The changes and its significance of peripheral blood NK cells in patients with tuberculous meningitis.

Objective: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). The purpose of this study was to explore the relationship between the number of natural killer (NK) cells and adaptive immune status, and disease severity in TBM patients. Methods: We conducted a retrospective study on 244 TB patients and 146 healthy control subjects in the 8th Medical Center of the PLA General Hospital from March 2018 and August 2023. Results: The absolute count of NK cells in the peripheral blood of TBM patients was significantly lower than that in normal controls (NC), latent tuberculosis infection (LTBI), and non-severe TB (NSTB) patients (p < 0.05). The proportion of TBM patients (48.7%) with a lower absolute count of NK cells than the normal reference value was significantly higher than that in NC (5.2%) and LTBI groups (4.0%) (p < 0.05), and slightly higher than that in NSTB group (36.0%) (p > 0.05). The absolute counts of lymphocyte subsets in TBM combined with other active TB group, etiology (+) group, IGRA (-) group, and antibody (+) group were lower than that in simple TBM group, etiology (-) group, IGRA (+) group, and antibody (-) group, respectively. The CD3+ T, NK, and B cells in BMRC-stage III TBM patients were significantly lower than those in stage I and stage II patients (p < 0.05). The counts of CD3+ T, CD4+ T, and B cells in the etiology (+) group were significantly lower than those in the etiology (-) group (p < 0.05). Conclusion: The absolute counts of lymphocyte subsets in the peripheral blood of TBM patients were significantly decreased, especially in NK cells. The reduction of these immune cells was closely related to the disease severity and had a certain correlation with cellular and humoral immune responses. This study helps to better understand the immune mechanism of TBM and provides reliable indicators for evaluating the immune status of TBM patients in clinical practice.

Building a model for the differential diagnosis of non-tuberculous mycobacterial lung disease and pulmonary tuberculosis: A case-control study based on immunological and radiological features.

BACKGROUND: Although the incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing annually, it is easily misdiagnosed as pulmonary tuberculosis (PTB). This study aimed to screen and identify the immunological and radiological characteristics that differentiate NTM-PD from PTB and to construct a discriminatory diagnostic model for NTM-PD, providing new tools for its differential diagnosis. METHODS: Hospitalised patients diagnosed with NTM-PD or PTB between January 2019 and June 2023 were included in the study. Immunological and radiological characteristics were compared between the two groups. Based on the selected differential features, a logistic regression algorithm was used to construct a discriminatory diagnostic model for NTM-PD, and its diagnostic performance was preliminarily analysed. RESULTS: Patients with NTM-PD were significantly older than those with PTB and the tuberculosis-specific interferon-gamma release assay (TB-IGRA) positivity rate was significantly lower in the NTM-PD group. Moreover, the absolute counts of total T lymphocytes, CD4+ T lymphocytes, CD8+ T lymphocytes, NK cells, and B lymphocytes were significantly lower in patients with NTM-PD and PTB than in healthy controls. Additionally, patients with NTM-PD had a significantly lower absolute count of B lymphocytes than the PTB group. Radiological analysis revealed significant differences between patients with NTM-PD and PTB in terms of cavity wall thickness, bronchial dilation, lung consolidation, pulmonary nodule size, pulmonary emphysema, lung bullae, lymph node calcification, pleural effusion, mediastinal and hilar lymphadenopathy, and the tree-in-bud sign. Bronchial dilation was identified as the predominant risk factor of NTM-PD, whereas TB-IGRA positivity, lymph node calcification, pleural effusion, and mediastinal and hilar lymphadenopathies were protective factors. Based on this, we constructed a discriminatory diagnostic model for NTM-PD. Its receiver operating characteristic curve demonstrated good diagnostic performance, with an area under the curve of 0.938. At the maximum Youden index of 0.746, the sensitivity and specificity were 0.835 and 0.911, respectively. CONCLUSIONS: Patients with NTM-PD and PTB exhibited impaired humoral and cellular immune functions as well as significant differences in radiological features. The constructed NTM-PD diagnostic model demonstrated good diagnostic performance. This study provides a new tool for the differential diagnosis of NTM-PD.

In vitro activities of contezolid (MRX-I) against drug-sensitive and drug-resistant Mycobacterium tuberculosis.

A novel oxazolidinone for the treatment of Mycobacterium tuberculosis has been developed, but the activity of contezolid (MRX-I) still needs to be clarified. In this study, we isolated Mycobacterium tuberculosis from 48 clinical patients with pulmonary tuberculosis. Roche drug susceptibility tests identified drug-sensitive and 39 drug-resistant M. tuberculosis isolates. Drug susceptibility assays indicated that MRX-I exhibited anti-Mycobacterium tuberculosis activity against both drug-sensitive and drug-resistant isolates, with an advantage against drug-resistant isolates. The results also showed that the anti-Mycobacterium tuberculosis activity was comparable to that of linezolid. IMPORTANCE Currently, Mycobacterium tuberculosis has exhibited increased drug resistance, leading to ineffective drug treatment in many patients with tuberculosis. Among the anti-Mycobacterium tuberculosis drugs, oxazolidinones have been gradually developed. Contezolid (MRX-I) has been newly developed in China with advantages versus the first oxazolidinone antibiotic approved by the Food and Drug Administration for clinical use, but the anti-M. tuberculosis activity needs to be further clarified. In this study, in vitro activities of MRX-I against M. tuberculosis were tested. The drug susceptibility assays indicated that MRX-I exhibited anti-M. tuberculosis activity comparable to that of linezolid, with an advantage against drug-resistant isolates.

Clinical characteristics of patients with non-tuberculous mycobacterial pulmonary disease: a seven-year follow-up study conducted in a certain tertiary hospital in Beijing.

Background: The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in recent years. However, the clinical and immunologic characteristics of NTM-PD patients have received little attention. Methods: NTM strains, clinical symptoms, underlying diseases, lung CT findings, lymphocyte subsets, and drug susceptibility tests (DSTs) of NTM-PD patients were investigated. Then, the counts of immune cells of NTM-PD patients and their correlation were evaluated using principal component analysis (PCA) and correlation analysis. Results: 135 NTM-PD patients and 30 healthy controls (HCs) were enrolled from 2015 to 2021 in a certain tertiary hospital in Beijing. The number of NTM-PD patients increased every year, and Mycobacterium intracellulare (M. intracellulare), M. abscessus, M. avium, and M. kansasii were the major pathogens of NTM-PD. The main clinical symptoms of NTM-PD patients were cough and sputum production, and the primary lung CT findings were thin-walled cavity, bronchiectasis, and nodules. In addition, we identified 23 clinical isolates from 87 NTM-PD patients with strain records. The DST showed that almost all of M. abscessus and M. avium and more than half of the M. intracellulare and M. avium complex groups were resistant to anti-tuberculosis drugs tested in this study. M. xenopi was resistant to all aminoglycosides. M. kansasii was 100% resistant to kanamycin, capreomycin, amikacin, and para-aminosalicylic acid, and sensitive to streptomycin, ethambutol, levofloxacin, azithromycin, and rifamycin. Compared to other drugs, low resistance to rifabutin and azithromycin was observed among NTM-PD isolates. Furthermore, the absolute counts of innate and adaptive immune cells in NTM-PD patients were significantly lower than those in HCs. PCA and correlation analysis revealed that total T, CD4+, and CD8+ T lymphocytes played an essential role in the protective immunity of NTM-PD patients, and there was a robust positive correlation between them. Conclusion: The incidence of NTM-PD increased annually in Beijing. Individuals with bronchiectasis and COPD have been shown to be highly susceptible to NTM-PD. NTM-PD patients is characterized by compromised immune function, non-specific clinical symptoms, high drug resistance, thin-walled cavity damage on imaging, as well as significantly reduced numbers of both innate and adaptive immune cells.

Endobronchial Valve Treatment of Tuberculous Cavities in Patients with Multidrug-Resistant Pulmonary Tuberculosis: A Randomized Clinical Study.

Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity.

The relationship between absolute counts of lymphocyte subsets and clinical features in patients with pulmonary tuberculosis.

BACKGROUND: The aim of the present study is to investigate the clinical value and characteristics of peripheral blood lymphocyte subsets in patients with pulmonary tuberculosis (PTB) using flow cytometry. METHODS: The absolute counts of T, CD4+ T, CD8+ T, natural killer (NK), NKT and B lymphocytes in 217 cases of PTB were detected, and the variations in lymphocyte subset counts between different ages and genders and between aetiological detection results and chest radiography results were analysed. RESULTS: In 75.3% of the patients with PTB, six subset counts were lower than the normal reference range, and 44% showed lower-than-normal CD4+ T lymphocyte levels. The counts of T, CD4+ T, CD8+ T and B lymphocytes were significantly lower in patients aged >60 years, and the NKT cell counts were significantly lower in female patients than in male patients. Among the patients with positive aetiological results, 40.8% had reduced CD8+ T counts; these were significantly lower than those in patients with negative aetiological results (P = 0.0295). The cell counts of T, CD4+ T, CD8+ T and B lymphocytes reduced as lesion lobe numbers increased. The counts of T, CD4+ T and CD8+ T lymphocytes were significantly higher in the group with lesions affecting one lobe than in the groups with two to three lobes or four to five lobes, and the counts of B lymphocytes were significantly higher in the group with one lobe and the group with two to three lobes than in the group with four to five lobes. The counts of CD4+ T and CD8+ T lymphocytes were highest in the no cavity group and showed a downward trend with the increase in cavities; the T lymphocyte count was significantly higher in the no cavity group than in the group with five or more cavities (P = 0.014), and the CD8+ T lymphocyte count was significantly higher in the no cavity group than in the group with one to two cavities and the group with five or more cavities (P = 0.001 and 0.01, respectively). CONCLUSIONS: In most patients with tuberculosis, immune function is impaired. The absolute counts of peripheral blood lymphocyte subsets are closely related to the aetiological results and lesion severity in patients with PTB; this could be used as evidence for immune intervention and monitoring curative effects.

Clinical Efficacy of a Combination of Thymopentin and Antituberculosis Drugs in Treating Drug-Resistant Pulmonary Tuberculosis: Meta Analysis.

Objective: To make a systematic evaluation of the clinical efficacy of thymopentin combined with antituberculous drugs in treating drug-resistant pulmonary TB (PTB). Methods: Relevant studies were retrieved from PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database, CNKI, and Wanfang Database. STATA software was used to evaluate the differences in focal absorption rate, the time to cough symptom remission, sputum culture-negative rate, CD3+ T, CD4+ T, and CD8+ T cell levels after treatment. Results: A total of 23 randomized controlled trials literature involving 2031 cases were included. Meta-analysis revealed that compared with conventional therapy, the sputum culture-negative rate was significantly increased after 2-3 months and 6-9 months of treatment and the whole course of combined thymopentin treatment. The risk ratio (RR, 95% CI) was 1.44 (1.26-1.64), 1.47 (1.21-1.78), and 1.27 (1.18-1.36), respectively. In the combined thymopentin treatment group, the focal absorption rate was higher, with RR (95% CI) = 1.36 (1.25-1.47), the time of cough remission was shortened, with WMD (95% CI) =-9.46d (-10.36,-8.57) and the differences were all statistically significant. Combined thymopentin therapy could effectively improve the levels of CD3+ T and CD4+ T lymphocytes in patients with drug-resistant PTB after 2-3 months, 6-9 months of treatment. The WMD (95% CI) were 9.96% (7.84, 12.08), 4.68% (2.90, 6.47) and 10.26% (7.81, 12.71), 7.21% (6.28, 8.15), respectively, and could also reduce the level of CD8+ T lymphocytes after 2-3 months and 6-9 months of treatment. The WMD (95% CI) were -4.06% (-4.96, -3.13), -3.52%, (-4.07,-2.98), respectively, and the differences were all statistically significant. Conclusion: Thymopentin adjuvant treatment for drug-resistant PTB can promote the therapeutic effect and improve the immune indexes in patients with drug-resistant PTB.

Meta-Analysis of the Factors Influencing the Restoration of Spontaneous Circulation After Cardiopulmonary Resuscitation.

Objective: This study aimed to systematically evaluate the factors influencing the restoration of spontaneous circulation (ROSC) after cardiopulmonary arrest (CA). Methods: Relevant papers on the factors influencing the ROSC in patients with CA were retrieved from PubMed, Embase, Cochrane Library, China Biology Medicine disk, China National Knowledge Infrastructure, Wanfang, and VIP databases. After screening, data extraction, and quality evaluation of the papers, a meta-analysis was carried out. Results: A total of 36 papers, involving a total sample size of 2,305 cases, were included. The meta-analysis revealed that the location and time of onset of CA, the type of cardiac rhythm at first monitoring, the start time of cardiopulmonary resuscitation (CPR), the use of electric defibrillation, and the cumulative dose of adrenaline all significantly impacted the ROSC (p < 0.05) and may have affected its success rate. The pH value at CA onset, combined use of adrenaline and vasopressin, CPR duration, mechanical cardiac compression use, and whether CA was caused by heart disease had no significant effect on ROSC. Conclusion: The location and time of onset of CA, the cardiac rhythm at first monitoring, the start time of CPR, the use of electric defibrillation, and the cumulative dose of adrenaline significantly impacted the ROSC.

Decreased mortality seen in rifampicin/multidrug-resistant tuberculous meningitis treated with linezolid in Shenzhen, China.

BACKGROUND: The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors. METHODS: We conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P < 0.05 was considered statistically significant. RESULTS: Most patients (111/137, 81%) were from southern or southwestern China, and a large proportion (72/137, 52.55%) belonged to migrant workers. 12 cases were RR/MDR-TBM (12/137, 8.8%) while 125 cases were NRR/MDR-TBM (125/137, 91.2%). The proportion of patients having prior TB treatment history in the RR/MDR-TBM group was significantly higher than that of the NRR/MDR-TBM group (6/12 vs. 12/125, 50% vs. 10.5%, P < 0.01). No significant difference was observed on other clinical and examination features between the two groups. Mortality was significantly lower in RR/MDR-TBM patients on linezolid-containing treatment regimen than those who were not (0/7 versus 3/5, 0% versus 60%, P = 0.045). CONCLUSIONS: The main related risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid-containing regimen appears to lower mortality rate of RR/MDR-TBM significantly in our study. We think Linezolid should be evaluated prospectively in the treatment of RR/MDR-TBM.

Exploratory development of PCR-fluorescent probes in rapid detection of mutations associated with extensively drug-resistant tuberculosis.

This study aims to evaluate the clinical value of PCR-fluorescent probes for detecting the mutation gene associated with extensively drug-resistant tuberculosis (XDR-TB). The molecular species identification of 900 sputum specimens was performed using polymerase chain reaction (PCR)-fluorescent probe. The mutations of the drug resistance genes rpoB, katG, inhA, embB, rpsL, rrs, and gyrA were detected. The conventional drug susceptibility testing (DST) and PCR-directed sequencing (PCR-DS) were carried out as control. DST demonstrated that there were 501 strains of rifampicin resistance, 451 strains of isoniazid resistance, 293 strains of quinolone resistance, 425 strains of streptomycin resistance, 235 strains of ethambutol resistance, and 204 strains of amikacin resistance. Furthermore, 427 (47.44%) or 146 (16.22%) strains were MDR-TB or XDR-TB, respectively. The mutations of the rpoB, katG, inhA, embB, rpsL, rrs, and gyrA genes were detected in 751 of 900 TB patients by PCR-fluorescent probe method, and the rate of drug resistance was 751/900 (83.44%). No mutant genes were detected in the other 149 patients. Compared with DST, the mutant rates of rpoB, katG/inhA, rpsL, rrs, embB, and gyrA of six drugs were higher than 88%; five of six drugs were higher than 90% except for SM (88.11%). The MDR and XDR mutant gene types were found in 398 (42.22%) and 137 (15.22%) samples. PCR-DS was also employed and confirmed the PCR-fluorescent probe method with the accordance rate of 100%. The PCR-fluorescent probe method is rapid and straightforward in detecting XDR-TB genotypes and is worthy of being applied in hospitals.

Mannose-binding lectin 2 gene polymorphisms and their association with tuberculosis in a Chinese population.

BACKGROUND: Immune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population. METHODS: We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis. RESULTS: We observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152-1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055-1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349-0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087-1.793) effect against the development of TB. CONCLUSIONS: This study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future.

Diagnostic performance and problem analysis of commercial tuberculosis antibody detection kits in China.

BACKGROUND: The diagnosis of bacterium-negative pulmonary tuberculosis (TB) and extra-pulmonary TB is challenging clinically. The detection of the anti-TB antibody has an important, auxiliary, clinical diagnostic value. Therefore, TB antibody detection kits should be screened and evaluated, and the reagents with the highest sensitivity and specificity should be chosen and used clinically. METHODS: The diagnostic performance of 7 commercially available TB antibody detection kits (kits A, B, C, D, E, F and G) based on the gold immunoassay detection of immunoglobulin (Ig) G or IgM antibodies were simultaneously evaluated and compared in 62 TB cases and 56 non-TB cases in a laboratory. A retrospective analysis including 2549 cases was carried out to assess the clinical diagnosis values of bacteriological examinations and TB antibody tests (kits B and H used in the clinic). RESULTS: The sensitivities of TB antibody kits A, B, C, D, E, F and G in the sera from 62 TB patients were 50.0%, 83.9%, 38.7%, 9.7%, 48.4%, 69.4% and 79.0%, respectively; the sensitivities in the sera from 24 smear-negative TB patients were 29.2%, 79.2%, 29.2%, 12.5%, 29.2%, 54.2% and 79.2%, respectively; the specificities in the sera from 56 non-TB patients were 73.2%, 25.0%, 85.7%, 96.4%, 78.6%, 78.6% and 50.0%, respectively. Of the 2549 clinically diagnosed cases, there were 1752 pulmonary TB cases, 505 extra-pulmonary TB cases, 87 old pulmonary TB cases and 205 non-TB cases. The positive results for smear, culture, TB antibody kit B and kit H in pulmonary TB cases were 39.8% (543/1365), 48.6% (372/765), 45.8% (802/1752) and 25.2% (442/1752), respectively; the results in extra-pulmonary TB cases were 3.4% (6/178), 5.8% (4/69), 35.4% (179/505), and 11.3% (57/505), respectively; the results in old pulmonary TB cases were 0% (0/64), 0% (0/30), 32.2% (28/87), and 9.2% (8/87), respectively; and the results in non-TB cases were 0% (0/121), 0% (0/56), 21.5% (44/205), and 2.4% (5/205), respectively. Of 624 smear-positive and/or culture-positive pulmonary TB cases, the sensitivities of antibody test kits B and H were 53.0% and 36.4%, respectively. Of 901 smear-negative and/or culture-negative pulmonary TB cases, the sensitivities of antibody test kits B and H were 42.5% and 19.0%, respectively. The positive rate of antibody detection in the bacterium-positive pulmonary TB cases was significantly higher than that in the bacterium-negative pulmonary TB cases (P < 0.05). CONCLUSIONS: The colloidal gold-labeled TB antibody IgG detection assay is a simple, rapid and economical method that provides a better clinical auxiliary diagnosis value on TB, especially in smear-negative pulmonary TB and extra-pulmonary TB. The production, quality control, screening and evaluation of antibody detection kits are very important for its clinical application.

Clinical efficacy of short-course chemotherapy combined with topical injection therapy in treatment of superficial lymph node tuberculosis.

To evaluate the clinical efficacy and safety of short-course chemotherapy combined with regional injection therapy in the treatment of superficial lymph node tuberculosis. 201 patients diagnosed with superficial lymph node tuberculosis were retrospectively analyzed. All patients were randomly divided into the study (n = 100) and control groups (n = 101). In the study group, the patients received 6-month chemotherapy with isoniazid (H), rifampin (R) and ethambutol (E) (6HRE) in combination with regional injection of streptomycin, and their counterparts in the control group underwent systemic regime of 3HRZE/6HRE. In the study group, the overall cure rate was calculated as 98% and the recurrence rate was 2%. Twenty-four of 25 nodular type patients and 36 among 37 inflammatory type patients were recovered and discharged. One patient with huge nodular type mass was treated for 4 months and the mass size was slightly reduced. In the control group, the overall cure rate was 48.5% and the recurrence rate was 7.9%. The recurrent patients were further administered with regional injection of streptomycin based upon the chemotherapy regime until they were recovered. Combined therapy of systemic chemotherapy and regional injection of streptomycin is probably an efficacious and safe approach in the treatment of superficial lymph node tuberculosis, which remains to be validated by more investigations.

Immune responses to latent tuberculosis antigen Rv2659c in Chinese populations.

BACKGROUND: The latency-associated antigen Rv2659c is a starvation-related protein of Mycobacterium tuberculosis (M. tuberculosis). It has potential use in tuberculosis (TB) control, but its immunological characteristics in Chinese populations are unclear. METHODS: In this study, immunological characteristics and potential diagnostic use of recombinant Rv2659c protein were assessed. Interferon-γ (IFN-γ) production from peripheral blood mononuclear cells (PBMC) was assayed by enzyme-linked immunospot (ELISPOT) in TB patients (80 cases), individuals who were purified protein derivative (PPD)-positive after Bacillus Calmette-Guérin (BCG) vaccination (27 cases), nontuberculous respiratory disease patients (30 cases), individuals who were identified by standard techniques as having latent TB infection (LTBI) (37 cases), and uninfected healthy individuals (75 cases). Serum immunoglobulin G (IgG) levels were assayed by enzyme-linked immunosorbent assay (ELISA) in TB patients (43 cases), LTBI individuals (36 cases) and uninfected healthy individuals (66 cases). RESULTS: When stimulated by rRv2659c, PBMC from LTBI individuals gave ELISPOT counts that were significantly higher than those from TB patients, BCG vaccinated individuals, non-TB respiratory disease patients and uninfected healthy individuals (p < 0.05). The rRv2659c stimulation gave detectable IFN-γ production in a higher proportion of persons with LTBI compared with TB patients and uninfected healthy individuals. BCG vaccination and non-TB respiratory disease had little influence on the PBMC response to rRv2659c. The levels of serum IgG specific for rRv2659c were not significantly different between LTBI individuals and TB patients (p > 0.05). CONCLUSION: These results suggest that rRv2659c has potential for the diagnosis of LTBI. This is the first clinical report of human immune recognition of Rv2659c in Chinese populations.

Polymorphisms in the interleukin 18 receptor 1 gene and tuberculosis susceptibility among Chinese.

Tuberculosis (TB), an infectious disease caused by infection of Mycobacterium tuberculosis, is a major public health challenge globally. Genetic epidemiological evidence suggests a genetic basis for TB, but the molecular mechanism for a genetic predisposition to TB remains largely unknown. Thirty-five tag single-nucleotide polymorphisms (SNPs) across 11 candidate cytokines and related genes, including IL-12/IFN-γ axis genes (IL12B, IL12RB1, IL18R1, IL27, IFNGR1, IFNGR2 and STAT1), the TNF gene locus (TNF and LTA), IL10, and CCL2, were genotyped using Sequenom's iPLEX assays in 1,032 patients with TB and 1,008 controls of Chinese Han origin. We did not find that any of the 35 tag SNPs individually or as haplotypes was significantly associated with susceptibility to TB, on the basis of multivariable logistic regression analysis with adjustment for age and sex. However, stratification analyses showed that, in those with age 46 years or older, carrying the rs1974675 T allele in the IL18R1 gene had a significantly decreased susceptibility to TB occurrence compared with carrying the C/C genotype (OR = 0.57, P = 5.0×10(-4)). Further analysis indicated that a SNP in absolute linkage disequilibrium with rs1974675, rs3755276, is located within a CpG dinucleotide and showed hypomethylation in controls than in patients (19.6% vs. 31.4%; P = 1.0×10(-4)) and genotype-specific DNA methylation at the IL18R1 promoter and IL18R1 mRNA levels. In addition, DNA methylation levels were significantly inversely correlated with mRNA levels. Thus, decreased mRNA levels of IL18R1 due to rs3755276 may partially mediate the increased susceptibility to TB risk.

[The relationship between carboxylesterase 1 gene polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity].

OBJECTIVE: To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CES1) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH). METHODS: Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200:273) after antituberculosis chemotherapy were analyzed by PCR-MassArray. RESULTS: In 4 tags of CES1 single nucleotide polymorphism (SNP), the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group(P = 0.0236). The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 (P = 0.044, OR = 0.649, 95%CI = 0.426 - 0.989, AC/AA) and rs1968753 (P = 0.048, OR = 0.556, 95%CI = 0.311 - 0.995, GG/AA). The diplotypes with 'CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P = 0.048, OR = 0.654, 95%CI = 0.430 - 0.996). CONCLUSIONS: The genetic polymorphisms of CES1 might have significant association with ATBDIH. SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.

NAT2 and CYP2E1 polymorphisms associated with antituberculosis drug-induced hepatotoxicity in Chinese patients.

1. The present study investigated the relationship between antituberculosis (anti-TB) drug-induced hepatotoxicity and genetic polymorphisms of two important drug-metabolizing enzymes involved in the metabolism of isoniazid, namely N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1). 2. A polymerase chain reaction direct sequencing approach was used to detect genetic polymorphisms of the NAT2 and CYP2E1 genes in tuberculosis (TB) patients with (n = 101) or without (n = 107) anti-TB drug-induced hepatotoxicity. Associations between various genetic polymorphisms and anti-TB drug-induced hepatotoxicity were then determined. 3. Patients with NAT2 (282TT , 590AA and 857GA) alleles had an increased susceptibility to anti-TB drug-induced hepatotoxicity. The slow acetylator NAT2 genotypes (especially NAT2*6A/7B and NAT2*6A/6A) were risk factors for hepatotoxicity (odds ratio (OR) 9.57 (P < 0.001) for NAT2*6A/7B; OR 5.24 (P = 0.02) for NAT2*6A/6A). 4. The CYP2E1 genotype per se was not significantly associated with the development of anti-TB drug-induced hepatotoxicity. However, the combination of the CYP2E1 C1/C1 genotype with a slow acetylator NAT2 genotype increased the risk of anti-TB drug-induced hepatotoxicity (OR 5.33; P = 0.003) compared with the combination of a rapid acetylator NAT2 genotype with either a C1/C2 or C2/C2 genotype. 5. Thus, slow acetylators with the NAT2*6A/7B and NAT2*6A/6A genotypes combined with the C1/C1 CYP2E1 genotype may be involved in the pathogenesis of anti-TB drug-induced hepatotoxicity. 6. The present findings may be explained, in part, by changes in the metabolism of the anti-TB drug isoniazid induced via NAT2 and CYP2E1, a metabolic process known to produce hepatotoxic intermediates.

[The associations of polymorphism of N-acetyltransferase 2 gene is associated with antituberculosis drug-induced hepatotoxicity in tuberculosis patients].

OBJECTIVE: To study the possible relationship between polymorphic N-acetyltransferase 2 (NAT2) acetylator status and antituberculosis drug-induced hepatotoxicity and to elucidate the molecular mechanism of antituberculosis drug-induced hepatotoxicity. METHODS: Blood samples from 101 tuberculosis cases with antituberculosis drug-induced hepatotoxicity and from 107 tuberculosis without antituberculosis drug-induced hepatotoxicity were collected for a case-control study. DNA of the subjects was extracted and amplified by polymerase chain reaction (PCR). The single nucleotide polymorphisms of NAT2 were determined by direct PCR sequencing. The genotype frequencies were compared between cases and controls by χ(2) test, using SPSS 12.0 software, and the association between the disease and genotypes was analyzed. RESULTS: Among the 101 patients with antituberculosis drug-induced liver injury, 36 patients (35.6%) were found with 282 T/T, 12 (11.9%) with 590 A/A, and 48 (47.5%) with 857 G/A or A/A. However, among the 107 controls, 9 patients (8.4%) were found with 282 T/T, 3 (2.8%) with 590 A/A, and 33 (33.8%) with 857 G/A or A/A. The patients with 282 T/T, 590 A/A, or 857 G/A or A/A genotype had a higher risk of antituberculosis drug-induced hepatotoxicity than those with 282 C/C or C/T, 590 G/G or G/A, or 857 G/G, and the OR values were 6.03 (95%CI: 2.88 - 12.62; χ(2) = 22.73, P < 0.05), 4.67 (95%CI: 1.42 - 15.44; χ(2) = 6.40, P < 0.05) and 2.03 (95%CI: 1.16 - 3.57; χ(2) = 6.08, P < 0.05) respectively. There were 40 patients with slow acetylator (39.6%) in cases with hepatotoxicity and 13 with slow acetylator (12.2%) in controls without hepatotoxicity. Patients with slow acetylator genotype (OR = 4.74, 95% CI = 2.42 - 9.28; χ(2) = 20.62, P < 0.05) had a significantly higher risk of antituberculosis drug-induced hepatotoxicity than those with rapid or intermediate acetylator genotypes. Among the cases, 19.8% (20/101) were found with NAT2(*)6A/7B, and 11.9% (12/101) with NAT2(*)6A/6A, whereas among the controls, 2.8% (3/107) were found with NAT2(*)6A/7B, and 2.8% (3/107) with NAT2(*)6A/6A respectively, the patients with NAT2(*)6A/7B and NAT2(*)6A/6A had a much higher risk of antituberculosis drug-induced hepatotoxicity, and the OR values were 8.40 (95%CI: 2.85 - 24.73; χ(2) = 14.90, P < 0.05) and 4.67 (95%CI: 1.42 - 15.44; χ(2) = 6.40, P < 0.05) respectively. CONCLUSION: Perhaps, the slow acetylation genotypes of NAT2 were the main risk factors of developing antituberculosis drug-induced hepatotoxicity.

[Tuberculosis after organ transplantation: clinical analysis and literature review].

OBJECTIVE: To describe the clinical features, diagnosis and treatment of tuberculosis after organ transplantation. METHOD: The clinical data of 25 cases of tuberculosis after organ transplantation were retrospectively analyzed. RESULTS: Sixty-eight percent of the patients presented only mild symptoms. Fever, cough, malaise and chest tightness were among the most common manifestations. Pulmonary tuberculosis, pleurisy, miliary lesions, lymph node disease, and kidney tuberculosis were common. Involvement of two organs were present in 72% (18/25) of the patients. Radiology showed soft lesions, miliary nodules, pleural effusion, hilar and mediastinal lymphadenopathy. Bacteriology and histology were used to confirm the diagnosis in most cases. The average time from presentation to diagnosis was 38 d. The effective rate of therapy was 76% (19/25). CONCLUSION: More attention should be paid to tuberculosis after organ transplantation and immunosuppression. Prompt diagnosis and treatment are important measures to reduce the mortality.