Guideline for clinical diagnosis and treatment of tuberculosis in kidney transplant recipients in China (2023 edition) / 器官移植

This guideline aims to provide comprehensive and practical guidance for clinical management of tuberculosis in kidney transplant recipients. First, it summarizes the particularity of tuberculosis in kidney transplant recipients, and highlights the high incidence and diverse clinical manifestations. To better understand the patients' conditions, relevant assessment of tuberculosis is recommended before kidney transplantation. Extensive attention should be paid to the monitoring of tuberculosis after kidney transplantation. Regarding the diagnosis, the guideline explicitly introduces common diagnostic approaches for tuberculosis, and evaluates the applicability in kidney transplant recipients. After the diagnosis is confirmed, it discusses how to balance the treatment and rejection of tuberculosis under the background of immunosuppressants, and focuses upon the potential drug interaction. In terms of prevention, it emphasizes the screening of tuberculosis prior to kidney transplantation. This guideline is designed to deepen the understanding of medical staff for tuberculosis management in kidney transplant recipients, promote more effective clinical practice and improve the quality of life of the recipients.

Meta-analysis of miRNA in discriminating active tuberculosis and latent tuberculosis / 国际检验医学杂志

Objective To investigate the Meta-analysis of microRNA(miRNA)in distinguishing active tu-berculosis and latent tuberculosis.Methods CNKI,Wanfang Data,VIP,PubMed,Cochrane Library,Web of Science and Embase databases were searched to select the literature on miRNA in discriminating active tuber-culosis and latent tuberculosis from the establishment of the database to April 2023,and screened strictly ac-cording to the inclusion and exclusion criteria.The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2,and data extraction and summary analysis were carried out with Stata16.0 software.Heterogeneity among studies was evaluated by calculating I2,and the sources of heteroge-neity were further explored by Meta-regression and subgroup analysis.Publication bias was assessed using Deeks funnel plot.Results The Meta-analysis encompassed 9 articles,comprising 13 studies.The combined sensitivity of miRNA in differentiating active tuberculosis and latent tuberculosis was found to be 0.79(95％CI:0.69-0.86,I2=86.24％),with a specificity of 0.73(95％CI:0.64-0.81,I2=81.80％).The positive likelihood ratio was 2.96(95％CI:2.22-3.95,12=63.84％),while the negative likelihood ratio was 0.29(95％CI:0.20-0.41,I2=84.04％).Furthermore,the diagnostic odds ratio was 10.33(95％CI:6.43-16.61,I2=99.90％),and the area under the receiver operating characteristic curve was 0.83(95％CI:0.79-0.86).The results of Meta-regression and subgroup analysis showed that sample size may be the source of sensitivity heterogeneity,and dysregulation of miRNA may be the source of specificity heterogeneity.Deeks funnel plot showed no publication bias among included studies.Conclusion miRNA shows good diagnostic a-bility in distinguishing active tuberculosis and latent tuberculosis,which has important significance for impro-ving the development of diagnostic strategies for tuberculosis management.

Expression profile of mRNA sequencing for plasma exosomes among patients with latent tuberculosis infection and active tuberculosis / 预防医学

Objective@#To analyse the expression of differential mRNA in the plasma exosomes in patients with latent tuberculosis infection (LTBI) and active tuberculosis (ATB) using high-throughput sequencing, so as to provide insights into differential diagnosis of LTBI and ATB.@*Methods@#The plasma samples were collected from the patients treated at The Affiliated Hospital of Hangzhou Normal University, including 16 cases of LTBI and 21 cases of ATB. The exosomes were extracted by Invitrogen extracellular extracts purification kit, and the size and morphology of exosomes were observed by transmission electron microscope (TEM). The exosomes were identified by Western blotting. Total RNA was extracted from plasma exosomes using high-throughput sequencing, differential expression mRNA was identified, and gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Two differential mRNAs with the highest differential expression fold were selected, and five patients with ATB and three patients with LTBI were recruited for verification using real-time quantitative PCR.@*Results@#The sequencing results of plasma exosomes showed that compared with ATB patients, 2 875 differentially expressed mRNAs were detected in exosomes of LTBI patients, of which 1 002 mRNAs were up-regulated and 1 873 mRNAs were down-regulated. The most significant differentially expressed downregulated and upregulated mRNA were M6PR and RGPD5, respectively. GO analysis and KEGG pathway analysis showed that differential mRNAs were enriched in protein serine kinase activity, rRNA binding molecular function, human cytomegalovirus infection, pancreatic cancer, endometrial cancer, insulin signaling pathway and FoxO signaling pathway. The real-time quantitative PCR showed that the expression of differential mRNA was consistent with sequencing. Compared with ATB patients, the relative expression level of M6PR in plasma exosomes in LTBI patients (0.954±0.212) was downregulated compared with that of ATB patients (2.168±0.226), while the relative expression level of RGPD5 (2.126±0.200) was upregulated compared with that of ATB patients (0.588±0.129) (both P<0.05).@*Conclusions@#There is a difference in mRNA expression of plasma exosomes between patients with LTBI and ATB. M6PR and RGPD5 may become markers for distinguishing plasma exosomes between LTBI and ATB.

Analysis of treatment outcomes of elderly pulmonary tuberculosis aged 65 and above in Chongqing from 2015 to 2020 / 中国热带医学

@#Abstract: Objective　To analyze the treatment outcomes of elderly patients with pulmonary tuberculosis in Chongqing, so as to provide reference for the prevention and control strategies of the epidemic of elderly pulmonary tuberculosis. Methods　The data of tuberculosis cases aged ≥65 years in Chongqing from 2015 to 2020 were collected from the National Health Insurance Information Project Disease Prevention and Control Information system. Descriptive statistical methods were used to analyze the data. Results The registration rates of elderly active pulmonary tuberculosis patients and etiological positive patients were 110.95/10-5and 32.25/10-5 in 2015 and 84.06/10-5 and 57.29/10-5 in 2020. The annual decline rate of active tuberculosis registration was 5.40%, and the annual increase rate of pathogenic-positive tuberculosis registration was 12.18%. The registration rates of active tuberculosis patients and etiological positive patients in the whole population were 70.75/10-5 and 17.63/10-5 in 2015 and 50.34/10-5 and 29.14/10-5 in 2020. The annual decline rate of active tuberculosis registration was 6.58%, and the annual increase rate of pathogenic-positive tuberculosis registration was 10.57%. From 2015 to 2020, a total of 25 931 cases of elderly pulmonary tuberculosis were registered, of which 21 374 (82.43%) cases were successfully treated and 4 010 (15.80%) cases had unfavorable outcomes. The proportion of cured and death patients showed an increasing trend year by year (χ2trend=313.853, 100.502, P<0.01). From 2015 to 2020, the average annual successful treatment rate of elderly pulmonary tuberculosis in the whole city was 82.43%, with the lowest rate in southeast Chongqing (74.23%), followed by urban areas (81.99%). The success rate of elderly pulmonary tuberculosis treatment in the whole city, west Chongqing, northeast Chongqing and southeast Chongqing showed a downward trend year by year (χ2trend=230.199, 35.278, 108.076, 112.130, all P<0.01), with annual decline rates of 2.77%, 2.26%, 3.0% and 4.12%, respectively. Among the registered elderly patients, female, 65-<75 years old, Han nationality, newly diagnosed, no complications, and negative for etiology (χ2=15.234, 255.910, 146.842, 179.998, 25.575, 131.170, P<0.01) had higher success treatment rates. Conclusions The prevalence of pulmonary tuberculosis in the elderly population in Chongqing City is declining, but the positive registration rate of etiology is increasing annually, and the success rate of treatment is decreasing. Therefore, it is necessary to strengthen the systematic management, publicity and education of elderly patients (especially those in southeast Chongqing, male, positive patients and severe patients) to effectively control the epidemic of tuberculosis in the elderly.

Novel biomarkers combination in the application of discriminating active tuberculosis and latent tuberculosis infection / 中华传染病杂志

Objective:To evaluate the expressions of three biomarkers combination of CD27, CD38 and human leucocyte antigen (HLA)-DR in the application of discrminating active tuberculosis (ATB) and latent tuberculosis infection (LTBI).Methods:Sixty cases of ATB and 44 cases of LTBI were enrolled from March 2021 to February 2022 in Huashan Hospital, Fudan University and Wuxi Fifth People′s Hospital. Freshly isolated peripheral blood mononuclear cells (PBMC) from patients were stimulated with 6 kDa early secretory antigenic target/culture filtrate protein 10 peptide pools. The expressions of CD27, CD38 and HLA-DR on Mycobacterium tuberculosis-specific CD4 + T lymphocytes were evaluated by polychromatic flow cytometry. Mann-Whitney U test was used for statistical analysis. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the diagnostic value of biomarkers in discriminating ATB and LTBI. Results:The frequencies of CD27 -, CD38 +, HLA-DR +, CD27 -CD38 +, CD27 -HLA-DR + and CD38 + HLA-DR + in ATB group were all higher than those in LTBI group, and the differences were all statistically significant ( U=26.00, 451.00, 384.00, 8.00, 7.00 and 184.00, respectively, all P<0.001). The AUROC of CD27 -CD4 + interferon-γ(IFN-γ) + T lymphocytes was 0.71 with a cut-off value of 52.31%, with the sensitivity of 50.00% and specificity of 87.20%. The AUROC of CD38 + CD4 + IFN-γ + T lymphocytes was 0.82 with a cut-off value of 30.25%, with the sensitivity of 73.40% and specificity of 89.70%. The AUROC of HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.85 with a cut-off value of 36.60%, with the sensitivity of 66.00% and specificity of 94.90%. The AUROC of CD27 -CD38 + CD4 + IFN-γ + T lymphocytes was 0.80 with a cut-off value of 8.82%, with the sensitivity of 90.60% and specificity of 61.50%. The AUROC of CD27 -HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.83 with a cut-off value of 18.62%, with the sensitivity of 75.00% and specificity of 79.50%. The AUROC of CD38 + HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.93 with a cut-off value of 22.35%, with the sensitivity of 79.70% and specificity of 100.00%. Conclusions:The expressions of CD27 -, CD38 + and HLA-DR + in Mycobacterium tuberculosis-specific CD4 + T lymphocytes are higher in ATB group compared to LTBI group. ATB and LTBI could be well discriminated by detecting the expressions of CD27, CD38 and HLA-DR on CD4 + IFN-γ + T lymphocytes with flow cytometry.

Preliminary study on the role of glycoprotein A repetitions predominant in regulating tuberculosis pathogenesis through regulatory T cells / 中华传染病杂志

Objective:To investigate the role of glycoprotein A repetitions predominant (GARP) in the pathogenesis of tuberculosis through regulatory T cell (Treg), in order to provide new targets for the treatment of tuberculosis.Methods:Sixty patients with active pulmonary tuberculosis (ATB) admitted to Huashan Hospital, Fudan University and Wuxi Fifth People′s Hospital from January to September 2021 were included. And six individuals with latent tuberculosis infection (LTBI), and 16 healthy controls (HC) were recruited during the same period. Flow cytometry was performed to detect the proportion of Treg in the peripheral blood, and the expressions of GARP and transforming growth factor-β1 (TGF-β1) on Treg in different groups. Mann-Whitney U test was used for statistical analysis. Results:Among the 60 patients with ATB, 23 patients did not receive anti-tuberculosis drug therapy, 17 patients were treated for less than three months, ten patients were treated for three to less than six months, and ten patients were treated for greater than or equal to six months. The percentage of CD4 + CD25 + forkhead box protein 3 (Foxp3) + Treg in untreated ATB patients was 7.50%(5.67%, 9.00%), which was higher than that in HC (5.57%(5.03%, 6.09%)), and the difference was statistically significant ( U=95.00, P=0.010). The percentage of GARP expressing in CD4 + CD25 + Foxp3 + Treg in untreated ATB patients was 10.37%(7.79%, 12.90%), which was higher than that in LTBI (7.02%(5.15%, 8.81%)) and HC (5.33%(4.26%, 6.67%)), respectively, and the differences were both statistically significant ( U=31.00, P=0.040; U=36.00, P<0.001, respectively), while there was no significant difference between LTBI and HC ( U=25.00, P=0.095). The percentage of CD4 + CD25 + Foxp3 + Treg expressing TGF-β1 in untreated ATB patients was 7.13%(4.25%, 8.89%), which was higher than that in HC (3.59%(2.10%, 5.17%)), and the difference was statistically significant ( U=71.00, P=0.001). The expressions of GARP in CD4 + CD8 -CD25 + Foxp3 + Treg in patients with ATB treated for less than three months group, three to less than six months group and greater than or equal to six months group were 7.82%(3.94%, 13.17%), 6.92%(5.61%, 9.47%) and 7.26%(5.82%, 9.64%), respectively. The expressions of TGF-β1 in CD4 + CD8 -CD25 + Foxp3 + Treg in the above three treatment groups were 11.16%(7.91%, 15.23%), 8.66%(5.43%, 12.54%) and 7.82%(6.01%, 9.53%), respectively, and the expression of TGF-β1 in CD4 + CD8 -CD25 + Foxp3 + Treg in the patients with ATB treated for less than three months group was higher than that in the greater than or equal to six months group, the difference was statistically significant ( U=37.50, P=0.024). Conclusions:Foxp3/GARP/TGF-β1 pathway may be involved in the immune mechanism of Treg regulating the pathogenesis of tuberculosis, and GARP may be a new target for anti-tuberculosis therapy.

Correlation between ILC2 and Th17/Treg ratio in peripheral blood of patients at different stages of Mycobacterium tuberculosis infection / 中华微生物学和免疫学杂志

Objective:To study the correlation between type 2 innate lymphocyte (ILC2) and Treg/Th17 ratio in the peripheral blood of patients at different stages of Mycobacterium tuberculosis ( Mtb) infection. Methods:This study recruited 30 individuals with active tuberculosis (ATB group), 26 with treated tuberculosis (RTB group), 22 with latent tuberculosis infection (LTBI group) and 17 negative for tuberculin skin test (TST-negative group). Flow cytometry was used to detect the proportion of ILC2 in CD45 + cells, and that of Th17 and Treg cells in CD4 + T lymphocytes in the peripheral blood of patients in each group. Expression of Foxp3 and RORγt at mRNA level was detected by real-time fluorescence quantitative PCR. Pearson method was used to analyze the correlation between Th17 and Treg, and that between ILC2 and Treg/Th17 ratio in the peripheral blood of patients with ATB and RTB. Results:The proportions of ILC2 in RTB and ATB groups were significantly higher than those of LTBI and TST-negative groups, and the proportion of ILC2 in RTB group was significantly higher than that of ATB group ( P<0.05). The proportion of Th17 in RTB group was lower than that of ATB group ( P<0.05), and the proportions of Th17 in ATB and RTB groups were lower than those of LTBI and TST-negative groups. The proportion of Treg in RTB group was lower than that of ATB group ( P<0.05), and close to that of LTBI group and TST-negative group, but the Treg/Th17 ratios in ATB and RTB groups were higher than those of LTBI and TST-negative groups. There was no significant difference in Treg/Th17 ratio between ATB and RTB groups ( P>0.05). The expression of Foxp3 and RORγt at mRNA level and Foxp3/RORγt ratio changed accordingly. Meanwhile, there was no correlation between Th17 and Treg in ATB or RTB group ( r=0.023, P=0.444; r=0.428, P=0.150). There was a positive correlation between ILC2 and Treg/Th17 ratio in ATB group ( r=0.794, P=0.000), while no correlation was found between ILC2 and Treg/Th17 ratio in RTB group ( r=0.197, P=0.297). Conclusions:In this study, the proportion of ILC2 was increased in the peripheral blood of TB patients, and the proportion of ILC2 in RTB group was higher than that of ATB group. In RTB group, Th17 accounted for a low proportion in the peripheral blood and was involved in inflammatory reactions, while Tregs were not involved in inflammatory reactions, but might have a certain inhibitory effect in patients with ATB. Further studies found that Th17-involved inflammatory reactions were not regulated by Tregs. ILC2 was involved in Treg/Th17 imbalance in ATB patients, but not in RTB patients.

Application value of respiratory endoscopy combined with rapid on-site evaluation in the diagnosis of active tuberculosis in children / 中华实用儿科临床杂志

Objective:To investigate the diagnostic value of rapid on-site evaluation (ROSE) technique in the mucosal biopsy under respiratory endoscopy in children with active tuberculosis.Methods:Clinical data of 40 patients with active tuberculosis diagnosed in Department of Respiratory Intervention, Qilu Children′s Hospital, Shandong University from June 2017 to January 2020 were retrospectively analyzed.Results:(1) There were 33 cases of tracheobronchial tuberculosis and 7 cases of tuberculous pleurisy in the 40 cases, among them 9 cases were difficult to diagnose.(2)Among 33 cases of tracheobronchial tuberculosis, 24 cases (72.7%) of caseous necrosis breaking into the lumen, and 9 cases (27.3%) of mucosal swelling and external pressure.Cytological ROSE (C-ROSE) showed granuloma, epithelioid cells and lymphocytic infiltration with all bronchial mucosal biopsies.Different positives results of microbiological ROSE (M-ROSE) in different biopsy parts: positive results were found 6 times at caseous necrosis (13.6%, 6/44 times), 4 times at granulation hyperplasia (12.5%, 4/32 times), 2 times at hyperemia and edema (22.2%, 2/18 times), 0 time at yellow-white necrosis, and 54 times at the junction between lesions and normal mucosa (81.8%, 54/66 times). The mucosal pathology showed granuloma, exudation and necrosis, including 22 cases with tuberculous granuloma, 5 cases with characteristic tuberculous nodules, and 11 cases with positive acid-fast staining.(3)Seven cases of tuberculous pleurisy, serious pleural adhesion, pleural hyperemia and edema were observed under thoracoscopy.After clearing the adhesive tape, scattered caseous miliary nodules were found in pleura in 4 cases with a difficult clinical diagnosis.The C-ROSE of smear on thoracoscopic biopsy were characterized by necrotic and histopathic cell, with multinucleated giant cells, but granuloma was rare.M-ROSE in different parts: 8 times positive for millet nodules (80.0%), 0 time positive for adhesion band, 2 times positive for congestion oedema (14.3%); biopsy pathology showed granuloma and necrosis, with 3 cases characteristic tuberculosis nodules and 2 cases positive for anti-acid staining.(4)Pathogenic microorganisms were detected in 19 children using next generation sequencing (NGS) and Mycobacterium tuberculosis/Rifampicin resistance real-time nucleic acid amplification detection technology (Xpert MTB/RIF), including 7 positive for NGS (36.8%), 8 positive (42.1%) and 5 positive for both NGS and Xpert MTB/RIF (26.3%).Conclusions:Respiratory endoscopy combined with ROSE technique has important clinical significance in early diagnosis of active tuberculosis in children, and it is worth of promotion and applying.

Evaluation of the potential diagnostic value of cytotoxic T lymphocyte-associated antigen-4 in differentiation of active and latent tuberculosis infection / 中华传染病杂志

Objective To analyze the expressions of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the peripheral blood of patients with active tuberculosis (ATB ) or latent tuberculosis infection (LTBI) ,and to evaluate its diagnostic value in differentiation of ATB and LTBI .Methods Forty-eight patients including 18 ATB cases and 30 LTBI cases were continuously enrolled from Wuxi No . 5 People′s Hospital and Huashan Hospital affiliated to Fudan University from January 2011 to March 2013 .Flow cytometry was applied to detect the CTLA-4 expression in CD4+CD25+ FoxP3+ T cells in the peripheral blood of the 48 subjects .CTLA-4 levels were compared using non-parametric Mann-Whitney U test .Results The median percentage of CTLA-4+ Treg in CD4+ CD25+ Foxp3+ Treg cells of ATB patients was 18 .95％ (quantile range :13 .86％ ,27 .73％ ) ,and that in LTBI patients was 6 .67％(quantile range :5 .74％ ,9 .59％ ) ,which was statistically significant (U=18 .0 , P< 0 .01) .Receiver operating curve (ROC) based on the CTLA-4 expression indicated that the area under the curve was 0 .96 , with the optimum cut-off value of 13 .25％ .Thus ,the sensitivity and specificity for the diagnosis of ATB were 86 .7％ and 94 .4％ ,respectively .Conclusion CTLA-4 has highly sensitivity and specificity for the differential diagnosis of ATB and LTBI whose interferon-gamma releasing assays are all positive ,which may also provide meaningful clue for the study of pathogenesis of ATB .

Clinical analysis of colorectal cancer combined with active tuberculosis / 肿瘤研究与临床

Objective To explore the treatment methods for colorectal cancer patients combined with active tuberculosis. Methods The clinical data of 8 cases of colorectal cancer combined with active tuberculosis from September 2011 to January 2017 in the Affiliated Hospital of Southwest Medical University were analyzed retrospectively. Results All the patients received tumor radical resection after given intensive anti-tuberculotherapy for 2 to 3 weeks. From the second day after surgery, isonicotinyl hydrazide was done through intravenous infusion. When gastrointestinal function was restored, the preoperative anti-tuberculosis treatment was reused. After 2 mouths, consolidation therapy was done. There were 3 cases of complicating pneumonia and 1 case of complicating anastomotic fistula after surgery.Six courses of FOLFOX4 chemotherapy combined with anti-tuberculosis consolidation treatment were carried out for all the patients. No tuberculosis dissemination or death case occurred. Conclusions After given anti-tuberculotherapy for 2 to 3 weeks, the colorectal cancer patients combined with active tuberculosis could receive tumor radical resection. It is safe and feasible to carry out assisted chemotherapy for tumor during the consolidation anti-tuberculotherapy.

The value of T cell spot test of tuberculosis infection and inflammatory indicators for diagnosis of active tuberculosis in patients with fever of unknown origin / 中华传染病杂志

Objective@#To evaluate the value of T cell spot test of tuberculosis infection(T-SPOT.TB) and inflammatory indicators for diagnosis of active tuberculosis in patients with fever of unknown origin (FUO). @*Methods@#Patients with FUO in Tongji Hospital from Jan 1st 2014 to Feb 28th 2015 were retrospectively enrolled, and general condition, laboratory examination including T-SPOT.TB, blood routine test, procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), serum ferritin (SF) and final diagnosis were collected and analyzed. @*Results@#A total of 395 hospitalized patients with FUO were retrospectively enrolled into this study, among which there were 36 (9.11%) confirmed active tuberculosis (including 7 pulmonary cases and 29 extra-pulmonary cases), 189 (47.85%) bacterial infections, 50 (12.66%) viral infections, 4 (6.32%) fungal infections, 20 (5.06%) neoplastic diseases, 51(12.91%) autoimmune diseases, 25 (6.32%) other diseases. While 20 (5.06%) patients remained un-diagnosed. The sensitivity of T-SPOT.TB for the diagnosis of active TB in patients with FUO was 80.56% (95%CI: 63.43%-91.20%), and the specificity was 83.57% (95%CI: 79.23%-87.16%). The positive predictive value was 32.95% (95%CI: 23.52%-43.89%), and the negative predictive value was 97.72% (95%CI: 95.16%-99.00%). There were significant differences in positive LDH levels (187[141, 255] U/L vs 209[160, 343] U/L) and SF levels (296.2[191.3, 494.8] g/L vs 528.1[281.1, 1 022.0] μg/L) between active tuberculosis group and bacterial infection group (χ2=77.692, H=13.442, H=16.142, all P<0.05). The combination of T-SPOT.TB and multiple inflammatory indicators obtained most valuable efficiency (AUC=0.866) for TB diagnosis. Similarly, there were significant differences in positive ESR (31[15, 78] mm/1 h vs 10[6, 19] mm/1 h), ratio of neutrophil granulocytes ([71.17±12.59]% vs [57.08±20.38]%) between active tuberculosis group and viral infection group (H=32.797, F=6.171, all P<0.05). The combination acquired most valuable efficiency (AUC=0.929). @*Conclusions@#For patients with FUO, T-SPOT.TB combined with inflammatory indicators are valuable for the diagnosis of active tuberculosis.

Imbalance of Th17 and Treg in peripheral blood mononuclear cells of active tuberculosis patients

Abstract Objective: Maintaining a right balance between Th17 and Treg might be critical to the immunopathogenesis of active tuberculosis (TB). This study aimed to assess whether the Th17/Treg balance is altered in active TB patients. Methods: 250 study subjects (90 active TB patients, 80 latent TB subjects, and 80 healthy controls) were recruited for the study. The expression of Th17 and Treg in peripheral blood mononuclear cells (PBMCs) in the 250 subjects was investigated by flow cytometry. Plasma levels of cytokines IL-17 and IL-10, which are related to Th17 and Treg, respectively, were determined by ELISA. Results: The percentages of Th17 and Treg in PBMCs from active TB patients were significantly higher than those from latent TB or control groups (Th17: 4.31 ± 1.35% vs. 1.58 ± 0.71% or 1.15 ± 0.49%, p < 0.05; Treg: 11.44 ± 2.69% vs. 7.54 ± 1.56% or 4.10 ± 0.99%, p < 0.05). The expression of IL-17 and IL-10 was significantly increased in active TB patients in comparison to that in latent TB or control groups (IL-17: 16.85 ± 9.68 vs. 7.23 ± 5.19 or 8.21 ± 5.51 pg/mL, p < 0.05; IL-10: 28.70 ± 11.27 vs. 20.25 ± 8.57 or 13.94 ± 9.00 pg/mL, p < 0.05). Conclusions: Our study demonstrated an altered balance of Treg/Th17 in active TB patients, with higher percentages of Th17 and Treg in PBMCs. Further research on this imbalance may offer a new direction for TB treatment.

The dynamic changes of serum TNF-α,IL-1,IL-10 and HMGB-1 during tuberculosis disease progres-sion / 实用医学杂志

Objective To investigate the dynamic changes and clinical significanes of TNF?α,IL?1,IL?10 and HMGB?1 in patients with tuberculosis. Methods Fifty?nine patients with active tuberculosis were enrolled in this study. The patients received the standard chemotherapy and the curative effect of the patient was evaluat ed according to the outcome classification in our country. The peripheral blood serum from the patients during the treatment and 12 healthy volunteers were collected. The concentrations of serum TNF?α,IL?1,IL?10 and HMGB?1 were detected by ELISA tests. Results Significant decreases of the concentrations of serum TNF?α,IL?1 and HMGB?1 were shown in patients from the initial treatment,to retreatment and extra?pulmonary tuberculosis (P0.05). At the end of the treatment , the levels of serum TNF?α,IL?1 and HMGB?1 of the uncompleted treatment group were significantly higher than the normal levels (P<0.01) ,but the level of IL?10 was significantly lower than the normal level (P<0.01). Conclusion The dynamic testing of the inflammatory cytokines contributes to evaluation and judgement of the curative effect and the condition of patients with the active tuberculosis.

Role of T?SPOT.TB test in diagnosis of active tuberculosis / 实用医学杂志

Objective To assess the value of T?SPOT.TB test in the diagnosis of active tuberculosis. Methods The clinical data of 975 hospitalized patients receiving T?SPOT.TB test were collected in our hospital. The clinical information and testing results were analyzed. The receiver operating curve (ROC) was used to determine the optimal threshold of T?SPOT.TB test for differentiating active tuberculosis. Results T?SPOT.TB test results showed that the positive rate was 29.26%for the non?active tuberculosis group(n=793),but was 91.21%for active tuberculosis patients group (n = 182),which indicated that the test had a significant value in active tuberculosis detection(P<0.001). The sensitivity of T?SPOT.TB test was 0.912 and the specificity was 0.707. The detection threshold of T?SPOT.TB was optimized. As the spot?forming count(sfc)of ESAT?6 antigen threshold was 11.5 and that of the CEP?10 threshold was 9.5,the efficiency of T?SPOT.TB test for detection of active pulmonary tuberculosis was the highest. Conclusions T?SPOT.TB test has a good diagnostic performance for active tuberculosis, and it can be further optimized to better serve the clinical practice.

Clinical value of CT in evaluation of anti -tuberculosis chemotherapy in elderly patients with active tuberculosis / 中国基层医药

Objective To explore the activity signs and clinical value of CT in evaluation of anti -tuberculosis chemotherapy in elderly patients with active tuberculosis.Methods Clinical and imaging data of 78 cases with elderly active tuberculosis were retrospectively analyzed.The changes of CT sign between bacterium negative and posi-tive,before and after chemotherapy were compared.Results The detection rates of ground glass opacity,thick -walled cavity in bacterium positive were 72.1% and 55.8%,which were significantly higher than those in bacterium negative 45.7% and 28.6%(P <0.05).Compared with before chemotherapy,the detection rates of ground glass opacity,tree -in -bud,thick -walled cavity,pulmonary consolidation,centrilobular nodule,lobular consolidation after chemotherapy were significantly reduced(P <0.05).The active CT signs of ground glass opacity,tree -in -bud were completely absorbed,and other signs were lapsed to non -active signs including cord -like shadow,thin -walled cav-ity,calcification,bronchia aggregation and circuity.Conclusion There is conversion rule of CT signs in elderly active pulmonary tuberculosis before and after anti -tuberculosis chemotherapy,and CT is helpful in the evaluation of anti -tuberculosis chemotherapy results of active tuberculosis.

Ratio of monocytes to lymphocytes in peripheral blood in patients diagnosed with active tuberculosis

Objective: The ratio of monocytes to lymphocytes in peripheral blood could reflect an indi- vidual's immunity to Mycobacterium tuberculosis. The objective of this study was to evaluate the relationship between ratio of monocytes to lymphocytes and clinical status of patients with active tuberculosis. Methods: This was a retrospective review of data collected from the clinical database of The Fifth People's Hospital of Wuxi, Medical College of Jiangnan University. A total of 419 patients who had newly diagnosed active tuberculosis and 108 cases from 419 patients with tuberculosis therapy either near completion or completed were selected. Controls were 327 healthy donors. Results: Median ratio of monocytes to lymphocytes was 0.36 (IQR, 0.22-0.54) in patients before treatment, and 0.16 (IQR, 0.12-0.20) in controls (p < 0.001). Ratio of monocytes to lymphocytes <9% or >25% was significant predictors for active tuberculosis (OR = 114.73, 95% CI, 39.80-330.71; OR = 89.81, 95% CI, 53.18-151.68, respectively). After treatment, the median ratio of monocytes to lymphocytes recovered to be nearly normal. Compared to other patients, patients with extrapulmonary tuberculosis and of age >60 years were more likely to have extreme ratio of monocytes to lymphocytes (AOR = 2.57, 95% CI, 1.08-6.09; AOR = 4.36, 95% CI, 1.43-13.29, respectively). Conclusions: Ratio of monocytes to lymphocytes <9% or >25% is predictive of active tuberculosis. .

Avaliação das subpopulações de monócitos em pacientes com tuberculose pulmonar / Evaluation of subpopulations of monocytes in patients with pulmonary tuberculosis

Os macrófagos são componentes importantes da resposta imune inata contra o Mycobaterium tuberculosis (Mtb) e podem desempenhar um papel importante na patogênese da tuberculose (TB). Macrófagos são derivados dos monócitos, os quais são classificados em subpopulações a partir da expressão da molécula de superfície CD14 e CD16. São denominados de clássicos, intermediários e não clássicos, e possuem diferenças funcionais e fenotípicas. Os fatores que levam ao desenvolvimento de TB ativa ainda não são claros. Um desequilíbrio entre subpopulações de monócitos circulantes pode estar envolvido na imunopatogênese da TB, uma vez que macrófagos são células importantes da resposta imune inicial da doença. Assim, neste estudo avaliou-se os subgrupos de monócitos em pacientes com TB ativa e latente (TBL). Voluntários com TB ativa, TBL e indivíduos saudáveis foram recrutados para avaliação de frequência, níveis de ativação e produção de citocinas dos subgrupos de monócitos circulantes e após a estimulação antigênica por citometria de fluxo. Nossos resultados não demonstraram diferenças significativas nas frequências, níveis de ativação e produções de citocinas das subpopulações de monócitos entre os grupos estudados. No entanto, pacientes com TB ativa tiveram um aumento na frequência dos monócitos clássicos ativados após estimulação antigênica comparados com os controles saudáveis. Não observou-se uma expansão das subpopulações CD16+ em pacientes TB. Por outro lado, se observou uma expansão dos monócitos CD16...

Macrophages are important components of the innate immune response against Mycobacterium tuberculosis (Mtb) and may play an important role in the pathogenesis of tuberculosis (TB). Macrophages are derived from monocytes, which are classified into subpopulations from the expression of CD14 and CD16 surface molecule. They are denominated classics, intermediate and non-classical, and have functional and phenotypic differences. The factors that lead to the development of active tuberculosis are not clear yet. However, an imbalance between subpopulations of monocytes may be involved in the immunopathogenesis of TB, since macrophages are important cells in the initial immune responses of the disease. In this study we evaluated the monocyte subsets in patients with active and latent TB (ILTB). Volunteers with active TB, ILTB and healthy subjects were recruited to evaluate the frequency, levels of activation and cytokine production of blood monocytes subsets circulating and after the antigenic stimulation by flow cytometry. Our results did not show significant differences in the frequency, activation levels and cytokine production of monocytes subsets between studies groups. However, patients with active TB have an increased of frequency and activated levels of classical monocytes after antigenic stimulation compared to healthy controls. An expansion of CD16+ in monocytes subsets of TB patient was not observed. Moreover, it was observed an expansion and increased activation of CD16...

Co-existence of HIV, active tuberculosis and aspergilloma in a single individual - A case report.

Summary: Tuberculosis (TB) is a disease as old as mankind, whereas in India the first case of Human Immunodeficiency Virus (HIV) was reported in 1986. HIV and TB are so closely connected that their relationship is often described as a coepidemic. Aspergilloma (Fungal Ball, Mycetoma) represents a saprophytic growth of aspergillus that colonizes in the preformed cavities commonly due to pulmonary tuberculosis (PTB). We report a case of HIV, active pulmonary tuberculosis and aspergilloma occurring in the same patient. Despite our best efforts, we could not lay our hands on any similar case in the medical literature.

Accuracy of an Interferon-gamma Release Assay to Detect Active Tuberculosis in Children: A Pilot Study / 소아감염

PURPOSE: Early diagnosis of active tuberculosis (TB) in children is difficult. The widely used tuberculin skin test has low sensitivity and cross reactivity with non-tuberculous mycobacteria or Bacille Calmette-Guerin vaccination. Interferon gamma release assays have been shown good diagnostic accuracy for active in adults. But studies in children were limited. The purpose of this study was to examine the performance of enzyme-linked immunospot assay (ELISpot) as an initial test in the diagnosis of active tuberculosis in children. METHODS: In a hospital-based study, we prospectively examined the performance of ELISPot in 33 children suspected of active TB. TB was confirmed bacteriologically or histologically. RESULTS: Among 33 patients, 9 had active tuberculosis. When tested, they all had a positive test result from the ELISpot. The sensitivity and specificity of the assay were 100% (95% CI, 66.4-100%) and 95.8% (95% CI, 78.9-99.9%) respectively. CONCLUSION: ELISpot might be an useful and improved clinical diagnostic method for the detection of active TB in children.

The Diagnostic Value of Interferon-gamma Assay in Patients with Active Tuberculosis / 결핵및호흡기질환

BACKGROUND: The interferon-gamma assay is reported to have high sensitivity and specificity for making the diagnosis of latent tuberculosis infection. The clinical usefulness of this essay for detecting active tuberculosis has not fully defined. We evaluated the diagnostic value of the commercial interferon-gamma assay kit (QuantiFERONTB GOLD) for patients with suspected tuberculosis. METHODS: From January to August 2007, we recruited 52 patients with suspected tuberculosis infection. We performed chest X-ray, sputum smear, culture, PCR and the QuantiFERON-TB GOLD test. Pleural fluid analysis and pleural biopsy were also done for the patients with pleural effusion. RESULTS: Of the 52 patients we studied, 30 patients had a positive QuantiFERON-TB GOLD test result. 35 patients were finally diagnosed with active tuberculosis: twenty-five with a positive QuantiFERON-TB GOLD test and 10 with a negative QuantiFERON-TB GOLD test. The sensitivity of the QuantiFERON-TB GOLD test was 71.4% and the specificity was 64.7%. The positive predictive value was 0.83 and the negative predictive value was 0.50. There was no significant difference of any of the clinical and laboratory characteristics between the two groups of patients except the C-reactive protein (CRP) level. The CRP level was 29.2+/-27.3 mg/dL in the pulmonary tuberculosis patients with a positive QuantiFERON-TB GOLD test and 72.9+/-67.9 mg/dL in the patients with a negative QuantiFERON-TB GOLD test (p<0.05). CONCLUSION: The sensitivity and specificity of the QuantiFERON-TB GOLD test were inadequate for making the diagnosis of active tuberculosis. We suggest that the QuantiFERON-TB GOLD test should not be used by itself to exclude the diagnosis of active tuberculosis. The relationship of the QuantiFERON-TB GOLD test and the CRP level in patients with TB would be further investigated.