Dataset Information

Clinical and CT characteristics of Xpert MTB/RIF-negative pulmonary tuberculosis.

ABSTRACT:

Purpose

To determine the diagnostic accuracy of the Xpert MTB/RIF assay in patients with smear-negative pulmonary tuberculosis (TB) and to assess clinical and CT characteristics of Xpert-negative pulmonary TB.

Material and methods

We retrospectively reviewed the records of 1,400 patients with suspected pulmonary TB for whom the sputum Xpert MTB/RIF assay was performed between September 1, 2014 and February 28, 2020. Clinical and CT characteristics of smear-negative pulmonary TB patients with negative Xpert MTB/RIF results were compared with positive results.

Results

Of 1,400 patients, 365 (26.1%) were diagnosed with pulmonary TB and 190 of 365 patients (52.1%) were negative for sputum acid-fast bacilli. The diagnosis of pulmonary TB was based on a positive culture, positive Xpert MTB/RIF or the clinical diagnoses of patients treated with an anti-TB medication. The sensitivity, specificity, positive predictive and negative predictive values of sputum Xpert MTB/RIF for smear-negative pulmonary TB were 41.1%, 100%, 100%, and 90.1%, respectively. Finally, 172 patients with smear-negative pulmonary TB who underwent chest CT within 2 weeks of diagnosis were included to compare Xpert-positive (n = 66) and Xpert- negative (n = 106) groups. Patients with sputum Xpert-negative TB showed lower positive rates for sputum culture (33.0% vs. 81.8%, p<0.001) and bronchoalveolar lavage culture (53.3% vs. 84.6%, p = 0.042) than in Xpert-positive TB. Time to start TB medication was longer in patients with Xpert-negative TB than in Xpert-positive TB (11.3±16.4 days vs. 5.0±8.7 days, p = 0.001). On chest CT, sputum Xpert-negative TB showed significantly lower frequency of consolidation (21.7% vs. 39.4%, p = 0.012), cavitation (23.6% vs. 37.9%, p = 0.045), more frequent peripheral location (50.9% vs. 21.2 p = 0.001) with lower area of involvement (4.3±4.3 vs. 7.6±6.4, p<0.001). Multivariate analysis revealed peripheral location (odds ratios, 2.565; 95% confidence interval: 1.157-5.687; p = 0.020) and higher total extent of the involved lobe (odds ratios, 0.928; 95% confidence interval: 0.865-0.995; p = 0.037) were significant factors associated with Xpert MTB/RIF-negative TB. Regardless of Xpert positivity, more than 80% of all cases were diagnosed of TB on chest CT by radiologists.

Conclusion

The detection rate of sputum Xpert MTB/RIF assay was relatively low for smear negative pulmonary TB. Chest CT image interpretation may play an important role in early diagnosis and treatment of Xpert MTB/RIF-negative pulmonary TB.

SUBMITTER: Lee HN

PROVIDER: S-EPMC8092799 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundXpert MTB/RIF ("Xpert") is a molecular test for detection of Mycobacterium tuberculosis (MTB) in sputum. Performance characteristics have been established for its use during passive tuberculosis (TB) case detection in symptomatic TB suspects, but Xpert performance has not been assessed in other settings. Objectives were to determine Xpert performance and costs in the context of a TB prevalence survey.Methodology/principal findingsThis was a diagnostic sub-study of a TB prevalence survey conducted in gold mining companies in South Africa. Sputa (one per participant) were tested using smear microscopy, liquid culture (reference comparator), and Xpert. Costs were collected using an ingredients approach and analyzed using a public health program perspective. 6893 participants provided a sputum specimen. 187/6893 (2.7%) were positive for MTB in culture, 144/6893 (2.1%) were positive for MTB by Xpert, and 91/6893 (1.3%) were positive for acid fast bacilli by microsocopy. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of MTB by Xpert were 62.6% (95% confidence interval [CI] 55.2, 69.5), 99.6% (99.4, 99.7), 81.3% (73.9, 87.3), and 98.9 (98.6, 98.8); agreement between Xpert and culture was 98.5% (98.2, 98.8). Sensitivity of microscopy was 17.6% (12.5, 23.9). When individuals with a history of TB treatment were excluded from the analysis, Xpert specificity was 99.8 (99.7, 99.9) and PPV was 90.6 (83.3, 95.4) for detection of MTB. For the testing scenario of 7000 specimens with 2.7% of specimens culture positive for MTB, costs were $165,690 for Xpert and $115,360 for the package of microscopy plus culture.ConclusionIn the context of a TB prevalence survey, the Xpert diagnostic yield was substantially higher than that of microscopy yet lower than that of liquid culture. Xpert may be useful as a sole test for TB case detection in prevalence surveys, particularly in settings lacking capacity for liquid culture.

Project description:BackgroundThe Xpert MTB/RIF (Xpert) assay offers rapid and accurate diagnosis of tuberculosis (TB) but still suffers from imperfect sensitivity. The newer Xpert MTB/RIF Ultra cartridge has shown improved sensitivity in recent field trials, but at the expense of reduced specificity. The clinical implications of switching from the existing Xpert cartridge to the Xpert Ultra cartridge in different populations remain uncertain.Methods and findingsWe developed a Markov microsimulation model of hypothetical cohorts of 100,000 individuals undergoing diagnostic sputum evaluation with Xpert for suspected pulmonary TB, in each of 3 emblematic settings: an HIV clinic in South Africa, a public TB center in India, and an adult primary care setting in China. In each setting, we used existing data to project likely diagnostic results, treatment decisions, and ultimate clinical outcomes, assuming use of the standard Xpert versus Xpert Ultra cartridge. Our primary outcomes were the projected number of additional unnecessary treatments generated, the projected number of TB deaths averted, and the projected number of unnecessary treatments generated per TB death averted, if standard Xpert were switched to Xpert Ultra. We also simulated alternative approaches to interpreting positive results of the Ultra cartridge's semi-quantitative trace call. Extensive sensitivity and uncertainty analyses were performed to evaluate the drivers and generalizability of projected results. In the Indian TB center setting, replacing the standard Xpert cartridge with the Xpert Ultra cartridge was projected to avert 0.5 TB deaths (95% uncertainty range [UR]: 0, 1.3) and generate 18 unnecessary treatments (95% UR: 10, 29) per 1,000 individuals evaluated-resulting in a median ratio of 38 incremental unnecessary treatments added by Ultra per incremental death averted by Ultra compared to outcomes using standard Xpert (95% UR: 12, indefinite upper bound). In the South African HIV care setting-where TB mortality rates are higher and Ultra's improved sensitivity has greater absolute benefit-this ratio improved to 7 unnecessary treatments per TB death averted (95% UR: 2, 43). By contrast, in the Chinese primary care setting, this ratio was much less favorable, at 372 unnecessary treatments per TB death averted (95% UR: 75, indefinite upper bound), although the projected number of unnecessary treatments using Xpert Ultra was lower (with a possibility of no increased overtreatment) when using specificity data only from lower-burden settings. Alternative interpretations of the trace call had little effect on these ratios. Limitations include uncertainty in key parameters (including the clinical implications of false-negative results), the exclusion of transmission effects, and restriction of this analysis to adult pulmonary TB.ConclusionsSwitching from the standard Xpert cartridge to the Xpert Ultra cartridge for diagnosis of adult pulmonary TB may have different consequences in different clinical settings. In settings with high TB and HIV prevalence, Xpert Ultra is likely to offer considerable mortality benefit, whereas in lower-prevalence settings, Xpert Ultra will likely result in considerable overtreatment unless the possibility of higher specificity of Ultra in lower-prevalence settings in confirmed. The ideal use of the Ultra cartridge may therefore involve a more nuanced, setting-specific approach to implementation, with priority given to populations in which the anticipated prevalence of TB (and HIV) is the highest.