Tuberculosis Group Research Articles

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.

Spiral CT Image Characteristics and Differential Diagnosis Secondary Pulmonary Tuberculosis and Lung Cancer Based on Visual Sensors.

Helical CT plain scan has high spatial and area resolution, which is beneficial to the extraction of CT features of pulmonary nodules, and is of great significance for the diagnosis and differential diagnosis of pulmonary diseases. In order to deeply study the role of visual sensor image algorithm in CT image, this paper adopts clinical simulation method, data fusion method, and image acquisition method to collect images, analyze CT image features, and simplify the algorithm and create a CT model that can better diagnose secondary tuberculosis and lung cancer. We selected 45 patients with lung disease in this group, with an average age of 38 years. At the same time, the consistency analysis results of the diameter and plain CT value data of the five groups of cases measured by two observers are between 0.82 and 0.88, which has a good consistency. We could find that the nodule diameters of the five groups of cases were different (F =16.99, P < 0.01), and the difference was statistically significant (P < 0.06), indicating that our data are not only accurate but also very reliable. ROC was used to analyze the precise value of CT values in the pulmonary tuberculosis group and lung cancer group, intrapulmonary lymph node group, and pulmonary hamartoma group to determine the cutoff value. The results showed that the AUC values of the pulmonary tuberculosis group and the lung cancer group were 0.788, and the middle was the largest, indicating that the values were guaranteed. The basic realization starts with visual sensor technology and designs a clinical model that can more accurately identify CT images and differential diagnosis.

Clinical Significance of Negative Costimulatory Molecule PD-1/PD-L1 on Peripheral Blood Regulatory T Cell Levels among Patients with Pulmonary Tuberculosis.

Objective This study aimed to investigate the expression and clinical significance of negative costimulatory molecules programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) on CD4+CD25+CD127low regulatory T cells (Tregs) in peripheral blood of patients with active pulmonary tuberculosis (TB). Methods A total of 30 patients with active pulmonary TB and 20 healthy controls were enrolled. The proportions of peripheral blood CD4+CD25+CD127low Tregs and the expression of PD-1 and PD-L1 on CD4+CD25+CD127low Tregs were detected among active pulmonary TB patients using flow cytometry. The associations of proportions of CD4+CD25+CD127low Tregs with the demographic and clinical characteristics of active pulmonary TB patients were evaluated, and the correlation between PD-1/PD-L1 expression and proportions of peripheral blood CD4+CD25+CD127low Tregs was examined among patients with active pulmonary TB using Pearson correlation analysis. Results Flow cytometry detected a significantly higher proportion of peripheral blood CD4+CD25+CD127low Tregs in the TB group than in the control group (9.14% ± 2.66% vs. 6.39% ± 1.73%; t = 4.067, P < 0.001), and a higher proportion of peripheral blood CD4+CD25+CD127low Tregs among active pulmonary TB patients with a positive anti-M. tuberculosis antibody than in those with a negative antibody (Figure 2(a)); however, there were no gender, M. tuberculosis culture, tuberculin test, CT examination, or sputum smear test-specific proportions of CD4+CD25+CD127low Tregs among patients with active pulmonary TB. The PD-1 (6.13% ± 3.53% vs. 24.78% ± 7.73%, P < 0.05) and PD-L1 levels (2.97% ± 2.00% vs. 9.23% ± 5.76%, P < 0.05) were lower on peripheral blood CD4+CD25+CD127low Tregs among the TB group than in the control group. In addition, Pearson correlation analysis revealed a positive correlation between PD-1 and PD-L1 expression on peripheral blood CD4+CD25+CD127low Tregs among patients with active pulmonary TB (r = 0.435, P=0.016) and a negative correlation between the proportion of peripheral blood CD4+CD25+CD127low Tregs and PD-1 (r = ‒0.344, P=0.024) and PD-L1 expression among patients with active pulmonary TB (r = ‒0.310, P=0.043). Conclusion The proportion of CD4+CD25+CD127low Tregs is higher in patients with active pulmonary TB than in healthy controls, and the negative costimulatory signal PD-1/PD-L1 expression is downregulated among active pulmonary TB patients. Our findings provide insights into the illustration of pathogenic mechanisms and immunotherapy of active pulmonary TB.

Comprehensive lipid and lipid-related gene investigations of host immune responses to characterize metabolism-centric biomarkers for pulmonary tuberculosis

Despite remarkable success in the prevention and treatment of tuberculosis (TB), it remains one of the most devastating infectious diseases worldwide. Management of TB requires an efficient and timely diagnostic strategy. In this study, we comprehensively characterized the plasma lipidome of TB patients, then selected candidate lipid and lipid-related gene biomarkers using a data-driven, knowledge-based framework. Among 93 lipids that were identified as potential biomarker candidates, ether-linked phosphatidylcholine (PC O–) and phosphatidylcholine (PC) were generally upregulated, while free fatty acids and triglycerides with longer fatty acyl chains were downregulated in the TB group. Lipid-related gene enrichment analysis revealed significantly altered metabolic pathways (e.g., ether lipid, linolenic acid, and cholesterol) and immune response signaling pathways. Based on these potential biomarkers, TB patients could be differentiated from controls in the internal validation (random forest model, area under the curve [AUC] 0.936, 95% confidence interval [CI] 0.865–0.992). PC(O-40:4), PC(O-42:5), PC(36:0), and PC(34:4) were robust biomarkers able to distinguish TB patients from individuals with latent infection and healthy controls, as shown in the external validation. Small changes in expression were identified for 162 significant lipid-related genes in the comparison of TB patients vs. controls; in the random forest model, their utilities were demonstrated by AUCs that ranged from 0.829 to 0.956 in three cohorts. In conclusion, this study introduced a potential framework that can be used to identify and validate metabolism-centric biomarkers.

Outcome of COVID-19 in Children With Tuberculosis: Single-Center Experience

ObjectiveTo evaluate the outcome of Coronavirus disease 2019 (COVID-19) infection in children and adolescents with tuberculosis.MethodsWe analyzed hospital records for the period May, 2020 to September, 2021 for children who were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) positive or SARS-CoV-2 antibody positive. They were divided into two groups viz., those with tuberculosis (tuberculosis group) and those without tuberculosis (non-TB group). Demographic information, symptoms, and outcomes of COVID-19 were compared between the two groups.ResultsMedian (IQR) age of participants was 11 (8,14) and 4.5 (2,9) year for the tuberculosis and non-TB groups, respectively. 93.5% and 36.1% of children were asymptomatic in the tuberculosis and non-TB group, respectively. No variable in the study was significantly associated with COVID-19 positivity in children with tuberculosis. No difference was found in the outcomes of COVID-19 infection in children having tuberculosis.ConclusionsNo differences were noted in the outcomes of COVID-19 infection in children having tuberculosis.

C-reactive protein Lymphocyte Ratio in the Diagnosis of Pulmonary Tuberculosis

Background: Tuberculosis (TB) is still a severe problem in underdeveloped and developing countries. Diagnostic tests are unavailable in every health institution, and TB culture can take up to 45 days. Therefore, there is a need for cheaper, faster, and easily accessible diagnostic methods that can guide the diagnosis. This study aimed to determine whether red blood cell distribution width (RDW), C-reactive protein (CRP)-lymphocyte ratio (CLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) can be used as biomarkers in the diagnosis of pulmonary TB in patients with no comorbidities.&#x0D; Material and Methods: Files of microbiologically confirmed 122 patients with pulmonary TB and 153 patients in whom pulmonary TB was excluded were retrospectively reviewed. Out of them, patients with comorbidities were excluded from the study. Eighty-one patients with TB and 100 controls were included in the study.&#x0D; Results: The lymphocyte, eosinophil, and LMR levels remained significantly lower in the TB group, while neutrophil, monocyte, RDW, platelet, and PLR levels were higher in the same group.&#x0D; Conclusion: In those patients suspicious of pulmonary TB, higher levels of RDW, PLR, and CLR, whereas lower levels of eosinophil, PDW, and LMR may predict the diagnosis of pulmonary TB in previously healthy individuals.

Alterations in the nasopharyngeal microbiota associated with active and latent tuberculosis

ObjectiveTo investigate the characteristic of nasopharyngeal microbiota at different states of Mycobacterium tuberculosis (MTB) infection. MethodsParticipants were recruited from a chest hospital and were divided into three groups: the active tuberculosis (ATB) group, the latent TB infection (LTBI) group and the healthy control (HC) group. Nasopharyngeal microbiota was analyzed by 16S rRNA sequencing and clinical laboratory test results of ATB patients were collected and statistically analyzed. ResultsEleven ATB patients, 19 LTBI individuals and 18 healthy controls were included. Compared with LTBI group, Proteobacteria (P=0.04) and Gammaproteobacteria (P=0.01) increased in the ATB group. Compared with HC group, Pseudomonadales (P=0.03) and Moraxellaceae (P=0.04) increased, while Bacillales (P=0.04) and Lachnospiraceae (P=0.03) decreased in ATB group. Furthermore, Staphylococcus and Corynebacterium accounted for 70–80% in HC and LTBI groups. While in ATB group, they were less than 40%. Moreover, relative abundance of Corynebacterium, Corynebacteriaceae and Mycobacteriales was positively correlated with serum adenosine deaminase while negatively correlated with albumin, hemoglobin, and platelet counts in ATB patients. ConclusionsThe composition of nasopharyngeal microbiota changed significantly after MTB infection. The correlations between Corynebacterium and nutritional status (hemoglobin and albumin), immune-related molecules (adenosine deaminase) and inflammation-related indicators (platelet) in ATB patients deserve further exploration.

Diagnostic Value of Mediastinal Lymphadenopathy in Differentiating Pulmonary Tuberculosis from Community-Acquired Pneumonia in Children

Background: Diagnosis of childhood pulmonary tuberculosis (TB) is often based on clinical features in combination with radiologic findings because of paucibacillary nature of the disease in children. It may be difficult to make a clinical diagnosis because of the overlapping clinical features of pulmonary TB and community-acquired pneumonia (CAP). On computed tomography (CT) scanning, the presence of typical LAP can suggest TB as a possible cause. Objectives: To compare the features of mediastinal LAPs between two patient groups based on contrast-enhanced chest CT. Methods: A total of 45 pulmonary patients with TB and 38 patients with CAP (aged ≤ 18 years) were enrolled in this retrospective study. The presence and CT features of lymph node involvement and the incidence of associating parenchymal/pleural findings were analyzed in two groups. Results: All patients with TB and 36 of the 38 patients with CAP had at least one mediastinal LAP. There was no significant difference between the two groups according to the incidence of lymph node and multiple site involvement and also involved lymph node stations (P &gt; 0.05). However, lymph node size was larger in the TB group (P = 0.04). Twenty-two percent of patients with TB had mediastinal LAP without parenchymal/pleural involvement. Conclusions: Although the lymph node size was larger in TB group than in CAP group, CT features of mediastinal lymph node involvement overlapped between two groups. Nevertheless, mediastinal LAP without parenchymal/pleural involvement on CT is seen in a significant number of TB patients.

The Comparison of Vitamin C between Pulmonary Tuberculosis and Healthy Control in Medan

Background: Pulmonary tuberculosis infection is high burden especially in developed country. Vitamin C is water soluble micronutrient contributes to immune defense by supporting various both of innate and adaptive immunity. Vitamin C protected the host from reactive oxygen and reactive nitrogen intermediates generated during Mycobacterial infection. Patient with pulmonary tuberculosis had lower vitamin C level because the Mycobacterium tuberculosis infection yield to a reactive oxygen species for replication and metabolism and because of the reduced of nutrition intake. Vitamin C as antioxidant also play role in killing Mycobacterium tuberculosis by drive fenton reaction.Method: This is a case control study of vitamin C in blood serum in pulmonary tuberculosis patient and healthy control. Vitamin C level measured with ELISA examination (Enzyme Linked Immunosorbent Assay). Results: Total subject was 40 people, 20 people pulmonary tuberculosis as a case and 20 people healthy control. Vitamin C levels are higher in pulmonary tuberculosis patient (83,64 ± 35,99 ng/ml) than healthy control (80,22 ± 26,44 ng/ml), but not statistically significant. Vitamin C levels tend to be low in elderly and lower in man than woman. Conclusion: Vitamin C levels in pulmonary tuberculosis group lower than healthy control. Vitamin C levels in men having lower than women, elderly had low the level of vitamin C.

Analysis of real-time PCR Melanocortin 3 (MC3R) gene expression to identify new biomarkers inflammation in tuberculosis

BackgroundDiagnosis of tuberculosis (TB) in the era of technological sophistication requires accuracy and speed to provide as much information as possible so that TB treatment can be carried out quickly and precisely. New studies have also begun to be carried out to diagnose TB, one of which is by examining genes, either by looking at polymorphisms, mutations, or expressions. Several previous studies have confirmed the association of MC3R and TB genes with polymorphisms; MC3R is a gene that participates in the regulation of the inflammatory process and is also found in macrophages; therefore, we tried to analyze gene expression in the active TB group, household contacts, and healthy controls for looked at the differences between the three groups and confirmed the correlation of MC3R with TB by seeing which group's gene expression increased the most expression of the three groups so that the results can be considered as a TB diagnostic biomarker in the future.MethodsThis study included 122 people, 49 patients with confirmed TB, 46 close relatives of patients, and 27 healthy controls. This study used a real-time PCR technique to analyze MC3R gene expression in the three groups, and all data were analyzed using Bio-Rad CFXTM software version 3.1 and one-way ANOVA using SPSS 21.0.ResultsThe value of MC3R gene expression in the active TB group increased 3.6-fold in the healthy group (p = 0.143), and that of gene expression in the healthy control group increased 1.09-fold in the healthy group (p = 0.007).ConclusionThere is a relationship between MC3R and TB based on the results of gene expression analysis that increased in the active TB group compared to the household contact group and healthy controls.

Validation of Serotransferrin in the Serum as Candidate Biomarkers for the Diagnosis of Pulmonary Tuberculosis by Label-Free LC/MS.

This study aimed to identify secreted protein biomarkers in serum from the label-free LC/MS proteomics of neutrophils in pulmonary tuberculosis (TB) patients for the diagnosis biomarkers of TB label-free LC/MS. The proteomic profiles of neutrophils from 15 active TB patients and 15 healthy controls (HCs) were analyzed using label-free LC/MS. We identified 358 differentially expressed proteins preliminarily, including 279 up-regulated proteins and 79 down-regulated proteins. Thirty-eight differentially expressed secreted proteins involved in the progress of platelet degranulation between TB patients and HCs were focused. Of these, serotransferrin (TRF), alpha-2-macroglobulin (AMG), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein 1 (AAG), alpha-1-acid glycoprotein 2 (AGP2), and alpha-1B-glycoprotein (A1BG) were selected for further verification in the serum of additional 134 TB patients and 138 HCs by nephelometry and ELISA in the training set. Statistically significant differences of TRF (P < 0.0001), AAT (P < 0.0001), AAG (P < 0.0001), AGP2 (P < 0.0001), and A1BG (P = 0.0003) were observed. The serum concentration of TRF was down-regulated in TB patients compared with healthy controls, which was coincident with the proteomics results. An additional validation of TRF was performed in an independent cohort of patients with active TB (n = 46), patients with lung cancer (n = 37), 20 HCs, and patients with pneumonia (n = 35) in the test set by nephelometry. The serum expression levels of TRF in the TB patients showed lower levels compared with those in patients with pneumonia (P = 0.0125), lung cancer (P = 0.0005), HCs (P < 0.0001), and the non-TB controls (P < 0.0001). Furthermore, the AUC value of TRF was 0.647 with 90.22% sensitivity and 42.86% specificity in discriminating the TB group from the pneumonia group, 0.702 with 93.48% sensitivity and 47.16% specificity in discriminating the TB group from the lung cancer group, 0.894 with 91.30% sensitivity and 71.62% specificity in discriminating the TB group from all HCs, and 0.792 with 91.30% sensitivity and 58.90% specificity in discriminating the TB group from the non-TB controls. This study obtained the proteomic profiles of neutrophils in the TB patients and HCs, which contribute to a better understanding of the pathogenesis molecules existing in the neutrophils of pulmonary tuberculosis and provide candidate biomarkers for the diagnosis of pulmonary tuberculosis.

Imbalance of T Helper and Regulatory Cells in Patients with Tuberculosis Co-infection Acquired Immunodeficiency Syndrome

Background: To ensure that patients with Acquired Immunodeficiency Syndrome (HIV) and active tuberculosis(TB) co-infection (HIV-TB) can get timely treatment, we investigated T helper cells17 (Th17), Tregulatorycells(Treg) levels in the peripheral blood mononuclear cells (PBMCs) of the TB, HIV, HIVTB patients provide a better consult for prediction of HIV-TB patients. Methods: A total of 62 patients with TB, HIV, HIV-TB and 30 healthy peoples were included in our study. The PBMCs were isolated from the peripheral blood and the level of Th17 and Treg cells were tested by flow cytometry. Serum levels of cytokines Interleukin 17 (IL-17), Interleukin 6 (IL-6) and Interleukin 10 (IL-10) were determined by ELISA. Results: Th17/Treg imbalance in HIV-TB patients, and is lower than HIV, TB and control group (Th17/Treg: 0.10±0.03 vs 0.25±0.08 vs 0.47±0.14 or 1.03±0.47, p&lt;0.05). The expression of IL-10 in HIV-TB patients were significantly increased than HIV, T Band control groups, IL-17 and IL-6 were significantly decased (IL-10: 28.8±4.3 vs 23.6±3.6 vs 18.5±2.9 or 14.3±1.8pg/mL, p&lt;0.05; IL- 17: 17.1±3.6 vs 24.2±4.2 vs 28.3±5.8 or 40.9±6.8pg/mL, p&lt;0.05; IL-6: 15.9±2.1 vs 23.8±3.4 vs 27.8±4.3 or 32.5±4.6pg/mL, p&lt;0.05). Conclusions: These studies revealed that Th17/Treg in HIV-TB patients was imbalanced, and suppressor T cell subsets are dominant, thus participate in immune pathogenesis of HIV-TB.

Study on the pharmacodynamic activity of combinations with the new anti-tuberculosis drug pyrifazimine in vitro and in vivo in mouse

Objective: To evaluate two-drug combination interaction between pyrifazimine(TBI-166) and anti-drug-resistant tuberculosis group A drugs Bedaquiline (BDQ), Moxifloxacin (MFX) and the new anti-tuberculosis drug Delamanid (DLM), SQ109, Q203, and PBTZ169 in vitro and in vivo in mouse, so as to provide basis for TBI-166 combination therapy. Methods: This study was performed from September 2020 to July 2021. The chessboard method was used to evaluate the interaction between TBI-166 and BDQ, MFX, DLM, SQ109, and PBTZ169. The time-killing kinetics method was used to evaluate the anti-tuberculosis activity of the two-drug combination with partial synergy. The BALB/c mouse acute infection model was used to evaluate the anti-tuberculosis activity at 4 and 8 weeks in the two-drug combination group (TBI-166+BDQ, TBI-166+SQ109, TBI-166+PBTZ169, TBI-166+Q203) and monotherapy groups (TBI-166, BDQ, SQ109, PBTZ169, Q203). Data analysis was performed using an independent sample t-test. Results: After TBI-166 combined with anti-tuberculosis drugs, MIC was reduced to 6.25% to 25.00% of TBI-166 monotherapy. After TBI-166 combined with BDQ, SQ109 and PBTZ169, the partial inhibitory concentration index (FICI) values were 0.53, 0.75 and 0.75, respectively; the time sterilization experiment showed that the viable population of Mycobacterium tuberculosis treated with two-drug combination of TBI-166 and BDQ, SQ109, PBTZ169 for 14 days decreased at least 3 log10 CFU/ml. In the mouse experiments, it was found that, the amount of viable bacteria in lung tissue of BDQ, SQ109 and PBTZ169 combined with TBI-166 groups was lower than that of the monotherapy group,respectively. The lung tissue culture of mice in the TBI-166+BDQ group was negative after 4 weeks of treatment, and the number of live bacteria in the lungs of the TBI-166+BDQ group was 1.49 log10CFU lower than that of the BDQ monotherapy group(P<0.01). Conclusion: In vitro and in vivo experiments in mice revealed that TBI-166 had synergistic anti-tuberculosis activity after being combined with BDQ, SQ109 and PBTZ169, respectively.

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial

BackgroundDiabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP).MethodsThe ‘Prevention of tuberculosis in diabetes mellitus’ (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM.DiscussionPROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control.Trial registrationClinicalTrials.govNCT04600167. Registered on 23 October 2020

КЛИНИЧЕСКИЙ АНАЛИЗ КРОВИ ПРИ ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКЕ ТУБЕРКУЛЕЗА ЛЕГКИХ И ВНЕБОЛЬНИЧНОЙ ПНЕВМОНИИ У ПАЦИЕНТОВ С ВИЧ-ИНФЕКЦИЕЙ

Abstract. Introduction. Nowadays, methods for detecting Mycobacterium tuberculosis are being improved, but at the same time, general clinical methods of laboratory diagnostics, which include a complete blood count, included in the diagnostic minimum of tuberculosis screening, do not lose their significance. Aim. The aim of the study is to evaluate the value of a complete blood count in the differential diagnosis of pulmonary tuberculosis and pneumonia in patients with HIV infection. Material and methods. The parameters of the complete blood count were studied in 159 patients in the pulmonology department who were at the stage of differential diagnosis with tuberculosis. For analysis, indicators of erythrocyte sedimentation rate, leukocytes, lymphocytes and hemoglobin were selected. According to the diagnostic results, the diagnoses of pulmonary tuberculosis (n=119) and pneumonia (n=40) were verified. Statistical processing was carried out using the statistical software package IBM SPSS Statistics 22.0. Results and discussion. In a comparative analysis of the complete blood count parameters of a group of patients with a confirmed diagnosis of tuberculosis and pneumonia, statistically significant differences were found in the average hemoglobin level (by 13.25 g/l more in tuberculosis, p&lt;0.001) and the average level of leukocytes (by 4.44*109/l less with tuberculosis, p&lt;0.001). When studying the dependence of changes in the main indicators of a clinical blood test in HIV-infected patients on the level of CD4+ T-lymphocytes, a direct correlation (r=0.451) between the number of CD4+ T-lymphocytes and the level of hemoglobin (p&lt;0.001) was established, the lower the number of CD4+ T-lymphocytes the lower the hemoglobin level. Conclusion. A complete blood count does not differentiate between pneumonia and tuberculosis in patients with HIV infection, but can be used in the algorithm for forming a risk group for tuberculosis in a pulmonology department. Being the most important laboratory test, it can evaluate the changes characteristic of inflammatory (infectious) lung diseases.

Evaluation of Host Protein Biomarkers by ELISA From Whole Lysed Peripheral Blood for Development of Diagnostic Tests for Active Tuberculosis.

Tuberculosis (TB) remains a significant global health crisis and the number one cause of death for an infectious disease. The health consequences in high-burden countries are significant. Barriers to TB control and eradication are in part caused by difficulties in diagnosis. Improvements in diagnosis are required for organisations like the World Health Organisation (WHO) to meet their ambitious target of reducing the incidence of TB by 50% by the year 2025, which has become hard to reach due to the COVID-19 pandemic. Development of new tests for TB are key priorities of the WHO, as defined in their 2014 report for target product profiles (TPPs). Rapid triage and biomarker-based confirmatory tests would greatly enhance the diagnostic capability for identifying and diagnosing TB-infected individuals. Protein-based test methods e.g. lateral flow devices (LFDs) have a significant advantage over other technologies with regard to assay turnaround time (minutes as opposed to hours) field-ability, ease of use by relatively untrained staff and without the need for supporting laboratory infrastructure. Here we evaluate the diagnostic performance of nine biomarkers from our previously published biomarker qPCR validation study; CALCOCO2, CD274, CD52, GBP1, IFIT3, IFITM3, SAMD9L, SNX10 and TMEM49, as protein targets assayed by ELISA. This preliminary evaluation study was conducted to quantify the level of biomarker protein expression across latent, extra-pulmonary or pulmonary TB groups and negative controls, collected across the UK and India, in whole lysed blood samples (WLB). We also investigated associative correlations between the biomarkers and assessed their suitability for ongoing diagnostic test development, using receiver operating characteristic/area under the curve (ROC) analyses, singly and in panel combinations. The top performing single biomarkers for pulmonary TB versus controls were CALCOCO2, SAMD9L, GBP1, IFITM3, IFIT3 and SNX10. TMEM49 was also significantly differentially expressed but downregulated in TB groups. CD52 expression was not highly differentially expressed across most of the groups but may provide additional patient stratification information and some limited use for incipient latent TB infection. These show therefore great potential for diagnostic test development either in minimal configuration panels for rapid triage or more complex formulations to capture the diversity of disease presentations.

Evaluating the efficacy of stool sample on Xpert MTB/RIF Ultra and its comparison with other sample types by meta-analysis for TB diagnostics.

Precise and timely detection of tuberculosis (TB) is crucial to reduce transmission. This study aims to assess the accuracy of Xpert MTB/RIF Ultra on stool samples and systematically review the performance of Xpert MTB/RIF Ultra with different sample types by meta-analysis. Stool samples of smear-negative pulmonary TB (PTB), cervical lymph node TB, and abdominal TB patients were tested on the Xpert MTB/RIF Ultra system. Meta-analysis was performed on a set of 44 studies. Data were grouped by sample type, and the pooled sensitivity and specificity of Xpert MTB/RIF Ultra were calculated. The sensitivity of Xpert MTB/RIF Ultra with stool samples was 100% for smear-negative PTB, 27.27% for cervical lymph node TB, and 50% for abdominal TB patients, with 100% specificity for all included TB groups. The summary estimate for all PTB samples showed 84.2% sensitivity and 94.5% specificity, and EPTB samples showed 88.6% sensitivity and 96.4% specificity. Among all sample types included in our meta-analysis, urine showed the best performance for EPTB diagnosis. This pilot study supports the use of stool as an alternative non-invasive sample on Xpert MTB/RIF Ultra for rapid testing, suitable for both PTB and EPTB diagnosis.

Lower vitamin D level is associated with higher prevalence of pulmonary tuberculosis in under-five children actively living in tropical countries

Objective: Indonesia accounted for 845.000 tuberculosis (TB) cases, ranked as the second-highest TB incidence in the world. Various studies in childhood TB and vitamin D has overgrown in recent years, but there is no study for vitamin D status in under-five children with pulmonary tuberculosis in Indonesia as tropical country that has an abundant sun exposure. This study evaluates the vitamin D level in under-five children with pulmonary TB compared with healthy children control group. Materials and Methods: This comparative study with a cross-sectional design was conducted in outpatient clinic from February 2019 – February 2020. We selected children ≤5 years old, diagnosed with pulmonary TB; the control group was the random siblings or neighbors who did not have tuberculosis. Differences in 25-hydroxyvitamin D levels in both groups were statistically analyzed with independent t-test. The vitamin D cutoff values were determined using receiver operating characteristic (ROC) curve analysis. Results: A total of 70 patients aged ≤5 years old met the inclusion criteria, 35 childrens were assigned for each group. The 25-hydroxy vitamin D mean level in the TB group was 42.72 nmol/L and 97.74 nmol/L in control group. The TB group has significantly lower 25-hydroxy vitamin D levels than control group (p&lt;0.001). With sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%, 97.1%, 97.2%, and 100%, respectively, the optimal cutoff point level for 25-hydroxy vitamin D was 80nmol/L. Conclusion: Serum levels of 25-hydroxy vitamin D in children with pulmonary TB are significantly lower than in healthy children. Further study should be conducted to determine the efficacy of vitamin D supplementation in the treatment of children with tuberculosis.

Diagnostic value of FCGR1B gene transcription level in active tuberculosis

Objective: To investigate the diagnostic potential of Fc fragment of IgG receptor 1b gene (FCGR1B) transcription level in active tuberculosis. Methods: From February to September of 2018, we collected peripheral blood from patients with active tuberculosis, latent tuberculosis infection (LTBI), cured patients with tuberculosis, healthy people and patients with pneumonia in the Eighth Medical Center of PLA General Hospital. Peripheral blood mononuclear cells (PBMCs) were isolated for total RNA extraction and cDNA synthesis. The expression of FCGR1B mRNA in PBMCs was detected by quantitative real-time PCR (QPCR). Nonparametric test was used to compare the differential expression of FCGR1B mRNA between patients with active tuberculosis and control groups, and the relationships between FCGR1B mRNA expression and patient's illness condition and inflammatory indexes were analyzed by Correlation analysis. The potential of FCGR1B mRNA as a diagnostic marker for active tuberculosis was evaluated by receiver operating characteristic curve (ROC) analysis. Results: The expression of FCGR1B mRNA in PBMCs from patients with active tuberculosis was significantly increased when compared with non-tuberculosis controls, including individuals with LTBI, healthy people, cured patients with tuberculosis and patients with pneumonia (u=2 081, P<0.001). The expression of FCGR1B mRNA was higher in patients with tuberculosis who had more bacteria(H=12.35, P=0.015), and was correlated with the C-reactive protein (CRP) (r=0.30, P=0.008). ROC analysis showed that FCGR1B mRNA could distinguish active tuberculosis from non-tuberculosis with area under curve (AUC) of 0.849. The sensitivity and specificity were 71.43% and 84.17% respectively. The AUC of FCGR1B mRNA in distinguishing extra-pulmonary tuberculosis from controls was 0.906. The sensitivity and specificity were 84.62% and 91.89%, respectively. Conclusion: FCGR1B mRNA is a potential molecular marker for diagnosis of active tuberculosis.

Surgical Treatment of Nontuberculous Mycobacterial Pulmonary Disease and a Combination of Nontuberculous Mycobacterium Pulmonary Disease and Pulmonary Tuberculosis

ObjectivesNontuberculous mycobacterial pulmonary disease (NTMPD) is an important health system problem worldwide. Surgical treatment experience is limited, and the safety of such operations is still unclarified. Therefore, improving our knowledge of NTMPD is important. DesignIn this retrospective observational study, we analyzed the medical records of 2,432 patients operated on from January 2011 through December 2017 in our hospital. There were 20 patients with NTMPD in group 1 and 23 patients with combined NTMPD and pulmonary tuberculosis in group 2. Patients received antibiotic treatment before and after surgery as per Russian Federal clinical guidelines and individual drug susceptibility. ResultsPostoperative complications occurred in 2 (10%) cases in group 1 and 4 (17.4%) in group 2, and intraoperative complications occurred in 2 (8.7%) cases in group 2. There was no 30-day mortality in both groups. After 1 year, all 40 traced patients had neither bacterial excretion nor cavities in the lungs. After 3 years and 5 years, the efficacy among 32 and 13 traced patients was 100%, respectively. ConclusionsModern surgery for small NTMPD forms is safe - helping improve outcomes for ineffective antibiotic treatment. Combined surgery and antibiotic treatment are acceptable in both the short and long term.