Clinical and Radiological Presentation of Patients with Smear Positive Pulmonary Tuberculosis.

Chest X-ray is an important diagnostic aid frequently used alongside microscopic smear of sputum for the confirmation of pulmonary tuberculosis (TB). However, there is a dearth of literature investigating the clinical and radiological pattern of sputum positive pulmonary TB among adults in Bangladesh. The current study explored these patterns in presentation. This descriptive cross-sectional study was conducted at outpatients in department of medicine of a tertiary care hospital. A total of 50 newly diagnosed adult cases of smear positive pulmonary TB attending at the Directly Observed Treatment Short-course (DOTS) corners were consecutively included. Informed written consent was taken before inclusion. Data were collected through face-to-face interview. Radiological presentation was explored using chest X-ray. Data were analyzed by SPSS version 26.0. The average age of patients was 41.0±17.12 years and majority were male (78.0%). The most prevalent respiratory symptom was cough (80.0%) followed by constitutional symptom like fever (70.0%) and weight loss (72.0%). Wasting was the predominant sign (60.0%). Radiologically both lungs were involved in 32.0%, left lung were involved in 30.0% cases and right lung were involved in 26.0% of cases. Twelve percent (12.0%) of patients had normal chest X-ray. Upper zone involvement was commonly observed in this study's patients (66.0%). The predominant pattern was consolidation (46.0%) followed by fibrosis (26.0%), nodular opacity (12.0%), collapse (10.0%), cavity (6.0%), pleural effusion (2.0%) and bronchiectasis (2.0%). Findings of this study would help familiarize and identify the common clinical and radiological presentations of sputum positive pulmonary TB patients in day-to-day practice.

Pulmonary tuberculosis diagnostic test using fluorescence immunoassay-based interferon gamma release assay with IchromaTM IGRA-TB.

INTRODUCTION: Tuberculosis (TB) is a serious global health problem in Indonesia, which is the country with the secondhighest TB burden after India. Accuracy in TB diagnosis is the key to effective treatment and decreased transmission rate. One of the latest diagnostic methods is interferon gamma release assay (IGRA), which measures the interferon-γ release associated with Mycobacterium tuberculosis (MTB) infection. This study aims to determine the diagnostic value of IGRA-TB using IchromaTM IGRA-TB diagnostic kit (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]), compared to Ziehl-Neelsen (AFB) staining, nucleic acid amplificationbased test (Xpert-MTB) and chest-X Ray as the gold standard in TB diagnosis. MATERIALS AND METHODS: A cross-sectional observational study design was used. Patients were recruited through purposive sampling from pulmonology outpatient clinic and inpatient ward at Jemursari Islamic Hospital (RSI Jemursari), Surabaya from July 2023 to December 2023. All enrolled patients should have been previously tested positive or negative for pulmonary TB using AFB staining, Xpert MTB and chest x-ray. Blood samples of the patients were collected and processed using the IchromaTM IGRA-TB diagnostic kit. The results were then compared with gold standard methods for calculating the IGRA-TB diagnostic value. RESULTS: A total of 56 adult patients were enrolled in this study. The sensitivity, specificity, PPV, NPV and accuracy rate of IGRA-TB using IchromaTM IGRA-TB diagnostic kit were 80.56%, 85%, 90.62%, 70.83% and 82.14%, respectively. CONCLUSION: IchromaTM IGRA-TB showed reasonably high diagnostic sensitivity and specificity, indicating that this method can be further utilised as a diagnostic and screening tool for pulmonary TB.

Coexistence of pulmonary thromboembolism and pulmonary tuberculosis: a diagnostic dilemma.

A man in his early 50s with previously treated pulmonary tuberculosis (TB) presented with a 3-month history of cough, expectoration and progressive breathlessness, accompanied by significant weight loss. Examination revealed tachycardia, tachypnoea, hypoxaemia and unilateral diminished breath sounds. Investigations showed anaemia, leucocytosis and a homogeneous opacity on the left side of the CXR. ECG and echocardiography suggested pulmonary thromboembolism (PTE). A CT pulmonary angiogram confirmed a chronic embolus and a severely fibrosed left lung. A comprehensive thrombophilia workup yielded normal results and the PTE was attributed to his history of TB. Sputum analysis confirmed reactivated TB, leading to the initiation of antitubercular therapy. The patient improved clinically with plans for a repeat CT pulmonary angiography to assess the need for pulmonary thromboendarterectomy after completing TB treatment. This case highlights the possible association of TB and PTE, its management and why it should be considered as a differential diagnosis in patients with a history of TB presenting with exacerbated breathlessness.

Genetic diversity within diagnostic sputum samples is mirrored in the culture of Mycobacterium tuberculosis across different settings.

Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants' frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.

Diagnostic value of the Xpert MTB/RIF assay combined with endobronchial ultrasonography with a guide sheath for peripheral nodular pulmonary tuberculosis.

BACKGROUND: The diagnosis of peripheral isolated nodular lesions that are suspected as pulmonary tuberculosis (PTB) is challenging, which are not easily accessible via conventional bronchoscopy. This study evaluated the combined use of Xpert MTB/RIF assay and endobronchial ultrasonography with a guide sheath (EBUS-GS) for detecting MTB infection in peripheral lung bands, for early detection of PTB. METHODS: The clinical data of 232 patients with suspected peripheral nodular PTB who underwent EBUS-GS between June 2020 and October 2023 were retrospectively reviewed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of acid-fast bacilli smear, culture, Xpert MTB/RIF assay, and pathological examination were calculated. To assess diagnostic accuracy, the results of the four methods were directly compared with the final clinical diagnosis. RESULTS: In total, 146 and 86 patients were clinically diagnosed with peripheral nodular PTB and non-PTB, respectively. The sensitivity, specificity, PPV, NPV, and AUC values of combined Xpert MTB/RIF assay and EBUS-GS were 47.26%, 100.0%, 100.0%, 52.76%, and 0.74; those of acid-fast bacilli smear were 8.22%, 97.67%, 85.71%, 38.53%, and 0.53; those of culture were 31.51%, 100.0%, 100.0%, 46.24%, and 0.66; and those of pathological examination were 23.97%, 97.67%, 94.59%, 43.08%, and 0.61, respectively. CONCLUSION: The diagnostic accuracy of the combined Xpert MTB/RIF assay and EBUS-GS was significantly better than that of other conventional tests. Hence, this novel technique can be routinely applied for diagnosing and managing peripheral nodular PTB.

A multicentre study to evaluate the diagnostic performance of a novel CAD software, DecXpert, for radiological diagnosis of tuberculosis in the northern Indian population.

Tuberculosis (TB) is the leading cause of mortality among infectious diseases globally. Effectively managing TB requires early identification of individuals with TB disease. Resource-constrained settings often lack skilled professionals for interpreting chest X-rays (CXRs) used in TB diagnosis. To address this challenge, we developed "DecXpert" a novel Computer-Aided Detection (CAD) software solution based on deep neural networks for early TB diagnosis from CXRs, aiming to detect subtle abnormalities that may be overlooked by human interpretation alone. This study was conducted on the largest cohort size to date, where the performance of a CAD software (DecXpert version 1.4) was validated against the gold standard molecular diagnostic technique, GeneXpert MTB/RIF, analyzing data from 4363 individuals across 12 primary health care centers and one tertiary hospital in North India. DecXpert demonstrated 88% sensitivity (95% CI 0.85-0.93) and 85% specificity (95% CI 0.82-0.91) for active TB detection. Incorporating demographics, DecXpert achieved an area under the curve of 0.91 (95% CI 0.88-0.94), indicating robust diagnostic performance. Our findings establish DecXpert's potential as an accurate, efficient AI solution for early identification of active TB cases. Deployed as a screening tool in resource-limited settings, DecXpert could enable early identification of individuals with TB disease and facilitate effective TB management where skilled radiological interpretation is limited.

Evaluation of testing face-mask filter samples with LAMP shows high rates of detection in pulmonary TB.

Detection of Mycobacterium tuberculosis (MTB) in bioaerosols derived from patients with active pulmonary TB is a potential alternative diagnostic method for patients with presumed TB who cannot expectorate sputum.To assess the efficacy of a bioaerosol particle collection method to capture MTB and diagnose TB.A mask-like filter holder (3D mask) with a water-soluble gelatine filter (GF) and one containing a water-insoluble polypropylene filter (PPF) were prepared. Eligible patients wore the 3D mask with GF or PPF within 3 days of starting anti-TB drugs. The GF and PPF filters were collected after 2 and 8 h. DNA was extracted from the filter samples and tested using loop-mediated isothermal amplification (LAMP).Filter samples were collected from 57 and 20 patients with and without active pulmonary TB, respectively. The GF and PPF sensitivity was 76.2% and 83.3%, respectively. The specificity of both methods was 100%. Of the 57 patients diagnosed with non-expectorated sputum samples, including suction phlegm, gastric lavage, and bronchial lavage fluid, 55.6% and 50.0% were positive by GF and PPF, respectively.We present a 3D mask filter sampling method for exhaled bioaerosol particles that can be used in clinical practice to diagnose patients with presumed TB..

A novel hematological score (HS) and its related nomogram model to predict nontuberculous mycobacterial pulmonary disease in patients with suspected multidrug-resistant pulmonary tuberculosis.

BACKGROUND: Nontuberculous mycobacteria pulmonary disease (NTM-PD) exhibits clinical and radiological characteristics similar to those of pulmonary tuberculosis (PTB). This study aimed to develop a novel hematological score (HS) and its related nomogram model to identify NTM-PD in patients with suspected multidrug-resistant pulmonary tuberculosis (SMDR-PTB) due to lack of response to first-line anti-TB treatment (ATT). METHODS: We retrospectively recruited patients with SMDR-PTB from Wuhan Jinyintan Hospital between January 2014 and January 2022. These patients were divided into NTM-PD and MDR-PTB groups based on pathogen test results. Participants were randomly allocated to training and validation set in a 7:3 ratio. The ROC and LASSO regression were employed to select variables. Multivariate logistic analysis was conducted on the training set to develop the HS and its related nomogram models, followed by internal validation on the validation set. RESULTS: The HS was constructed and developed on CKMB, ADA, GGT, LDL, and UHR, demonstrating good predictive value with AUCs of 0.900 and 0.867 in the training and validation sets, respectively. The HS-based nomogram model consists of Age, Gender, DM, HIV infection, ILD and HS, and exhibited strong discriminative ability, accuracy, and clinical utility in two sets. The AUCs were 0.930 and 0.948 in the training set and validation set, respectively. CONCLUSION: HS may be a useful biomarker for identifying NTM-PD in patients with SMDR-PTB. The HS-based nomogram model serves as a convenient and efficient tool for guiding the treatment of SMDR-PTB patients.

Performance evaluation of the national tuberculosis control program 2016-2020: Souss-Massa region, Morocco.

BACKGROUND: Tuberculosis constitutes a public health problem in Morocco. In an environment where results-based management and the evaluation of public policies become an imperative; the evaluation of the performance of the national tuberculosis control program finds its interest. OBJECTIVES: This study aims to analyze the performance of the tuberculosis control program in the Souss Massa region, based on the systemic approach model over a five-year period 2016-2020. METHODS: This is a descriptive secondary data analysis carried out in the Souss-Massa region in southern Morocco over a five year period 2016-2020. Data collection was carried out through the health information system of the NTCP and the various periodic reports produced by the primary health care establishments and diagnostic centers for tuberculosis and respiratory diseases, the delegations and the regional health directorate of the Ministry of Health. RESULTS: The incidence of tuberculosis has fluctuated between 63 and 72 cases/100,000 inhabitants; the average number of cases detected is 1871 cases per year; the survey completion rate is 57.10%; the therapeutic success rate varies between 82% and 89%, the treatment failure rate varies between 0.62% and 2.32%; the death rate varies between 0.63% and 2.92%; the failure rate for tuberculosis/HIV cases is between 3.10% and 6.09%. CONCLUSIONS: The results of the program tracer indicators at the level of the Souss-Massa region show that the latter combs to achieve the target objectives.

My tuberculosis epidemiology journey: Implications for TB program interventions, activities and strategy.

Key learnings from some landmark studies that the author has been associated with and their implications on program strategies are highlighted. Learnings from prevalence surveys provide justification for active TB Case finding (ACF), role of Chest X-ray screening, justification of the elderly as a key vulnerable population and suggest re-think of the methods of sub-national certification for progress towards tuberculosis free status. Risk of infection studies suggest 14 million people acquiring new tuberculous infection each year in India suggesting a re-think on the targets for TB elimination. Justification is given for 'TB deaths averted' as a parameter for monitoring program impact, reviving risk of infection surveys using CyTB and higher emphasis on careful analysis of routine surveillance data for monitoring epidemiological trends rather than oft-repeated surveys. The modelling outputs suggest higher focus on reducing transmission of infection in urban and reducing treatment delay in rural areas and the need to scale up active case finding and TB preventive treatment in order to achieve End TB targets. Case finding studies justify upfront molecular diagnostics, need to confirm a single sputum result by another specimen or radiology during ACF and futility of X-ray based diagnosis during ACF. High rates of recurrence with intermittent treatment regimen providing evidence in favor of daily regimen, role of family centric approach to nutritional supplementation to prevent TB mortality and reduce TB incidence among household contacts are highlighted besides the need to address high proportion of families suffering catastrophic expenses during pre-treatment period.

A retrospective study differentiating nontuberculous mycobacterial pulmonary disease from pulmonary tuberculosis on computed tomography using radiomics and machine learning algorithms.

OBJECTIVE: To evaluate the effectiveness of a machine learning based on computed tomography (CT) radiomics to distinguish nontuberculous mycobacterial pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB). METHODS: In this retrospective analysis, medical records of 99 individuals afflicted with NTM-PD and 285 individuals with PTB in Zhejiang Chinese and Western Medicine Integrated Hospital were examined. Random numbers generated by a computer were utilized to stratify the study cohort, with 80% designated as the training cohort and 20% as the validation cohort. A total of 2153 radiomics features were extracted using Python (Pyradiomics package) to analyse the CT characteristics of the large disease areas. The identification of significant factors was conducted through the least absolute shrinkage and selection operator (LASSO) regression. The following four supervised learning classifier models were developed: random forest (RF), support vector machine (SVM), logistic regression (LR), and extreme gradient boosting (XGBoost). For assessment and comparison of the predictive performance among these models, receiver-operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were employed. RESULTS: The Student's t-test, Levene test, and LASSO algorithm collectively selected 23 optimal features. ROC analysis was then conducted, with the respective AUC values of the XGBoost, LR, SVM, and RF models recorded to be 1, 0.9044, 0.8868, and 0.7982 in the training cohort. In the validation cohort, the respective AUC values of the XGBoost, LR, SVM, and RF models were 0.8358, 0.8085, 0.87739, and 0.7759. The DeLong test results noted the lack of remarkable variation across the models. CONCLUSION: The CT radiomics features can help distinguish between NTM-PD and PTB. Among the four classifiers, SVM showed a stable performance in effectively identifying these two diseases.

The Clinical Characteristics, Treatment and Prognosis of Tuberculosis-Associated Chronic Obstructive Pulmonary Disease: A Protocol for a Multicenter Prospective Cohort Study in China.

Background: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation. Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred. Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.

Breaking the threshold: Developing multivariable models using computer-aided chest X-ray analysis for tuberculosis triage.

OBJECTIVES: Computer-aided detection (CAD) software packages quantify tuberculosis (TB)-compatible chest X-ray (CXR) abnormality as continuous scores. In practice, a threshold value is selected for binary CXR classification. We assessed the diagnostic accuracy of an alternative approach to applying CAD for TB triage: incorporating CAD scores in multivariable modeling. METHODS: We pooled individual patient data from four studies. Separately, for two commercial CAD, we used logistic regression to model microbiologically confirmed TB. Models included CAD score, study site, age, sex, human immunodeficiency virus status, and prior TB. We compared specificity at target sensitivities ≥90% between the multivariable model and the current threshold-based approach for CAD use. RESULTS: We included 4,733/5,640 (84%) participants with complete covariate data (median age 36 years; 45% female; 22% with prior TB; 22% people living with human immunodeficiency virus). A total of 805 (17%) had TB. Multivariable models demonstrated excellent performance (areas under the receiver operating characteristic curve [95% confidence interval]: software A, 0.91 [0.90-0.93]; software B, 0.92 [0.91-0.93]). Compared with threshold scores, multivariable models increased specificity (e.g., at 90% sensitivity, threshold vs model specificity [95% confidence interval]: software A, 71% [68-74%] vs 75% [74-77%]; software B, 69% [63-75%] vs 75% [74-77%]). CONCLUSION: Using CAD scores in multivariable models outperformed the current practice of CAD-threshold-based CXR classification for TB diagnosis.

Subtracting the background by reducing cell-free DNA's confounding effects on Mycobacterium tuberculosis quantitation and the sputum microbiome.

DNA characterisation in people with tuberculosis (TB) is critical for diagnostic and microbiome evaluations. However, extracellular DNA, more frequent in people on chemotherapy, confounds results. We evaluated whether nucleic acid dyes [propidium monoazide (PMA), PEMAX] and DNaseI could reduce this. PCR [16S Mycobacterium tuberculosis complex (Mtb) qPCR, Xpert MTB/RIF] was done on dilution series of untreated and treated (PMA, PEMAX, DNaseI) Mtb. Separately, 16S rRNA gene qPCR and sequencing were done on untreated and treated sputa before (Cohort A: 11 TB-negatives, 9 TB-positives; Cohort B: 19 TB-positives, PEMAX only) and 24-weeks after chemotherapy (Cohort B). PMA and PEMAX reduced PCR-detected Mtb DNA for dilution series and Cohort A sputum versus untreated controls, suggesting non-intact Mtb is present before treatment-start. PEMAX enabled sequencing-based Mycobacterium-detection in 7/12 (58%) TB-positive sputa where no such reads otherwise occurred. In Cohort A, PMA- and PEMAX-treated versus untreated sputa had decreased α- and increased ß-diversities. In Cohort B, ß-diversity differences between timepoints were only detected with PEMAX. DNaseI had negligible effects. PMA and PEMAX (but not DNaseI) reduced extracellular DNA in PCR and improved pathogen detection by sequencing. PEMAX additionally detected chemotherapy-associated taxonomic changes that would otherwise be missed. Dyes enhance microbiome evaluations especially during chemotherapy.

Epidemiological characteristics, diagnosis and treatment effect of rifampicin-resistant pulmonary tuberculosis (RR-PTB) in Guizhou Province.

BACKGROUND: Rifampicin-resistant pulmonary tuberculosis (RR-PTB) presents a significant threat to global public health security. China bears a substantial burden of RR-PTB cases globally, with Guizhou Province experiencing particularly alarming trends, marked by a continual increase in patient numbers. Understanding the population characteristics and treatment modalities for RR-PTB is crucial for mitigating morbidity and mortality associated with this disease. METHODS: We gathered epidemiological, diagnostic, and treatment data of all RR-PTB cases recorded in Guizhou Province from January 1, 2017 to December 31, 2023. Utilizing composition ratios as the analytical metric, we employed Chi-square tests to examine the spatiotemporal distribution patterns of RR-PTB patients and the evolving trends among different patient classifications over the study period. RESULTS: In our study, 3396 cases of RR-PTB were analyzed, with an average age of 45 years. The number of RR-PTB patients rose significantly from 176 in 2017 to 960 in 2023, peaking notably among individuals aged 23-28 and 44-54, with a rising proportion in the 51-80 age group (P < 0.001). Since 2021, there has been a notable increase in the proportion of female patients. While individuals of Han ethnic group comprised the largest group, their proportion decreased over time (P < 0.001). Conversely, the Miao ethnicity showed an increasing trend (P < 0.05). The majority of patients were farmers, with their proportion showing an upward trajectory (P < 0.001), while students represented 4.33% of the cases. Geographically, most patients were registered in Guiyang and Zunyi, with a declining trend (P < 0.001), yet household addresses primarily clustered in Bijie, Tongren, and Zunyi. The proportion of floating population patients gradually decreased, alongside an increase in newly treated patients and those without prior anti-tuberculosis therapy. Additionally, there was a notable rise in molecular biological diagnostic drug sensitivity (real-time PCR and melting curve analysis) (P < 0.001). However, the cure rate declined, coupled with an increasing proportion of RR-PTB patients lost to follow-up and untreated (P < 0.05). CONCLUSIONS: Enhanced surveillance is crucial for detecting tuberculosis patients aged 23-28 and 44-54 years. The distribution of cases varies among nationalities and occupations, potentially influenced by cultural and environmental factors. Regional patterns in RR-PTB incidence suggest tailored prevention and control strategies are necessary. Despite molecular tests advances, challenges persist with low cure rates and high loss to follow-up. Strengthening long-term management, resource allocation, and social support systems for RR-PTB patients is essential.

Clinical profiles and related factors in tuberculosis patients with positive sputum smear mycobacterium tuberculosis tests.

The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75-89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease.

Addressing the burden and detection gap of latent tuberculosis infection in schoolchildren and adolescents in China: a cross-sectional study.

BACKGROUND: The latent tuberculosis infection (LTBI) burden is still unclear in schoolchildren and adolescents in China. Previous study and daily surveillance data indicate a LTBI detection gap. The research objective was to evaluate the LTBI burden and detection gap among schoolchildren and adolescents in China. METHODS: A cross-sectional study was conducted among 69,667 schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 implemented by Chongqing Municipal Institute of Tuberculosis using tuberculin skin test (TST) and creation tuberculin skin test (C-TST). To evaluate the LTBI detection gap, the pulmonary tuberculosis (PTB) screening data implemented by Chongqing Municipal Institute of Tuberculosis have been compared with the data in 2021 implemented by community-level medical and health care institutions. RESULTS: The LTBI prevalence rate using TST and C-TST implemented by Chongqing Municipal Institute of Tuberculosis was 12.8% (95%CI, 12.5-13%) and 6.4% (95%CI, 6-6.8%) respectively. The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions (χ2 = 2931.9, P < 0.001). CONCLUSIONS: The LTBI detection gap existed among schoolchildren and adolescents in Chongqing, and it also may exist in other similar countries and regions. National screening strategy needs improvement. Regular training and quality assurance could improve the performance of TST and C-TST and close the detection gap of LTBI.

PPE59 antibodies in tuberculous patients and potential use for diagnosis when assayed with other rapid biomarkers.

BACKGROUND: PPE 59, which is absent from bacillus Calmette Guérin (BCG) strains, seems to induce a humoral immune response in patients with tuberculosis (TB). Additional studies are needed to better evaluate this protein in immune response to tuberculosis. OBJECTIVES: To evaluate the response of antibodies to PPE59 in TB individuals, its combination with IgG response to other, previously tested mycobacterial antigens (Ag) and with sputum smear microbiology (SM) results. METHODS: We have cloned and expressed the rv3429 gene that encodes PPE59, then IgG, IgM, and IgA against PPE59 antigens measured by enzyme-linked immunosorbent assay (ELISA) in 212 sera samples obtained from the following subject cohorts: TB residents from Italy (79) and in Brazil (52); and an all-Brazilian cohort of 55 patients with other respiratory disorders; 10 patients infected with non-tuberculous mycobacteria, and 16 asymptomatic subjects. Drawing on results from a previous study(17) of serum samples from Brazilian subjects tested for IgG by ELISA against mycobacterial antigens ESAT-6, 16kDa, MT10.3, MPT-64 and 38kDa, the results were analysed in combination with those of the PPE59 and SM tests. FINDINGS: Keeping the specificity rate at 97%, the overall PPE59 IgA sensitivity was 42.7%, while IgG and IgM showed lower performance (p < 0.0001). Combining PPE59 IgA/16kDa IgG results increased sensitivity to 71%, and even higher rates when the results were combined with SM results (86.5%, p = 0.001), at 88.9% specificity. Positive IgA was associated with pulmonary image alterations of high TB probability (p < 0.05). MAIN CONCLUSIONS: Tests with TB patients found a moderate frequency of positivity for PPE59 IgA. However, the higher level of sensitivity attained in combination with PPE59 IgA/16kDa IgG/SM results unheard of before, although imperfect, suggests that this may be a potential additional tool for rapid detection of TB in low-resource areas.

A serum B-lymphocyte activation signature is a key distinguishing feature of the immune response in sarcoidosis compared to tuberculosis.

Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).