Using TBAg/PHA Ratio for Monitoring TB Treatment: A Prospective Multicenter Study.

The way to monitor tuberculosis (TB) treatment is extremely lacking in clinical practice. The aim of the study is to assess the role of the TBAg/PHA ratio in the treatment monitoring of TB. TB patients were followed up for 6 months and serial T-SPOT.TB (T-SPOT) assays were performed. In patients with successful treatment outcomes, the ESAT-6 sfc, CFP-10 sfc, and TBAg/PHA ratio all showed a decreased trend after the initiation of treatment. Conversely, PHA sfc showed an increased trend after 2 months of treatment. However, these indicators had moderate performance in distinguishing between before and after 6 months of treatment, and the AUC ranged from 0.702 to 0.839. Notably, the TBAg/PHA ratio in patients without risk factors was of important value in differentiation between before and after treatment. The optimal AUC of TBAg/PHA ratio reached up to 0.890. Patients with unsuccessful treatment outcomes showed persistently high levels of TBAg/PHA ratio. The TBAg/PHA ratio in patients after 6 months of treatment showed a certain potential in distinguishing between patients with successful and unsuccessful treatment outcomes. A further calculation of the TBAg/PHA ratio in T-SPOT assay has potential value in the treatment monitoring of TB, but further confirmation is needed.

Combined IFN-γ and IL-2 release assay for detect active pulmonary tuberculosis: a prospective multicentre diagnostic study in China.

BACKGROUND: We performed a prospective multicentre diagnostic study to evaluate the combined interferon-γ (IFN-γ) and interleukin-2 (IL-2) release assay for detect active pulmonary tuberculosis (TB) in China. METHODS: Adult patients presenting symptoms suggestive of pulmonary TB were consecutively enrolled in three TB-specialized hospitals. Sputum specimens and blood sample and were collected from each participant at enrolment. The levels of Mycobacterium tuberculosis (MTB)-specific antigen-stimulated IFN-γ and IL-2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: Between July 2017 and December 2018, a total of 3245 patients with symptoms suggestive of pulmonary TB were included in final analysis. Of 3245 patients, 2536 were diagnosed as active TB, consisting of 1092 definite TB and 1444 clinically diagnosed TB. The overall sensitivity and specificity of IFN-γ were 83.8% and 81.5%, respectively. In addition, compared with IFN-γ, the specificity of IL-2 increased to 94.3%, while the sensitivity decreased to 72.6%. In addition, the highest sensitivity was achieved with parallel combination of IFN-γ/IL-2, with a sensitivity of 87.9%, and its overall specificity was 79.8%. The sensitivity of series combination test was 68.5%. Notably, the sensitivity of series combination test in definite TB (72.1%) was significantly higher than that in clinically diagnosed TB (65.8%). CONCLUSION: In conclusion, we develop a new immunological method that can differentiate between active TB and other pulmonary diseases. Our data demonstrates that the various IFN-γ/IL-2 combinations provides promising alternatives for diagnosing active TB cases in different settings. Additionally, the diagnostic accuracy of series combination correlates with severity of disease in our cohort.

Combination of Xpert MTB/RIF and TBAg/PHA Ratio for Prompt Diagnosis of Active Tuberculosis: A Two-Center Prospective Cohort Study.

The prompt diagnosis of active tuberculosis (ATB) is still a challenge in clinical practice, especially in TB-endemic countries. We prospectively enrolled consecutive patients with suspected pulmonary TB from two tertiary hospitals. Acid-fast staining (AFS), Xpert MTB/RIF (Xpert), Mycobacterium tuberculosis culture, and T-SPOT.TB were simultaneously performed. 226 ATB and 348 non-TB patients were diagnosed in Tongji hospital (test cohort), and 86 ATB and 110 non-TB patients were diagnosed in Guangzhou Chest Hospital (validation cohort). Using ATB as patient group and non-TB as control group, for diagnosis of ATB in Tongji Hospital, the sensitivity of AFS was 17.70% (95% CI: 13.08-23.44%). The sensitivity of Xpert and culture were 53.54% (95% CI: 46.81-60.14%) and 46.46% (95% CI: 39.86-53.19%), respectively. The sensitivity of T-SPOT.TB was 81.42% (95% CI: 75.60-86.14%), but the specificity was 71.55% (95% CI: 66.60-76.04%). Calculation of the ratio of TB-specific antigen to phytohaemagglutinin (TBAg/PHA) of T-SPOT.TB assay increased the specificity but with a loss of sensitivity. Combination of Xpert and culture slightly increased the sensitivity compared to using these methods separately. Combination of Xpert and TBAg/PHA ratio (defined as Xpert positive or TBAg/PHA ≥ 0.2) increased diagnostic accuracy, and the sensitivity and specificity of combination of them were 85.84% (95% CI: 80.45-89.98%) and 95.98% (95% CI: 93.36-97.59%), respectively. The diagnostic model was also established based on combination of Xpert and TBAg/PHA ratio. The area under the curve of the diagnostic model was 0.952 (95% CI: 0.932-0.973) for diagnosis of ATB, with a sensitivity of 88.05% (95% CI: 83.10-91.98%) and a specificity of 96.26% (95% CI: 93.70-98.00%) when a cutoff value of 0.44 was used in Wuhan cohort. The performance of combination of Xpert and TBAg/PHA ratio was similar in Guangzhou Chest Hospital. Our data suggest that combination of Xpert and TBAg/PHA ratio may be a good algorithm for prompt diagnosis of ATB in high endemic areas.

Epidemiology of pulmonary disease due to nontuberculous mycobacteria in Southern China, 2013-2016.

BACKGROUND: Pulmonary nontuberculous mycobacteria (NTM) disease is of increasing public health concern in China. Information is limited regarding risk factors associated with this disease in China. The objective of this study was to describe the epidemiology of pulmonary disease due to NTM in Southern China. METHODS: We retrospectively reviewed the medical records of pulmonary NTM patients registered in the Guangzhou Chest Hospital with positive mycobacterial cultures during 2013-2016. We described sex, age, residence, treatment history, laboratory examination results and comorbidities of pulmonary NTM patients. RESULTS: Among the 607 NTM cases, the most prevalent species were Mycobacterium avium complex (44.5%), Mycobacterium abscessus complex (40.5%), Mycobacterium kansasii (10.0%) and Mycobacterium fortuitum (2.8%). The male:female ratio was significantly lower among patients infected with rapidly growing mycobacteria (RGM) than among those with slowly growing mycobacteria (SGM). The risk of developing SGM disease significantly increased with advancing age. In addition, pulmonary RGM diseases were more common in migrant population than resident population. Notably, patients with pulmonary RGM diseases were significantly more likely to have bronchiectasis underlying noted than those with SGM diseases. No significant difference was observed in in vitro drug susceptibility among NTM species. CONCLUSION: Our data illustrate that the M. avium complex is the most predominant causative agent of pulmonary NTM disease in Southern China. Female, migrant population, the presence of bronchiectasis are independent risk factors for pulmonary diseases due to RGM. In addition, the prevalence of SGM increases significantly with advancing age.

Endoscopic characteristics of multidrug-resistant tuberculosis combined with tracheobronchial tuberculosis / 中国内镜杂志

Objective To explore the endoscopic characteristics of multidrug-resistant tuberculosis (MDR-TB) combined with tracheobronchial tuberculosis (TBTB). Methods 248 MDR-TB as study group, they hospitalized from October 1st 2008 to June 31st, 2016. 274 cases of non MDR-TB with bacteria positive as control group over 2015, all of them received bronchoscopy, sputum cultured and drug sensitivity tested of Isoniazid and Rifampicin. We analyzed the results of bronchoscopy and demographic data. Results 248 cases of MDR-TB patients, of 175 (70.56%) were diagnosed TBTB by bronchoscopy, of 73 (29.44%) without TBTB. 274 cases of non MDR-TB with bacteria positive patients, of 146 (53.28%) were diagnosed TBTB, of 128 (46.72%) non TBTB, the difference of comparisons was statistically significant (χ2 = 16.42, P = 0.000). MDR-TB combined with TBTB median age was 32 years, non MDR-TB combined with TBTB median age 42 years, the difference was statistically significant (U = 9932.00, P = 0.001). Among the MDR-TB patients, of 75 (42.86%) TBTB in the upper right bronchial, of71 (40.57%) upper left bronchus, while non MDR-TB patients, of 70 (47.95%) and 60 (41.10%), there was no statistically significant difference (χ2 = 2.44, P = 0.786). Among the MDR-TB, of 76 (43.43%) were inflammation infiltration type, of 11 (6.29%) were necrosis type, of 13 cases (7.43%) granulation proliferative type, of 72 (41.14%) were scar stricture type, of 3 (1.71%) tube wall softening type. Among the non MDR-TB, in turn, TBTB type were 50 (34.25%), 41 (28.08%), 9 (6.16%), 40 (27.40%), 5 (3.43%), the difference were statistically significant (χ2 = 30.50, P = 0.000). Conclusions The detection rate of TBTB was higher in MDR-TB patients, that common occur in younger patients. TBTB common infringe on upper right bronchial and upper left bronchus, TBTB type most are inflammatory infiltration type and scar stricture type. More attention should be paid to bronchoscopy among MDR-TB patients.

Role of pncA and rpsA gene sequencing in detection of pyrazinamide resistance in Mycobacterium tuberculosis isolates from southern China.

We sequenced pncA and rpsA genes plus flanking regions of 161 Mycobacterium tuberculosis isolates and found 10 new pncA and 3 novel rpsA mutations in pyrazinamide-resistant strains determined by the Bactec MGIT 960 system. The 3' end of rpsA might be added as the target of molecular detection of pyrazinamide susceptibility.