Effects of low dose computed tomography (LDCT) on lung cancer screening on incidence and mortality in regions with high tuberculosis prevalence: A systematic review.

BACKGROUND: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) is a strategy for early-stage diagnosis. The implementation of LDCT screening in countries with a high prevalence/incidence of tuberculosis (TB) is controversial. This systematic review and meta-analysis aim to identify whether LCS using LDCT increases early-stage diagnosis and decreases mortality, as well as the false-positive rate, in regions with a high prevalence of TB. METHODS/DESIGN: Studies were identified by searching BVS, PUBMED, EMBASE, and SCOPUS. RCT and cohort studies (CS) that show the effects of LDCT in LC screening on mortality and secondary outcomes were eligible. Two independent reviewers evaluated eligibility and a third judged disagreements. We used the Systematic Review Data Repository (SRDR+) to extract the metadata and record decisions. The analyses were stratified by study design and incidence of TB. We used the Cochrane "Risk of bias" assessment tool. RESULTS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were used. Thirty-seven papers were included, referring to 22 studies (10 RCTs and 12 cohorts). Few studies were from regions with a high incidence of TB (One RCT and four cohorts). Nonetheless, the evidence is compatible with European and USA studies. RCTs and CS also had consistent results. There is an increase in early-stage (I-II) diagnoses and reduced LC mortality in the LCDT arm compared to the control. Although false-positive rates varied, they stayed within the 20 to 30% range. DISCUSSION: This is the first meta-analysis of LDCT for LCS focused on its benefits in regions with an increased incidence/prevalence of TB. Although the specificity of Lung-RADS was higher in participants without TB sequelae than in those with TB sequelae, our findings point out that the difference does not invalidate implementing LDCT LCS in these regions. TRIAL REGISTRATION: Systematic review registration Systematic review registration PROSPERO CRD42022309581.

Clinicopathological analysis of nasopharyngeal tuberculosis.

BACKGROUND: The aim of this study is to examine the clinical and pathological attributes of nasopharyngeal tuberculosis. METHODS: We conducted a retrospective analysis of the clinicopathologic characteristics of nasopharyngeal tuberculosis in 14 patients. The medical records and imaging data obtained between March 2004 and February 2023 were scrutinized. During the pathological review, we classified the types of granulomatous inflammation and graded the extent of caseation. RESULTS: Results indicate a 100% female predominance, with chief complaints including hearing loss, postnasal drip, and nasal obstruction. Cervical lymphadenopathy occurred in 21.4% of patients. Chest radiograph abnormalities were found in 58.3%, with three showing active pulmonary tuberculosis. Endoscopic examination revealed three types of lesions, and CT/MRI findings correlated with gross lesions. A statistically significant association was found between lesion characteristics (bulging, ulcerative, necrotic) and pathology patterns (sarcoidosis-like, caseation). Bulging masses exhibited sarcoidosis-like patterns, while ulcerative/necrotic lesions were often associated with caseation. All lesions responded well to over six months of anti-tuberculosis medication, leading to favourable outcomes. CONCLUSION: We studied 14 cases of nasopharyngeal tuberculosis, mostly in females, with common ear and nose symptoms. Lesions were typically visible on nasopharyngeal endoscopy, and endoscopically bulging mass-like lesions had pathologically sarcoidosis-like granulomas. All patients had favourable outcomes.

Chest Radiograph Screening for Detecting Subclinical Tuberculosis in Asymptomatic Household Contacts, Peru.

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.

Integrating molecular and radiological screening tools during community-based active case-finding for tuberculosis and COVID-19 in southern Africa.

OBJECTIVES: To evaluate diagnostic yield and feasibility of integrating testing for TB and COVID-19 using molecular and radiological screening tools during community-based active case-finding (ACF). METHODS: Community-based participants with presumed TB and/or COVID-19 were recruited using a mobile clinic. Participants underwent simultaneous point-of-care (POC) testing for TB (sputum; Xpert Ultra) and COVID-19 (nasopharyngeal swabs; Xpert SARS-CoV-2). Sputum culture and SARS-CoV-2 RT-PCR served as reference standards. Participants underwent ultra-portable POC chest radiography with computer-aided detection (CAD). TB infectiousness was evaluated using smear microscopy, cough aerosol sampling studies (CASS), and chest radiographic cavity detection. Feasibility of POC testing was evaluated via user-appraisals. RESULTS: Six hundred and one participants were enrolled, with 144/601 (24.0%) reporting symptoms suggestive of TB and/or COVID-19. 16/144 (11.1%) participants tested positive for TB, while 10/144 (6.9%) tested positive for COVID-19 (2/144 [1.4%] had concurrent TB/COVID-19). Seven (7/16 [43.8%]) individuals with TB were probably infectious. Test-specific sensitivity and specificity (95% CI) were: Xpert Ultra 75.0% (42.8-94.5) and 96.9% (92.4-99.2); Xpert SARS-CoV-2 66.7% (22.3-95.7) and 97.1% (92.7-99.2). Area under the curve (AUC) for CAD4TB was 0.90 (0.82-0.97). User appraisals indicated POC Xpert to have 'good' user-friendliness. CONCLUSIONS: Integrating TB/COVID-19 screening during community-based ACF using POC molecular and radiological tools is feasible, has a high diagnostic yield, and can identity probably infectious persons.

Adapted generative latent diffusion models for accurate pathological analysis in chest X-ray images.

Respiratory diseases have a significant global impact, and assessing these conditions is crucial for improving patient outcomes. Chest X-ray is widely used for diagnosis, but expert evaluation can be challenging. Automatic computer-aided diagnosis methods can provide support for clinicians in these tasks. Deep learning has emerged as a set of algorithms with exceptional potential in such tasks. However, these algorithms require a vast amount of data, often scarce in medical imaging domains. In this work, a new data augmentation methodology based on adapted generative latent diffusion models is proposed to improve the performance of an automatic pathological screening in two high-impact scenarios: tuberculosis and lung nodules. The methodology is evaluated using three publicly available datasets, representative of real-world settings. An ablation study obtained the highest-performing image generation model configuration regarding the number of training steps. The results demonstrate that the novel set of generated images can improve the performance of the screening of these two highly relevant pathologies, obtaining an accuracy of 97.09%, 92.14% in each dataset of tuberculosis screening, respectively, and 82.19% in lung nodules. The proposal notably improves on previous image generation methods for data augmentation, highlighting the importance of the contribution in these critical public health challenges.

The Diagnosis of Esophageal Tuberculosis through an Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy.

A 54-year-old woman presented with an elevated esophageal lesion. Computed tomography (CT) and magnetic resonance imaging revealed a mass in the pancreatic head. Endoscopic ultrasound (EUS) showed a well-defined, round, hypoechoic mass, which was considered lymph node enlargement. An EUS-guided fine-needle aspiration biopsy (FNAB) was performed on the esophagus and the mass above the pancreatic head. The pathologically confirmed epithelial cells and multinucleated giant cells were positive for T-SPOT. Clinically, tuberculous lymphadenitis and esophageal tuberculosis were suspected, with successful treatment with anti-tuberculosis therapy resulting in a good response. Our findings suggest that an EUS-FNAB is useful for diagnosing esophageal tuberculosis.

Imaging of supra-thoracic tuberculosis.

Tuberculosis (TB) typically affects the lungs, but may involve many extra-pulmonary sites; with the latter especially prone in patients with human immunodeficiency virus infection. The clinical features of extra-pulmonary TB are often non-specific, mimicking many different disease entities. Application of the most appropriate imaging modality and knowing the imaging findings with clinical context awareness help initiation of further investigations, diagnosis and early treatment. This pictorial essay highlights the imaging spectrum of extra-pulmonary TB affecting the supra-thoracic region, i.e. brain, neck, and ear, nose and throat.

Explainable deep-neural-network supported scheme for tuberculosis detection from chest radiographs.

Chest radiographs are examined in typical clinical settings by competent physicians for tuberculosis diagnosis. However, this procedure is time consuming and subjective. Due to the growing usage of machine learning techniques in applied sciences, researchers have begun applying comparable concepts to medical diagnostics, such as tuberculosis screening. In the period of extremely deep neural nets which comprised of hundreds of convolution layers for feature extraction, we create a shallow-CNN for screening of TB condition from Chest X-rays so that the model is able to offer appropriate interpretation for right diagnosis. The suggested model consists of four convolution-maxpooling layers with various hyperparameters that were optimized for optimal performance using a Bayesian optimization technique. The model was reported with a peak classification accuracy, F1-score, sensitivity and specificity of 0.95. In addition, the receiver operating characteristic (ROC) curve for the proposed shallow-CNN showed a peak area under the curve value of 0.976. Moreover, we have employed class activation maps (CAM) and Local Interpretable Model-agnostic Explanations (LIME), explainer systems for assessing the transparency and explainability of the model in comparison to a state-of-the-art pre-trained neural net such as the DenseNet.

Does PET-CT Have a Role in the Evaluation of Tuberculosis Treatment in Phase 2 Clinical Trials?

Positron emission tomography-computed tomography (PET-CT) has the potential to revolutionize research in infectious diseases, as it has done with cancer. There is growing interest in it as a biomarker in the setting of early-phase tuberculosis clinical trials, particularly given the limitations of current biomarkers as adequate predictors of sterilizing cure for tuberculosis. PET-CT is a real-time tool that provides a 3-dimensional view of the spatial distribution of tuberculosis within the lung parenchyma and the nature of lesions with uptake (ie, whether nodular, consolidative, or cavitary). Its ability to provide functional data on changes in metabolism, drug penetration, and immune control of tuberculous lesions has the potential to facilitate drug development and regimen selection for advancement to phase 3 trials in tuberculosis. In this narrative review, we discuss the role that PET-CT may have in evaluating responses to drug therapy in active tuberculosis treatment and the challenges in taking PET-CT forward as predictive biomarker of relapse-free cure in the setting of phase 2 clinical trials.

18 F-FDG PET/CT in Renal Allograft Tuberculosis Mimicking as Posttransplant Malignancy.

ABSTRACT: The most common complications after the renal transplant are infections and malignancies, including posttransplant lymphoproliferative disorders. Tubercular infection in renal allograft recipients is a relatively rare entity. However, nonspecific constitutional symptoms often delay diagnosis, leading to significant morbidity and mortality. We present the 18 F-FDG PET/CT findings in a patient with renal allograft tuberculosis who had clinical and imaging suspicion of posttransplant lymphoproliferative disorder or renal cell carcinoma. Histopathology from the renal lesion revealed tuberculosis.

Point-of-care ultrasound for tuberculosis and HIV-revisiting the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol and its differential diagnoses.

BACKGROUND: The 'Focused assessment with sonography for HIV-associated tuberculosis' (FASH) protocol has been applied and researched for over a decade in HIV-infected patients with suspected extra-pulmonary tuberculosis. Interpretation of target FASH features may be challenging as they can also indicate alternative opportunistic diseases. OBJECTIVES: The primary aim of the review was summarizing the accumulated evidence on the diagnostic accuracy of the FASH protocol including description of diagnoses of target FASH features. SOURCES: Literature was searched using PubMed, Google Scholar, and publications referencing the original FASH publications; data from identified studies were compiled with data from studies identified by a preceding Cochrane review. A meta-analysis was performed based on a generalized linearized mixed model. Data on differential diagnoses were compiled by literature review and retrospective evaluation of clinical data. CONTENT: We identified ten studies; abdominal target FASH features were most studied. Sensitivity and specificity estimates were 39% (95% CI 25-54) and 89% (95% CI 83-96) for enlarged lymph nodes (ten studies), and 30% (95% CI 16-45%) and 93% (95% CI 89-98%) for hypoechoic spleen lesions (eight studies). In people living with HIV differential diagnoses of target FASH features are multiple and primarily include other opportunistic infections and malignancies such as non-tuberculous mycobacterial infection, bacillary angiomatosis, hepato-splenic brucellosis, meliodiosis, visceral leishmaniasis, invasive fungal infections, and lymphoma as well as Kaposi sarcoma. Ultrasound-guided diagnostic sampling may assist obtention of a definitive diagnosis. IMPLICATIONS: On the basis of current evidence, although limited by methodology, and personal experience, we recommend basic ultrasound training, including the FASH protocol and ultrasound-guided diagnostic interventions, for all healthcare providers working with people living with HIV in resource-limited settings.

Frequency of abnormal findings on chest radiograph after positive PPD in children and adolescents in an urban setting in the United States.

BACKGROUND: Chest radiographs (CXR) for tuberculosis (TB) screening in children are valuable in high-burden settings. However, less certain in low prevalence contexts. In the United States, positive PPD is sufficient to treat for "latent" TB, or TB infection in asymptomatic patients. OBJECTIVE: We sought to determine frequency of abnormal CXR findings after a positive purified protein derivative (PPD) test at a tertiary pediatric center in the United States. METHOD: A retrospective evaluation was conducted of patients (0-18 years) with a CXR after a positive PPD (e.g., known exposure, employment, migratory requirements or before immunosuppression) between 2011 and 2021. Clinical information, demographics, and reason for PPD were recorded from health record. CXRs were evaluated using initial report and by a pediatric radiologist with special interest in TB and 8 years of experience. RESULT: Of 485 patients, median [interquartile range (IQR)] age 8.5[3.3-14.4], abnormal CXRs were described in 5 (1%). Most common reasons for PPD included: close contact with someone with TB or with high risk for TB. Most patients 373 (76.9%) received treatment for latent TB, and 111 (22.9%) no treatment. One patient (0.2%) received treatment for active disease. Radiographic findings included isolated lymphadenopathy (n = 2), consolidation (n = 1), pleural fluid/thickening (n = 1) and a patient with lymphadenopathy and a calcified nodule (n = 1). CONCLUSION: In our experience, prevalence of chest radiographs findings for patients with positive PPD was very low. Moreover, no cases of severe disease were seen and those with abnormal findings would not merit treatment change under current WHO guidelines.

Seeing is believing: Efficiency evaluation of multifunctional ionic-dependent AIEgens for tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant public health threat with high rates of infection and mortality. Rapid and reliable theranostics of TB are essential to control transmission and shorten treatment duration. In this study, we report two cationic aggregation-inducing emission luminogens (AIEgens) named TTVP and TTPy, which have different functional charged moieties, to investigate their potential for simultaneous tracing and photodynamic therapy in TB infection. TTVP and TTPy exhibit intrinsic positive charges, excellent water solubility, and near-infrared (NIR) emission. Based on ionic-function relationships, TTVP, with more positive charges, demonstrates a stronger binding affinity to Mycobacterium marinum (M.m), (a close genetic relative of Mtb), compared to TTPy. Both TTVP and TTPy exhibit high efficiency in generating reactive oxygen species (ROS) when exposed to white light irradiation, enabling effective photodynamic killing of M.m in vitro. Additionally, we achieved long-term, real-time, noninvasive, continuous tracing, and evaluated therapeutic performance in vivo. Notably, TTVP outperformed TTPy in intracellular killing of M.m, suggesting a possible correlation between the labeling and photodynamic killing abilities of AIEgens. These findings provide valuable insights and a design basis for cationic AIEgens in TB research, offering potential advancements in TB theranostics.

Doomed for carcinomatosis? An unusual presentation of abdominal tuberculosis.

A 35-year old male from Brazil presented with intermittent abdominal pain. Abdominal computed tomography revealed a nodule adjacent to splenic hilum and multiple abdominal nodules, suspicious of carcinomatosis. The patient underwent gastroscopy and endoscopic ultrasound (EUS), that revealed an ill-defined hypoechogenic lesion adjacent to the spleen and two hypoechogenic subepithelial lesions located in the 4th layer of the stomach and duodenal bulb. Biopsies revealed non-necrotizing granulomatous inflammation with multinucleated giant cells. Soon after, a 18cm palpable mass within the rectus abdominis muscle was identified, and the biopsy was positive for Mycobacterium tuberculosis DNA, confirming the diagnosis of disseminated abdominal tuberculosis.

Assessment of non-tuberculosis abnormalities on digital chest x-rays with high CAD4TB scores from a tuberculosis prevalence survey in Zambia and South Africa.

BACKGROUND: Chest X-rays (CXRs) have traditionally been used to aid the diagnosis of TB-suggestive abnormalities. Using Computer-Aided Detection (CAD) algorithms, TB risk is quantified to assist with diagnostics. However, CXRs capture all other structural abnormalities. Identification of non-TB abnormalities in individuals with CXRs that have high CAD scores but don't have bacteriologically confirmed TB is unknown. This presents a missed opportunity of extending novel CAD systems' potential to simultaneously provide information on other non-TB abnormalities alongside TB. This study aimed to characterize and estimate the prevalence of non-TB abnormalities on digital CXRs with high CAD4TB scores from a TB prevalence survey in Zambia and South Africa. METHODOLOGY: This was a cross-sectional analysis of clinical data of participants from the TREATS TB prevalence survey conducted in 21 communities in Zambia and South Africa. The study included individuals aged ≥ 15 years who had high CAD4TB scores (score ≥ 70), but had no bacteriologically confirmed TB in any of the samples submitted, were not on TB treatment, and had no history of TB. Two consultant radiologists reviewed the images for non-TB abnormalities. RESULTS: Of the 525 CXRs reviewed, 46.7% (245/525) images were reported to have non-TB abnormalities. About 11.43% (28/245) images had multiple non-TB abnormalities, while 88.67% (217/245) had a single non-TB abnormality. The readers had a fair inter-rater agreement (r = 0.40). Based on anatomical location, non-TB abnormalities in the lung parenchyma (19%) were the most prevalent, followed by Pleura (15.4%), then heart & great vessels (6.1%) abnormalities. Pleural effusion/thickening/calcification (8.8%) and cardiomegaly (5%) were the most prevalent non-TB abnormalities. Prevalence of (2.7%) for pneumonia not typical of pulmonary TB and (2.1%) mass/nodules (benign/ malignant) were also reported. CONCLUSION: A wide range of non-TB abnormalities can be identified on digital CXRs among individuals with high CAD4TB scores but don't have bacteriologically confirmed TB. Adaptation of AI systems like CAD4TB as a tool to simultaneously identify other causes of abnormal CXRs alongside TB can be interesting and useful in non-faculty-based screening programs to better link cases to appropriate care.

Differential diagnosis of lung cancer and tuberculosis based on 18 F-fluorodeoxyglucose PET/CT multi-time points imaging.

OBJECTIVE: To investigate the value of 18 F-fluorodeoxyglucose(FDG) PET/CT multi-time points imaging (MTPI) on the differential diagnosis between lung cancer (LC) and tuberculosis (TB). METHODS: Sixty-four patients underwent 18 F-FDG PET/CT MTPI. The stdSUVmax, stdSUVavg, retention index, metabolic tumor volume, total lesion glycolysis at four-time points and slope of metabolic curve were measured and calculated, and the sex, age, and uniformity of FDG uptake were recorded. The difference in each index between LC and TB was analyzed, and dynamic metabolic curves (DMCs) of LC and TB were fitted by significance indexes. Artificial neural network (ANN) prediction models were established between squamous cell carcinoma (SCC) and TB, as well as between adenocarcinomas and TB. RESULTS: Differences between SCC and TB, stdSUVmax/avg at four-time points, total lesion glycolysis, stdSUVmax/avg slope (1-2 h,1-3 h and 1-4 h), uniformity of FDG uptake and age were significant. stdSUVavg has the largest area under the 4 h curve; age was only significant between adenocarcinomas and TB. DMCs at 1-4 h fitted by stdSUVavg were more helpful in differentiating LC and TB than stdSUVmax. stdSUVavg(1 h and 4 h), stdSUVavg slope 1-4 h, age, and uniformity of FDG uptake were selected to establish an ANN prediction model between SCC and TB; the area under the curve (AUC) was 100.0%. The same indices were used to establish the prediction model between adenocarcinomas and TB; the AUC was up to 83.5, and after adding stdSUVavg (2 and 4 h) to adenocarcinomas and TB models, the AUC was 87.7%. CONCLUSION: 18 F-FDG PET/CT MTPI fitting DMCs and establishing an ANN prediction model would distinguish SCC from TB relatively accurately and provide certain help in the differentiation between adenocarcinomas and TB.

New Onset of Tuberculosis Complicating FDG PET/CT Evaluation in Patient With Recent Chimeric Antigen Receptor T-Cell Therapy.

ABSTRACT: A 16-year-old adolescent girl with CD19 chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia experienced new onset of the fever. 18 F-FDG PET/CT studies acquired at 1 and 2 months, respectively, after CAR-T, showed foci of abnormal activity in the mediastinal lymph nodes not seen on the study before therapy. However, these foci of abnormal activity were later proven due to newly developed tuberculosis after CAR T-cell therapy.

The use of multiplex imaging techniques to characterize tuberculous granuloma heterogeneity.

Caseous granulomas are pathological hallmarks of tuberculosis (TB), and increasing evidence suggests that TB granuloma composition is highly temporally and spatially heterogenous in both animal models and humans. Traditional pathological techniques are limited in their ability to reveal the heterogeneity present in TB granulomas. Multiplex tissue imaging tools combined with powerful, high resolution spatial analysis have enabled the detection of various cell phenotypes, aiding in the visualization of the granuloma complex and revealing the interactions between immune cells and nonimmune cells. This updated understanding of tuberculous granuloma heterogeneity offers vital insights for researchers aiming to uncover the immunoregulatory mechanisms underlying granuloma formation during TB pathogenesis. More detailed granuloma classification systems will also be of use for precision medicine, and for identifying biological targets for host-directed therapeutics in TB patients. This article is categorized under: Infectious Diseases > Genetics/Genomics/Epigenetics Infectious Diseases > Biomedical Engineering Infectious Diseases > Molecular and Cellular Physiology.