Detection of Esophageal Tuberculosis, a Rare Cause of Abdominal Pain, on 18F-FDG PET/CT.

The esophagus is rarely affected by Mycobacterium A 75-y-old man presented with upper abdominal pain and significant weight loss for 2 mo. Contrast-enhanced CT, upper gastrointestinal endoscopy, and abdominal vessel angiography gave normal results. To clarify the facts, 18F-FDG PET/CT was performed, revealing an 18F-FDG-avid lesion in the posterior wall of the lower thoracic esophagus. On endoscopic ultrasound-guided fine-needle aspiration of this lesion, puslike material was released. On microscopic examination, acid-fast bacilli were noted. The patient then began receiving standard antitubercular therapy.

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.

Point-of-care ultrasound for diagnosing extrapulmonary TB.

Despite the high morbidity and mortality globally, standard microbiologic diagnosis for TB requires laboratory infrastructure inaccessible in many resource-limited areas and may be insufficient for identifying extrapulmonary disease. Point-of-care (POC) ultrasound facilitates visualization of extrapulmonary manifestations, permitting laboratory-independent diagnosis, but its diagnostic utility remains unclear.We conducted a systematic review of five online databases for studies reporting ultrasound findings among cases with and without extrapulmonary TB (EPTB). A minimum of two authors independently screened and reviewed each article, and extracted data elements of interest. We conducted a series of univariate meta-analyses using a random-effects model to calculate the pooled effect estimate and 95% confidence interval (CI) for each outcome: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Of 279 articles identified, 6 were included. There were 699 cases of EPTB among 1,633 participants. The pooled sensitivity estimate was 0.72 (95% CI 0.57-0.88). The pooled specificity estimate was 0.77 (95% CI 0.63-0.90). The pooled PPV and NPV estimates were respectively 0.67 (95% CI 0.47-0.87) and 0.85 (95% CI 0.77-0.93).POC ultrasound showed modest test characteristics for diagnosing EPTB, which may constitute an improvement over some currently available diagnostics..

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.

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.

From Bench to Clinic: A Nitroreductase Rv3368c-Responsive Cyanine-Based Probe for the Specific Detection of Live Mycobacterium tuberculosis.

Tuberculosis (TB), characterized by high mortality and low diagnosis, is caused by a single pathogen, Mycobacterium tuberculosis (Mtb). Imaging tools that can be used to track Mtb without pre-labeling and to diagnose live Mtb in clinical samples can shorten the gap between bench and clinic, fuel the development of novel anti-TB drugs, strengthen TB prevention, and improve patient treatment. In this study, we report an unprecedented novel nitroreductase-responsive cyanine-based fluorescent probe (Cy3-NO2-tre) that rapidly and specifically labels Mtb and detects it in clinical samples. Cy3-NO2-tre generated fluorescence after activation by a specific nitroreductase, Rv3368c, which is conserved in the Mycobacteriaceae. Cy3-NO2-tre effectively imaged mycobacteria within infected host cells, tracked the infection process, and visualized Mycobacterium smegmatis being endocytosed by macrophages. Cy3-NO2-tre also detected Mtb in the sputum of patients with TB and exhibited excellent photostability. Furthermore, the Cy3-NO2-tre/auramine O percentage change within 7 ± 2 days post drug treatment in the sputum of inpatients was closely correlated with the reexamination results of the chest computed tomography, strongly demonstrating the clinical application of Cy3-NO2-tre as a prognostic indicator in monitoring the therapeutic efficacy of anti-TB drugs in the early patient care stage.

PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study.

BACKGROUND: Incipient tuberculosis, a progressive state of Mycobacterium tuberculosis infection with an increased risk of developing into tuberculosis disease, remains poorly characterised. Animal models suggest an association of progressive infection with bacteraemia. Circulating M tuberculosis DNA has previously been detected in pulmonary tuberculosis by use of Actiphage, a bacteriophage-based real-time PCR assay. We aimed to investigate whether serial [18F]fluorodeoxyglucose ([18F]FDG)-PET-CT could be used to characterise the state and progressive trajectory of incipient tuberculosis, and examine whether these PET-CT findings are associated with Actiphage-based detection of circulating M tuberculosis DNA. METHODS: We did a prospective 12-month cohort study in healthy, asymptomatic adults (aged ≥16 years) who were household contacts of patients with pulmonary tuberculosis, and who had a clinical phenotype of latent tuberculosis infection, in Leicester, UK. Actiphage testing of participants' blood samples was done at baseline, and [18F]FDG PET-CT at baseline and after 3 months. Baseline PET-CT features were classified as positive, indeterminate, or negative, on the basis of the quantitation (maximum standardised uptake value [SUVmax]) and distribution of [18F]FDG uptake. Microbiological sampling was done at amenable sites of [18F]FDG uptake. Changes in [18F]FDG uptake after 3 months were quantitatively categorised as progressive, stable, or resolving. Participants received treatment if features of incipient tuberculosis, defined as microbiological detection of M tuberculosis or progressive PET-CT change, were identified. FINDINGS: 20 contacts were recruited between Aug 5 and Nov 5, 2020; 16 of these participants had a positive result on IFNγ release assay (QuantiFERON-TB Gold Plus [QFT]) indicating tuberculosis infection. Baseline PET-CT scans were positive in ten contacts (all QFT positive), indeterminate in six contacts (three QFT positive), and negative in four contacts (three QFT positive). Four of eight PET-CT-positive contacts sampled had M tuberculosis identified (three through culture, one through Xpert MTB/RIF Ultra test) from intrathoracic lymph nodes or bronchial wash and received full antituberculosis treatment. Two further unsampled PET-CT-positive contacts were also treated: one with [18F]FDG uptake in the lung (SUVmax 9·4) received empirical antituberculosis treatment and one who showed progressive [18F]FDG uptake received preventive treatment. The ten untreated contacts with [18F]FDG uptake at baseline (seven QFT positive) had stable or resolving changes at follow-up and remained free of tuberculosis disease after 12 months. A positive baseline Actiphage test was associated with the presence of features of incipient tuberculosis requiring treatment (p=0·018). INTERPRETATION: Microbiological and inflammatory features of incipient tuberculosis can be visualised on PET-CT and are associated with M tuberculosis detection in the blood, supporting the development of pathogen-directed blood biomarkers of tuberculosis risk. FUNDING: MRC Confidence in Concept.

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.

Revisiting Computer-Aided Tuberculosis Diagnosis.

Tuberculosis (TB) is a major global health threat, causing millions of deaths annually. Although early diagnosis and treatment can greatly improve the chances of survival, it remains a major challenge, especially in developing countries. Recently, computer-aided tuberculosis diagnosis (CTD) using deep learning has shown promise, but progress is hindered by limited training data. To address this, we establish a large-scale dataset, namely the Tuberculosis X-ray (TBX11 K) dataset, which contains 11 200 chest X-ray (CXR) images with corresponding bounding box annotations for TB areas. This dataset enables the training of sophisticated detectors for high-quality CTD. Furthermore, we propose a strong baseline, SymFormer, for simultaneous CXR image classification and TB infection area detection. SymFormer incorporates Symmetric Search Attention (SymAttention) to tackle the bilateral symmetry property of CXR images for learning discriminative features. Since CXR images may not strictly adhere to the bilateral symmetry property, we also propose Symmetric Positional Encoding (SPE) to facilitate SymAttention through feature recalibration. To promote future research on CTD, we build a benchmark by introducing evaluation metrics, evaluating baseline models reformed from existing detectors, and running an online challenge. Experiments show that SymFormer achieves state-of-the-art performance on the TBX11 K dataset.

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.

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.

Endobronchial optical coherence tomography helps to estimate the cartilage damage of the central airway in TBTB patients.

Purpose: At present, there are few examination methods used to evaluate tracheobronchial cartilage damage. In our study, we explored whether endobronchial optical coherence tomography (EB-OCT) can be used to estimate central airway cartilage damage in tracheobronchial tuberculosis (TBTB) patients. Methods: In our study, we used the OCTICS Imaging system to perform EB-OCT scanning for TBTB patients. The thickness of the central airway wall and cartilage was measured by the OCTICS software system workstation. Results: There were 102 TBTB patients included in our study cohort. Their EB-OCT images of the central airway cartilage showed that abnormal cartilage manifests as thinning of the cartilage, cartilage damage, cartilage destruction, and even cartilage deficiency. The cartilage morphology becomes irregular and discontinuous. Some parts of the cartilage become brighter in grayscale. The intima of the cartilage is thickened and discontinuous, and the boundary with submucosa and mucosa is unclear. Conclusion: Our study conducted EB-OCT examination of the central airway cartilage of TBTB patients in vivo for the first time. EB-OCT helps to estimate the cartilage damage of the central airway in TBTB patients to some extent.

Early diagnosis and meta-agnostic model visualization of tuberculosis based on radiography images.

Despite being treatable and preventable, tuberculosis (TB) affected one-fourth of the world population in 2019, and it took the lives of 1.4 million people in 2019. It affected 1.2 million children around the world in the same year. As it is an infectious bacterial disease, the early diagnosis of TB prevents further transmission and increases the survival rate of the affected person. One of the standard diagnosis methods is the sputum culture test. Diagnosing and rapid sputum test results usually take one to eight weeks in 24 h. Using posterior-anterior chest radiographs (CXR) facilitates a rapid and more cost-effective early diagnosis of tuberculosis. Due to intraclass variations and interclass similarities in the images, TB prognosis from CXR is difficult. We proposed an early TB diagnosis system (tbXpert) based on deep learning methods. Deep Fused Linear Triangulation (FLT) is considered for CXR images to reconcile intraclass variation and interclass similarities. To improve the robustness of the prognosis approach, deep information must be obtained from the minimal radiation and uneven quality CXR images. The advanced FLT method accurately visualizes the infected region in the CXR without segmentation. Deep fused images are trained by the Deep learning network (DLN) with residual connections. The largest standard database, comprised of 3500 TB CXR images and 3500 normal CXR images, is utilized for training and validating the recommended model. Specificity, sensitivity, Accuracy, and AUC are estimated to determine the performance of the proposed systems. The proposed system demonstrates a maximum testing accuracy of 99.2%, a sensitivity of 98.9%, a specificity of 99.6%, a precision of 99.6%, and an AUC of 99.4%, all of which are pretty high when compared to current state-of-the-art deep learning approaches for the prognosis of tuberculosis. To lessen the radiologist's time, effort, and reliance on the level of competence of the specialist, the suggested system named tbXpert can be deployed as a computer-aided diagnosis technique for tuberculosis.

¿Tuberculosis, sarcoidosis o ambas? / Tuberculosis, sarcoidosis or maybe both?

Presentamos un caso clínico de una paciente de 34 años con diagnóstico simultáneo de sarcoidosis y tuberculosis, sin ser inmunodeprimida ni tener factores de riesgo para ello. Esto supone un hallazgo muy poco común, y cuando aparece suele deberse a la inmunosupresión ocasionada por el tratamiento con esteroides de la sarcoidosis. En el caso que vamos a describir a continuación este hecho no sucede, motivo por el que se le otorga relevancia. Para llegar a los dos diagnósticos se realizaron las pruebas complementarias necesarias (analíticas sanguíneas, biopsias transbronquiales, pruebas de imagen, toracocentesis y biopsias pleurales), lo que permitió instaurar el tratamiento adecuado y, en consecuencia, la mejoría de la paciente. Con la presentación de este caso se pretende recalcar la importancia de hacer un buen enfoque diagnóstico en el servicio de urgencias, haciendo un hincapié en todos los signos y síntomas tanto directos como indirectos. (AU)

We report a case study of a 34-year-old patient with a simultaneous diagnosis of sarcoidosis and tuberculosis. The patient was not immunosuppressed and did not have risk factors for this. This is a very rare finding, and when it appears it is usually due to immunosuppression caused by corticosteroid treatment of sarcoidosis. In the case reported below, this does not occur, which is why it is relevant. To make both diagnoses, the necessary complementary tests were performed (blood tests, transbronchial biopsies, imaging tests, thoracentesis and pleural biopsies), which enabled appropriate treatment to be established and, consequently, the patient's improvement. Reporting this case enables us to emphasize the importance of making a good diagnosis in A&E, emphasizing all direct and indirect signs and symptoms. (AU)

Ultrasonography - a novel auxiliary interpretive approach for tuberculin-purified pure protein derivative skin test: a comparative study.

BACKGROUND: The tuberculin-purified protein derivative (PPD) test is commonly used as a screening tool for tuberculosis (TB). However, the traditional judgment standard of the PPD test is influenced by subjective factors, which can lead to less accurate and intuitive test results. OBJECTIVES: To evaluate the accuracy of ultrasonography as a novel auxiliary judgment method for the tuberculin-PPD test and its clinical application. DESIGN: This study was designed as a comparative study following the STROBE guidance. METHODS: From February to May 2022, 208 patients with active tuberculosis infection were enrolled. Manual judgment and ultrasonography were employed in a double-blind-utilized manner, and the PPD examination results were recorded. Kappa statistic was performed to measure the concordance between the two diagnostic methods. Fisher's exact test was used for the analyses of the PPD test results of all 208 active tuberculosis infection patients' PPD results. RESULTS: There was a significant difference between the two methods in the PPD result judgment (p < 0.001), particularly in the positive ratio of the PPD test results, (p < 0.05). Overall, 50 patients were determined as PPD positive based on manual judgment. However, only 24 patients' PPD test results were determined as positive via ultrasonography. The remaining 26 patients should have been classified as strong positive but were misclassified as positive. The misdiagnosis ratio was 52% (26/50). CONCLUSION: Ultrasonography has superior accuracy to traditional manual judgment. Moreover, it does not rely on sophisticated clinical experience or training and can reveal subtle changes of the skin corresponding to each PPD test result providing intuitive results. In conclusion, ultrasonography can be used as an auxiliary interpretive approach for PPD test and has a promising future for clinical application.

Deep learning and radiomics of longitudinal CT scans for early prediction of tuberculosis treatment outcomes.

BACKGROUND: To predict tuberculosis (TB) treatment outcomes at an early stage, prevent poor outcomes ofdrug-resistant tuberculosis(DR-TB) and interrupt transmission. METHODS: An internal cohort for model development consists of 204 bacteriologically-confirmed TB patients who completed anti-tuberculosis treatment, with one pretreatment and two follow-up CT images (612 scans). Three radiomics feature-based models (RM) with multiple classifiers of Bagging, Random forest and Gradient boosting and two deep-learning-based models (i.e., supervised deep-learning model, SDLM; weakly supervised deep-learning model, WSDLM) are developed independently. Prediction scores of RM and deep-learning models with respectively highest performance are fused to create new fusion models under different fusion strategies. An additional independent validation was conducted on the external cohort comprising 80 patients (160 scans). RESULTS: For RM scheme, 16 optimal radiomics features are finally selected using longitudinal scans. The AUCs of RM for Bagging, Random forest and Gradient boosting were 0.789, 0.773 and 0.764 in the internal cohort and 0.840, 0.834 and 0.816 in the external cohort, respectively. For deep learning-based scheme, AUCs of SDLM and WSDLM were 0.767 and 0.661 in the internal cohort, and 0.823 and 0.651 in the external. The fusion model yields AUCs from 0.767 to 0.802 in the internal cohort, and from 0.831 to 0.857 in the external cohort. CONCLUSIONS: Fusion of radiomics features and deep-learning model may have the potential to predict early failure outcome of DR-TB, which may be combined to help prevent poor TB treatment outcomes.

Ultrasound and magnetic resonance imaging in thoracic tuberculosis in the pediatric population: moving beyond conventional radiology.

Imaging is crucial in the diagnostic work-up and follow-up after treatment in children with thoracic tuberculosis (TB). Despite various technological advances in imaging modalities, chest radiography is the primary imaging modality for initial care and in emergency settings, especially in rural areas and where resources are limited. Ultrasonography (US) of the thorax in TB is one of the emerging applications of US as a radiation-free modality in children. Magnetic resonance imaging (MRI) is the ideal radiation-free, emerging imaging modality for thoracic TB in children. However, only limited published data is available regarding the utility of MRI in thoracic TB. In this pictorial review, we demonstrate the use of US and rapid lung MRI in evaluating children with thoracic TB, specifically for mediastinal lymphadenopathy and pulmonary complications of TB.