Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. RESULTS: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. CONCLUSIONS: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

Predictors for Treatment Outcomes in Patients with Multi-drug Resistant Tuberculosis - China, 2018-2020.

What is already known about this topic?: Multi-drug resistant tuberculosis (MDR-TB) is a critical global public health problem. What is added by this report?: Sputum cultures and lung images show a strong association with treatment outcomes, serving as a multi-dimensional approach to identify MDR-TB patients with poor outcomes. What are the implications for public health practice?: The results imply that funds and policy investments should be increased by early monitoring of MDR-TB patients, especially regarding imaging and sputum bacterium. By informing physicians on changes to the therapeutic schedule, treatment outcomes can be improved.

Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China.

OBJECTIVE: Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. METHODS: Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. RESULTS: The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). CONCLUSIONS: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.

A highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis: a multicenter prospective study in China.

BACKGROUND: To verify the efficacy and safety of an inexpensive standardized regimen for multidrug-resistant tuberculosis (MDR-TB) with low resistance to isoniazid (INH), a multicenter prospective study was conducted in eastern China. METHODS: Patients diagnosed as MDR-TB with low concentration INH resistance and rifampicin resistance, second-line/injectable agents sensitive were prospectively enrolled, given the regimen of Amikacin (Ak)-Fluoroquinolones (FQs)-Cycloserine (Cs)-Protionamide (Pto)-PasiniaZid (Pa)-Pyrazinamide (Z) for 6 months followed by 12 months of FQs-Cs-Pto-Pa-Z, and then followed up for treatment outcomes and adverse events (AEs). RESULTS: A total of 114 patients were enrolled into the study. The overall favorable treatment rate was 79.8% (91/114). Among 91 cases with favorable treatment, 75.4% (86/114) were cured and 4.4% (5/114) were completed treatment. Regarding to unfavorable outcomes, among 23 cases, 8.8% (10/114) had failures, 8.8% (10/114) losing follow up, 0.9% (1/114) had treatment terminated due to intolerance to drugs and 1.8% (2/114) died. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78, p 0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients (26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42). CONCLUSIONS: The regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population, especially for newly-treated patients, which could be expected to be developed into a short-course regimen. Clinical trials registration China Clinical Trial Registry ChiCTR-OPC-16009380.

PCR-reverse blot hybridization assay in respiratory specimens for rapid detection and differentiation of mycobacteria in HIV-negative population.

BACKGROUND: Rapid identification of pathogenic Mycobacterium species is critical for a successful treatment. However, traditional method is time-consuming and cannot discriminate isolated non-tuberculosis mycobacteria (NTM) at species level. In the retrospective study, we evaluated the clinical applicability of PCR-reverse blot hybridization assay (PCR-REBA Myco-ID) with clinical specimens for rapid detection and differentiation of mycobacterial species. METHODS: A total of 334 sputum and 362 bronchial alveolar lavage fluids (BALF) from 696 patients with mycobacterium pulmonary disease (MPD) and 210 patients with non-mycobacterium pulmonary disease used as controls were analyzed. Sputum or BALF were obtained for MGIT 960-TBc ID test and PCR-REBA Myco-ID assay. High resolution melt analysis (HRM) was used to resolve inconsistent results of MGIT 960-TBc ID test and PCR-REBA Myco-ID assay. RESULTS: A total of 334 sputum and 362 BALF specimens from 696 MPD patients (292 MTB and 404 NTM) were eventually analyzed. In total, 292 MTBC and 436 NTM isolates (mixed infection of two species in 32 specimens) across 10 Mycobacterium species were identified. The most frequently isolated NTM species were M. intracellulare (n = 236, 54.1%), followed by M. abscessus (n = 106, 24.3%), M. kansasii (n = 46, 10.6%), M. avium (n = 36, 8.3%). Twenty-two cases had M. intracellulare and M. abscessus mixed infection and ten cases had M. avium and M. abscessus mixed infection. A high level of agreement (n = 696; 94.5%) was found between MGIT 960-TBc ID and PCR-REBA Myco-ID (k = 0.845, P = 0.000). PCR-REBA Myco-ID assay had higher AUC for both MTBC and NTM than MGIT 960-TBc ID test. CONCLUSION: PCR-REBA Myco-ID has the advantages of rapid, comparatively easy to perform, relatively low cost and superior accuracy in mycobacterial species identification compared with MGIT 960-TBc ID. We recommend it into workflow of mycobacterial laboratories especially in source-limited countries.

Improvement cues of lesion absorption using the adjuvant therapy of traditional Chinese medicine Qinbudan tablet for retreatment pulmonary tuberculosis with standard anti-tuberculosis regimen.

BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0-73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02-0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02-0.31; χ2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21-0.12; χ2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610.

Diagnostic performance of nucleic acid tests in tuberculous pleurisy.

BACKGROUND: Tuberculous pleurisy (TBP) is the most common form of extrapulmonary tuberculosis (TB). However, rapid diagnostic methods with high accuracy for tuberculous pleurisy are urgently needed. In the present study, we evaluated the diagnostic accuracy of Xpert MTB/RIF, LAMP and SAT-TB assay with pleural fluids from culture-positive TBP patients. METHODS: We prospectively enrolled 300 patients with exudative pleural effusions used as the samples for Xpert MTB/RIF, LAMP and SAT-TB assay. Of these, 265 including 223 patients diagnosed with TBP and 42 non-TBP patients used as controls were analyzed. RESULTS: The sensitivities of Xpert MTB/RIF (27.4%), LAMP (26.5%) and SAT-TB assay (32.3%) were significantly higher than that of pleural effusion smear (14.3%, X2 = 20.65, P <  0.001), whereas they were much lower than expected for the analysis of pleural effusion samples. Both SAT-TB assay and Xpert MTB/RIF demonstrated high specificities (100%) and PPVs (100%), but the NPVs of all of the tests were < 22%. The area under ROC curve of pleural effusion smear, LAMP, Xpert MTB/RIF and SAT-TB assays was 0.524 (95% CI 0.431-0.617), 0.632 (95% CI 0.553-0.71), 0.637 (95% CI 0.56-0.714) and 0.673 (95% CI 0.6-0.745). SAT-TB assays had the highest AUC. CONCLUSION: Nucleic acid amplification tests are not the first choice in the diagnosis of tuberculous pleurisy. In this type of test, SAT-TB is recommended because of its low cost, relatively more accurate compared with the other two tests. This prospective study was approved by The Ethics Committee of the Shanghai Pulmonary Hospital (approval number: K19-148). TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR1900026234 (Retrospectively registered). The registration date is September 28, 2019.

Performance of Interferon-Gamma Release Assays in the Diagnosis of Nontuberculous Mycobacterial Diseases-A Retrospective Survey From 2011 to 2019.

There is an urgent need for precise diagnosis to distinguish nontuberculous mycobacterial (NTM) diseases from pulmonary tuberculosis (PTB) and other respiratory diseases. The aim of this study is to evaluate the diagnostic performance of Interferon-gamma (IFN-γ) release assays (IGRAs), including antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT.TB) and QuantiFERON-TB-Gold-Test (QFT-G), in differentiating NTM infections (N = 1,407) from culture-confirmed PTB (N = 1,828) and other respiratory diseases (N = 2,652). At specie level, 2.56%, 10.73%, and 16.49% of NTM-infected patients were infected by Mycobacterium kansasii, M. abscessus, and with M. avmm-intracellulare complex (MAC), respectively. Valid analyses of T-SPOT.TB (ESAT-6, CFP-10) and QFT-G were available for 37.03% and 85.79% in NTM-infected patients, including zero and 100% (36/36) of M. kansasii infection, 21.85% (33/151) and 92.05% (139/151) of M. abscessus infection, and 17.67% (41/232) and 91.24% (211/232) of MAC infection. Based on means comparisons and further ROC analysis, T-SPOT.TB and QFT-G performed moderate accuracy when discriminating NTM from PTB at modified cut-off values (ESAT-6 < 4 SFCs, CFP-10 < 3 SFCs, and QFT-G < 0.667 IU/ml), with corresponding AUC values of 0.7560, 0.7699, and 0.856. At species level of NTM, QFT-G effectively distinguished between MAC (AUC=0.8778), M. kansasii (AUC=0.8834) or M. abscessus (AUC=0.8783) than T-SPOT.TB. No significant differences in discriminatory power of these three IGRA tools were observed when differentiating NTM and Controls. Our results demonstrated that T-SPOT.TB and QFT-G were both efficient methods for differentiating NTM disease from PTB, and QFT-G possessed sufficient discriminatory power to distinguish infections by different NTM species.

Genetic Polymorphisms in Antioxidant Enzymes Modulate the Susceptibility of Idiosyncratic Antituberculous Drug-Induced Liver Injury and Treatment Outcomes in Patients with Tuberculosis.

BACKGROUND: The pathogenic mechanism of antituberculous drug-induced liver injury (ATDILI) is associated with antioxidant enzymes. The objective of the present study was to investigate the associations of ATDILI susceptibility with genetic polymorphisms of antioxidant enzyme genes including nitric oxide synthase 2 (NOS2), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 2 (SOD2), BTB domain and CNC homolog 1 (BACH1), and MAF bZIP transcription factor K (MAFK). METHODS: Thirty tag single nucleotide polymorphisms (tag-SNPs) from the all candidate genes were genotyped in a 2-stage cohort study including an initial discovery stage with 461 ATDILI patients and 466 controls and a replication stage with 216 ATDILI patients and 432 controls. The frequencies and distributions of genotypes and haplotypes were compared between the case and control groups. Three different genetic models including dominant, recessive, and additive models were used to determine the associations with susceptibility to ATDILI. RESULTS: The SNPs rs9906835, rs944725, and rs3794764 of the NOS2 gene were significantly associated with an increased risk of ATDILI. The MAFK rs3735656 SNP was significantly associated with a decreased risk for ATDILI. The AAA haplotype of the NOS2 gene was associated with susceptibility to ATDILI. The treatment outcomes of patients with tuberculosis were further affected by genetic variants of the NOS2 and MAFK genes. CONCLUSIONS: Genetic polymorphisms of NOS2 and MAFK are associated with ATDILI susceptibility in Chinese patients with tuberculosis. The variants in NOS2 and MAFK affect treatment outcomes of tuberculosis patients. Further studies are needed to better understand the molecular mechanisms of ATDILI susceptibility via regulation of the expression of ATDILI-susceptibility genes and proteins.

Multidrug-resistant tuberculosis (MDR-TB) strain infection in macaques results in high bacilli burdens in airways, driving broad innate/adaptive immune responses.

Tuberculosis (TB) has become the most deadly infectious diseases due to epidemics of HIV/AIDS and multidrug-resistant/extensively drug-resistant TB (MDR-/XDR-TB). Although person-to-person transmission contributes to MDR-TB, it remains unknown whether infection with MDR strains resembles infection with drug-sensitive (DS) TB strains, manipulating limited or broad immune responses. To address these questions, macaques were infected with MDR strain V791 and a drug-sensitive Erdman strain of TB. MDR bacilli burdens in the airway were significantly higher than those of the Erdman control after pulmonary exposure. This productive MDR strain infection upregulated the expression of caspase 3 in macrophages/monocytes and induced appreciable innate-like effector responses of CD3-negative lymphocytes and Ag-specific γδ T-cell subsets. Concurrently, MDR strain infection induced broad immune responses of T-cell subpopulations producing Th1, Th17, Th22, and CTL cytokines. Furthermore, MDR bacilli, like the Erdman strain, were capable of inducing typical TB disease characterized by weight loss, lymphocytopenia, and severe TB lesions. For the first time, our results suggest that MDR-TB infection acts like DS to induce high bacterial burdens in the airway (transmission advantage), innate/adaptive immune responses, and disease processes. Because nonhuman primates are biologically closer to humans than other species, our data may provide useful information for predicting the effects of primary MDR strain infection after person-to-person transmission. The findings also support the hypothesis that a vaccine or host-directed adjunctive modality that is effective for drug-sensitive TB is likely to also impact MDR-TB.

Using simultaneous amplification and testing method for evaluating the treatment outcome of pulmonary tuberculosis.

BACKGROUND: To evaluate the utility of Simultaneous Amplification and Testing (SAT-TB) Method for monitoring anti-TB treatment response. METHODS: Serial morning sputum specimens were obtained from 377 active pulmonary tuberculosis (PTB) cases at baseline, weeks 2, months 2, 5 and 6 (newly diagnosed patients) or 8 (previously treated patients) for AmpSure assay, smear fluorescence microscopy (FM) and BACTEC MGIT 960 culture assay. RESULTS: After treatment of 2 weeks, sputum culture was positive in 280 patients (74.27%). Among whom, 219 patients tested positive for SAT-TB assay and 143 patients smear FM positive. The detection rate of SAT-TB (78.21%) was significantly higher than sputum FM (51.07%, χ2 = 45.128, P < 0.001). At the end of the second month of treatment, 157 patients (41.64%) were still culture-positive, 115 patients of them SAT-TB positive and 79 smear FM positive. The difference of detection rate between SAT-TB (73.25%) and sputum FM (50.32%) was significant (χ2 = 17.480, P < 0.001). When patients underwent five months of treatment, 65 patients (17.24%) with sputum culture positive was defined as treatment failure. Among whom, 60 patients (92.31%) were SAT-TB positive and 38 patients (58.46%) were smear FM positive. The detection rate of SAT-TB assay was significantly higher than sputum FM (χ2 = 17.333, P < 0.001). CONCLUSION: Results of AmpSure assays for monitoring treatment responses can be obtained without waiting for the results of BACTEC MGIT 960 assays and most patients with treatment failures could be detected after 5 months.

MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches.

Characteristics of peripheral Vγ2Vδ2 T cells in interferon-γ release assay negative pulmonary tuberculosis patients.

BACKGROUND: It is not fully explained why some active tuberculosis patients show negative interferon-γ release assays (IGRAs). In this study, we tried to explore associations of IGRAs with the characteristics of peripheral Vγ2Vδ2 T cells and their functions of producing cytokines. METHODS: 32 pulmonary tuberculosis patients were enrolled and divided into two groups according to their IGRAs results: 16 with IGRA-negative as test group and 16 with IGRA-positive as control group. Chest X-rays and T-SPOT.TB tests were performed and the severity of the lung lesions was scored. The amount of Vγ2Vδ2T cell and their expression levels of the apoptosis-related membrane surface molecule Fas and FasL in peripheral blood were analyzed by flow cytometry, and the function of secreting cytokines (IFN-γ, TNF-α and IL-17A) of Vγ2Vδ2 T cell were determined by intracellular cytokine staining. RESULTS: The IGRA-negative TB patients had more lesion severity scores and displayed reduced peripheral blood Vγ2Vδ2 T cell counts (p = 0.009) as well as higher Fas and FasL expression in peripheral blood Vγ2Vδ2 T cells (p = 0.043, 0.026). A high lesion severity score was correlated with a decreased Vδ2+ T cell number and increased Vγ2Vδ2 T cells Fas/FasL expression leve in the peripheral blood (p = 0.00, P < 0.01). The function of secreting cytokines was slightly impaired in IGRA-negative TB patients (p = 0.402). There is no significant differences in expression levels of Fas and FasL in CD4+ T cells (p = 0.224, 0.287) or CD8+ T cells (p = 0.184, 0.067) between test and control groups. CONCLUSION: Compared with IGRA-positive TB patients, the IGRA-negative TB patients had more lesion severity scores, the number of Vγ2Vδ2 T cells decreased and the function of secreting cytokines impaired. In addition, we suggest that increased expression of Fas/FasL triggers Vγ2Vδ2 T cell apoptosis.

Immunological recovery in patients with pulmonary tuberculosis after intensive phase treatment.

Objectives This study aimed to examine the change and significance of immune parameters in patients with sputum smear-positive pulmonary tuberculosis (TB) after 2 months of intensive phase anti-TB treatment. Methods The immune parameters of 232 cases of sputum smear-positive pulmonary TB were detected before and after 2 months of intensive phase anti-TB treatment and compared with 50 cases from healthy volunteers (controls). The T lymphocyte cell population in peripheral blood was detected using flow cytometry. Serum levels of interleukin (IL)-1ß, soluble interleukin-2 receptor, IL-6, and tumour necrosis factor-α were measured by ELISA. Results After 2 months of intensive phase anti-TB treatment, a reduction in the percentage of CD4+ T cells showed a significant restoration similar to that of controls. Moreover, after intensive anti-TB treatment, serum levels of IL-1ß, soluble interleukin-2 receptor, IL-6, and tumour necrosis factor-α were significantly decreased compared with before treatment. Additionally, serum levels of IL-1ß and IL-6 showed a diminished recovery compared with controls. Conclusions Our findings suggest immunological recovery in patients with pulmonary TB after intensive phase treatment. Therefore, serum cytokine levels are considered potential host biomarkers for monitoring the response of treatment for pulmonary TB.

A target-responsive liposome activated by catalytic hairpin assembly enables highly sensitive detection of tuberculosis-related cytokine.

Here, we propose a new fluorescence method to detect tuberculosis-related cytokine by using a target-responsive liposome activated by catalytic hairpin assembly. The method combines a DNA self-assembly based amplification process with a liposome-based signal amplification process, therefore offering a very high sensitivity.

Comparison of closed-chest drainage with rib resection closed drainage for treatment of chronic tuberculous empyema.

BACKGROUND: This study aimed to compare the efficacy of closed-chest drainage with rib resection closed drainage of chronic tuberculous empyema. METHODS: This retrospective study reviewed 86 patients with tuberculous empyema in Shanghai Pulmonary Hospital from August 2010 to November 2015. Among these included patients, 22 patients received closed-chest drainage, and 64 patients received rib resection closed drainage. RESULTS: The results showed that after intercostal chest closed drain treatment, 2 (9.09%) patients were recovery, 13 (59.09%) patients had significantly curative effect, 6 (27.27%) patients had partly curative effect, and 1 (4.55%) patient had negative effect. After treatment of rib resection closed drainage, 9 (14.06%) patients were successfully recovery, 31 (48.44%) patients had significantly curative effect, 19 (29.69%) patients had partly curative effect, and 5 (7.81%) patients had negative effect. There was no significant difference in the curative effect (P>0.05), while the average catheterization time of rib resection closed drainage (130.05±13.12 days) was significant longer than that (126.14±36.84 days) in course of intercostal chest closed drain (P<0.05). CONCLUSIONS: This study had demonstrated that closed-chest drainage was an effective procedure for treating empyema in young patients. It was less invasive than rib resection closed drainage and was associated with less severe pain. We advocated closed-chest drainage for the majority of young patients with empyema, except for those with other diseases.

Short-course Regimen for Subsequent Treatment of Pulmonary Tuberculosis: A Prospective, Randomized, Controlled Multicenter Clinical Trial in China.

PURPOSE: We designed a prospective, multicenter, randomized, controlled study to assess a 5-month regimen compared with the standard regimen on previously treated patients with pulmonary tuberculosis (TB). METHODS: We enrolled 917 sputum smear-positive patients undergoing additional treatment in 27 major tuberculosis hospitals in China. Patients were randomly assigned to a test group (n = 626)treated with a 5-month regimen of moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide or a reference group (n = 291) treated with an 8-month regimen of isoniazid, rifampicin, and streptomycin. All patients with a favorable response were followed up for 5 years after the end of treatment. FINDINGS: Of the study patients, 61 in the test group and 19 in the reference group had multidrug-resistant (MDR) TB. The treatment success rate in the study group was 74.12%, which was significantly higher than the 67.70% in the reference group (P = 0.04), whereas the treatment success rate of patients with MDR-TB was not significantly different between the test and reference groups (70.5% vs 63.1%, P =0.79). The adverse effects rates in the test and reference groups were 7.4% and 3.1%, respectively (P = .01). The difference in the TB recurrence rates between the group arm (9.6%) and the reference group (21.8%) was statistically significant (P < 0.001). IMPLICATIONS: The moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide test regimen yielded higher success and lower recurrence rates than the currently recommended isoniazid, rifampicin, and streptomycin regimen, but the rate of adverse effects was higher. ClinicalTrials.gov identifier: NCT02331823.

Genetic Polymorphisms of SLCO1B1, CYP2E1 and UGT1A1 and Susceptibility to Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Chinese Population-Based Prospective Case-Control Study.

BACKGROUND: Drug transporters and drug-metabolizing enzymes have been linked to drug-induced hepatotoxicity. Solute carrier organic anion transporter family member 1B1 (SLCO1B1), cytochrome P450 2E1 (CYP2E1), and UDP glucuronosyltransferase 1A1 (UGT1A1) were selected as candidate genes to explore their association with susceptibility to anti-tuberculosis drug-induced hepatotoxicity (ATDH). METHODS: Thirty-four tag single nucleotide polymorphisms (tagSNPs) in SLCO1B1, CYP2E1, and UGT1A1 with 10-kb expansion up- and down-stream were genotyped in 461 patients with ATDH and 466 patients without ATDH in a prospective 1:1 matched case-control study. The frequencies and distributions of genotypes and haplotypes were compared between the groups using three genetic models (dominant, recessive, and additive) to identify associations with susceptibility to ATDH. RESULTS: Patients with the rs4149034 G/A, rs1564370 G/C, and rs2900478 T/A genotypes of SLCO1B1 had a significantly lower risk of ATDH, while those carrying the rs2417957 T/T and rs4149063 T/T genotypes had an increased risk. The rs4148323 A/A genotype of UGT1A1 was found to significantly reduce the risk of ATDH. Haplotype analysis showed the TGTG, TTTC, and GTTC haplotypes of SLCO1B1 were associated with an increased ATDH risk, whereas the GACC haplotype was related to a reduced risk. The ATG haplotype of UGT1A1 reduced the risk of ATDH. Moreover, treatment outcomes in tuberculosis patients were further affected by genetic variants of SLCO1B1. CONCLUSIONS: Genetic polymorphisms of SLCO1B1 and UGT1A1 were found to be associated with susceptibility to ATDH. Molecular identification of susceptibility genes provides a theoretical foundation for predicting the likelihood of ATDH and predicting treatment outcomes in tuberculosis patients.

Clinical diagnostic value of simultaneous amplification and testing for the diagnosis of sputum-scarce pulmonary tuberculosis.

BACKGROUND: Since 20% of pulmonary tuberculosis (PTB) patients are asymptomatic, the early detection of PTB is a challenge particularly in sputum-scarce patients and diagnostic accuracy based solely on clinical characteristics and chest X-ray/CT scans are not always satisfactory. The AmpSure simultaneous amplification and testing method for the detection of Mycobacterium tuberculosis (SAT-TB assay) is an alternative approach to diagnose PTB. In the present study, we analyzed the usefulness of the SAT-TB assay for PTB diagnosis in sputum-scarce patients. METHODS: A total of 840 patients were prospectively enrolled for PTB diagnosis with bronchial alveolar lavage fluid (BALF) used as the samples for the SAT-TB assay. Of these, 536 had a definite diagnosis of PTB confirmed by positive microbiology culture, or clinical diagnosis of active PTB following anti-TB treatment with a favorable response. RESULTS: The SAT-TB assay showed a 76.44% agreement with the culture test. The sensitivity and specificity of the SAT-TB assay were 50.75% and 94.73%, respectively. The sensitivity of SAT-TB was significantly higher than that of BALF cultures (21.64%) (X2 = 49.1503; P < 0.001) and smears (4.48%) (X2 = 175.2315; P < 0.001). The specificity of SAT-TB was slightly lower than that of BALF cultures (98.25%) (X2 = 2.0727; P = 0.150) and smears (98.25%) (X2 = 2.0727; P = 0.150). The accuracy rates were 63.87% for SAT-TB, 44.50% for BALF cultures and 29.84% for BALF smears. CONCLUSION: The high accuracy of the SAT-TB assay indicated that active PTB is present and anti-TB treatment is strongly recommended regardless of smear and culture test results for sputum scarce active PTB suspected patients when BALF SAT-TB is positive.