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An Optimal Diagnostic Strategy for Tuberculosis in Hospitalized HIV-Infected Patients Using GeneXpert MTB/RIF and Alere Determine TB LAM Ag.

ABSTRACT: The diagnosis of tuberculosis (TB) in HIV-infected patients is challenging. Both a urinary lipoarabinomannan (LAM) test (Alere TB LAM) and GeneXpert-MTB/RIF (Xpert) are useful for the diagnosis of TB. However, how to optimally integrate Xpert and LAM tests into clinical practice algorithms remain unclear. We performed a post hoc analysis of 561 HIV-infected sputum-expectorating patients (median CD4 count of 130 cells/ml) from a previously published randomized controlled trial evaluating the LAM test in hospitalized HIV-infected patients with suspected TB. We evaluated 5 different diagnostic strategies using sputum culture as a reference standard (Xpert alone, LAM alone, sequential Xpert followed by LAM and vice versa [LAM in Xpert-negative patients and Xpert in LAM-negative patients], and both tests concurrently [LAM + Xpert]). A cost-consequence analysis was performed. Strategy-specific sensitivity and specificity, using culture as a reference, were similar with the Xpert-only and sequential and concurrent strategies. However, when any positive TB-specific test was used as a reference, the incremental yield of LAM over Xpert was 29.6% (45/152) and that of Xpert over LAM was 75% (84/11). The incremental yield of LAM increased with decreasing CD4 count. The costs per TB case diagnosed were similar for the sequential and concurrent strategies ($1,617 to $1,626). In sputum-expectorating hospitalized patients with advanced HIV and access to both tests, concurrent testing with Xpert and LAM may be the best strategy for diagnosing TB. These data inform clinical practice in settings where TB and HIV are endemic.

SUBMITTER: Esmail A

PROVIDER: S-EPMC7512177 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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An Optimal Diagnostic Strategy for Tuberculosis in Hospitalized HIV-Infected Patients Using GeneXpert MTB/RIF and Alere Determine TB LAM Ag.

Esmail Aliasgar A Pooran Anil A Sabur Natasha F NF Fadul Mohammed M Brar Mantaj S MS Oelofse Suzette S Tomasicchio Michele M Dheda Keertan K

Journal of clinical microbiology 20200922 10

The diagnosis of tuberculosis (TB) in HIV-infected patients is challenging. Both a urinary lipoarabinomannan (LAM) test (Alere TB LAM) and GeneXpert-MTB/RIF (Xpert) are useful for the diagnosis of TB. However, how to optimally integrate Xpert and LAM tests into clinical practice algorithms remain unclear. We performed a <i>post hoc</i> analysis of 561 HIV-infected sputum-expectorating patients (median CD4 count of 130 cells/ml) from a previously published randomized controlled trial evaluating t ...[more]

PMID: 32727831

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Project description:BackgroundEthiopia is one of the high burden countries for extrapulmonary tuberculosis (EPTB); however, the prompt diagnosis of EPTB remains challenging. This study is aimed to evaluate the diagnostic performance of Xpert MTB/RIF and DetermineTM TB-LAM Ag (TB-LAM) for the prompt diagnosis of EPTB in Ethiopia.MethodsA total of 147 presumptive EPTB patients, including 23 HIV- positive participants were enrolled. Extra-pulmonary samples were collected from all presumptive EPTB cases and tested for Mycobacterium tuberculosis complex (MTBC) using fluorescent microscopy, Xpert MTB/RIF, and culture. Additionally, urine samples were also collected from 126 participants and were tested by DetermineTM TB-LAM Ag (Alere Inc, Waltham, USA). The Sensitivity and specificity of Xpert and TB- LAM tests were calculated by comparing with a composite reference standard (CRS), which comprises smear microscopy, culture and response to empirical anti-TB treatment.ResultsOf 147 patients, 23 (15.6%) were confirmed EPTB cases (culture-positive), 14 (9.5%) were probable EPTB (clinically, radiologically or cytologically positive and received anti-TB treatment with good response), and 110 (74.8%) were classified as "non- TB" cases. Compared to the composite reference standard (CRS), the overall sensitivity and specificity of Xpert MTB/RIF were 43.2% and 100%, respectively with the highest sensitivity for Lymph node aspirate (85.7%) and lower sensitivity for pleural fluid (14.3%) and 100% specificity for all specimen types. The sensitivity and specificity of TB-LAM were 33.3% and 94.4% respectively with the highest sensitivity for HIV co-infected participants (83.3%). The sensitivity of the combination of Xpert MTB/RIF and TB-LAM tests regardless of HIV status was 61.1% whereas the sensitivity was improved to 83.3% for HIV-positive cases.ConclusionTB-LAM alone has low sensitivity for EPTB diagnosis; however, the combination of TB-LAM and Xpert MTB/RIF improves the diagnosis of EPTB particularly for countries with high EPTB and HIV cases.

Project description:BackgroundMeningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM).MethodsPatients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M. tuberculosis using GeneXpert, Ziehl-Neelsen smear and culture on solid and liquid media. Drug susceptibility testing used Mycobacteria Growth Indicator Tube (MGIT 960) and the proportions method.Results81% (30/37) of patients received a final clinical diagnosis of TBM, of whom 63% (19/30, 95% confidence intervals, CI: 44-80%) were HIV-positive. 22% (8/37, 95%CI: 9.8-38%), of patients had definite TBM. Because definite TBM was defined by positivity in any laboratory test, all laboratory tests had 100% specificity. Considering the 30 patients who had a clinical diagnosis of TBM: diagnostic sensitivity was 23% (7/30, 95%CI: 9.9-42%) for GeneXpert and was the same for all culture results combined; considerably greater than 7% (2/30, 95%CI: 0.82-22%) for microscopy; whereas all laboratory tests had poor negative predictive values (20-23%). Considering only the 8 patients with definite TBM: diagnostic sensitivity was 88% (7/8, 95%CI: 47-100%) for GeneXpert; 75% (6/8, 95%CI: 35-97%) for MGIT culture or LJ culture; 50% (4/8, 95%CI 16-84) for Ogawa culture and 25% (2/8, 95%CI: 3.2-65%) for microscopy. GeneXpert and microscopy provided same-day results, whereas culture took 20-56 days. GeneXpert provided same-day rifampicin-susceptibility results, whereas culture-based testing took 32-71 days. 38% (3/8, 95%CI: 8.5-76%) of patients with definite TBM with data had evidence of drug-resistant TB, but 73% (22/30) of all clinically diagnosed TBM (definite, probable, and possible TBM) had no drug-susceptibility results available.ConclusionsCompared with traditional culture-based methods of CSF testing, GeneXpert had similar yield and faster results for both the detection of M. tuberculosis and drug-susceptibility testing. Including use of the GeneXpert has the capacity to improve the diagnosis of TBM cases.

Project description:India has been engaged in tuberculosis (TB) control activities for over 50 years and yet TB continues to remain India's important public health problem. The present study was conducted to compare the performance of GeneXpert MTB/RIF (GXpert) assay with composite reference standard in diagnosing cases of tubercular pleural effusion (TPE) and to evaluate the reliability of rifampicin resistance. A cross-sectional study was performed in a Department of Medicine of a rural teaching tertiary care hospital in central India. In all consecutive patients with pleural effusion on chest radiograph presenting to Department of Medicine, GXpert assay and composite reference standard was performed to evaluate the diagnostic accuracy of GXpert assay for detecting TPE in comparison to composite reference standard. Standard formulae were used to calculate the sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios (LR+) and negative likelihood ratios (LR-). Mc-Nemar's test was applied to compare variables. All comparisons were two-tailed. We considered the difference to be statistically significant if the P value was less than 0.05. The sensitivity of the GXpert assay in diagnosing TPE was 16.6% among 158 study participants, the specificity was 100% and diagnostic accuracy was 52.5% which was statistically significant (p value < 0.05). It had a PPV of 100% (95%CI: 88.3% - 100%) and a NPV of 47.5% (95%CI: 39.3% - 55.7%). The LR+ and LR-were 23.5 (95%CI: 1.43-38.6) and 0.83 (95%CI: 0.76-0.91) respectively. GXpert assay has a very high specificity in diagnosing TPE but has a low sensitivity. In comparison to composite reference standard Thus its clinical utility is limited when used as a standalone test. A physician's clinical acumen in combination with routine pleural fluid analysis should be the key factor in the diagnosis of TPE in clinically and radiologically suspected patients, especially in high TB burden countries.

Project description:BACKGROUND:Many high burden countries are scaling-up GeneXpert® MTB/RIF (Xpert) testing for tuberculosis (TB) using a hub-and-spoke model. However, the effect of scale up on reducing TB has been limited. We sought to characterize variation in implementation of referral-based Xpert TB testing across Uganda, and to identify health system factors that may enhance or prevent high-quality implementation of Xpert testing services. METHODS:We conducted a cross-sectional study triangulating quantitative and qualitative data sources at 23 community health centers linked to one of 15 Xpert testing sites between November 2016 and May 2017 to assess health systems infrastructure for hub-and-spoke Xpert testing. Data sources included a standardized site assessment survey, routine TB notification data, and field notes from site visits. RESULTS:Challenges with Xpert implementation occurred at every step of the diagnostic evaluation process, leading to low overall uptake of testing. Of 2192 patients eligible for TB testing, only 574 (26%) who initiated testing were referred for Xpert testing. Of those, 54 (9.4%) were Xpert confirmed positive just under half initiated treatment within 14?days (n?=?25, 46%). Gaps in required infrastructure at 23 community health centers to support the hub-and-spoke system included lack of refrigeration (n?=?14, 61%) for sputum testing and lack of telephone/mobile communication (n?=?21, 91%). Motorcycle riders responsible for transporting sputum to Xpert sites operated variable with trips once, twice, or three times a week at 10 (43%), nine (39%) and four (17%) health centers, respectively. Staff recorded Xpert results in the TB laboratory register at only one health center and called patients with positive results at only two health centers. Of the 15 Xpert testing sites, five (33%) had at least one non-functioning module. The median number of tests per day was 3.57 (IQR 2.06-4.54), and 10 (67%) sites had error/invalid rates >?5%. CONCLUSIONS:Although Xpert devices are now widely distributed throughout Uganda, health system factors across the continuum from test referral to results reporting and treatment initiation preclude effective implementation of Xpert testing for patients presenting to peripheral health centers. Support for scale up of innovative technologies should include support for communication, coordination and health systems integration.

Dataset Information

An Optimal Diagnostic Strategy for Tuberculosis in Hospitalized HIV-Infected Patients Using GeneXpert MTB/RIF and Alere Determine TB LAM Ag.

Publications

An Optimal Diagnostic Strategy for Tuberculosis in Hospitalized HIV-Infected Patients Using GeneXpert MTB/RIF and Alere Determine TB LAM Ag.

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