Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis: A diagnostic accuracy study from India

Sharma, Kusum; Sharma, Megha; Shree, Ritu; Modi, Manish; Goyal, Manoj; Narang, Dhawal; Sharma, Aman; Lal, Vivek; Sharma, Navneet; Ray, Pallab

doi:10.1016/j.tube.2020.101990

Cited by 18 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the drawbacks of these conventional tests included limited sensitivity and length of time consumed (13,14). Although a rapid diagnosis has been enhanced by various molecular techniques such as GeneXpert MTB/RIF and GeneXpert MTB/RIF Ultra (15)(16)(17)(18)(19)(20), these tests also showed unsatisfactory utility, especially for paucibacillary cases (21)(22)(23)(24). Interferon gamma release assays, including T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT), were widely used for identifying MTB infection (25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Luo

Xue

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

BackgroundRapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue.MethodsParticipants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation.ResultsA total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833–0.969), with a sensitivity of 93.75% (95% CI, 79.85–98.27%) and specificity of 72.97% (95% CI, 57.02–84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19–97.47%) sensitivity and 68.97% (95% CI, 50.77–82.73%) specificity.ConclusionsWe demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.

show abstract

Section: Introductionmentioning

confidence: 99%

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Luo

Xue

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Furthermore, it has been reported that Xpert/Ultra was not superior to the version of Xpert MTB/RIF in CSF of individuals with tuberculous meningitis, using either clinical or culture reference standards 16 . In this study, the positive results were determinant for clinical decisions (including the "trace" category); likewise, with a mortality approaching 100% in untreated tuberculous meningitis, it is less probable that the trace category could have been due to previous infection 17 . Therefore, these data highlight the importance of routine molecular testing of CSF; Xpert/ Ultra is valuable when it is positive, and any load should be considered.…”

Section: Discussionmentioning

confidence: 75%

“…Sensitivity can be affected by the volume of CSF tested and by whether CSF was centrifuged before testing 18 . According to the previous findings, the use of fresh or frozen CSF samples, with a proper cryopreservation, does not alter the yield of detection of M. tuberculosis 17 . Furthermore, it has been reported that Xpert/Ultra was not superior to the version of Xpert MTB/RIF in CSF of individuals with tuberculous meningitis, using either clinical or culture reference standards 16 .…”

Section: Discussionmentioning

confidence: 83%

“…Regarding the type of sample, CFS was more predominant during the study period; it had a sensitivity of 80.5% and a specificity of 95.7%. The previous studies have reported sensitivities ranging from 59.5% to 72.05%, and specificities around 100% [14][15][16][17] . Sensitivity can be affected by the volume of CSF tested and by whether CSF was centrifuged before testing 18 .…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Performance of Real-Time Semi-Quantitative Polymerase Chain Reaction Assay for Optimum Diagnosis of Extrapulmonary Tuberculosis and Sensitivity to Rifampin in a Tertiary Care Center

Peñata-Bedoya¹,

Zuluaga-Avendaño²,

Castaño-Sepúlveda³

et al. 2021

RIC

View full text Add to dashboard Cite

Background: Tuberculosis represents a public health problem, with extrapulmonary disease occurring in 15% of incident cases annually. Early diagnosis is a challenge due to its paucibacillary nature. Recently, a molecular real-time semi-quantitative assay (GeneXpert Ultra) was developed to overcome limitations of the previous assay version (Xpert MTB/RF). Objective: The objective of the study was to assess the usefulness of the novel next-generation GeneXpert assay in extrapulmonary samples from different anatomic sites under routine diagnostic conditions at a university medical center. Methods: A total of 519 samples from patients with presumptive diagnosis of extrapulmonary TB were subjected to smear microscopy, culture, and molecular assay. Univariate analyses for demographic and microbiological characteristics were performed. The sensitivity, specificity, and Kappa index with a 95% confidence interval were determined. Results: Molecular assay was positive in 53 samples (10.2%), of which 38 (71.6%) belonged to the "low" and "trace" semi-quantitative categories. The overall sensitivity and specificity were 86.4% (95% confidence intervals [CI]: 74.1-98.8) and 95.6% (95% CI: 93.7-97.6), respectively. Phenotypic drug susceptibility testing for rifampin was 100% concordant. Conclusions: Molecular assay showed significant results when compared to other standard tests, making it a useful tool that could lead in the improvement to a rapid diagnosis of extrapulmonary disease.

show abstract

“…To overcome issues associated with reduced sensitivity of Xpert® MTB/RIF assay, in 2017 WHO recommended replacing existing Xpert® MTB/RIF cartridges with next generation Xpert® MTB/RIF assay (Xpert® MTB/RIF Ultra)14 . These Xpert ultra cartridges are designed to include a large chamber for higher sample volume along with two MTB targets for higher diagnostic sensitivity in smear negative cases.…”

mentioning

confidence: 99%

Controlling the drug-resistant tuberculosis epidemic in India: challenges and implications

2021

View full text Add to dashboard Cite

India is highest Tuberculosis (TB) burden country accounting for an estimated one-fourth of the global burden. Drug resistant TB (DR-TB) represents major public health problem in India.Patients with DR-TB may often require profound changes in their drug regimen which are invariably linked to poor adherence and sub-optimal treatment outcomes compared to drug sensitive TB. The challenge of addressing DR-TB is critical for India, as it accounts for over 27% of the global DR cases. In recent decade, India has been upfront in its battle against TB and even set up revised National Strategic plan (NSP) to eliminate TB by 2025. However, to achieve this ambitious goal, country will need multifaceted approach with respect to management of DR-TB.Despite concerted efforts driven by National TB elimination program, India faces substantial challenges with respect to DR-TB care especially in peripheral and resource limited endemic zones. The current article, describes some of the major challenges along with its implications associated with reducing the growing DR-TB epidemic in India.

show abstract

Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis: A diagnostic accuracy study from India

Cited by 18 publications

References 20 publications

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Performance of Real-Time Semi-Quantitative Polymerase Chain Reaction Assay for Optimum Diagnosis of Extrapulmonary Tuberculosis and Sensitivity to Rifampin in a Tertiary Care Center

Controlling the drug-resistant tuberculosis epidemic in India: challenges and implications

Contact Info

Product

Resources

About