Evaluation of the Xpert MTB/RIF Assay for the Diagnosis of Pulmonary Tuberculosis in a High HIV Prevalence Setting

Theron, Grant; Peter, Jonny; Zyl-Smit, Richard van; Mishra, Hridesh; Streicher, Elizabeth M.; Murray, Samuel; Dawson, Rodney; Whitelaw, Andrew; Höelscher, Michael; Sharma, Surendra Kumar; Pai, Madhukar; Warren, Robin M.; Dheda, Keertan

doi:10.1164/rccm.201101-0056oc

Cited by 284 publications

(300 citation statements)

References 21 publications

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“…There is a large number of studies evaluating Xpert on pulmonary specimens [5,6,[17][18][19][20][21][22][23]; the sensitivity varies from 95% to 100% in smear-positive sputa, and from 47% to 77% in smear-negative ones. Our data score high within these ranges, despite the well-known lower yield of extrapulmonary samples in term of sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis

Tortoli¹,

et al. 2012

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Extrapulmonary tuberculosis (EPTB) accounts for more than 20% of tuberculosis (TB) cases. Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA, USA) is a fully automated amplification system, for which excellent results in the diagnosis of pulmonary TB in highly endemic countries have been recently reported. We aimed to assess the performance of the Xpert system in diagnosing EPTB in a low incidence setting.We investigated with Xpert a large number of consecutive extrapulmonary clinical specimens (1,476, corresponding to 1,068 patients) including both paediatric (494) and adult samples.We found, in comparison with a reference standard consisting of combination of culture and clinical diagnosis of TB, an overall sensitivity and specificity of 81.3% and 99.8% for Xpert, while the sensitivity of microscopy was 48%. For biopsies, urines, pus and cerebrospinal fluids the sensitivity exceeded 85%, while it was slightly under 80% for gastric aspirates. It was, in contrast, lower than 50% for cavitary fluids. High sensitivity and specificity (86.9% and 99.7%, respectively) were also obtained for paediatric specimens.Although the role of culture remains central in the microbiological diagnosis of EPTB, the sensitivity of Xpert in rapidly diagnosing the disease makes it a much better choice compared to smear microscopy. The ability to rule out the disease still remains suboptimal.

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Section: Discussionmentioning

confidence: 99%

Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis

Tortoli¹,

et al. 2012

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“…3C). NanoDisk-MS results are thus expected to permit robust TB diagnosis in HIVpositive patients with sensitivity exceeding that of most conventional methods (31).…”

Section: Nanodisk-ms Diagnostic Sensitivity and Specificity In An Hivmentioning

confidence: 99%

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Liu

Zhao

Fan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tuberculosis (TB) is a major global health threat, resulting in an urgent unmet need for a rapid, non-sputum-based quantitative test to detect active Mycobacterium tuberculosis (Mtb) infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains. We have identified Mtb-specific peptide fragments and developed a method to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nanoparticles (nanodisks) and high-throughput mass spectrometry (MS) to enhance sensitivity and specificity. NanoDisk-MS diagnosed active Mtb cases with high sensitivity and specificity in a case-control study with cohorts reflecting the complexity of clinical practice. Similar robust sensitivities were obtained for cases of culture-positive pulmonary TB (PTB; 91.3%) and extrapulmonary TB (EPTB; 92.3%), and the sensitivities obtained for culture-negative PTB (82.4%) and EPTB (75.0%) in HIV-positive patients significantly outperformed those reported for other available assays. NanoDisk-MS also exhibited high specificity (87.1-100%) in both healthy and high-risk groups. Absolute quantification of serum Mtb antigen concentration was informative in assessing responses to antimycobacterial treatment. Thus, a NanoDisk-MS assay approach could significantly improve the diagnosis and management of active TB cases, and perhaps other infectious diseases as well.D espite international efforts and initiatives, tuberculosis (TB) remains a major public health concern worldwide, associated with high morbidity and mortality (1, 2). Detecting active TB cases and monitoring their responses to therapy are fraught with challenges, relying predominantly on microbiologic techniques that use sputum samples, including acid-fast Bacillus (AFB) smear microscopy-widely used as an initial test for TB diagnosis (3, 4)-and Mycobacterium tuberculosis (Mtb) culture, both of which have only moderate sensitivity and specificity and a long turnaround time (5, 6). Moreover, sputum samples are difficult to obtain after symptom improvement, and often are not diagnostically useful for extrapulmonary TB (EPTB) cases. The PCR-based Xpert MTB/RIF sputum assay was introduced to improve the speed and specificity of TB diagnosis, but this assay has poor sensitivity under low bacterial loads and cannot distinguish live and nonviable Mtb contributions (7,8). A recent World Health Organization (WHO) policy update acknowledged the low quality of evidence supporting the use of Xpert MTB/RIF to diagnose EPTB (9). Diagnostic challenges can be further magnified in patients coinfected with HIV and TB (10). In addition, none of these techniques provides quantitative results that can be used to monitor treatment effects (11,12).Consequently, there is an urgent need, highlighted as a high priority in a recent WHO consensus report (13), for the development of rapid, quantitative, non-sputum-based biomarker tests that do not require bacterial isolation to detect active TB (13). Non-s...

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“…In immunocompetent patients the Xpert MTB/RIF test has a very high diagnostic accuracy; especially in patients with acid-fast bacilli, sputum-smear positive pulmonary TB [160,161]. However, the diagnostic sensitivity for pulmonary TB is substantially reduced in immunocompromised patients with HIV-infection and acid-fast bacilli, sputumsmear negative pulmonary TB [162] and the value of this method for the rapid diagnosis of TB in transplant patients still needs to be established.…”

Section: Future Research Directionsmentioning

confidence: 99%

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

Bumbăcea

Arend

Eyüboğlu³

et al. 2012

Eur Respir J

232

261

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Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-c based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking. KEYWORDS: Guideline, management, Mycobacterium tuberculosis, transplantation, tuberculosis T uberculosis (TB) is caused by the pathogenic species of the Mycobacterium tuberculosis complex. Only a minority of individuals who develop an adaptive immune response following infection with M. tuberculosis will ever develop TB, with the actual risk depending on the extent to which the host immune system provides a successful or inadequate response [1,2]. Therefore, individuals with impaired immune response, such as solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are more prone to develop TB than immunocompetent persons. TB in transplant recipients is more frequent compared to the general population (estimates from the last decades state 20-74 times as frequent in SOT [3,4] and twice as frequent in HSCT [5]), and more often fatal (up to 31% in SOT [6] and up to 50% in HSCT recipients [7]), thus adding effectiveness to interventions for its prevention, even in the face of difficulties, with treatment related to adverse drug events and drug-drug interactions. Active TB in transplant recipients can result from latent infection with M. tuberculosis (LTBI) in the transplant candidate or in the donor tissue, or from de novo post-transplant infection. These various scenarios prompt for targeted pre-transplant screening of both recipient and, if possible, donors to allow focused management of recipients selected for preventive intervention in the pre-and/or posttransplant period. The term ''preventive chemotherapy'' is used to denote treatmen...

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Evaluation of the Xpert MTB/RIF Assay for the Diagnosis of Pulmonary Tuberculosis in a High HIV Prevalence Setting

Cited by 284 publications

References 21 publications

Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis

Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

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