the diagnostic efficacy of Xpert MTB/RIF (Xpert) in lymph node tuberculosis (LNTB). MethodsSensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of Xpert, pathological examination and culture for LNTB were calculated. Results421 suspected LNTB cases were categorized into the LNTB group (377 cases) and non-LNTB group (44 cases). The sensitivities of Xpert, pathological examination, and culture were 72.15%, 20.69%, 30.24%, respectively, with NPVs of 29.53%, 12.83%, 14.33%. The AUC values were 0.861, 0.603, 0.651, respectively. The sensitivity of Xpert varied across sample types: tissue (64.73%), puncture fluid (74.42%), and pus (96.05%). For specific lymph node locations, the sensitivity was head-and-neck (72.51%), mediastinal (84.21%), and axillary (45.83%). ConclusionsXpert demonstrates high diagnostic value for LNTB, particularly in pus samples. It also performs better in mediastinal and head-and-neck lymph node samples compared to axillary lymph node samples.

Evaluation of droplet digital polymerase chain reaction by detecting cell-free deoxyribonucleic acid in pleural effusion for the diagnosis of tuberculous pleurisy: a multicentre cohort study

ObjectivesTuberculous pleurisy is one of the most common types of extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicentre cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing tuberculous pleurisy. MethodsPatients with suspected tuberculosis (≥5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR, and cf-ddPCR were performed simultaneously for all specimens. ResultsA total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite tuberculous pleurisy, 113 possible tuberculous pleurisy and 63 non-tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI, 82.8–95.1%) in the definite tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI, 47.1–66.6%, p < 0.001), Xpert (46.7%, 49/105, 95% CI, 37.0–56.6%, p < 0.001), Ultra (69.5%, 73/105, 95% CI, 59.7–77.9%, p < 0.001) and real-time PCR (75.2%, 79/105, 95% CI, 65.7–82.9%, p < 0.001). In possible tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI, 51.4–70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI, 19.7–36.8%, p < 0.001) and real-time PCR (38.9%, 44/113, 95% CI, 30.0–48.6%, p < 0.001). DiscussionThe performance of cf-ddPCR is superior to Culture, Xpert, Ultra, and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay.

Diagnostic Value of Combined-Diagnostic Methods of Brain Tuberculoma Tissue Specimens: A Case Series.

Background: The diagnosis of brain tuberculoma (BT) is sometimes challenging. Herein, we presented a case series to evaluate the combined-diagnostic methods, including acid-fast bacilli (AFB) stain, polymerase chain reaction (PCR), Gene Xpert, and histopathology, of tuberculoma tissue specimens (TTSs). Patients and Methods: A total of 16 patients (11 human immunodeficiency virus [HIV]-positive, 5 HIV-negative) with BT confirmed by combined-diagnostic methods of TTS were included in this study. Clinical data, including clinical symptoms, laboratory tests, neuroimaging features, histopathology, treatment, and prognosis, were assessed in all patients. Results: There were 10 male and 6 female patients (range, 18-73 years). Acid-fast bacilli stain and PCR of TTSs were positive in 11 and 10 patients, respectively. The sensitivity of Gene Xpert of TTSs was (80.0%; 8/10). Nine (56.3%; 9/16) patients were diagnosed with BT by histopathology. After receiving antituberculosis treatment, 12 (75.0%; 12/16) patients improved clinically to a considerable extent. Conclusions: The combined-diagnostic methods of TTS may improve the diagnostic efficiency of BT.

The diagnostic performance of GeneXpert MTB/RIF in tuberculosis meningitis: A multicentre accuracy study

To evaluate the performance of GeneXpert MTB/RIF (Xpert) for tuberculous meningitis (TBM) and to identify additional indicators to improve diagnostic accuracy. An accuracy study was conducted. During 2011-2019, 243 TBM with 140 non-TBM in three TB-designated facilities in China were enrolled. Microbiological evidence of M tuberculosis (Mtb) in CSF was used as the reference. Additional indicators were identified by Boosted-Classification and Regression Tree (CART), the improvement of diagnostic performance was evaluated by ROC. The diagnostic sensitivity of Xpert was 71.1 % for definite TBM, and 5.5 % for probable/possible TBM. The positive rate of Xpert was improved with cerebrospinal fluid (CSF) increasing volume and was associated with CSF color (yellow). The additional indicators obtained by CART were CSF lactate and glucose and increased the sensitivity to 96.1 % (definite TBM) and 84.6 % (probable/possible TBM). The diagnostic performance of Xpert was satisfactory in definite TBM and would significantly be improved by the additional use of CSF lactate and glucose.

Comparison of Xpert MTB RIF (G4) With Xpert MTB (Ultra) in Diagnosis of Mycobacterium Tuberculosis in Clinical Samples

Abstract Background: Tuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide. The main strategy to fight the pandemic is the development of rapid, accurate diagnostic tests, which helps to reduce the time for initiation of therapy. In 2010, WHO recommended the use of Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) (G4), which is a cartridge-based semi-automated nucleic acid amplification test (NAAT) as a primary test with an aim to improve the detection of MTB. Later on, to improve the diagnostic efficacy, the new and improved cartridges called Xpert Ultra were introduced in 2017. Materials and Methods: One thousand and sixty-nine clinical samples were utilized for the study for microscopy, culture, and NAATs (Xpert MTB/RIF G4 and Ultra). The samples were randomly allocated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated while assuming trace results as positive and negative in two separate scenarios. Results: The sensitivity of Xpert MTB/RIF Ultra cartridge was higher (100%) than Xpert MTB/RIF G4 cartridge (95.23%) and the specificity of Ultra cartridge was lower (71.79%) when compared to G4 cartridge (91.63%). However, the specificity of Xpert Ultra cartridge improved by reclassifying the “trace” interpretation as negative (89.1%). The NPV was 100% and 99.09% for Xpert Ultra cartridge and the Xpert G4 cartridge, respectively, and did not change by reclassifying the “trace” interpretation as negative. In contrast, the PPV varied greatly between the two tests, 26.66% for Xpert Ultra cartridge and 66.66% for Xpert G4 cartridge. The PPV of Xpert Ultra cartridge was improved to 48.48% by including “trace” samples in the negative pool. Conclusion: Xpert Ultra and G4 shows good performance as a first line diagnostic test. Caution should be exercised when interpreting ‘trace’ results in a country like India without parallel confirmatory tests like microscopy and culture. Data is limited on this newly incorporated value assigned in the automated report. Conducting further studies on results interpreted as ‘trace’ will help in improving the guidelines and as well as utilisation of such tests.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

ObjectiveTo evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis (EPTB). MethodsThis study was conducted at the Shanghai Public Health Clinical Center. A total of 115 patients underwent ultrasound-guided puncture biopsy, followed by MGIT 960 culture (culture), smear, GeneXpert MTB/RIF (Xpert), and histopathological examination. These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria: liquid culture and composite reference standard (CRS). ResultsWhen CRS was used as the reference standard, the sensitivity and specificity of culture, smear, Xpert, and histopathological examination were (44.83%, 89.29%), (51.72%, 89.29%), (70.11%, 96.43%), and (85.06%, 82.14%), respectively. Based on liquid culture tests, the sensitivity and specificity of smear, Xpert, and pathological examination were (66.67%, 72.60%), (83.33%, 63.01%), and (92.86%, 45.21%), respectively. Histopathological examination showed the highest sensitivity but lowest specificity. Further, we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80% and a specificity of 89.29%. ConclusionUltrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB. Compared with culture, smear, and Xpert, histopathological examination showed higher sensitivity but lower specificity. The combination of histopathology with Xpert showed the best performance characteristics.

Xpert MTB/RIF Ultra for the rapid diagnosis of extrapulmonary tuberculosis in a clinical setting of high tuberculosis prevalence country and interpretation of ‘trace’ results

To evaluate the diagnostic performance of Xpert MTB/RIF Ultra (Ultra) for the diagnosis of extrapulmonary tuberculosis (EPTB) from different types of extrapulmonary specimens in comparison with culture and composite microbiological reference standard (CRS). A total of 240 specimens were prospectively collected from presumptive EPTB patients between July 2021–January 2022 and tested by Ultra, Xpert, culture and acid-fast bacilli (AFB) smear microscopy. Out of 240 specimens, 35.8 %, 20.8 %, 11.3 %, and 7.1 % were detected as Mycobacterium tuberculosis complex by Ultra, Xpert, culture and AFB microscopy, respectively. An additional 15.0 % cases were detected by Ultra compared to Xpert MTB/RIF (Xpert) assay. A total of 28 (11.7 %) cases were identified as ‘trace’ category by Ultra with indeterminate rifampicin resistance result; of which 36.4 % were clinically confirmed as EPTB. Compared to culture, the sensitivity and specificity of Ultra and Xpert were 100 % and 72.3 %; 92.6 % and 88.3 %, respectively. In comparison with CRS, these were respectively: 98.9 % and 100 %; 57.5 % and 100 %. For individual category of specimens, sensitivity of Ultra was 100 % with varying specificity. We found that Ultra was highly sensitive for the rapid diagnosis of EPTB and has extensive potential over current diagnostics in high TB burden countries, but ‘trace’ results should be interpreted with caution.

Higher Sensitivity of Xpert MTB/RIF Ultra Over Tuberculosis Culture for the Diagnosis of Spinal Tuberculosis With Open or Computed Tomography-Guided Biopsies.

Diagnostic specimens for spinal tuberculosis (STB) are mostly collected via open surgery. Percutaneous computed tomography (CT)-guided biopsies are used in times of limited surgical availability. However, poor diagnostic accuracy of Mycobacterium tuberculosis (Mtb) culture has been reported with this method, due to limited sample volume and the paucibacillary nature of STB. We evaluated Xpert MTB/RIF Ultra on open and CT-guided biopsies as compared with the gold standard Mtb culture and histopathology. We conducted a prospective diagnostic accuracy study of Xpert Ultra, as compared with tuberculosis culture and histopathology, in adults with signs and symptoms of STB at a tertiary academic hospital in South Africa from November 2020 to December 2021. Diagnostic testing was performed on 31 patients with available samples. Xpert Ultra had a sensitivity of 94.7% (95% CI, 75.3%-99.7%) and specificity of 100% (95% CI, 75.7%-100.0%) against a reference standard of Mtb culture and histopathology. Xpert Ultra had high diagnostic accuracy in open and CT-guided biopsy samples with sensitivity and specificity of 100% and 100% (open) and 89% and 100% (CT), respectively. Mtb culture had limited specificity for CT-guided biopsies (43%; 95% CI, 15.8%-74.9%). HIV-1 coinfection did not affect Mtb abundance measures by Xpert Ultra or culture. Xpert Ultra was also superior to culture for STB diagnosis in patients concurrently treated for pulmonary tuberculosis. Xpert Ultra detected more STB cases than culture for CT-guided biopsy samples. There was also no difference in sensitivity for open biopsies, irrespective of HIV-1 status, making it an important tool for rapid diagnosis, especially during times or in locations where open surgery is not possible or concurrent pulmonary tuberculosis treatment is initiated.

Xpert MTB/RIF assay for the differential diagnosis between sarcoidosis and tuberculosis intrathoracic lymphadenopathy

BackgroundThe aim of this study was to evaluate the role of Xpert MTB/RIF assay in the detection of Mycobacterium tuberculosis for differentiating tuberculosis intrathoracic lymphadenopathy from sarcoidosis intrathoracic lymphadenopathy.MethodsThe patients who were suspected to having sarcoidosis or tuberculosis intrathoracic lymphadenopathy at the Shanghai Pulmonary Hospital between October 1, 2020 and June 30, 2021 were retrospectively evaluated in this study. All patients underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and Xpert analysis. Differences in clinical and radiological features were recorded. The diagnostic performances of EBUS-TBNA Xpert, acid-fast bacilli, culture, and peripheral blood QuantiFERON-TB Gold (QFT) for differentiating sarcoidosis from tuberculosis intrathoracic lymphadenopathy were analyzed.ResultsA total of 119 patients were included in this analysis. Of those, 83 patients were finally diagnosed with sarcoidosis (N = 50) and tuberculosis (N = 33) intrathoracic lymphadenopathy. Young individuals were more likely to have tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P = 0.006). Markers of inflammation, including fever, leukocytes, and serum ferritin levels, were significantly higher in tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P < 0.01). Bilateral lung involvement and symmetry intrathoracic lymphadenopathy were more common in sarcoidosis intrathoracic lymphadenopathy (P < 0.01). In addition, the longest diameter of intrathoracic lymphadenopathy (in cm) was significantly larger in sarcoidosis intrathoracic lymphadenopathy (P = 0.001). However, the largest diameter of lung lesions was significantly shorter (P = 0.005). The sensitivity and specificity values of Xpert and QFT for differentiating these two diseases were 69.70% and 100%, and 96.43% and 91.84%, respectively.ConclusionXpert MTB/RIF is recommended for the diagnosis of tuberculosis intrathoracic lymphadenopathy using EBUS-TBNA samples. A negative QFT suggests the exclusion of the diagnosis of tuberculosis intrathoracic lymphadenopathy.

Diagnostic Utility of Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) on Induced Sputum Versus Gastric Aspirate Samples for the Diagnosis of Paediatric Pulmonary Tuberculosis.

Tuberculosis (TB) in children is neglected, mainly due to a lack of sensitive diagnostic tools. Paediatric TB is now a global priority. More paediatric TB cases are being recorded as a result of the introduction of Xpert® Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Cepheid Inc., Sunnyvale, USA). This study was undertaken to evaluate the performance of Xpert MTB/RIF in the diagnosis of pulmonary TB in children. We recruited 70 paediatric patients with probable pulmonary TB and their gastric aspirate (GA), and induced sputum (IS) samples were collected between January 2021 and June 2022 in Saifai, Etawah, Uttar Pradesh, at the Microbiology Department of the Uttar Pradesh University of Medical Sciences (U.P.U.M.S.). All samples were subjected to smear examination, Bacterial Activation ofContinuousTemperature andEnvironmentalControl -MycobacterialGrowthIndicatorTube (BACTEC-MGIT) culture, and Xpert MTB/RIF. The specimens included 70 GAs and 70 IS samples. The total number of specimens were 140 and we collected GA as well as IS from each of the patient enrolled in the study.When compared to microscopy, GeneXpert provides a quicker and earlier detection of paediatric TB. The sensitivity of the cartridge-based nucleic acid amplification test (CBNAAT) against mycobacterial growth indicator tube (MGIT) was 75.0% for GA samples and 63.64% for IS samples. Paediatric TB, owing to its paucibacillary nature and difficulty in the collection of samples, makes the diagnosis difficult by conventional methods. Our study shows that smear and culture yield in GA samples are superior to those of IS samples and the sensitivity of Xpert MTB/RIF assay is also significantly different in GA and IS samples, but a combination of GA and IS yielded the best results.

The Efficiency of TB LAM Antigen Test to Xpert MTB/RIF Ultra Test for the Diagnosis of Tuberculous Pericarditis Using Pericardial Fluid Samples.

Medical considerations for early diagnosis of tuberculous pericarditis (TBP) include Xpert MTB/RIF Ultra and TB lipoarabinomannan (LAM) antigen (Ag) tests, with immunological status influencing the performance of the latter. An evaluation of the efficiency of Xpert MTB/RIF Ultra and TB LAM Ag in detecting TBP was conducted using pericardial fluid samples from 46 patients with suspected TBP. Fifteen patients (34.1%) were diagnosed with TBP according to culture results. TB LAM Ag's sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 33.3%, 100%, 100%, 74.4%, 0, and 0.67, respectively. The sensitivity, specificity, PLR, NLR, PPV, and NPV of Xpert MTB/RIF Ultra were 80%, 93.1%, 11.6, 0.21, 85.7%, and 90%, respectively. There was an association observed between a positive TB LAM Ag test and HIV status. When compared to the Xpert MTB/RIF Ultra test, TB LAM Ag has lower accuracy for the detection of microbiologically proven tuberculous pericarditis, yet its usage in HIV-positive populations may be worth exploring. The TB LAM Ag assay is not the best first-line test for the diagnosis of tuberculous pericarditis, and it should be used in conjunction with other diagnostic tests.

Evaluation of Xpert MTB/XDR test for susceptibility testing of Mycobacterium tuberculosis to first and second-line drugs in Uganda.

Drug-Resistant Tuberculosis (DR-TB) is one of the major challenges to TB control. This was a blinded, laboratory-based cross-sectional study using sputum samples or culture isolates. Samples were from patients with rifampicin-resistant-TB and/or with high risk for isoniazid (INH) resistance and/or 2nd line fluoroquinolones (FQ) and injectable agents (IAs). The diagnostic accuracy of the Xpert® MTB/XDR test was compared to MGIT960 and the Hain Genotype® MTBDRplus and MDRsl assays (LPA) as reference DST methods. Factors for laboratory uptake of the Xpert® MTB/XDR test were also evaluated. Of the 100 stored sputum samples included in this study, 65/99 (65.6%) were resistant to INH, 5/100 (5.0%) were resistant to FQ and none were resistant to IAs using MGIT960. The sensitivity and specificity, n (%; 95% Confidence Interval, CI) of Xpert® MTB/XDR test for; INH was 58 (89.2; 79.1-95.5) and 30 (88.2; 72.5-96.6) and for FQ; 4 (80.0; 28.3-99.4) and 95 (100; 96.2-100), respectively. Using LPA as a reference standard, a total of 52/98 (53.1%) were resistant to INH, 3/100 (3.0%) to FQ, and none to IA. The sensitivity and specificity, n (%; 95%CI) of Xpert® MTB/XDR test compared to LPA for; INH was 50 (96.1; 86.7-99.5) and 34 (74.0; 58.8-85.7) for FQ 3 (100; 29.2-100) and 96 (99.0; 94.3-99.9) respectively. The factors for laboratory uptake and roll-out of the Xpert® MTB/XDR test included: no training needed for technicians with, and one day for those without, previous Xpert-ultra experience, recording and reporting needs were not different from those of Xpert-ultra, the error rate was 4/100 (4%), one (1%) indeterminate rate and test turn-around-time were 1hr/45 minutes. There is high sensitivity and specificity of Xpert® MTB/XDR test for isoniazid and fluoroquinolones. There are acceptable Xpert® MTB/XDR test attributes for the test uptake and roll-out.

Comparison of Xpert MTB/RIF Ultra with Xpert MTB/RIF for the detection of Mycobacterium tuberculosis and rifampicin resistance in a primary-level clinic in rural China

The Xpert MTB/RIF Ultra (Ultra) is not yet used for the diagnosis of tuberculosis (TB) in China. We compared the performance of the Xpert and Ultra for detecting Mycobacterium tuberculosis and rifampicin resistance in a primary-level clinic in rural China. Sputum samples from suspected pulmonary TB patients were collected and subjected to smear microscopy, liquid culture, Xpert and Ultra tests. We then compared the sensitivity and specificity of Xpert and Ultra for diagnosing TB against liquid culture. Whole-genome sequencing was performed to predict rifampicin resistance and the results were compared with the Xpert and Ultra tests. The sensitivities of Xpert and Ultra were 88.1% and 95.1%, and the specificities were 91.9% and 84.4%, respectively. Among the 61 smear-negative culture-positive patients, the sensitivities of Xpert and Ultra were 80.3% and 91.8%. All Xpert-positive patients were Ultra-positive. Among culture-negative Xpert or Ultra-positive patients, 69.6% were taking anti-TB drugs or had a previous history of TB. Of the samples that Ultra classified as trace, nearly 25% were probably false-positives. Both Xpert and Ultra accurately detected all rifampicin-resistant patients. In conclusion, Ultra was more sensitive than Xpert, especially for smear-negative patients but had decreased specificity with more false-positives, especially with Ultra trace results.

Xpert MTB/RIF Ultra Assay Using Stool: an Effective Solution for Bacilli Identification from Adult Pulmonary Tuberculosis Suspects without Expectorated Sputum.

This study evaluated the diagnostic performance of stool-based Xpert MTB/RIF Ultra assay (Xpert-Ultra, Cepheid, USA) against other tests using respiratory tract specimens (RTS) and stool for diagnosing adult pulmonary tuberculosis. A prospective study on patients with presumptive pulmonary tuberculosis was conducted in Beijing Chest Hospital from June to November 2021. The smear test, MGIT960 liquid culture, and Xpert MTB/RIF (Xpert, Cepheid, USA) were performed simultaneously on RTS, and smear, culture Xpert, and Xpert-Ultra were performed simultaneously using stool. Patients were grouped based on the outcomes of RTS examination and other tests. In total, 130 eligible patients were enrolled that included 96 pulmonary tuberculosis and 34 non-TB patients. The sensitivity of smear, culture, Xpert, and Xpert-Ultra using stool was 10.96%, 23.28%, 60.27%, and 79.45%, respectively. The specificities of Xpert and Xpert-Ultra using RTS and stool were all 100% (34/34). Notably, all five confirmed cases detected by bronchoalveolar lavage fluid (BALF) examination yielded Xpert-Ultra positive outcomes with the stool specimens. Xpert-Ultra assay on stool sample harbors comparable sensitivity with Xpert on RTS. Thus, the Xpert-Ultra testing on stool specimens could be a very promising and practical strategy to improve pulmonary tuberculosis (PTB) diagnosis, especially among patients who could not expectorate sputum. IMPORTANCE This study is aimed at assessing the value of Xpert MTB/RIF Ultra (Xpert-Ultra) in PTB on stool in adult in low HIV settings and Xpert-Ultra assay on stool sample harboring comparable sensitivity with Xpert MTB/RIF on respiratory tract specimens. Although the yield in stool samples by Xpert-Ultra is lower than RTS, it may be useful in detecting disease in presumptive TB patients who cannot expectorate sputum and are not open to BALF collection. In addition, Xpert-Ultra with a "trace call" on stool in adult was highly supportive of PTB.

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis.

Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

Xpert MTB/RIF Assay for the Diagnosis of Pulmonary Tuberculosis Based on Bronchoalveolar Lavage Fluid: A Systematic Review and Meta-analysis

Abstract Currently, tuberculosis (TB) is the second most lethal disease in the world caused by a single infectious pathogen. Rapid diagnosis of TB is of great importance for its treatment and management. Xpert MTB/RIF is a novel rapid diagnostic assay for the diagnosis of pulmonary TB (PTB). Use of the Xpert assay based on bronchoalveolar lavage fluid (BALF) samples is indicated when TB is suspected and sputum smears or cultures are negative. The aim of this meta-analysis was to systematically evaluate the diagnostic performance of the Xpert assay based on BALF samples for the diagnosis of PTB. A systematic review of previously published articles was performed, and relevant data were extracted. Meta-DiSc 1.4 and Stata 12.0 were used to analyze the data. When Mycobacterium tuberculosis cultures were used as the criterion standard, the combined sensitivity of BALF-based Xpert was 0.89 (95% CI, 0.87–0.91), the specificity was 0.87 (95% CI, 0.85-0.88), the positive likelihood ratio was 8.28 (95% CI, 5.39–12.71), the negative likelihood ratio was 0.14 (95% CI, 0.10–0.19) and the diagnostic ratio was 84.08 (95% CI, 42.00–168.31). When composite reference standard was used as the criterion standard, the above observations were 0.69 (95% CI, 0.67–0.72), 0.98 (95% CI, 0.97–0.98), 41.40 (95% CI, 14.56–117.71), 0.28 (95% CI, 0.21–0.37) and 190.47 (95% CI, 50.56–717.54), respectively. The area under the summary receiver operating characteristic curve was close to 1 for both. Overall, the Xpert MTB/RIF assay based on BALF samples showed high sensitivity and specificity for the diagnosis of PTB and seems to be a reliable rapid detection method.

Accuracy of Xpert® MTB/RIF in diagnosing extrapulmonary tuberculosis in Indian children.

Background Diagnosing extrapulmonary tuberculosis (EPTB) can be challenging because of a variety of presentations. We assessed the accuracy of the Xpert MTB/RIF assay in diagnosing EPTB in children. Methods Of the 255 children diagnosed to have tuberculosis (TB) who underwent testing by the Xpert MTB/ RIF assay at the TB clinic from December 2014 to April 2017, 182 had EPTB and were included in the study. The diagnostic accuracy, specificity and sensitivity of the Xpert assay were calculated with Mycobacterium growth indicator tube (MGIT) as a reference standard. Results Lymph node TB was present in 58 (32%) children, 37 (20%) had neurological TB, 36 (20%) had bone TB, 31 (17%) had pleural TB, 15 (8%) had abdominal TB, 2 (1%) had abscess, 2 (1%) had congenital TB and disseminated TB was seen in 1 (0.4%) child. Xpert MTB/RIF assay was positive in 84 (46.2%) patients. The sensitivity and specificity of the Xpert MTB/RIF assay were 72% and 72.04%, respectively. Compared to MGIT, a kappa coefficient of 0.44 shows moderate agreement between the Xpert assay and MGIT. The sensitivity of Xpert MTB/RIF assay in abdominal TB, bone TB, lymph node TB, neurological TB and pleural TB was 50% (15%-85%), 72.7% (15.9%- 86.9%), 80.8% (62.1%-91.5%), 75% (50.5%-90%) and 25% (4.6%-70%), respectively. The specificity of abdominal TB, bone TB, lymph node TB, neurological TB and pleural TB was 83.3% (43.7%-97%), 69.2% (42.4%- 87.3%), 55.2% (37.6%-71.6%), 85% (64%-94.8%) and 82.6% (62.9%-93%), respectively. Forty-seven (26%) patients had drug-resistant TB (DR-TB), of which 15 (8%) were rifampicin-resistant (RR), 2 (1%) were polyresistant, 14 (8%) had multi-DR (MDR), 15 (8%) had pre-extremely DR (XDR) and 1 (1%) had XDR-TB. Of the 15 patients with MDR-TB, Xpert MTB/RIF assay detected only 10 (71%) as RR (p=0.06). Of the 15 pre-XDR cases, Xpert MTB/RIF detected only 8 (53%) as RR (p=0.02). Conclusion Xpert MTB/RIF assay is useful in the diagnosis of EPTB. It shows good concordance with MGIT. However, it may be negative in patients with DR-TB.

Diagnostic Performance of Different Laboratory Methods for the Detection of Extrapulmonary Tuberculosis.

Accurate and appropriate extrapulmonary tuberculosis (EPTB) diagnosis remains challenging due to its paucibacillary nature, requirement of invasive collection procedures, and lack of sensitive tests. This study investigated the diagnostic performance of different methods for the diagnosis of EPTB. A total of 1340 EPTB specimens were collected from presumptive EPTB patients from four different hospitals between November 2015 and March 2017. The collected specimens were tested with AFB microscopy, culture, Xpert MTB/RIF assay (Xpert), and MTBDRplus assay. Among the 1340 EPTB specimens, 49 (3.66%), 141 (10.52%), 166 (12.39%), and 154 (11.49%) were positive in AFB microscopy, culture, Xpert MTB/RIF, and MTBDRplus assay, respectively. A total of 194 (14.9%) cases were found positive in at least one of these methods. Using culture as a reference standard, the sensitivity and specificity of AFB microscopy, Xpert MTB/RIF, and MTBDRplus assay were: 27.0%/99.1%, 83.7%/96.0%, and 79.4%/96.5%, respectively. Compared to the composite reference standard, the sensitivity of culture, AFB microscopy, Xpert MTB/RIF, and MTBDRplus assay was 72.7%, 25.3%, 85.6%, and 79.4%, respectively, with a specificity of 100% for all the methods. The Xpert MTB/RIF assay showed the highest sensitivity compared to other methods. Considering the short turnaround time and promising findings, Xpert MTB/RIF assay should be integrated into national TB guidelines as a routine diagnostic test.