Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment

Friedrich, Sven O.; Rachow, Andrea; Saathoff, Elmar; Singh, Kasha; Mangu, Chacha; Dawson, Rodney; Phillips, Patrick P. J.; Venter, Amour; Bates, Matthew; Boehme, Catharina; Heinrich, Norbert; Hunt, Robert D.; Boeree, Martin J.; Zumla, Alimuddin; McHugh, Timothy D.; Gillespie, Stephen H.; Diacon, Andreas H.; Höelscher, Michael

doi:10.1016/s2213-2600(13)70119-x

Cited by 172 publications

(140 citation statements)

References 26 publications

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“…The close comparability between MBL and culture contrasts with data for treatment monitoring using the GeneXpert MTB/RIF assay (Xpert; Cepheid, CA, USA). GeneXpert MTB/RIF did not respond to changes in bacterial load as rapidly as did culture (17). Within-subject variation of Xpert was high, at 56.7%.…”

mentioning

confidence: 79%

The Molecular Bacterial Load Assay Replaces Solid Culture for Measuring Early Bactericidal Response to Antituberculosis Treatment

Honeyborne

Mtafya²,

Phillips

et al. 2014

J Clin Microbiol

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confidence: 79%

The Molecular Bacterial Load Assay Replaces Solid Culture for Measuring Early Bactericidal Response to Antituberculosis Treatment

Honeyborne

Mtafya²,

Phillips

et al. 2014

J Clin Microbiol

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“…NanoDisk-MS also was able to precisely quantify serum antigen concentrations, a highly desirable feature for monitoring responses to anti-TB therapy, given that assays currently used to monitor treatment response provide only qualitative or semiquantitative results (smear and culture) or exhibit significant latency (Xpert). A study evaluating serial sputum samples from patients with smear-positive TB found that assay positivity and grade decreased linearly starting at ∼2 wk (smear), 4 wk (culture), or 6 wk (Xpert) posttreatment (37). CD4 + T-cell responses also have been reported to differentiate LTBI and active TB cases and to monitor treatment responses, although only HIV-negative and culture-and/or smear-positive PTB patients were analyzed using this labor-intensive method, so that its clinical utility remains unclear (38).…”

Section: Discussionmentioning

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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“…This may have to some extent contributed to further lowering the yield of culture compared to Xpert. As the excretion of residual persistent DNA from dead organisms has been suggested as a reason for positive Xpert but negative smear and/or culture results on samples taken during and at the end of treatment, 18 a positive Xpert result in recently treated TB patients should be correlated with the clinical condition of the patient, and should ideally be confirmed by culture, although in GS the culture yield is known to be low.…”

Section: Discussionmentioning

confidence: 99%

Gastric specimens for diagnosing tuberculosis in adults unable to expectorate in Rawalpindi, Pakistan

Aslam¹,

Tahseen²,

Schomotzer

et al. 2017

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Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment

Abstract: Global Alliance for TB Drug Development, Bill & Melinda Gates Foundation, UK Medical Research Council, German Ministry of Science and Technology.

Cited by 172 publications

References 26 publications

The Molecular Bacterial Load Assay Replaces Solid Culture for Measuring Early Bactericidal Response to Antituberculosis Treatment

The Molecular Bacterial Load Assay Replaces Solid Culture for Measuring Early Bactericidal Response to Antituberculosis Treatment

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

Gastric specimens for diagnosing tuberculosis in adults unable to expectorate in Rawalpindi, Pakistan

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