Cases Of Active Pulmonary Tuberculosis Research Articles

Integrating systemic immune-inflammation index, fibrinogen, and T-SPOT.TB for precision distinction of active pulmonary tuberculosis in the era of mycobacterial disease research.

The clinical challenge of differentiating suspected tuberculosis with positive T-SPOT.TB results persist. This study aims to investigate the utility of the Systemic Immune-Inflammation Index (SII), Fibrinogen, and T-SPOT.TB in distinguishing between active pulmonary tuberculosis (PTB) and non-tuberculous lung diseases. A retrospective analysis included 1,327 cases of active PTB with positive T-SPOT.TB results and 703 cases of non-tuberculous lung diseases from May 2016 to December 2020 at Meizhou People's Hospital. These were designated as the case group and the control group, respectively. The detection indicators of T-SPOT.TB: Early Secreted Antigenic Target 6 (ESAT-6), Culture Filtrate Protein 10 (CFP-10), as well as SII and Fibrinogen levels-were compared and analyzed for association and joint diagnostic value between the two groups. The case group showed higher values of ESAT-6, CFP-10, SII, and Fibrinogen compared to the control group (all p < 0.001). In the case group, SII and Fibrinogen did not correlate with ESAT-6 and CFP-10 (∣rs∣ all < 0.3) but were positively correlated with C-reactive protein (CRP; rs all > 0.3). SII and Fibrinogen values in smear-positive pulmonary tuberculosis were higher than in smear-negative cases (all p < 0.05). The optimal diagnostic thresholds for ESAT-6, CFP-10, SII, and Fibrinogen in differentiating between active PTB and non-tuberculous lung diseases were 21.50 SFCs/106 PBMC, 22.50 SFCs/106 PBMC, 2128.32, and 5.02 g/L, respectively. Regression logistic analysis showed that ESAT-6 < 21.5 (OR: 1.637, 95% CI: 1.311-2.043, p < 0.001), CFP-10 < 22.5 (OR: 3.918, 95% CI: 3.138-4.892, p = 0.025), SII < 2128.32 (OR: 0.763, 95% CI: 0.603-0.967, p < 0.001), and FIB < 5.02 (OR: 2.287, 95% CI: 1.865-2.806, p < 0.001) were independent risk factors for active PTB. The specificity for ESAT-6 + CFP-10, ESAT-6 + CFP-10 + SII, ESAT-6 + CFP-10 + FIB, and ESAT-6 + CFP-10 + SII + FIB was 82.5%, 83.2%, 95.8%, and 80.1%, respectively, while sensitivity was 52.6%, 53.0%, 55.8%, and 44.7%, and positive predictive values were 85.0%, 85.6%, 84.1%, and 89.6%, respectively. SII and Fibrinogen are positively correlated with the degree of tuberculosis inflammation and the bacterial load of Mycobacterium tuberculosis. The combined detection of SII, Fibrinogen, and T-SPOT.TB is significant in distinguishing between active PTB with positive T-SPOT.TB results and non-tuberculous lung diseases.

Tuberculosis Severity Predictive Model Using Mtb Variants and Serum Biomarkers in a Colombian Cohort of APTB Patients.

Currently, tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (Mtb) that primarily affects the lungs. The severity of active pulmonary TB (APTB) is an important determinant of transmission, morbidity, mortality, disease experience, and treatment outcomes. Several publications have shown a high prevalence of disabling complications in individuals who have had severe APTB. Furthermore, certain strains of Mtb were associated with more severe disease outcomes. The use of biomarkers to predict severe APTB patients who are candidates for host-directed therapies, due to the high risk of developing post-tuberculous lung disease (PTLD), has not yet been implemented in the management of TB patients. We followed 108 individuals with APTB for 6 months using clinical tools, flow cytometry, and whole-genome sequencing (WGS). The median age of the study population was 26.5 years, and the frequency of women was 53.7%. In this study, we aimed to identify biomarkers that could help us to recognize individuals with APTB and improve our understanding of the immunopathology in these individuals. In this study, we conducted a follow-up on the treatment progress of 121 cases of APTB. The follow-up process commenced at the time of diagnosis (T0), continued with a control visit at 2 months (T2), and culminated in an exit appointment at 6 months following the completion of medical treatment (T6). People classified with severe APTB showed significantly higher levels of IL-6 (14.7 pg/mL; p < 0.05) compared to those with mild APTB (7.7 pg/mL) at T0. The AUCs for the ROC curves and the Matthews correlation coefficient values (MCC) demonstrate correlations ranging from moderate to very strong. We conducted WGS on 88 clinical isolates of Mtb, and our analysis revealed a total of 325 genes with insertions and deletions (Indels) within their coding regions when compared to the Mtb H37Rv reference genome. The pattern of association was found between serum levels of CHIT1 and the presence of Indels in Mtb isolates from patients with severe APTB. A key finding in our study was the high levels of CHIT1 in severe APTB patients. We identified a biomarker profile (IL-6, IFN-γ, IL-33, and CHIT1) that allows us to identify individuals with severe APTB, as well as the identification of a panel of polymorphisms (125) in clinical isolates of Mtb from individuals with severe APTB. Integrating these findings into a predictive model of severity would show promise for the management of APTB patients in the future, to guide host-directed therapy and reduce the prevalence of PTLD.

Distributed lag effects and vulnerable groups of PM and active pulmonary TB in Qingdao, China.

There has been a gap regarding current knowledge of the effect of PM on pulmonary TB, such as the exposure-time-response between them. This study aimed to explore the distributed lag effects of particulate matter (PM) on active pulmonary tuberculosis (TB) and identify the vulnerable groups. A generalized additive mixed model combined with a distributed lag non-linear model was applied to quantify the association between PM and active pulmonary TB with adjustment for potential confounders. Relative risk (RR) and cumulative RR with 95% confidence interval (CI) were calculated to quantify the exposure-time-response. A total of 16,486 cases of active pulmonary TB were notified. Results suggested that a unit 10µg/m3 increase of daily PM2.5 concentration was positively associated with active pulmonary TB morbidity at 36-115 lag day and RR reached maximum at 66 lag day (1.0076; 95%CI, 1.0031-1.0122), and the cumulative RR was 2.1940 (95%CI, 1.2292-3.9161). For PM10, this association was significantly positive at 73-117 lag day, and RR reached maximum at 100 lag day (1.0036; 95%CI, 1.0003-1.0067), and the cumulative RR was not significant. This study provides evidence that PM significantly associate with active pulmonary TB. Vulnerability to PM2.5 was identified in male, female, 0-18 ages, 19-64 ages, workers, and students. Our findings have significant implications for developing local strategies to prevent and reduce health impact in PM polluted areas.

Construction and Validation of a Diagnostic Scoring System for Predicting Active Pulmonary Tuberculosis in Patients with Positive T-SPOT Based on Indicators Associated with Coagulation and Inflammation: A Retrospective Cross-Sectional Study.

Tuberculosis (TB) is a life-threatening single infectious disease, which remains a major global public health concern. This study was to establish and validate a clinically practical diagnostic scoring system for predicting active pulmonary tuberculosis (APTB) in patients with positive tuberculosis T cell spot test [T-SPOT] using indicators associated with coagulation and inflammation. A single-center retrospective cross-sectional study was performed to include patients with positive T-SOPT registered and hospitalized at Wuhan Jinyintan Hospital between January 2017 and December 2019. All patients were separated into the active pulmonary tuberculosis (APTB) group and the inactive pulmonary tuberculosis (IPTB) group, according to the diagnostic criteria from China's Expert Consensus for APTB and IPTB. Subsequently, the patients were randomized into a training set and a validation set at a ratio of 2:1. Indicators associated with coagulation and inflammation, including prothrombin time activity (PTA), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration (Fbg-C), C-reactive protein/albumin ratio (CAR), C-reactive protein/prealbumin ratio (CPR), neutrophils count/lymphocyte count ratio (NLR), platelet count/lymphocyte count ratio (PLR), monocyte count/lymphocyte count ratio (MLR), and erythrocyte sedimentation rate (ESR) were obtained from electronic medical record system (EMRS). Stepwise logistic regression was performed in the training set to build a diagnostic model for predicting APTB, which was transformed into an easily applicable scoring system via nomogram. Receiver operating characteristic (ROC) analysis, calibration curve (CC), and decision curve analysis (DCA) were conducted to evaluate the predictive performance of the established diagnostic scoring system. A total of 508 patients [training set (211 cases of APTB and 116 cases of IPTB) and validation set (103 cases of APTB and 78 cases of IPTB)] with positive T-SPOT were recruited in the study. Stepwise logistic regression showed that CPR, MLR, ESR, APTT and Fbg-C were independent predictors for APTB. The scoring system was subsequently formulated based on the abovementioned predictors, which correspond to scores of 10, 6, 7, 5, and 5, respectively. In addition, patients are more likely to be diagnosed as APTB when the cut-off score was ≥16 scores, while patients with <16 scores are more likely to be diagnosed as IPTB. The scoring system showed good predictive efficacy in both the training set [area under the curve (AUC): 0.887] and the validation set (AUC: 0.898). Furthermore, both CC and DCA confirmed the clinical utility of the scoring system. The data suggest that the combination of indicators associated with coagulation and inflammation could serve as biomarkers to identify APTB in patients with positive T-SPOT. In addition, patients with positive T-SPOT were more prone to be diagnosed with APTB when having a combined total of scores ≥16 in the scoring system.

Tuberculosis Related Ischemic Stroke : A Case Report

Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium Tubercle Bacilli. In 15-20 % cases of active pulmonary TB, infection spreads to extrapulmonary foci, including the nervous system complications. Ischemic stroke related tuberculosis without meningitis is rare. We report a 74-year-old female presented with rapid onset confusion, unconsciousness, and left hemiparesis. She had been recently diagnosed with active TB 3 months ago and treated with combination anti tuberculosis regiment. Her recent acute neurological manifestations began within 24 hours prior to admission in the hospital. The brain CT showed  middle cerebral artery territory infarction. The risk factors tracing found no significant abnormality. The only abnormal finding was high CRP. This report describes rare case of a patient with active TB and who presented with acute ischemic stroke.

Pulmonary Tuberculosis Coinfected with COVID-19 Compounded by Bacterial Superinfection: A Case Report and Critical Appraisal of The Evidence Regarding Its Mortality

Background: The WHO has declared COVID-19 as a global pandemic. However, Indonesia is also challenged by high burden of tuberculosis (TB). In this study, reported an active pulmonary TB case coinciding with COVID-19 but deceased due to bacterial infection. There is a need to further explore this new problem in developing countries to determine the prognosis of COVID-19 patients with tuberculosis infection.Methods: A comprehensive literature search was conducted by using databases such as The Cochrane Library, PubMed, Google Scholar, EBSCO-Host, and Scopus, including systematic reviews of cohort studies, cohorts, and case controls. As many as 309 studies were identified, after screening for duplicates and against the inclusion and exclusion criteria, three studies were included for critical appraisal.Results: The meta-analysis by Gao et al included two studies with an odds ratio (OR) of 1.4 [95% CI=0.1-18.93], the cohort study by Sy et al reported a relative risk (RR) of 2.17 [95% CI=1.4-3.37], and Motta et al showed that COVID-19 patients with tuberculosis had a mortality rate of 11.8% [95% CI=7.75-15.45]. Conclusion: TB has yet to be an identified as a major predictor of increased mortality in COVID-19 patients but can be considered a predictor of increased severity in COVID-19 patients. Studies with a bigger sample size and better study design are suggested to obtain new evidence.

Cardiac dysfunction in active pulmonary tuberculosis: Mysterious facts of TB’s pandora

&lt;b&gt;Introduction&lt;/b&gt;: Cardiac dysfunction in pulmonary tuberculosis is relatively more common and underestimated due to lack of suspicion. We have studied prevalence of cardiac dysfunction in pulmonary tuberculosis with special emphasis on echocardiography, serum cortisol and its correlation in cases with unstable cardiorespiratory parameters.&lt;br /&gt; &lt;b&gt;Methods:&lt;/b&gt; Prospective, observational, complete workup, and one year follow up study conducted during January 2016 to December 2020 included 800 cases of active pulmonary tuberculosis with specified inclusion criteria of disproportionate tachycardia, tachypnea with or without hypoxia and shock. Cases with known risk factor for cardiac disease and taking cardiac medicines, and cases with pericardial effusion were excluded from study. All study cases were undergone protocolized analysis such as chest radiograph, pulse oximetry, ECG, sputum examination, cardiac enzymes (CPK-MB, NT-Pro-BNP, and cardiac troponins), serum cortisol, and echocardiography at entry point, at two and six months of treatment with anti-tuberculosis medicines as per NTEP. Statistical analysis was carried out by Chi-square test.&lt;br /&gt; &lt;b&gt;Observations and analysis: &lt;/b&gt;In a study of 800 pulmonary tuberculosis cases, 56.00% (448/800) cases were males, and 44.00% (352/800) cases were females. Cases with BMI&amp;lt;18 was 41.62% (333/800) and BMI&amp;gt;18 was 58.37% (467/800). Radiological patterns as unilateral disease in 33.62% (269/800) &amp;amp; bilateral disease in 66.37% (531/800). Hemoglobin less than 10 gm% were documented in 85.12% (681/800) and above 10 gm% were in 14.87% (119/800) cases. Serum albumin less than 3.5 gm% and more than 3.5 gm% were observed in 48.12% (385/800) and 51.12% (415/800) cases respectively. Hypoxia was documented 26.12% (209/800) cases and normal oxygen saturation in 73.87% (591/800) cases. cases with normal and abnormal serum cortisol were 61.37% (491/800) &amp;amp; 38.62% (309/800) respectively. Sputum examination for AFB observed in 30.00% (240/800) and gene Xpert MTB/RIF documented in 51.37% (411/800) cases respectively. Bronchoscopy guided techniques were used in 149 cases and BAL smear AFB in 44.96% (67/149) cases, gene Xpert MTB/RIF in 97.31% (145/149) cases and MGIT culture in four cases (positive in 100% cases subjected to MGIT culture). We have observed global hypokinesia is predominant cardiac dysfunction documented in 82.21% (171/208) cases, followed by left heart systolic dysfunction in 16.34% (34/208) cases and left heart diastolic dysfunction in 75% (156/208) cases. Right heart dysfunction as dilated right atrium and right ventricle documented in 52.88% (110/208) cases and pulmonary hypertension in 40.38% (84/208) cases. Covariates such as age, gender, hemoglobin, BMI, serum cortisol, serum albumin, oxygen saturation and radiological involvement has significant association with cardiac dysfunction. (p&amp;lt;0.00001) Response to treatment with antituberculosis medicines and steroids has documented as improved in 77.40% cases (161/208) cases, persistent in 13.46% (28/2028) cases and progressive in 9.13% (19/208) cases. Final outcome of cardiac dysfunction in Pulmonary tuberculosis cases has significant association with serum cortisol level (p&amp;lt;0.00086).&lt;br /&gt; &lt;b&gt;Conclusion:&lt;/b&gt; Cardiac dysfunction is active pulmonary tuberculosis needs prompt workup in presence of disproportionate tachypnea, tachycardia with or without hypoxia and shock. Echocardiography is basic tool to evaluate these cases and global hypokinesis is most common abnormality. Serum cortisol abnormality documented in fair number of cases and very well correlated with left ventricular dysfunction abnormalities. Steroids with antituberculosis treatment backup is mainstay protocol during management of these cases. Cardiac dysfunction is reversible in majority of cases and proportionate number shown complete improvement in cardiac dysfunction.

A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis.

Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden's J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.

Deep learning based CT images automatic analysis model for active/non-active pulmonary tuberculosis differential diagnosis.

Active pulmonary tuberculosis (ATB), which is more infectious and has a higher mortality rate compared with non-active pulmonary tuberculosis (non-ATB), needs to be diagnosed accurately and timely to prevent the tuberculosis from spreading and causing deaths. However, traditional differential diagnosis methods of active pulmonary tuberculosis involve bacteriological testing, sputum culturing and radiological images reading, which is time consuming and labour intensive. Therefore, an artificial intelligence model for ATB differential diagnosis would offer great assistance in clinical practice. In this study, computer tomography (CT) scans images and corresponding clinical information of 1160 ATB patients and 1131 patients with non-ATB were collected and divided into training, validation, and testing sets. A 3-dimension (3D) Nested UNet model was utilized to delineate lung field regions in the CT images, and three different pre-trained deep learning models including 3D VGG-16, 3D EfficientNet and 3D ResNet-50 were used for classification and differential diagnosis task. We also collected an external testing set with 100 ATB cases and 100 Non-ATB cases for further validation of the model. In the internal and external testing set, the 3D ResNet-50 model outperformed other models, reaching an AUC of 0.961 and 0.946, respectively. The 3D ResNet-50 model reached even higher levels of diagnostic accuracy than experienced radiologists, while the CT images reading and diagnosing speed was 10 times faster than human experts. The model was also capable of visualizing clinician interpretable lung lesion regions important for differential diagnosis, making it a powerful tool assisting ATB diagnosis. In conclusion, we developed an auxiliary tool to differentiate active and non-active pulmonary tuberculosis, which would have broad prospects in the bedside.

A protein signature associated with active tuberculosis identified by plasma profiling and network-based analysis.

Annually, approximately 10 million people are diagnosed with active tuberculosis (TB), and 1.4 million die of the disease. If left untreated, each person with active TB will infect 10-15 new individuals. The lack of non-sputum-based diagnostic tests leads to delayed diagnoses of active pulmonary TB cases, contributing to continued disease transmission. In this exploratory study, we aimed to identify biomarkers associated with active TB. We assessed the plasma levels of 92 proteins associated with inflammation in individuals with active TB (n= 20), latent TB (n= 14), or healthy controls (n= 10). Using co-expression network analysis, we identified one module of proteins with strong association with active TB. We removed proteins from the module that had low abundance or were associated with non-TB diseases in published transcriptomic datasets, resulting in a 12-protein plasma signature that was highly enriched in individuals with pulmonary and extrapulmonary TB and was further associated with disease severity.

The diagnostic value of an interferon gamma release assay in new cases of active pulmonary tuberculosis and the factors influencing its negative results

ObjectiveThe aim of the study was to investigate the diagnostic value of an interferon gamma release assay (IGRA) - QuantiFERON-TB GOLD in-tube (QFT-GIT) - to identify new cases of active pulmonary tuberculosis (PTB) in Quzhou City, and to assess possible factors associated with false-negative IGRA results in bacteriologically confirmed PTB. MethodsThis study collected clinical data of suspected adult PTB patients who underwent QFT-GIT in Quzhou People's Hospital between January 1, 2020 and December 31, 2020, and calculated the total sensitivity, specificity of QFT-GIT in new case of active PTB patients were 90.9% (401/448) and 72.9%(929/1275), respectively. Univariate and multivariate logistic regression were used to analyze the influencing factors of the false-negative results of QFT-GIT. ResultsA total of 1723 patients were enrolled, including 448(448/1723,26.0%) with new case of active PTB (389 cases were bacteriologically confirmed and 59 cases were clinically diagnosed) and 1275 non-PTB patients. There were 747(747/1723,43.4%) patients with positive results of QFT-GIT, among whom 401 were new case of active PTB patients (347 cases were bacteriologically confirmed and 54 cases were clinically diagnosed) and 346 were non-PTB patients. The total sensitivity and specificity of QFT-GIT in the diagnosis of new case of active PTB patients were 90.9% and 72.8% respectively. In bacteriologically comfirmed PTB patients, multivariate conditional logistic regression analysis showed that BMI and diabetes, malignant tumors and severe infections were all independent risk factors for the false-negative results of QFT-GIT. ConclusionQFT-GIT showed high sensitivity and relatively low specificity in the diagnosis of new case of active PTB patients. In clinical practice, we should analyze the suspected PTB patients comprehensively in terms of whether they are overweight or complicated with diabetes, malignant tumors or severe infections, and avoid missing the diagnosis of PTB.

Bridging the Gap in End Tuberculosis Targets in the Elderly Population in Eastern China: Observational Study From 2015 to 2020.

BackgroundWith a progressive increase in the aging process, the challenges posed by pulmonary tuberculosis (PTB) are also increasing for the elderly population.ObjectiveThis study aimed to identify the epidemiological distribution of PTB among the elderly, forecast the achievement of the World Health Organization’s 2025 goal in this specific group, and predict further advancement of PTB in the eastern area of China.MethodsAll notified active PTB cases aged ≥65 years from Zhejiang Province were screened and analyzed. The general epidemiological characteristics were depicted and presented using the ArcGIS software. Further prediction of PTB was performed using R and SPSS software programs.ResultsAltogether 41,431 cases aged ≥65 years were identified by the surveillance system from 2015 to 2020. After excluding extrapulmonary TB cases, we identified 39,832 PTB cases, including laboratory-confirmed (23,664, 59.41%) and clinically diagnosed (16,168, 40.59%) PTB. The notified PTB incidence indicated an evident downward trend with a reduction of 30%; however, the incidence of bacteriologically positive cases was steady at approximately 60/100,000. Based on the geographical distribution, Quzhou and Jinhua Cities had a higher PTB incidence among the elderly. The delay in PTB diagnosis was identified, and a significantly prolonged treatment course was observed in the elderly. Moreover, a 50% reduction of PTB incidence by the middle of 2024 was predicted using a linear regression model. It was found that using the exponential smoothing model would be better to predict the PTB trend in the elderly than a seasonal autoregressive integrated moving average model.ConclusionsMore comprehensive and effective interventions such as active PTB screening combined with physical checkup and succinct health education should be implemented and strengthened in the elderly. A more systematic assessment of the PTB epidemic trend in the elderly population should be considered to incorporate more predictive factors.

Quality assurance practices in tuberculosis diagnostic health facilities in Ethiopia.

The quality of tuberculosis laboratory services in health facilities is a mandatory component of detecting active pulmonary TB cases and treatment follow-up. However, ensuring the quality of laboratory test results is a concern. This study aimed to assess the quality assurance practices in the tuberculosis diagnostic health facilities of Ethiopia. A cross-sectional study was conducted from October 2018 to March 2019 at nine governmental TB-culture laboratories and 34 randomly selected GeneXpert® MTB/RIF (Xpert® MTB/RIF) testing health facilities in Ethiopia. Participating health facilities were interviewed and laboratory documents and records present since 2017 were observed. Prior to the data collection, training was given to the data collectors. Descriptive statistics were used to produce results and were presented with tables and graphs. From a total of 34 Xpert® MTB/RIF testing laboratories, 50% run Internal Quality Control (IQC) for Acid-Fast Bacillus (AFB) Microscopy and 67.6% had lot-to-lot verification of staining reagents. For the Xpert® MTB/RIF assay, a lot-to-lot verification of cartridge and method validation was performed only in 8.8%and 20.6% of Xpert® MTB/RIF testing laboratories respectively. All TB-culture laboratories included in the study ran negative control (start and end IQC) during TB-culture sample processing and performed lot-to-lot verification for Mycobacteria Growth Indicator Tube (MGIT) in 88.9% of TB-culture laboratories. External Quality Assessment (EQA) Proficiency Testing (PT) for AFB microscopy is practiced in 79.4% Xpert® MTB/RIF testing laboratories and 100.0% for the Xpert® MTB/RIF assay. TB-Culture PT participation practice among TB-culture laboratories was 88.9%. A major challenge for health facilities during PT participation was the AFB PT-sample transportation delay (40.7%) and the Xpert® MTB/RIF assay EQA-PT feedback missing (38.2%). This assessment reveals that IQC for AFB microscopy, lot-to-lot verification, method validation, and equipment calibration were not well-practiced. The majority of TB diagnostic health facility laboratories had EQA-PT participation practice, but a significant gap in PT-sample transportation and missing feedback was identified.

Diagnosis of Active Pulmonary Tuberculosis and Community Acquired Pneumonia Using Convolution Neural Network Based on Transfer Learning

A convolutional neural network (CNN) model for the diagnosis of active pulmonary tuberculosis (APTB) and community-acquired pneumonia (CAP) using chest radiographs (CRs) was constructed and verified based on transfer learning. CRs of 1247 APTB cases, 1488 CAP cases and 1247 normal cases were collected. All CRs were randomly divided into training set (1992 cases), validation set (1194 cases) and test set (796 cases) by stratified sampling in 5:3:2 radio. After normalization of CRs, the convolution base of pre-trained CNN (VGG16) model on ImageNet dataset was used to extract features, and the grid search was used to determine the optimal classifier module, which was added to the convolution base for transfer learning. After the training, the model with the highest accuracy of the validation set was selected as the optimal model to verify in the test set and calculate the accuracy of the model. The accuracy of validation set in the 63rd epochs was the highest, which was 0.9430, and the corresponding Categorical crossentropy was 0.1742. The accuracy of the training set was 0.9428, and the Categorical crossentropy was 0.1545. When the optimal model was applied to the test set, the accuracy was 0.9447, and the Categorical crossentropy was 0.1929. The transfer learning-based CNN model has good classification performance in the diagnosis of APTB, CAP and normal patients using CRs.

Influencing factors for delay of pulmonary tuberculosis case finding in students in Jiaxing, Zhejiang, 2010–2019

Objective  To investigate the delay of pulmonary tuberculosis (TB) case finding in students in Jiaxing, Zhejiang province, and the influencing factors, and provide data support for health decision-making. Methods  The information of pulmonary TB cases in students in child care settings, primary schools, junior high schools, senior high schools and colleges were collected form National Tuberculosis Information System for statistical analysis. The risk factors for the pulmonary TB case finding delay were analyzed by χ2 test and multivariate Logistic regression model. Results  A total of 443 pulmonary TB cases were reported in students. The cases in boys accounted for 60.05% and the cases in college students accounted for 34.09%. In the reported pulmonary TB cases, 55.40% had negative etiological test results. The median delay days of pulmonary TB case finding in students was 16 days and the proportion of the cases with delayed finding was 30.70%. The risk factors of diagnostic delay were medical care seeking due to illness, referral, cavity, being etiological positive and severe pulmonary TB. Conclusion  It is necessary to promote the active pulmonary TB case finding at school entrance and take systematic intervention measures to reduce pulmonary TB case finding delay in schools.

The impact of age when screening for latent tuberculosis infection - is it a problem?

Abstract Background Older population in developed countries represents a large reservoir of tuberculosis (TB) infection. Knowledge if age can contribute to false negative results in the immunological tests available for screening latent TB infections (LTBI) is critical to improve their usefulness in Public Health strategies for TB control. The aim of this study was to ascertain whether age was a risk factor for false negative (FN) results in the tuberculin skin test (TST) and in an interferon gamma release assay (IGRA). Methods Retrospective cohort study carried out using data from the Portuguese National Tuberculosis Surveillance system (2008-2015). Were included all active pulmonary TB cases with an IGRA (n = 597) and/or TST (n = 6185) result. TST outcomes were interpreted using a 5mm (TST-5mm) and 10mm (TST-10mm) cutoff. Logistic regression analysis crude and sex-adjusted was used to evaluate the association of age to the risk of FN results. Results Patients with a TST result presented a mean age of 42.7 years and patients with an IGRA result presented a median age of 45.5 years. TST-5mm, TST-10mm and IGRA had 36.5%, 43.9% and 24.5% FN results, respectively. Older patients presented a statistically significant association with the risk of FN TST results, regardless of using a 5mm [71-80years: OR 2.209; &amp;gt;80years: OR 2.491; p &amp;lt; 0.001] or 10mm [71-80years: OR 1.986; &amp;gt;80years: OR 2.308; p &amp;lt; 0.001] cut-off. Age was not a predictive factor for FN IGRA results. However, older patients presented a significant association with indeterminate IGRA results [71-80years: OR 3.808; &amp;gt;80years: OR 5.214; p &amp;lt; 0.001]. Conclusions When using TST as part of the Public Health strategies for screening elderly patients, healthcare professionals should bear in mind that there is an increased risk of obtaining a FN result. On the other hand, age did not show an association with the occurrence of FN IGRA results, which suggests that this test could perform better when screening for LTBI in older patients. Key messages TST in elderly people is associated with false negative results thus, when using this test for screening for LTBI, a negative result should be interpreted with caution. IGRA was not associated with false negative results in elderly people, however indeterminate results can occur more frequently, thus performing better in this population group.

Assessment of Interferon Gamma-Induced Protein 10 mRNA Release Assay for Detection of Latent Tuberculosis Infection in Egyptian Pediatric Household Contacts

ObjectivesCurrent diagnostic tests for tuberculosis (TB) in children living in low-endemic countries are limited by low specificity and the inability of the current tests to differentiate between active TB and latent TB infection (LTBI). This study aimed to evaluate the blood IP-10 mRNA expression level to detect LTBI in Egyptian pediatric household contacts (PHC). MethodsTB-specific IP-10 and IFN-γ mRNA levels were assessed by real-time quantitative PCR (RT-qPCR) in 72 Egyptian PHC of active pulmonary TB cases. All study participants were also assessed by Tuberculin Skin Test (TST) and Quantiferon gold in tube (QFN-GIT) assay. ResultsIP-10 and IFN-γ mRNA expression levels were significantly higher in PHC with active TB or LTBI than TB negative (p < 0.0001). The level of IP-10 mRNA expression was significantly higher in PHC with active TB than LTBI (p = 0.0008). In contrast, there was no significant differences in the IFN-γ mRNA expression between PHC with active TB compared to LTBI (p = 0.49). The sensitivity and specificity of the IP-10 RT-qPCR were 94.2% and 95.2%, respectively, in PHC with active TB compared to 85.7% and 81.8% in PHC with LTBI. The negative and positive predictive values and accuracy of IP-10 RT-qPCR for distinguishing active TB from LTBI were 85.2%, 58.3%, and 72.6% respectively. ConclusionBlood IP-10 mRNA expression level may be a potential diagnostic marker to help distinguish active TB from LTBI in PHC.

Factores predictivos de tuberculosis pulmonar en personas privadas de la libertad, Ecuador 2019

Objective: To determine the predictive factors and the proportion of cases of active pulmonary tuberculosis. Material and method: A cross-sectional study was realized with the prisoners who were admitted between February and April 2019 to the center with the highest prison density in Ecuador. Incidence, prevalence and risk factors for pulmonary tuberculosis were calculated. Results: 634 prisoners were surveyed, 14% with respiratory symptoms and 0,2% were diagnosed with pulmonary tuberculosis. The prevalence of pulmonary tuberculosis was 1,4%, of which 22,2% were MDR and 11,1% presented coinfection with HIV. The TB prevalence rate was 1.419,6 per 100.000 prisoners (95% CI, 488,7-2.540,4) and MDR TB was 11% (95% CI, 8,7-205,9). Conclusion: The proportion of pulmonary tuberculosis cases were higher than those found in the general population and lower than those registered inside the prison and HIV infection was the main predictive factor found, so it is necessary to optimize the preadmission diagnostic algorithms for avoid transmission in these enclosures.

The Relation Between the Emergence of Fluoroquinolone Resistance and Fluoroquinolone Exposure in New Cases of Active Pulmonary Tuberculosis.

This study aimed to determine the ratio of fluoroquinolone (FQ) exposure before the diagnosis of patients with a new case of active pulmonary tuberculosis (TB) and to investigate the correlation of this treatment with the emergence of FQ-resistant strains. In this retrospective comparative case series study, a total of 132 patients, who had been diagnosed with adult, culture-positive, active pulmonary TB were reviewed. The FQ group had 30 patients who had had ≥1 time and ≥7 days of FQ exposure within 1 year before the diagnoses. The control group included an equal number of patients with TB with similar demographic characteristics (non-FQ group). Ofloxacin (OFX) and moxifloxacin (MFX) resistance were examined at 2 different concentrations (2 and 4 mg/L for OFX; 0.25 and 0.5 mg/L for MFX). Of the 132 patients, 30 (22%) had 7 days or longer of FQ monotherapy within 1 year of initiation of anti-TB treatment. FQ resistance was detected in 2 (3.3%) patients. In the FQ group, MFX resistance at 0.25 mg/L concentration was observed in 1 patient, whereas another patient had OFX and MFX resistance at 4 mg/L and 0.5 mg/L concentrations, respectively. In the non-FQ group, no FQ resistance was detected in any of the patients. No statistically significant difference in terms of development of FQ resistance was found between the ratios of FQ and non-FQ groups (p=0.492). Although there was no statistically significant difference, 2 patients, in whom resistance was detected, had FQ exposure before their diagnosis. The FQ exposure ratio before the diagnosis is high (22%) in this cohort that includes patients with new active pulmonary TB, and the presence of patients with FQ resistance (even if only a few) should be a noteworthy and cautionary result in terms of FQ exposure and resistance development.

The diagnostic yield and safety of sputum induction in suspected pulmonary tuberculosis: The experience of a single tertiary care center in Saudi Arabia.

Sputum smear microscopy examination and culture for tuberculosis (TB) remain a fundamental tool of diagnosis but may be negative up to 50% case of active pulmonary TB. Bronchoscopy to obtain sputum is invasive and not readily available. Alternative methods of obtaining sputum specimens are crucial in suspected pulmonary TB cases who are unable to expectorate. In this context, it may be beneficial to stimulate sputum production by administering a mist of hypertonic saline produced by ultrasonic nebulization. The aims of the study are to describe the experience of a tertiary center in Saudi Arabia with sputum induction (SI) for the investigation of patients suspected to have sputum scare TB. A retrospective cohort study was performed. All patients suspected of sputum scare TB and investigated with SI were included. Standard descriptive statistics were used. Categorical data presented as frequency were compared using the Chi square test. Continuous data presented as mean ± standard deviation were compared using Student's t test. Sensitivity, specificity, and predictive values were calculated. Of 252 patients with suspected TB who underwent SI, 78 (31%) were ultimately diagnosed to have TB. Culture of induced sputum confirmed the diagnosis of TB in 44 (56.4%) of these patients. However, the diagnosis of TB would have been missed in 13.5% of the cohort if no further investigations were done. The incidence of complications was low. No patients required hospitalization or specialist intervention. SI is safe well tolerated and inexpensive. It may reduce the need for bronchoscopy in patients with suspected sputum scare TB. However, around 20% of TB can be missed by SI unless further investigations are performed. Hence, patients suspected to have sputum scare TB in whom the risk of bronchoscopy is high, a clinical decision on the appropriateness of empirical therapy is often required.