Diagnostic Performance Of Xpert Research Articles

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.

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.

Diagnostic Performance of Xpert MTB/RIF Ultra Compared with Predecessor Test, Xpert MTB/RIF, in a Low TB Incidence Setting: a Retrospective Service Evaluation.

ABSTRACTThe aim of this study was to evaluate the performance of Xpert MTB/RIF Ultra (Ultra) compared with its predecessor, Xpert MTB/RIF (Xpert), in the diagnosis of tuberculosis (TB) in a low TB incidence country. Retrospective analysis was performed on 689 clinical samples received between 2015 and 2018, on which Xpert was performed, and on 715 samples, received between 2018 and 2020, on which Ultra was performed. Samples were pulmonary (n = 830) and extrapulmonary (n = 574) in nature, and a total of 264 were culture positive for Mycobacterium tuberculosis complex (MTBC). The diagnostic performance of both assays was analyzed using culture as the reference standard. The sensitivity of Ultra for culture positive (smear positive and smear negative) MTBC samples, was 93.2% (110/118) compared with 82.2% (120/146) for Xpert (P = 0.0078). In smear negative-culture positive samples, Ultra had a sensitivity of 74.2% (23/31) versus 36.11% (13/36) for Xpert (P = 0.0018). Specificity of both assays was comparable at 94.8% (566/597) for Ultra and 95.8% (520/543) for Xpert (P = 0.4475). The sensitivity of Ultra and Xpert assays among exclusively pulmonary samples was 95.3% (82/86) and 90.3% (84/93), respectively (P = 0.1955), and 87.5% (28/32) and 67.9% (36/53), respectively, among extrapulmonary samples (P = 0.0426). Ultra showed improved performance compared with Xpert in a low TB incidence setting, particularly in smear negative and extrapulmonary MTBC disease. The specificity of Ultra was lower than Xpert, however, this was not statistically significant.IMPORTANCE The study demonstrates the improved sensitivity of the Ultra compared with the Xpert, particularly in smear negative TB disease, for both pulmonary and extrapulmonary samples in a low TB incidence setting. Cycle threshold (Ct) value for both assays was found to positively correlate with time to TB culture positivity, suggesting that Ct and semiquantitative results could be used as indicators of sample MTBC bacillary burden, and thus, perhaps, of transmission potential. This may have implications for the designation of patient isolation precautions.

Diagnostic Performance of Xpert MTB/RIF Ultra for Tuberculosis Diagnosis in the Context of Passive and Active Case Finding Strategies in Rural Mozambique

Background: Xpert MTB/RIF Ultra (Ultra) is a novel molecular assay which is replacing Xpert MTB/RIF (Xpert) as a front-line test for tuberculosis (TB) diagnosis. We conducted a field evaluation of the diagnostic accuracy of Ultra using two cohorts of participants (from passive and active case finding interventions) in a high TB/HIV burden area in Southern Mozambique. Methods: Respiratory specimens obtained from symptomatic adults accessing health care services (passive case finding (PCF) cohort), and from household and community close contacts (active case finding (ACF) cohort), were tested for smear microscopy, culture, Xpert and Ultra (same specimen). Liquid and solid culture results served as a composite reference standard. We also explored trace results’ impact on test specificity by their recategorization to negative (in all cases or just in previously treated individuals) and active follow-up. Findings: A total of 1419 and 252 participants were enrolled in the ACF and PCF cohorts respectively. For the PCF cohort, Ultra showed higher sensitivity compared to Xpert, overall (0·95 (95% CI: 0·90, 0·98) vs 0·88 (0·82, 0·93); p<0·001) and among smear negative patients (0·84 (95% CI: 0·71, 0·93) vs 0·63 (95% CI: 0·48, 0·76) p<0·001). Conversely, specificity of Ultra was lower and similar than Xpert’s (0·98 (0·97, 0·99) vs 0·96 (0·95, 0·97); p= 0·008). In the ACF-group, sensitivity and specificity for both tests were the same (0·67 (95% CI: 0·22,0·96), although Ultra doubled Xpert in the number of microbiologically confirmed samples (4·7% (12/252) vs 2·7% (7/252)). Conditional recategorization of trace results, maintained differences in specificity in the PCF cohort. Interpretation: Our results add evidence on the improved sensitivity of Ultra and suggest that overall differences in specificity among assays might be driven by misclassification of true-positive results. These findings support the use of Ultra as initial front-line test for diagnosis in health care settings, and advocate for a comprehensive clinical and epidemiological evaluation of patients with single trace results in order to inform treatment initiation. Funding Statement: We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. B.S receives a pre-doctoral fellowship from the Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and co-funded by European Social Fund (AGAUR). This project has received consumables donations from Cepheid. Cepheid was not involved in the data analysis or decision to submit this manuscript for publication. Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: The protocol was approved by CISM’s Internal Scientific Committee, CISM’s Internal Bioethics Committee (CIBS – Comite Institucional de Bioetica para a Saude) and the National Bioethics Committee (CNBS - Comite Nacional de Bioetica para a Saude, reference 369/CNBS/17).

Performance of Xpert® MTB/RIF and Determine™ TB-LAM Ag in HIV-infected adults in peri-urban sites in Zambia.

Peri-urban health facilities providing HIV and TB care in Zambia. To evaluate 1) the impact of Xpert® MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays. Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm3 vs. 31.7% overall. Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.

Diagnostic Performance of Xpert MTB/RIF in Bronchoalveolar Lavage of Sputum-Scarce Recurrent Pulmonary Tuberculosis Cases

Abstract Introduction Xpert MTB/RIF has greater sensitivity and specificity than smear microscopy. Bronchoalveolar lavage (BAL) is safe and valuable tool in sputum-scarce and sputum-negative tuberculosis (TB) patients. Our study evaluated the performance of Xpert in BAL specimen of sputum-scarce recurrent TB cases exclusively. Materials and Methods Sputum-scarce recurrent TB patients who underwent BAL between July 2018 and July 2019 were included. The diagnostic performance of Xpert and acid-fast bacilli (AFB) smear examination in BAL specimen was compared with liquid culture Mycobacterium TB (MTB) and composite reference standard. Results A total of 126 patients were included in the study. MTB culture was positive in 70 cases and nontuberculous mycobacteria were seen in five cases. Xpert was positive was in 63 patients. Sensitivity of Xpert and AFB smear was 84.29% (95% confidence interval [CI]: 73.62–91.89) and 18.57% (95% CI: 10.28–29.66), respectively, with p &lt; 0.001 proving the superiority of Xpert. Xpert had a specificity of 97.96 (89.15–99.95), positive predictive value of 93.65% (95% CI 85.19–97.42), and negative predictive value of 80.36% (95% CI: 70.26–87.63). Smear had a specificity of 91.84% (95% CI: 80.21–97.58) against 97.96 (89.15–99.95) of Xpert, and smear was positive in nontuberculous mycobacterium cases as well. Xpert showed no cross-reactivity between mycobacterial species. Rifampicin resistance was seen in 8 (12.69%) cases, and 21 patients had other diagnoses. Conclusion Xpert has greater sensitivity in comparison to AFB smear in BAL specimen. Sputum-scarce recurrent TB cases have a similar chance of rifampicin resistance as sputum smear-positive cases should undergo BAL for Xpert analysis routinely.

A comparative study on the value of Xpert MTB/RIF and T-SPOT.TB tests in the diagnosis of bone and joint tuberculosis

BackgroundWe evaluated the application value of Xpert MTB/RIF and T-SPOT.TB in the diagnosis of bone and joint tuberculosis. MethodsOne hundred two patients with suspected bone and joint tuberculosis (BJTB) were admitted to Zhengzhou Orthopaedics Hospital, Henan, China from April 2018 to February 2019. The Xpert MTB/RIF and T-SPOT.TB tests were performed using pus specimens and peripheral blood, respectively. The diagnostic performance of Xpert MTB/RIF and T-SPOT.TB tests was evaluated on the basis of the composite reference standard (CRS). ResultA Total of 73 suspected BJTB were enrolled and categorized, including 12 confirmed BJTB, 27 probable BJTB and 34 non-BJTB. When CRS was used as the reference, the specificity, PPV and NLR values of the Xpert MTB/RIF assay were significantly higher than those of the T-SPOT.TB assay (97.1% vs. 82.4%, p < 0.05; 96.7% vs. 85.4%, p < 0.05; 0.26 vs. 0.12, p < 0.05). However, the sensitivity, NPV and PLR values of the T-SPOT. TB assay were significantly higher than those of the Xpert MTB/RIF assay (89.7% vs. 74.4%, p < 0.05; 87.5% vs. 76.7%, p < 0.05; 5.08 vs. 2.52, p < 0.05). The AUCs from Xpert MTB/RIF and T-SPOT. TB tests were 0.857 and 0.860, respectively. However, the difference was not statistically significant. The Xpert MTB/RIF and T-SPOT. TB tests demonstrated medium concordance in diagnosing BJTB. ConclusionThe sensitivity of T-SPOT.TB test combined with the specificity of Xpert MTB/RIF not only shorten the time of diagnosis but also improve the accuracy of diagnosis of BJTB and reduce the misdiagnosis rate. Therefore, they are useful for early diagnosis of BJTB.

Akciğer ve Akciğer Dışı Tüberkülozda Xpert MTB/RIF Testinin Tanısal Performansının Değerlendirilmesi

Akciğer ve Akciğer Dışı Tüberkülozda Xpert MTB/RIF Testinin Tanısal Performansının Değerlendirilmesi

Diagnostic Usefulness of Bronchoalveolar Lavage Fluid Xpert MTB/RIF in Patients with Suspected Pauci-bacillary Pulmonary Tuberculosis

BackgroundRapid and accurate diagnosis of tuberculosis (TB) is important for appropriate treatment initiation and control of disease transmission. Xpert TB/RIF has been widely used for rapid diagnosis especially in sputum AFB smear-negative pulmonary TB. However, about one-third of patients with pauci-bacillary pulmonary TB still reveal negative Xpert TB/RIF results from sputum specimens. Theoretically, bronchoalveolar lavage (BAL) fluid can provide more sensitive specimen in those with sputum-scarce or AFB smear-negative pulmonary TB than sputum.However, there is limited data on the diagnostic performance of Xpert TB/RIF from BAL fluid in patients with pauci-bacillary pulmonary TB.MethodsAll patients with suspected pulmonary TB who underwent BAL due to sputum-scarcity or negative AFB smear results and underwent Xpert TB/RIF from BAL fluid were retrospectively reviewed at a tertiary hospital, Seoul, South Korea (an intermediate TB-burden country) between October 2014 and April 2017. Confirmed TB was defined to those with clinical specimens positive for M. tuberculosis by culture or PCR assays. Patients those with caseating granuloma in biopsy tissue and shows a good response to anti-tuberculous therapy were classified as having probable TB.ResultsA total of 113 patients were included in the analysis. Of these 113 patients, 30 (27%) were classified as confirmed TB, 7 (6%) as probable TB, and 76 (67%) as not TB. Of these 37 patients with confirmed or probable TB, 8 (22%) had miliary TB and 12 (32%) were immunocompromised. Only 15 (50%) of the 30 confirmed TB patients revealed positive Xpert TB/RIF results from BAL fluid. Overall sensitivity, specificity, positive predictive value, and negative predictive value of Xpert TB/RIF from BAL fluid for the diagnosis of TB were 41% (95% CI, 31%-41%), 100% (95% CI, 95%-100%), 100% (95% CI 77%-100%), and 78% (95% CI 74%-77%), respectivelyConclusionXpertTB/RIF from BAL fluid appears to be suboptimal to rule out pulmonary TB. The development of more sensitive and rapid test for pauci-bacillary pulmonary TB is needed.Disclosures All authors: No reported disclosures.

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings.

The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

Comparison of Xpert MTB/RIF Assay and the Conventional Sputum Microscopy in Detecting Mycobacterium tuberculosis in Northern Thailand.

Background. Despite low sensitivity in detection of Mycobacterium tuberculosis, sputum acid-fast smear remains the main diagnostic method. This study aimed to compare the diagnostic performance of Xpert MTB/RIF assay versus conventional sputum acid-fast smear. Materials and Methods. A cross-sectional study was conducted at Chiang Mai University Hospital, Thailand. Patients who were ≥15 years old and had clinically suspected pulmonary tuberculosis were included. Results. 109 specimens from 57 patients were included. Using MGIT sputum culture as a reference standard, the sensitivity (SEN) and specificity (SPEC) for Xpert were 95.3% (95% CI, 84.2%, 99.4%) and 86.4% (95% CI, 75.7%, 93.6%). The SEN and SPEC for sputum acid-fast smear were 60.5% (95% CI, 44.4%, 75.0%) and 98.5% (95% CI, 91.8%, 100%). Xpert had significantly higher sensitivity (p value < 0.001) and lower specificity (p value = 0.022) than sputum acid-fast smear. Among 43 culture-proven M. tuberculosis specimens, sensitivity of Xpert was 100% (95% CI, 86.7%, 100%) in acid-fast positive smears (n = 26) and 88.2% (95% CI, 63.5%, 98.5%) in acid-fast negative smears (n = 17). Conclusions. The good sensitivity and specificity of Xpert assay in detecting M. tuberculosis from sputum specimens may help in early diagnosis and treatment of pulmonary tuberculosis, particularly among patients who had acid-fast negative sputum smear.

Rapid and Accurate Detection of Mycobacterium tuberculosis in Sputum Samples by Cepheid Xpert MTB/RIF Assay—A Clinical Validation Study

BackgroundA crucial impediment to global tuberculosis control is the lack of an accurate, rapid diagnostic test for detection of patients with active TB. A new, rapid diagnostic method, (Cepheid) Xpert MTB/RIF Assay, is an automated sample preparation and real-time PCR instrument, which was shown to have good potential as an alternative to current reference standard sputum microscopy and culture.MethodsWe performed a clinical validation study on diagnostic accuracy of the Xpert MTB/RIF Assay in a TB and HIV endemic setting. Sputum samples from 292 consecutively enrolled adults from Mbeya, Tanzania, with suspected TB were subject to analysis by the Xpert MTB/RIF Assay. The diagnostic performance of Xpert MTB/RIF Assay was compared to standard sputum smear microscopy and culture. Confirmed Mycobacterium tuberculosis in a positive culture was used as a reference standard for TB diagnosis.ResultsXpert MTB/RIF Assay achieved 88.4% (95%CI = 78.4% to 94.9%) sensitivity among patients with a positive culture and 99% (95%CI = 94.7% to 100.0%) specificity in patients who had no TB. HIV status did not affect test performance in 172 HIV-infected patients (58.9% of all participants). Seven additional cases (9.1% of 77) were detected by Xpert MTB/RIF Assay among the group of patients with clinical TB who were culture negative. Within 45 sputum samples which grew non-tuberculous mycobacteria the assay's specificity was 97.8% (95%CI = 88.2% to 99.9%).ConclusionsThe Xpert MTB/RIF Assay is a highly sensitive, specific and rapid method for diagnosing TB which has potential to complement the current reference standard of TB diagnostics and increase its overall sensitivity. Its usefulness in detecting sputum smear and culture negative patients needs further study. Further evaluation in high burden TB and HIV areas under programmatic health care settings to ascertain applicability, cost-effectiveness, robustness and local acceptance are required.