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TB is a public health problem, and its diagnosis can be challenging. Among imaging methods, chest X-ray (CXR) is the leading choice for assessing pulmonary TB (PTB). Recent advancements in the field of artificial intelligence have stimulated studies evaluating the performance of machine learning (ML) for medical diagnosis. This study validated a new original Brazilian tool, the XmarTB, applied to CXR images to support the early diagnosis of PTB.An ML model was trained on 3,800 normal images, 3,800 abnormal CXRs without PTB and 1,376 with PTB manifestations from the publicly available TBX11K database.The binary classification can distinguish between normal and abnormal CXR with a sensitivity of 99.4% and specificity of 99.4%. The XmarTB tool had a sensitivity of 98.1% and a specificity of 99.7% in detecting TB cases among CXRs with abnormal CXRs; sensitivity was 96.7% and specificity 98.7% in detecting TB cases among all samples.This diagnostic tool can accurately and automatically detect abnormal CXRs and satisfactorily differentiate PTB from other pulmonary diseases. This tool holds significant promise in aiding the proactive detection of TB cases, providing rapid and accurate support for early diagnosis..

Patient delay increases the morbidity and mortality due to tuberculosis (TB). This study aimed to assess patient delay among patients with pulmonary tuberculosis in Yantai from 2013 to 2022, and to analyze factors related to patient delay. Data of patients with pulmonary tuberculosis in Yantai City from 2013 to 2022 were obtained from the Tuberculosis Management Information System of the Chinese Disease Prevention and Control System. Statistical analyses were performed using the SPSS.26.0 software. The trend in patient delay rate was tested using the chi-square trend test. Univariate analyses were performed using the chi-square test, and factors with statistically significant differences in the univariate analysis were included in the binary logistic regression analysis to identify the factors affecting patient delay. Patient delay was defined as an interval of more than 14 days between the onset of clinical symptoms and the patient first visit to a healthcare facility. From 2013 to 2022, the median delay time for patients with pulmonary tuberculosis in Yantai was 28 ± 52 days and the patient delay rate was 69.5%. There was an overall increasing trend in the rate of patient delay as the number of years increased. Univariate analyses revealed statistically significant differences in patient delay in terms of age, occupation, patient source, domicile, pathogenetic results, and the presence of comorbidities (all P < .05). The results of logistic regression analysis showed that the age was 20 to 39, 40 to 59, and ≥ 60 years (OR = 1.365, 95%CI: 1.156-1.612; OR = 1.978, 95%CI: 1.660-2.356; OR = 1.767, 95%CI: 1.480-2.110), occupation was domestic and un-employed (OR = 1.188, 95%CI: 1.071-1.317), domicile as mobile population (OR = 1.212, 95%CI: 1.099-1.337), and positive pathogenic results (OR = 1.242, 95%CI: 1.015-1.520) were risk factors for patient delay. Patient delays were serious among pulmonary tuberculosis patients in Yantai City, 2013 to 2022, and patient delay was related to factors such as age, occupation, domicile, patient source, and pathogenetic results., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The differentiation between latent tuberculosis infection (LTBI) and tuberculosis (TB) relies on radiological changes. Confirming the diagnosis remains a challenge because typical findings are often missing in children. This study evaluates diagnostic sensitivity, specifity and interobserver agreement on the radiological diagnosis of TB by chest-x-rays in accordance to professional specialization and work experience., Methods: Chest x-rays of 120 children with proven tuberculosis infection were independently evaluated by general radiologists, paediatric radiologists and paediatric pulmonologists. Results were compared to a reference diagnosis created by group of experienced paediatric radiologists and paediatric pulmonologists. Primary endpoints were diagnostic sensitivity and specificity and interobserver variability defined as Krippendorfs alpha of thesel groups compared to the reference diagnosis., Results: Of the 120 chest x-rays 33 (27,5%) were diagnosed as TB by the reference standard . Paediatric pulmonologist had the highest diagnostic sensitivity (90%) but were less specific (71%) whereas general radiologist were less sensitive (68%) but more secific (95%). The best diagnostic accuracy was achieved by pediatric radiologists with a diagnostic sensitivity of 77% and specificity 95% respectively., Conclusions: We demonstrated significant interobserver variability and relevant differences in sensitivity and specificity in the radiological diagnosis of TB between the groups. Paediatric radiologists showed the best diagnostic performance. As the diagnosis of pulmonary TB has significant therapeutic consequences for children they should be routinely involved in the diagnostic process., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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 [ 18 F]fluorodeoxyglucose ([ 18 F]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 [ 18 F]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 [SUV max ]) and distribution of [ 18 F]FDG uptake. Microbiological sampling was done at amenable sites of [ 18 F]FDG uptake. Changes in [ 18 F]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 [ 18 F]FDG uptake in the lung (SUV max 9·4) received empirical antituberculosis treatment and one who showed progressive [ 18 F]FDG uptake received preventive treatment. The ten untreated contacts with [ 18 F]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., Competing Interests: Declaration of interests PH has received consultancy fees for two advisory board meetings with PBD Biotech since study inception. CR and BS hold stocks in PBD Biotech, the company commercialising the Actiphage technology. CR and BS have a pending patent on Actiphage bacteriophage-mediated mycobacterial DNA release assay testing (PCT/GB2020/050524). PBD Biotech supplied PCR reagents and components of the Actiphage kit for use in the study but had no role in design, execution, analysis, or reporting. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure: There is no conflict of interest or other disclosures.

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., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Early diagnosis and treatment of tuberculosis (TB) is one of the key strategies to achieve the WHO End TB targets. This study aimed to develop and validate a simple, convenient risk score to diagnose pulmonary TB among presumptive TB cases., Methods: This prediction model used Ethiopian national TB prevalence survey data and included 5459 presumptive TB cases from all regions of Ethiopia. Logistic regression was used to determine which variables are predictive of pulmonary TB. A risk prediction model was developed, incorporating significant variables (p<0.05). The Youden Index method was used to choose the optimal cut-off point to separate the risk score of the patients as high and low. Model performance was assessed using discrimination power and calibration. Internal validation of the model was assessed using Efron's enhanced bootstrap method, and the clinical utility of the risk score was assessed using decision curve analysis., Results: Of total participants, 94 (1.7%) were confirmed to have TB. The final prediction model included three factors with different scores: (1) TB contact history, (2) chest X-ray (CXR) abnormality and (3) two or more symptoms of TB. The optimal cut-off point for the risk score was 6 and was found to have a good discrimination accuracy (c-statistic=0.70, 95% CI: 0.65 to 0.75). The risk score has sensitivity of 51.1%, specificity of 79.9%, positive predictive value of 4.3% and negative predictive value of 98.9%. After internal validation, the optimism coefficient was 0.003, which indicates the model is internally valid., Conclusion: We developed a risk score that combines TB contact, number of TB symptoms and CXR abnormality to estimate individual risk of pulmonary TB among presumptive TB cases. Though the score is easy to calculate and internally validated, it needs external validation before widespread implementation in a new setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease., Methods: We conducted a systematic review and meta-analysis. We searched for prospective trials evaluating the efficacy of TB regimens against placebo, observation, or alternative regimens, for the treatment of adults and children with radiographic evidence of TB but culture-negative respiratory samples. Databases were searched up to 18 Oct 2022. Study quality was assessed using ROB 2·0 and ROBINS-I. The primary outcome was progression to culture-positive TB. Meta-analysis with a random effects model was conducted to estimate pooled efficacy. This study was registered with PROSPERO (CRD42021248486)., Findings: We included 13 trials (32,568 individuals) conducted between 1955 and 2018. Radiographic and bacteriological criteria for inclusion varied. 19·1% to 57·9% of participants with active x-ray changes and no treatment progressed to culture-positive disease. Progression was reduced with any treatment (6 studies, risk ratio [RR] 0·27, 95%CI 0·13-0·56), although multi-drug TB treatment (RR 0·11, 95%CI 0·05-0·23) was significantly more effective than isoniazid treatment (RR 0·63, 95%CI 0·35-1·13) (p = 0·0002)., Interpretation: Multi-drug regimens were associated with significantly reduced risk of progression to TB disease for individuals with radiographically apparent, but culture-negative TB. However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens. New clinical trials are required to identify the optimal treatment approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although the incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing annually, it is easily misdiagnosed as pulmonary tuberculosis (PTB). This study aimed to screen and identify the immunological and radiological characteristics that differentiate NTM-PD from PTB and to construct a discriminatory diagnostic model for NTM-PD, providing new tools for its differential diagnosis., Methods: Hospitalised patients diagnosed with NTM-PD or PTB between January 2019 and June 2023 were included in the study. Immunological and radiological characteristics were compared between the two groups. Based on the selected differential features, a logistic regression algorithm was used to construct a discriminatory diagnostic model for NTM-PD, and its diagnostic performance was preliminarily analysed., Results: Patients with NTM-PD were significantly older than those with PTB and the tuberculosis-specific interferon-gamma release assay (TB-IGRA) positivity rate was significantly lower in the NTM-PD group. Moreover, the absolute counts of total T lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, NK cells, and B lymphocytes were significantly lower in patients with NTM-PD and PTB than in healthy controls. Additionally, patients with NTM-PD had a significantly lower absolute count of B lymphocytes than the PTB group. Radiological analysis revealed significant differences between patients with NTM-PD and PTB in terms of cavity wall thickness, bronchial dilation, lung consolidation, pulmonary nodule size, pulmonary emphysema, lung bullae, lymph node calcification, pleural effusion, mediastinal and hilar lymphadenopathy, and the tree-in-bud sign. Bronchial dilation was identified as the predominant risk factor of NTM-PD, whereas TB-IGRA positivity, lymph node calcification, pleural effusion, and mediastinal and hilar lymphadenopathies were protective factors. Based on this, we constructed a discriminatory diagnostic model for NTM-PD. Its receiver operating characteristic curve demonstrated good diagnostic performance, with an area under the curve of 0.938. At the maximum Youden index of 0.746, the sensitivity and specificity were 0.835 and 0.911, respectively., Conclusions: Patients with NTM-PD and PTB exhibited impaired humoral and cellular immune functions as well as significant differences in radiological features. The constructed NTM-PD diagnostic model demonstrated good diagnostic performance. This study provides a new tool for the differential diagnosis of NTM-PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Even though the Gaza Strip is a low pulmonary tuberculosis (TB) burden region, it is well-known that TB is primarily a socioeconomic problem associated with overcrowding, poor hygiene, a lack of fresh water, and limited access to healthcare, which is the typical case in the Gaza Strip. Therefore, this study aimed at assessing the accuracy of the automatic software computer-aided detection for tuberculosis (CAD4TB) in diagnosing pulmonary TB on chest radiography and compare the CAD4TB software reading with the results of geneXpert. Using a census sampling method, the study was conducted in radiology departments in the Gaza Strip hospitals between 1 December 2022 and 31 March 2023. A digital X-ray, printer, and online X-ray system backed by CAD4TBv6 software were used to screen patients with lower respiratory tract symptoms. GeneXpert analysis was performed for all patients having a score > 40. A total of 1,237 patients presenting with lower respiratory tract symptoms participated in this current study. Chest X-ray readings showed that 7.8% ( n = 96) were presumptive for TB. The CAD4TBv6 scores showed that 11.8% ( n = 146) of recruited patients were presumptive for TB. GeneXpert testing on sputum samples showed that 6.2% ( n = 77) of those with a score > 40 on CAD4TB were positive for pulmonary TB. Significant differences were found in chest X-ray readings, CAD4TBv6 scores, and GeneXpert results among sociodemographic and health status variables ( P -value < 0.05). The study showed that the incidence rate of TB in the Gaza Strip is 3.5 per 100,000 population in the Gaza strip. The sensitivity of the CAD4TBv6 score and the symptomatic review for tuberculosis with a threshold score of >40 is 80.2%, and the specificity is 94.0%. The positive Likelihood Ratio is 13.3%, Negative Likelihood Ratio is 0.2 with 7.8% prevalence. Positive Predictive Value is 52.7%, Negative Predictive Value is 98.3%, and accuracy is 92.9%. In a resource-limited country with a high burden of neglected disease, combining chest X-ray readings by CAD4TB and symptomatology is extremely valuable for screening a population at risk. CAD4TB is noticeably more efficient than other methods for TB screening and early diagnosis in people who would otherwise go undetected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abuzerr and Zinszer.)

Tuberculosis (TB) remains a global health problem and is the second leading cause of death from a single infectious agent, behind the novel coronavirus disease of 2019. Children are amongst the most vulnerable groups affected by TB, and imaging manifestations are different in children when compared to adults. TB primarily involves the lungs and mediastinal lymph nodes. Clinical history, physical examination, laboratory examinations and various medical imaging tools are combined to establish the diagnosis. Even though chest radiography is the accepted initial radiological imaging modality for the evaluation of children with TB, this paper, the first of two parts, aims to discuss the advantages and limitations of the various medical imaging modalities and to provide recommendations on which is most appropriate for the initial diagnosis and assessment of possible complications of pulmonary TB in children. Practical, evidence-based imaging algorithms are also presented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pulmonary tuberculosis (PTB) is a bacterial infection that affects the lung. PTB remains one of the infectious diseases with the highest global mortalities. Chest radiography is a technique that is often employed in the diagnosis of PTB. Radiologists identify the severity and stage of PTB by inspecting radiographic features in the patient's chest X-ray (CXR). The most common radiographic features seen on CXRs include cavitation, consolidation, masses, pleural effusion, calcification, and nodules. Identifying these CXR features will help physicians in diagnosing a patient. However, identifying these radiographic features for intricate disorders is challenging, and the accuracy depends on the radiologist's experience and level of expertise. So, researchers have proposed deep learning (DL) techniques to detect and mark areas of tuberculosis infection in CXRs. DL models have been proposed in the literature because of their inherent capacity to detect diseases and segment the manifestation regions from medical images. However, fully supervised semantic segmentation requires several pixel-by-pixel labeled images. The annotation of such a large amount of data by trained physicians has some challenges. First, the annotation requires a significant amount of time. Second, the cost of hiring trained physicians is expensive. In addition, the subjectivity of medical data poses a difficulty in having standardized annotation. As a result, there is increasing interest in weak localization techniques. Therefore, in this review, we identify methods employed in the weakly supervised segmentation and localization of radiographic manifestations of pulmonary tuberculosis from chest X-rays. First, we identify the most commonly used public chest X-ray datasets for tuberculosis identification. Following that, we discuss the approaches for weakly localizing tuberculosis radiographic manifestations in chest X-rays. The weakly supervised localization of PTB can highlight the region of the chest X-ray image that contributed the most to the DL model's classification output and help pinpoint the diseased area. Finally, we discuss the limitations and challenges of weakly supervised techniques in localizing TB manifestations regions in chest X-ray images.

Bovine tuberculosis might be seen in low-income countries, especially in children fed with raw milk. The most common transmission route is fecal-oral way, and it is most likely through unpasteurized dairy products. Although clinical and radiological findings are like non-zoonotic tuberculosis, treatment approaches may differ in individuals with zoonotic tuberculosis. Prevention of zoonotic diseases requires multidisciplinary approaches. These approaches include the development of veterinary and surveillance studies for the detection of communicable diseases in farm animals, as well as informing the public about raw milk consumption. In this case report, a patient with zoonotic pulmonary tuberculosis related to Mycobacterium bovis because of consumption of raw milk was presented. A five-month-old male was admitted to the hospital due to a persistent, feverless, non-productive cough since birth. Empirical antibiotic treatment was started with a preliminary diagnosis of pneumonia because of left upper lobe and right pericardial infiltration on chest X-ray. However, after two weeks of antimicrobial therapy, the patient's clinical and laboratory findings did not improve. This led to the referral for a computed tomography imaging, which revealed tracheomalacia, consolidation on the right upper lobe, an indistinguishable mass or consolidation on the left middle lobe of the lung, peribronchial thickening on the basal segment of the lower lobe, and mediastinal lymphadenopathy. Three consecutive days of fasting gastric lavage fluid was sent to the reference laboratory for acid-resistant bacillus examination, polymerase chain reaction (PCR) and culture studies. As the clinical findings were compatible and PCR was positive, the patient was started on quadruple antituberculous therapy. After initiation of anti-tuberculosis drugs, the patient's findings radiologically and clinically were improved. Mycobacterium bovis was grown in the culture. In the meantime, it was discovered that the patient was fed with raw milk. Due to the patient's clinical symptoms and the growth of Mycobacterium bovis in the gastric lavage fluid culture, the diagnosis of bovine tuberculosis was made. The culprit was that the milk of the cow belonging to the patient's family, which was later found to be infected with M.bovis, was milked and given to the patient without boiling. Today, unpasteurized dairy products continue to be consumed, especially in rural areas. One of the most important steps to prevent zoonotic diseases is to raise awareness about not consuming raw milk and undercooked meat. To elucidate the epidemiological link in childhood, taking a good anamnesis, including questioning raw milk consumption, is essential in the diagnosis of tuberculosis.

Backgrounds: Tuberculosis (TB) is an infectious disease that needs to be diagnosed and enrolled for treatment. Artificial intelligence for TB (AI4TB) software screens TB suspected cases at the point of care and helps in quick diagnosis. This study aims to explore the significance and usefulness of AI4TB by comparing its performance with different diagnostic test results., Methods: A cross-sectional study was conducted among 197 participants who had symptoms suggestive to TB. The chest X-ray images were analyzed by AI4TB software and human expert readers. The bacteriological test results were obtained, and Kappa test was applied to calculate the inter-reader reliability. The sensitivity, specificity, positive predictive value and negative predictive value was calculated and ROC curve was generated., Results: Among 85 sputum smear microscopy, about 21% of the had sputum positivity rate. At 0.4 threshold: 62.4%, at 0.5 threshold: 58.4% and at 0.6 threshold: 50.3% symptoms suggestive cases were identified having abnormal X-ray images. Reader-I identified 28.4% and Reader-II identified 37.1% of the symptoms suggestive cases of TB as positive cases. There was a significant substantial agreement between two human expert readers (k-0.783, p-value: <0.001). The ROC curve explored the fair sensitivity accuracy of the AI4TB test results at 0.5 threshold level (AUC = 0.72) and at 0.6 threshold level (AUC = 0.77)., Conclusion: The sensitivity of the AI4TB was higher compared to different human readers. AI4TB can be the relevant screening tool for the TB symptoms suggestive cases prior to the laboratory test in the countries like Nepal with deficient health manpower., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2022 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to investigate the relationship between active pulmonary tuberculosis (TB) and type 2 diabetes mellitus (T2DM) by analysing the clinical features and computed tomography (CT) findings of patients with active pulmonary TB and comorbid T2DM (TB-DM) in the LiangShan Yi regions., Methods: We collected data from 154 hospitalised patients with TB-DM initially confirmed at an infectious disease hospital in the Liangshan Yi Autonomous Prefecture between 1 and 2019, and 31 December 2021. These were matched by sex and age ± 3 years to 145 hospitalised patients with initially confirmed pulmonary TB without comorbid T2DM (TB-NDM) over the same period. The clinical characteristics of the two groups were analysed separately. Three group-blinded radiologists independently analysed the CT findings and classified them into mild-to-moderate and severe groups. Severe chest CT lesion refers to a lesion that is less diffused or moderately dense and either exceeds the total volume of one lung, a high-density fused lesion greater than one-third of the volume of one lung, or a cavitary lesion with a maximum diameter ≥ 4 cm., Results: No significant differences were observed in the presentation of clinical features. Regarding the severity of chest CT manifestation, patients with TB-DM had significantly more severe TB than those with TB-NDM (89.61% vs. 68.97%, P < 0.0001). Regarding CT findings, patients with TB-DM had higher proportions of consolidation (79.22% vs. 52.41%, P < 0.0001), cavitary lesions (85.06% vs. 59.31%, P < 0.0001), bronchiectasis (71.43% vs. 31.03%, P < 0.0001), exudative lesions (88.96% vs. 68.28%, P < 0.0001), and fibrous lesions (93.51% vs. 68.97%, P < 0.0001) than patients with TB-NDM. In conclusion, patients with TB-DM have more severe pulmonary TB CT findings than those without. There were no significant differences in the distribution of lesions in the lung lobes between TB-DM and TB-NDM patients., Conclusions: Among patients hospitalised with pulmonary TB, those with T2DM had more severe findings on chest CT than those without T2DM. However, the clinical presentation was not significantly different., (© 2023. The Author(s).)

Mobile digital chest radiography (CR) is a commonly used method for pulmonary tuberculosis (PTB) screening among homeless people in Nishinari District, Osaka City, Japan. We investigated mobile CR screening (MCS) to calculate the case-finding rate of culture-confirmed PTB among homeless examinees in Nishinari District from 2013 to 2019. PTB was defined as a sputum culture-confirmed case. Examinees with culture-confirmed PTB >90 days after MCS were defined as having no progression to active tuberculosis when undergoing MCS. We collected participants' information, including their name, date of birth, age, sex, date of MCS, CR classification (whether the abnormal CR result required further investigation), date of PTB diagnosis, and sputum smear results. Of 10,111 homeless people, 175 (1.7%) with abnormal CR results underwent further investigation at medical facilities. Of those with abnormal CR results, 22 (0.22%) were diagnosed with culture-positive PTB within 90 days of MCS. Of 22 PTB cases with culture-positive results, 13 (59.1%) were smear-positive. We found that MCS contributed to the detection of PTBs with a lower smear-positive rate among patients with PTB analyzed by MCS compared with all culture-confirmed PTB cases in Nishinari District.

Purpose: To evaluate the accuracy of a deep learning-based computer-aided detection (CAD) system in identifying active pulmonary tuberculosis on chest radiographs (CRs) of patients with positive interferon-gamma release assay (IGRA) results in different scenarios of clinical implementation., Materials and Methods: We collected the CRs of consecutive patients with positive IGRA results. Findings of active pulmonary tuberculosis on CRs were independently evaluated by the CAD and a thoracic radiologist, followed by interpretation using the CAD. Sensitivity and specificity were evaluated in different scenarios: (a) radiologists' interpretation, (b) radiologists' CAD-assisted interpretation, and (c) CAD-based prescreening (radiologists' interpretation for positive CAD results only). We conducted a reader test to compare the accuracy of the CAD with those of 5 radiologists., Results: Among 1780 patients (men, 53.8%; median age, 56 y), 44 (2.5%) were diagnosed with active pulmonary tuberculosis. The CAD-assisted interpretation exhibited a higher sensitivity (81.8% vs. 72.7%; P =0.046) but lower specificity than the radiologists' interpretation (84.1% vs. 85.7%; P <0.001). The CAD-based prescreening exhibited a higher specificity than the radiologists' interpretation (88.8% vs. 85.7%; P <0.001) at the same sensitivity, with a workload reduction of 85.2% (1780 to 263). In the reader test, the CAD exhibited a higher sensitivity than radiologists (72.7% vs. 59.5%; P =0.005) at the same specificity (88.0%), and CAD-assisted interpretation significantly improved the sensitivity of radiologists' interpretation (72.3%; P <0.001)., Conclusions: For identifying active pulmonary tuberculosis among patients with positive IGRA results, deep learning-based CAD can enhance the sensitivity of interpretation. CAD-based prescreening may reduce the radiologists' workload at an improved specificity., Competing Interests: E.J.H. received a research grant from Lunit Inc. outside the present study. J.G.N. received a research grant from Vuno, outside the present study. C.M.P. received a research grant from Lunit Inc. outside the present study, and holds stock of Promedius and stock options of Lunit Inc. and Coreline Soft. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Stages of tuberculosis disease can be delineated by radiology, microbiology, and symptoms, but transitions between these stages remain unclear. In a systematic review and meta-analysis of studies of individuals with untreated tuberculosis who underwent follow-up (34 cohorts from 24 studies, with a combined sample of 139 063), we aimed to quantify progression and regression across the tuberculosis disease spectrum by extracting summary estimates to align with disease transitions in a conceptual framework of the natural history of tuberculosis. Progression from microbiologically negative to positive disease (based on smear or culture tests) in participants with baseline radiographic evidence of tuberculosis occurred at an annualised rate of 10% (95% CI 6·2-13·3) in those with chest x-rays suggestive of active tuberculosis, and at a rate of 1% (0·3-1·8) in those with chest x-ray changes suggestive of inactive tuberculosis. Reversion from microbiologically positive to undetectable disease in prospective cohorts occurred at an annualised rate of 12% (6·8-18·0). A better understanding of the natural history of pulmonary tuberculosis, including the risk of progression in relation to radiological findings, could improve estimates of the global disease burden and inform the development of clinical guidelines and policies for treatment and prevention., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Chest X-rays are the most economically viable diagnostic imaging test for active pulmonary tuberculosis screening despite the high sensitivity and low specificity when interpreted by clinicians or radiologists. Computer aided detection (CAD) algorithms, especially convolution based deep learning architecture, have been proposed to facilitate the automation of radiography imaging modalities. Deep learning algorithms have found success in classifying various abnormalities in lung using chest X-ray. We fine-tuned, validated and tested EfficientNetB4 architecture and utilized the transfer learning methodology for multilabel approach to detect lung zone wise and image wise manifestations of active pulmonary tuberculosis using chest X-ray. We used Area Under Receiver Operating Characteristic (AUC), sensitivity and specificity along with 95% confidence interval as model evaluation metrics. We also utilized the visualisation capabilities of convolutional neural networks (CNN), Gradient-weighted Class Activation Mapping (Grad-CAM) as post-hoc attention method to investigate the model and visualisation of Tuberculosis abnormalities and discuss them from radiological perspectives. EfficientNetB4 trained network achieved remarkable AUC, sensitivity and specificity of various pulmonary tuberculosis manifestations in intramural test set and external test set from different geographical region. The grad-CAM visualisations and their ability to localize the abnormalities can aid the clinicians at primary care settings for screening and triaging of tuberculosis where resources are constrained or overburdened., (© 2023. The Author(s).)

Background: Artificial Intelligence (AI) systems have demonstrated potential in detecting tuberculosis (TB) associated abnormalities from chest X-ray (CXR) images. Thus, they might provide a solution to radiologist shortages in high TB burden countries. However, the cost of implementing computer-aided detection (CAD) software has thus far been understudied. In this study, we performed a costing analysis of CAD software when used as a screening or triage test for pulmonary TB, estimated the incremental cost compared to a radiologist reading of different throughput scenarios, and predicted the cost for the national scale-up plan in Pakistan., Methods: For the study, we focused on CAD software reviewed by the World Health Organization (CAD4TB, Lunit INSIGHT CXR, qXR) or listed in the Global Drug Facility diagnostics catalogue (CAD4TB, InferRead). Costing information was obtained from the CAD software developers. CAD4TB and InferRead use a perpetual license pricing model, while Lunit and qXR are priced per license for restricted number of scans. A major implementer in Pakistan provided costing information for human resource and software training. The per-screen cost was estimated for each CAD software and for radiologist for 1) active case finding, and 2) facility based CXR testing scenarios with throughputs ranging from 50,000-100,000 scans. Moreover, we estimated the scale-up cost for CAD or radiologist CXR reading in Pakistan based on the National Strategic Plan, considering that to reach 80% diagnostic coverage, 50% of TB patients would need to be found through facility-based triage and 30% through active case finding (ACF)., Results: The per-screen cost for CAD4TB (0.25 USD- 2.33 USD) and InferRead (0.19 USD- 2.78 USD) was lower than that of a radiologist (0.70 USD- 0.93 USD) for high throughput scenarios studied. In comparison, the per-screen cost for Lunit (0.94 USD- 1.69 USD) and qXR (0.95 USD-1.9 USD) were only comparable with that of the radiologists in the highest throughput scenario in ACF. To achieve 80 percent diagnostic coverage at scale in Pakistan, the projected additional cost of deploying CAD software to complement the current infrastructure over a four-year period were estimated at 2.65-19.23 million USD, whereas Human readers, would cost an additional 23.97 million USD., Conclusions: Our findings suggest that using CAD software could enable large-scale screening programs in high TB-burden countries and be less costly than radiologist. To achieve minimum cost, the target number of screens in a specific screening strategy should be carefully considered when selecting CAD software, along with the offered pricing structure and other aspects such as performance and operational features. Integrating CAD software in implementation strategies for case finding could be an economical way to attain the intended programmatic goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Bashir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To analyze the association of dysglycemia with clinical, laboratory, and radiographic characteristics of patients with pulmonary tuberculosis (PTB), as well as with their tuberculosis treatment outcomes., Methods: This was a longitudinal study involving 140 patients diagnosed with PTB (positive cultures for Mycobacterium tuberculosis or positive Xpert MTB/RIF results from sputum samples). Patients were evaluated at diagnosis (M0), after completing the second month of treatment (M2), and at the end of treatment (MEND). At M0, the patients were classified into three groups: normoglycemia+PTB (NGTB); pre-diabetes mellitus+PTB (PDMTB), and diabetes mellitus+PTB (DMTB), in accordance with glycated hemoglobin levels (< 5.7%, 5.7%-6.4%, and ≥ 6.5%, respectively). Treatment outcomes were classified as favorable (cure or treatment completion) and unfavorable (death, loss to follow-up, or treatment failure)., Results: In our sample, 76 patients (61.4%) had dysglycemia, 20 of whom (14.3%) had DM at M0. The patients with dysglycemia, in comparison with those in the NGTB group, more frequently presented with positive sputum smear microscopy (94.2% vs. 75.9%; p = 0.003); cavities (80.2% vs. 63.0%; p = 0.03); bilateral lesions (67.4% vs. 46.0%; p = 0.02); and higher median of affected thirds of the lungs (3.0 vs. 2.0; p = 0.03) on chest radiography. No significant differences regarding outcomes were found among the groups, but tuberculosis lethality was higher in the DMTB group than in the PDMTB and NGTB groups (20% vs. 2.2%)., Conclusions: PTB patients with dysglycemia had laboratory and radiographic manifestations indicative of more advanced disease, and the risk of death was higher in the DMTB group. These findings reinforce the recommendation for early screening for DM in patients with newly diagnosed tuberculosis in order to reduce the risk of death during treatment.

Objectives: We aimed to determine the prevalence, associated factors and describe the chest radiographic findings for active pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM) attending a diabetic clinic in Tanzania., Design: Cross-sectional study., Setting: A diabetic clinic at Temeke Regional Referral Hospital in Dar es salaam, Tanzania., Participants: Patients with diabetes., Main Outcome Measures: The prevalence and factors associated with active TB in patients with DM., Results: Among 623 patients with DM screened, 11 (1.8%); 95% CI 0.9 to 3.1, had active TB of which 6 (54.5%) were GeneXpert positive and 5 (45.5%) were diagnosed based on clinical symptoms and suggestive chest radiographs. The risk of active TB was lower in patients aged 45-64 years compared with age below 45 years (adjusted prevalence ratio (aPR) 0.39, 95% CI (0.11 to 0.42), p=0.001) and in patients with normal chest examination findings compared with patients with crackles or bronchial breathing sounds (aPR 0.02, 95% CI (0.01 to 0.15), p<0.01). The predominant chest radiographic findings were opacification 100% mainly in the upper and mid-lung zones., Conclusion: Diabetics should be screened for pulmonary TB, particularly among individuals aged 45 years and below with crackles or bronchial breathing on auscultation of the chest. High index of suspicion could help in the early detection and control of TB., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The study aimed to explore the key points of computed tomography (CT) differential diagnosis of nontuberculous mycobacteria (NTM) and secondary pulmonary tuberculosis in elderly patients., Methods: We retrospectively analyzed 45 patients with NTM pulmonary disease and 65 patients with secondary pulmonary tuberculosis. All patients were older than 60 years. The diseases were confirmed by laboratory examination. The general data and CT images of the 2 groups were compared and analyzed using χ 2 tests, single-factor analysis, and multivariate logistic regression analysis., Results: Single-factor analysis showed significant differences between the 2 groups in 9 factors: bronchiectasis of the left upper lobe lingual segment, bronchiectasis of the right middle lobe, small nodules, large nodules, thin-walled cavities, thick-walled cavities, nonsubpleural hollows, strip opacity, and mediastinal lymph node enlargement ( P < 0.05). Multivariate logistic regression analysis showed that thin-walled cavities, bronchiectasis of the right middle lobe, small nodules, and large nodules were important factors in the differential diagnosis of the two groups., Conclusions: Nontuberculous mycobacteria show certain characteristics on CT, which are helpful for differential diagnosis when coupled with clinical and sputum smear examinations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The chest radiograph (CR) remains a key tool in the diagnosis of pediatric tuberculosis (TB). In children with presumptive intrathoracic TB, we aimed to identify CR features that had high specificity for, and were strongly associated with, bacteriologically confirmed TB., Methods: We analyzed CR data from children with presumptive intrathoracic TB prospectively enrolled in a cohort study in a high-TB burden setting and who were classified using standard clinical case definitions as "confirmed," "unconfirmed," or "unlikely" TB. We report the CR features and inter-reader agreement between expert readers who interpreted the CRs. We calculated the sensitivity and specificity of the CR features with at least moderate inter-reader agreement and analyzed the relationship between these CR 
features and the classification of TB in a multivariable regression model., Results: Of features with at least moderate inter-reader agreement, enlargement of perihilar and/or paratracheal lymph nodes, bronchial deviation/compression, cavities, expansile pneumonia, and pleural effusion had a specificity of > 90% for confirmed TB, compared with unlikely TB. Enlargement of perihilar (adjusted odds ratio [aOR]: 6.6; 95% confidence interval [CI], 3.80-11.72) and/or paratracheal lymph nodes (aOR: 5.14; 95% CI, 2.25-12.58), bronchial deviation/compression (aOR: 6.22; 95% CI, 2.70-15.69), pleural effusion (aOR: 2.27; 95% CI, 1.04-4.78), and cavities (aOR: 7.45; 95% CI, 3.38-17.45) were associated with confirmed TB in the multivariate regression model, whereas alveolar opacification (aOR: 1.16; 95% CI, .76-1.77) and expansile pneumonia (aOR: 4.16; 95% CI, .93-22.34) were not., Conclusions: In children investigated for intrathoracic TB enlargement of perihilar or paratracheal lymph nodes, bronchial compression/deviation, pleural effusion, or cavities on CR strongly support the diagnosis., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Few evaluations of computer-aided detection (CAD) software for analyzing chest radiographs for tuberculosis have used mycobacterial culture as the reference standard., Methods: Using data from a prospective study of symptomatic adults and household contacts of persons with tuberculosis who were seeking care in Karachi, we evaluated the accuracy of LUNIT INSIGHT version 3.1.0.0 (LUNIT, South Korea) for detecting pulmonary tuberculosis in the triage use case. The reference standard was liquid culture. We estimated the diagnostic accuracy using three developer-recommended threshold scores for tuberculosis: 15, 30, and 45., Results: A total 269 of 2190 (12%) participants had culture-confirmed pulmonary tuberculosis. LUNIT-reported abnormalities of nodule, consolidation, fibrosis, and pleural effusion were more common with culture-confirmed tuberculosis. At the tuberculosis threshold score of 30, sensitivity and specificity were, respectively, 87.7% [95% CI: 83.2-91.4%] and 64.3% [62.1-66.4%]. Sensitivity was similar at scores of 15, 88.1% [95% CI: 83.6-91.7%] and 45, 86.6% [82.0 - 90.5%]; and specificity was 57.9% [55.7-60.2%] and 69.9% [67.8-71.9%], respectively. Sensitivity was lower for smear-negative disease, and specificity was lower with increasing age, previous tuberculosis, and decreasing body mass index. Diabetes and tobacco smoking did not modify accuracy., Conclusion: In a population where most tuberculosis was smear-positive, LUNIT-reported radiographic abnormalities were associated with culture-confirmed disease. Manufacturer-recommended threshold scores had limited sensitivity., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tuberculosis (TB) has a heterogeneous phenotype, which makes it challenging to diagnose. Our study aimed to identify TB phenotypes through cluster analysis and compare their initial symptomatic, microbiological and radiographic characteristics. We systemically collected data of notified TB patients notified in Korea and constructed a prospective, observational cohort database. Cluster analysis was performed using K-means clustering, and the variables to be included were determined by correlation network. A total of 4,370 subjects with pulmonary TB were enrolled in the study. Based on the correlation network, age and body mass index (BMI) were selected for the cluster analysis. Five clusters were identified and characterised as follows: (1) middle-aged overweight male dominance, (2) young-aged relatively female dominance without comorbidities, (3) middle-aged underweight male dominance, (4) overweight elderly with comorbidities and (5) underweight elderly with comorbidities. All clusters had distinct demographic and symptomatic characteristics. Initial microbiologic burdens and radiographic features also varied, including the presence of cavities and bilateral infiltration, which reflect TB-related severity. Cluster analysis of age and BMI identified five phenotypes of pulmonary TB with significant differences at initial clinical presentations. Further studies are necessary to validate our results and to assess their clinical implications., (© 2022. The Author(s).)

The drug resistance and influencing factors of patients with pulmonary tuberculosis were investigated, and a dual attention dilated residual network (DADRN) algorithm was proposed. The algorithm was applied to process and analyze lung computed tomography (CT) images of 400 included patients with pulmonary tuberculosis. Besides, sparse code book algorithm and bag of visual word (BOVW) algorithms were introduced and compared, and the influencing factors of pulmonary tuberculosis drug resistance were analyzed. The results demonstrated that the localization precision of lung consolidation, nodules, and cavities by the DADRN algorithm reached 91.2%, 92.5%, and 93.8%, respectively. The recall rate of the three algorithms amounted to 83.55%, 84.5%, and 86.4%, respectively. Both localization precision and recall rate of the DADRN algorithm were higher than those of other two algorithms ( P < 0.05). The drug resistance rate of streptomycin, isoniazid, and rifampin of the patients aged between 40 and 59 was all higher than those of the patients in other age groups. The drug resistance rate of streptomycin, isoniazid, and rifampin of retreated patients was all higher than those of patients initially treated. The drug resistance rate of streptomycin, isoniazid, and rifampin of the patients with tuberculosis contact was all higher than those of the patients without tuberculosis contact ( P < 0.05). Based on the above results, the accuracy of CT images processed by dual attention-based dilated residual classification network algorithm was higher than that processed by other two algorithms. Age, medical history, and history of exposure to tuberculosis were the influencing factors of the drug resistance of patients with pulmonary tuberculosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yanping Jiang et al.)

Sarcoidosis is frequently misdiagnosed as tuberculosis (TB) and consequently mistreated due to inherent limitations in radiological presentations. Clinically, to distinguish sarcoidosis from TB, physicians usually employ biopsy tissue diagnosis and blood tests; this approach is painful for patients, time-consuming, expensive, and relies on techniques prone to human error. This study proposes a computer-aided diagnosis method to address these issues. This method examines seven EfficientNet designs that were fine-tuned and compared for their abilities to categorize X-ray images into three categories: normal, TB-infected, and sarcoidosis-infected. Furthermore, the effects of stain normalization on performance were investigated using Reinhard's and Macenko's conventional stain normalization procedures. This procedure aids in improving diagnostic efficiency and accuracy while cutting diagnostic costs. A database of 231 sarcoidosis-infected, 563 TB-infected, and 1010 normal chest X-ray images was created using public databases and information from several national hospitals. The EfficientNet-B4 model attained accuracy, sensitivity, and precision rates of 98.56%, 98.36%, and 98.67%, respectively, when the training X-ray images were normalized by the Reinhard stain approach, and 97.21%, 96.9%, and 97.11%, respectively, when normalized by Macenko's approach. Results demonstrate that Reinhard stain normalization can improve the performance of EfficientNet -B4 X-ray image classification. The proposed framework for identifying pulmonary sarcoidosis may prove valuable in clinical use.

Pulmonary tuberculosis (TB) is one of the top 10 causes of death worldwide caused by an infection. TB is curable with an adequate diagnosis, normally performed through bacilloscopies. Automate TB diagnosis implies bacilli detection and counting usually based on smear images processing and artificial intelligence. Works reported in the literature usually consider images with similar coloring characteristics, which are difficult to obtain due to the Ziehl - Neelsen staining method variations (excess or deficiency of coloration), provoking errors in the bacilli segmentation. This paper presents an image preprocessing technique, based on simple, fast and well-known processing techniques, to improve and standardize the contrast in the Acid-Fast Bacilli (AFB) images used to diagnose TB; these techniques are used previously to the segmentation stage to obtain accurate results. The results are validated with and without the preprocessing stage by the Jaccard index, pixel detection accuracy and UAC obtained in an Artificial Neural Network (ANN) and a Bayesian classifier with Gaussian mixture model (GMM). Obtained results indicate that the proposed approach can be applied to automate the Tuberculosis diagnostic., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Automated radiologic analysis using computer-aided detection software (CAD) could facilitate chest X-ray (CXR) use in tuberculosis diagnosis. There is little to no evidence on the accuracy of commercially available deep learning-based CAD in different populations, including patients with smear-negative tuberculosis and people living with human immunodeficiency virus (HIV, PLWH)., Methods: We collected CXRs and individual patient data (IPD) from studies evaluating CAD in patients self-referring for tuberculosis symptoms with culture or nucleic acid amplification testing as the reference. We reanalyzed CXRs with three CAD programs (CAD4TB version (v) 6, Lunit v3.1.0.0, and qXR v2). We estimated sensitivity and specificity within each study and pooled using IPD meta-analysis. We used multivariable meta-regression to identify characteristics modifying accuracy., Results: We included CXRs and IPD of 3727/3967 participants from 4/7 eligible studies. 17% (621/3727) were PLWH. 17% (645/3727) had microbiologically confirmed tuberculosis. Despite using the same threshold score for classifying CXR in every study, sensitivity and specificity varied from study to study. The software had similar unadjusted accuracy (at 90% pooled sensitivity, pooled specificities were: CAD4TBv6, 56.9% [95% confidence interval {CI}: 51.7-61.9]; Lunit, 54.1% [95% CI: 44.6-63.3]; qXRv2, 60.5% [95% CI: 51.7-68.6]). Adjusted absolute differences in pooled sensitivity between PLWH and HIV-uninfected participants were: CAD4TBv6, -13.4% [-21.1, -6.9]; Lunit, +2.2% [-3.6, +6.3]; qXRv2: -13.4% [-21.5, -6.6]; between smear-negative and smear-positive tuberculosis was: were CAD4TBv6, -12.3% [-19.5, -6.1]; Lunit, -17.2% [-24.6, -10.5]; qXRv2, -16.6% [-24.4, -9.9]. Accuracy was similar to human readers., Conclusions: For CAD CXR analysis to be implemented as a high-sensitivity tuberculosis rule-out test, users will need threshold scores identified from their own patient populations and stratified by HIV and smear status., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Abstract: A 57-year-old woman was admitted to the hospital with persisting cough and sputum for 2 months. Chest CT revealed multiple nodules in the left lung. 18F-FDG PET/CT scan was carried out to further evaluate these pulmonary lesions. In addition to multiple hypermetabolic nodules in the upper lobe of left lung, diffuse thickening of the trachea and left bronchial wall with increased FDG uptake was also found. Inflammatory granulation tissue with Mycobacterium tuberculosis was confirmed through the pathological examination of bronchoscopy., Competing Interests: Conflicts of interest and sources of funding: This work was supported by funds from the National Natural Science Foundation of China (81971645). The authors declare that they have no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Diagnosing childhood tuberculosis (TB) is challenging, and novel diagnostic tools are urgently needed. Mediastinal lymphadenopathy is a hallmark of primary pulmonary TB (PTB) in children. We aimed to summarise available methodological and diagnostic data of transthoracic mediastinal ultrasound for childhood TB. Literature review identified two prospective and three retrospective studies, a case report, and a technical report including cases. All reported on suprasternal scanning of the mediastinum; additional parasternal scanning was reported by five studies. The proportion of children with lymphadenopathy detected by mediastinal ultrasound ranged between 15% and 85%, with studies including both supra- and parasternal scanning achieving higher detection ratios. Three retrospective studies reported mediastinal lymphadenopathy on ultrasound for most cases presenting with a normal or inconclusive CXR. Data on ultrasound for mediastinal lymphadenopathy in children are limited but indicate that mediastinal ultrasound can successfully detect mediastinal lymphadenopathy in children with TB., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Tuberculosis is a significant health problem in many parts of the world. According to the Global Tuberculosis Report 2020, 10 million new tuberculosis cases were reported worldwide in 2019, with only 57% of these cases being bacteriologically confirmed. Current tuberculosis diagnostic tests depend on the quality of the sputum, leaving many diagnostic uncertainties. Diagnostic delays result in ongoing transmission and more severe, progressive disease in the affected person. This shows that current diagnostic tests are not sufficient to establish all tuberculosis cases accurately, and there is a need for a new diagnostic technique. 99mTc-ethambutol scintigraphy was recently reported as a new diagnostic test for tuberculosis, with a sensitivity and specificity of 93.9% and 85.7%, respectively. Here, we report a case of the importance of this new technique for diagnosing tuberculosis when the existing bacteriological and molecular tests failed to confirm the diagnosis., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Prayudi Santoso, Basuki Hidayat, Chica Pratiwi, Kevin Yonatan Budiman, Hari Soekersi, Arto Yuwono Soeroto.)

Background: Although computer-aided detection (CAD) software employed with Artificial Intelligence (AI) system has been developed aiming to assist tuberculosis (TB) triage, screening, and diagnosis, its clinical performance for tuberculosis screening remains unknown., Objective: To evaluate performance of an CAD software for detecting TB on chest X-ray images at a pilot active TB screening project., Methods: A CAD software scheme employed with AI was used to screen chest X-ray images of participants and produce probability scores of cases being positive for TB. CAD-generated TB detection scores were compared with on-site and senior radiologists via several performance evaluation indices including area under the ROC curves (AUC), specificity, sensitive, and positive predict value. Pycharm CE and SPSS statistics software packages were used for data analysis., Results: Among 2,543 participants, eight TB patients were identified from this screening pilot program. The AI-based CAD system outperformed the onsite (AUC = 0.740) and senior radiologists (AUC = 0.805) either using thresholds of 30% (AUC = 0.978) and 50% (AUC = 0.859) when taking the final diagnosis as the ground truth., Conclusions: The AI-based CAD software successfully detects all TB patients as identified from this study at a threshold of 30%. It demonstrates feasibility and easy accessibility to carry out large scale TB screening using this CAD software equipped in medical vans with chest X-ray imaging machine.

To determine association of clinico-radiological factors and radiological activity with diagnostic yield in sputum-smear negative tuberculosis (TB). Prospective observational study in the Military Hospital Rawalpindi (Pakistan) from July to December 2018. Adult patients having no contraindications to bronchoscopy were included. HIV positive patients and those on anti-tuberculosis therapy for more than one week were excluded. High-resolution computed tomography (HRCT) findings were classified based on active and inactive tuberculosis features. Washings were sent for acid-fast bacillus (AFB) smear, GeneXpert assay and cultures. Out of 215 patients, 42.3% (91) were diagnosed with microbiological or histological evidence of TB. On univariate analysis, cavitation (p-value <0.001), soft-tissue nodules (p-value 0.04), and endobronchial mucosal changes (p-value 0.02) were associated with culture positivity. Presence of cavitation (OR= 4.10; CI= 2.18,7.73; p-value<0.001) was the only independent predictor of microbiological yield. Diagnostic yield was 70%, 50%, 12.5% and 8.6% in patients with definitely active, probably active, indeterminate and inactive tuberculosis HRCT features respectively. Sensitivity, specificity, positive predictive value and negative predictive value of HRCT active TB were 95.38% (95% CI 87.10-99.04), 48.00 % (95% CI 39.78-56.30), 44.29% (95% CI 40.31-48.33), 96.00 % (95%CI 88.70-98.66) respectively. There was no significant association between age groups, smoking status and gender with diagnosis of tuberculosis in our study. Radiological activity and certain visualized bronchoscopic changes were associated with good diagnostic performance and can be used as predictive factors in diagnosis of active smear negative tuberculosis.

Background: Accessibility to chest radiography remains a major challenge in high burden and low-income countries. The World Health Organization (WHO) guidelines acknowledge that for child contacts under 5 years, a negative symptom-based screening is sufficient to exclude active tuberculosis (TB), but in child contacts older than 5 years, a chest radiograph should be considered. We performed a systematic review and meta-analysis to assess the performance of symptom-based screening compared with chest radiography in household contacts under 15 years in low-income and middle-income countries., Methods: Screening articles published prior 1 October 2020 and data extraction were performed by 2 independent reviewers. The primary outcome was the concordance between symptom screening and chest radiography using the prevalence adjusted bias adjusted kappa coefficient (PABAK) and the proportion of asymptomatic children with negative chest radiography. The analysis was stratified by age group., Results: Of 639 identified articles, 10 were included. PABAK varied between 0.09 and 0.97 and between 0.22 and 0.98, in children less than 5 years and 5-14 years, respectively. The pooled proportion of children with both non-TB suggestive symptoms and chest radiography findings was 98.7% (96.9-99.8) in children less than 5 years and 98.1% (93.8-100) in children of age 5-14 years., Conclusions: Despite low concordance between symptom-based screening and chest radiography, most children without TB suggestive symptoms did not have chest radiography findings suggestive of TB. These results suggest that a negative symptom screening is sufficient to rule out active TB, supporting the WHO recommendation to use symptom-based screening alone when chest radiography is not available., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Presentation We describe a case of reactivation of latent pulmonary tuberculosis (TB) invading the larynx and causing dysphonia. Diagnosis A previously healthy 30-year old woman was found to have bilateral pulmonary TB 5-months after being thoroughly investigated for hoarseness. Initial chest x-ray (CXR) and CT-neck were normal. Vocal cord biopsies were negative for granulomata. Treatment The patient was commenced on standard four drug Anti-TB treatment (ATT) and completed a one-year course. Unfortunately, the development of a laryngeal web caused persistent dysphonia. Discussion Patients with laryngeal TB are more likely to present to ENT surgeons, because of the initial symptom of hoarseness. Multiple tests must be completed before out-ruling TB. HRCT or sputum culture is recommended, as TB may not be evident on initial CXR. A collaborative approach between Respiratory and ENT teams is required. Prompt diagnosis is essential. Speech therapy input will be important in our patient's recovery., Competing Interests: The authors have no conflict of interests to declare.

Objectives: Identify barriers and facilitators to integrating community tuberculosis screening with mobile X-ray units into a health system., Methods: Reach, effectiveness, adoption, implementation and maintenance evaluation., Setting: 3-district region of Lima, Peru., Participants: 63 899 people attended the mobile units from 7 February 2019 to 6 February 2020., Interventions: Participants were screened by chest radiography, which was scored for abnormality by computer-aided detection. People with abnormal X-rays were evaluated clinically and by GeneXpert MTB/RIF (Xpert) sputum testing. People diagnosed with tuberculosis at the mobile unit were accompanied to health facilities for treatment initiation., Primary and Secondary Outcome Measures: Reach was defined as the percentage of the population of the three-district region that attended the mobile units. Effectiveness was defined as the change in tuberculosis case notifications over a historical baseline. Key implementation fidelity indicators were the percentages of people who had chest radiography performed, were evaluated clinically, had sputum samples collected, had valid Xpert results and initiated treatment., Results: The intervention reached 6% of the target population and was associated with an 11% (95% CI 6 to 16) increase in quarterly case notifications, adjusting for the increasing trend in notifications over the previous 3 years. Implementation indicators for screening, sputum collection and Xpert testing procedures all exceeded 85%. Only 82% of people diagnosed with tuberculosis at the mobile units received treatment; people with negative or trace Xpert results were less likely to receive treatment. Suboptimal treatment initiation was driven by health facility doctors' lack of familiarity with Xpert and lack of confidence in diagnoses made at the mobile unit., Conclusion: Mobile X-ray units were a feasible and effective strategy to extend tuberculosis diagnostic services into communities and improve early case detection. Effective deployment however requires advance coordination among stakeholders and targeted provider training to ensure that people diagnosed with tuberculosis by new modalities receive prompt treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mycobacterium tuberculosis culture from gastric lavage from apparently healthy children following tuberculin skin test conversion, despite normal chest radiography (CR), is well known but is a contentious subject. A consensus statement regarding classification of childhood tuberculosis excluded this condition, stating that more data were needed. To assist in this discussion, we reviewed early publications that reported the occurrence of this phenomenon and early anatomical pathology studies that described changes that occur in children following tuberculosis infection. Pathology studies describe frequent cavitation in primary foci in children from whom positive M. tuberculosis cultures might easily arise. These foci were very small in some children who might have normal CR. Positive cultures might also arise from ulcerated mediastinal lymph nodes that are invisible on CR. Young children with recent infection very likely have active primary pulmonary tuberculosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In a retrospective study of adolescents with intrathoracic tuberculosis (TB), 26 out of the 81 (32%) patients had undergone chest computed tomography (CT). Chest CT was considered unnecessary in 7 (27%), necessary in 7 (27%), and possibly/probably helpful in 12 (46%). Promptly obtaining specimens for sputum smear microscopy, molecular testing, as well as culture for Mycobacterium tuberculosis could avoid several unnecessary CTs., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The coexistence of pulmonary tuberculosis and pulmonary sarcoidosis is rare. Further, the morphological features of pulmonary tuberculosis with comorbid pulmonary sarcoidosis are similar to those of tuberculosis alone. There are obvious clinical, histological, and radiological similarities between sarcoidosis and tuberculosis, which makes differential diagnosis very challenging, particularly in countries with a high burden of tuberculosis. Here, a rare case of computed tomography (CT) findings of sarcoidosis that developed during tuberculosis treatment is reported. The 46-year-old male patient had no significant symptoms and was undergoing treatment for Mycobacterium tuberculosis infection. Chest CT revealed enlargement of multiple lymph nodes, without cystic or necrotic changes, in the mediastinum and both hili, and post-infectious changes consistent with the sequelae of tuberculosis infection in the left upper lobe. Chest radiographic evidence was accompanied by compatible clinical features and noncaseating granulomas on biopsy. As the patient was clinically stable, corticosteroid treatment was not initiated. To date, the patient remains without specific symptoms and outpatient follow-ups continue. Although rare, sarcoidosis may occur during treatment of pulmonary tuberculosis, and requires attention for diagnosis and treatment. The present case draws a radiological picture of how tuberculosis evolved to sarcoidosis.

Early bactericidal activity studies monitor daily sputum bacterial counts in individuals with tuberculosis (TB) for 14 days during experimental drug treatment. The rate of change in sputum bacterial load over time provides an informative, but imperfect, estimate of drug activity and is considered a critical step in development of new TB drugs. In this clinical study, 160 participants with TB received isoniazid, pyrazinamide, or rifampicin, components of first-line chemotherapy, and moxifloxacin individually and in combination. In addition to standard bacterial enumeration in sputum, participants underwent 2-deoxy-2-[ 18 F]fluoro-d-glucose positron emission tomography and computerized tomography ([ 18 F]FDG-PET/CT) at the beginning and end of the 14-day drug treatment. Quantitating radiological responses to drug treatment provided comparative single and combination drug activity measures across lung lesion types that correlated more closely with established clinical outcomes when combined with sputum enumeration compared to sputum enumeration alone. Rifampicin and rifampicin-containing drug combinations were most effective in reducing both lung lesion volume measured by CT imaging and lesion-associated inflammation measured by PET imaging. Moxifloxacin was not superior to rifampicin in any measure by PET/CT imaging, consistent with its performance in recent phase 3 clinical trials. PET/CT imaging revealed synergy between isoniazid and pyrazinamide and demonstrated that the activity of pyrazinamide was limited to lung lesion, showing the highest FDG uptake during the first 2 weeks of drug treatment. [ 18 F]FDG-PET/CT imaging may be useful for measuring the activity of single drugs and drug combinations during evaluation of potential new TB drug regimens before phase 3 trials., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The incidence rate of pulmonary nontuberculous mycobacterial disease (PNTMD) in Japan is the highest among major industrialized nations. Although the typical clinical course and radiological manifestations of PNTMD are different from those of pulmonary tuberculosis (TB), confusion about these mycobacterial diseases leads to a diagnostic pitfall. Diagnostic challenges include the coexistence of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), false positives for NTM in MTB nucleic acid amplification tests, microbial substitution, and abnormal radiological manifestations caused by NTM. Features of extrapulmonary NTM diseases, such as pleurisy, vertebral osteomyelitis, and disseminated disease, are different from the corresponding tuberculous diseases. Moreover, the immunological background of the patient (status of human immunodeficiency virus infection with or without antiviral therapy, continuation or discontinuation of immunosuppressive therapy, use of immune checkpoint inhibitor, pregnancy and delivery, etc.) influences the pathophysiology of mycobacterial diseases. This review describes the varying clinical presentations of NTM disease with emphasis on the differences from TB. J. Med. Invest. 68 : 220-227, August, 2021.