Detection Of Active Tuberculosis Research Articles

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

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

How useful is the tuberculin skin test for tuberculosis detection: Assessing diagnostic accuracy metrics through a large Tunisian case-control study

Background and aim During the past decade, the frequency of extrapulmonary forms of tuberculosis (TB) has increased. These forms are often miss-diagnosed. This statement of the TB epidemiological profile modification, conduct us to reflect about the utility of the Tuberculin Skin Test (TST) in active TB detection. This study aimed to evaluate the diagnostic accuracy performance of the TST for active tuberculosis detection. Methods This was a case-control, multicenter study conducted in 11 anti-TB centers in Tunisia (June-November2014). The cases were adults aged between 18 and 55 years with newly diagnosed and confirmed tuberculosis. Controls were free from tuberculosis. A data collection sheet was filled out and a TST was performed for each participant. Diagnostic accuracy measures of TST were estimated using Receiver Operating Curve (ROC) curve and Area Under Curve (AUC) to estimate sensitivity and specificity of a determined cut-off point. Results Overall, 1050 patients were enrolled, composed of 336 cases and 714 controls. The mean age was 38.3±11.8 years for cases and 33.6±11 years for controls. The mean diameter of the TST induration was significantly higher among cases than controls (13.7mm vs.6.2mm; p=10-6). AUC was 0.789 [95% CI: 0.758-0.819; p=0.01], corresponding to a moderate discriminating performance for this test. The most discriminative cut-off value of the TST, which was associated with the best sensitivity (73.7%) and specificity (76.6%) couple was ≥ 11 mm with a Youden index of 0.503. Positive and Negative predictive values were 3.11% and 99.52%, respectively. Conclusions TST could be a useful tool used for active tuberculosis detection, with a moderate global performance and accepted sensitivity and specificity at the cut-off point of 11 mm. However, it cannot be considered as a gold standard test due to its multiple disadvantages.

Advancing Tuberculosis Detection in Chest X-rays: A YOLOv7-Based Approach

In this work, we propose a CAD (computer-aided diagnosis) system using advanced deep-learning models and computer vision techniques that can improve diagnostic accuracy and reduce transmission risks using the YOLOv7 (You Only Look Once, version 7) object detection architecture. The proposed system is capable of accurate object detection, which provides a bounding box denoting the area in the X-rays that shows some possibility of TB (tuberculosis). The system makes use of CNNs (Convolutional Neural Networks) and YOLO models for the detection of the consolidation of cavitary patterns of the lesions and their detection, respectively. For this study, we experimented on the TBX11K dataset, which is a publicly available dataset. In our experiment, we employed class weights and data augmentation techniques to address the data imbalance present in the dataset. This technique shows a promising improvement in the model’s performance and thus better generalization. In addition, it also shows that the developed model achieved promising results with a mAP (mean average precision) of 0.587, addressing class imbalance and yielding a robust performance for both obsolete pulmonary TB and active TB detection. Thus, our CAD system, rooted in state-of-the-art deep-learning and computer vision methodologies, not only advances diagnostic accuracy but also contributes to the mitigation of TB transmission risks. The substantial improvement in the model’s performance and the ability to handle class imbalance underscore the potential of our approach for real-world TB detection applications.

How useful is the tuberculin skin test for the detection of active tuberculosis: Assessing diagnostic accuracy metrics and selection of best cut-off value through a large Tunisian multicenter case-control study

Background and aim: During the past decade, the frequency of extrapulmonary forms of tuberculosis (TB) has increased. These forms are often miss-diagnosed. This statement of the TB epidemiological profile modification, conduct us to reflect about the utility of the Tuberculin Skin Test (TST) in active TB detection. This study aimed to evaluate the diagnostic accuracy performance of the TST for active tuberculosis detection. Methods: This was a case-control, multicenter study conducted in 11 anti-TB centers in Tunisia (June-November2014). The cases were adults aged between 18 and 55 years with newly diagnosed and confirmed tuberculosis. Controls were free from tuberculosis. A data collection sheet was filled out and a TST was performed for each participant. Diagnostic accuracy measures of TST were estimated using Receiver Operating Curve (ROC) curve and Area Under Curve (AUC) to estimate sensitivity and specificity of a determined cut-off point. Results: Overall, 1050 patients were enrolled, composed of 336 cases and 714 controls. The mean age was 38.3±11.8 years for cases and 33.6±11 years for controls. The mean diameter of the TST induration was significantly higher among cases than controls (13.7mm vs.6.2mm; p=10-6). AUC was 0.789 [95% CI: 0.758-0.819; p=0.01], corresponding to a moderate discriminating performance for this test. The most discriminative cut-off value of the TST, which was associated with the best sensitivity (73.7%) and specificity (76.6%) couple was ≥ 11 mm with a Youden index of 0.503. Positive and Negative predictive values were 3.11% and 99.52%, respectively. Conclusions: TST could be a useful tool used for active tuberculosis detection, with a moderate global performance and accepted sensitivity and specificity at the cut-off point of 11 mm. However, it cannot be considered as a gold standard test due to its multiple disadvantages.

COVID-19 and Tuberculosis: Unveiling the Dual Threat and Shared Solutions Perspective.

The year 2020 will likely be remembered as the year dominated by COVID-19, or coronavirus disease. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for this pandemic, can be traced back to late 2019 in China. The COVID-19 pandemic has significantly impacted the tuberculosis (TB) care system, reducing TB testing and reporting. This can be attributed to the disruption of TB services and restrictions on patient movement, consequently increasing TB-related deaths. This perspective review aims to highlight the intersection between COVID-19 and TB, highlighting their dual threat and identifying shared solutions to address these two infectious diseases effectively. There are several shared commonalities between COVID-19 and tuberculosis, particularly the transmission of their causative agents, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Mycobacterium tuberculosis. Both pathogens are transmitted via respiratory tract secretions. TB and COVID-19 are diseases that can be transmitted through droplets and airborne particles, and their primary target is typically the lungs. Regarding COVID-19 diagnostics, several methods are available for rapid and accurate detection. These include RT-PCR, which can provide results within two hours, and rapid antigen test kits that offer results in just a few minutes. The availability of point-of-care self-testing further enhances convenience. On the other hand, various approaches are employed for TB diagnostics to swiftly identify active TB. These include sputum microscopy, sputum for reverse transcription polymerase chain reaction (RT-PCR), and chest X-rays. These methods enable the rapid detection of active TB on the same day, while culture-based testing may take significantly longer, ranging from 2 to 8 weeks. The utilization of diverse diagnostic tools helps ensure the timely identification and management of COVID-19 and TB cases. The quality of life of patients affected by COVID-19 and tuberculosis (TB) can be significantly impacted due to the nature of these diseases and their associated challenges. In conclusion, it is crucial to emphasize the urgent need to address the dual threat of COVID-19 and TB. Both diseases have devastated global health, and their convergence poses an even greater challenge. Collaborative efforts, research investments, and policy reforms are essential to tackle this dual threat effectively.

Performance of T-Track® TB, a Novel Dual Marker RT-qPCR-Based Whole-Blood Test for Improved Detection of Active Tuberculosis.

Tuberculosis (TB) is one of the leading causes of death by an infectious disease. It remains a major health burden worldwide, in part due to misdiagnosis. Therefore, improved diagnostic tests allowing the faster and more reliable diagnosis of patients with active TB are urgently needed. This prospective study examined the performance of the new molecular whole-blood test T-Track® TB, which relies on the combined evaluation of IFNG and CXCL10 mRNA levels, and compared it to that of the QuantiFERON®-TB Gold Plus (QFT-Plus) enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and agreement analyses were conducted on the whole blood of 181 active TB patients and 163 non-TB controls. T-Track® TB presented sensitivity of 94.9% and specificity of 93.8% for the detection of active TB vs. non-TB controls. In comparison, the QFT-Plus ELISA showed sensitivity of 84.3%. The sensitivity of T-Track® TB was significantly higher (p < 0.001) than that of QFT-Plus. The overall agreement of T-Track® TB with QFT-Plus to diagnose active TB was 87.9%. Out of 21 samples with discordant results, 19 were correctly classified by T-Track® TB while misclassified by QFT-Plus (T-Track® TB-positive/QFT-Plus-negative), and two samples were misclassified by T-Track® TB while correctly classified by QFT-Plus (T-Track® TB-negative/QFT-Plus-positive). Our results demonstrate the excellent performance of the T-Track® TB molecular assay and its suitability to accurately detect TB infection and discriminate active TB patients from non-infected controls.

ОЦЕНКА ПОСЛЕДСТВИЙ ВЛИЯНИЯ ПАНДЕМИИ COVID-19 НА СИСТЕМУ АКТИВНОГО ВЫЯВЛЕНИЯ СЛУЧАЕВ ТУБЕРКУЛЁЗА В РОССИЙСКОЙ ФЕДЕРАЦИИ

Significance. The COVID-19 pandemic has disrupted the system of active detection of many diseases, including tuberculosis (TB). However, the assessment of this effect based on the decreased TB incidence alone is not correct, since the regiment to fight COVID-19 has created conditions for preventing the spread of other infectious diseases. The purpose of the study was: to assess dynamics in active TB detection, as well as the number of late detected TB cases due to the COVID-19 pandemic. Material and methods. The study analyzed statistical observation forms # 8 and #33. The excess number of newly diagnosed cases of fibrous-cavernous pulmonary tuberculosis (FCPTb) was calculated as multiplied by the number of newly diagnosed TB cases to the difference in the average share of fibrous-cavernous pulmonary tuberculosis cases in 2016-2019 and the share of fibrous-cavernous pulmonary tuberculosis cases in the year under study (2020, 2021, 2022). The excess number of TB patients diagnosed postmortem was calculated as multiplied by the number of newly diagnosed TB cases to the difference in the average share of TB cases detected postmortem in 2015-2019 and the share of TB cases detected postmortem in the year under study (2020, 2021, 2022). Results. In 2020, the population coverage with preventive medical examination for TB decreased to 66.7%, which is close to the 2015 level (68.1%) followed by a growth to 70.6% in 2021 (the 2017 level) and further to 73.6% in 2022 (the 2019 level). The share of newly diagnosed fibrous-cavernous pulmonary tuberculosis cases in 2016-2019 equaled to 1.1%, increased to 1.4% in 2020, to 1.5% in 2021, and 1.4% in 2022. The share of TB cases detected postmortem equaled to 1.6-1.8% in 2008-2019; to 2.7% in 2020, and to 2.9% in 2021 and 2022. The excess number of newly diagnosed fibrous-cavernous pulmonary tuberculosis cases equaled to 109 in 2020, 188 in 2021, and 128 in 2022. The excess number of TB cases detected postmortem equaled to 480 in 2020, 566 in 2021, and 540 in 2022. Conclusion. The impact of the COVID-19 pandemic on the system of active TB detection in the Russian Federation was strong, yet rather short-run. However, the three years of the COVID-19 pandemic has resulted in the delay in detection of 2011 TB patients (1.5% of the total number of newly diagnosed TB cases)

Quality of life in children with latent tuberculosis infection

The number of children newly infected with Mycobacterium tuberculosis continues to increase. Children from foci of tuberculosis infection are most often susceptible to primary infection. In recent years, the number of children diagnosed with latent tuberculosis infection has tended to increase. It is also important that the detection of active tuberculosis also continues to grow among such children.Objective. To establish the role of risk factors and identify deviations in the quality of life in children with latent tuberculosis infection living in the foci of tuberculosis infection.Characteristics of children and research methods. The researchers examined 110 children aged 0-14 years. They analyzed the risk factors for infection with Mycobacterium tuberculosis. The effectiveness of BCG vaccination was assessed by the presence and size of the scar. The quality of life was determined using the PedsQL questionnaire version 4.0 for children of 0-14 years old.Results and discussion. There were much more children whose mothers suffered from tuberculosis in the family. There were much more children whose mothers released bacteria as compared to the children whose mothers did not excrete mycobacterium tuberculosis. The patients with an infiltrative form of pulmonary tuberculosis were the predominant source of infection in children. The children with diagnosed active tuberculosis with a history of latent tuberculosis infection were in close contact with a family member who had previously been in the penitentiary zone, and also had unsatisfactory living conditions.Conclusion. The presence of an active form of tuberculosis in a child creates the preconditions for a comprehensive deterioration of all parameters of the life quality, while latent tuberculosis infection has an adverse effect only on certain aspects of the life quality. Psychosocial functioning is most commonly affected.

Descriptive study of chest x-ray examination in mandatory annual health examinations at the workplace in Japan

The utility of chest x-ray examination (CXR) in mandatory annual health examinations for occupational health is debatable in Japan. This study aimed to provide basic data to consider future policies for mandatory annual health examinations in the workplace. A nationwide descriptive survey was performed to determine the rate of detection of tuberculosis, lung cancer, and other diseases through CXR in organizations associated with National Federation of Industrial Health Association. The rate of finding on CXR conducted during annual health examinations in FY2016 was evaluated. Data regarding diagnosis based on follow-up examination findings were obtained and compared with the national statistics. In addition, CXR findings were compared with the results of low-dose lung computed tomography performed at the Hitachi Health Care Center. From 121 surveyed institutions, 88 institutions with 8,669,403 workers were included. For all ages, 1.0% of examinees required follow-up examination. Among 4,764,985 workers with diagnosis data, the tuberculosis detection rate was 1.8-5.3 per 100,000 persons. For Lung cancer, 3,688,396 workers were surveyed, and 334 positive cases were detected. The lung cancer detection rate using CXR was 9.1-24.4 per 100,000 persons. From 164 cases with information regarding the clinical stage, 72 (43.9%) had Stage I lung cancer. From 40,045 workers who underwent low-dose computed tomography multiple times, 31 lung cancer cases, all with Stage I disease, were detected (detection rate: 77.4 per 100,000 persons). Our findings suggest that CXR plays a little role in the detection of active tuberculosis. With regard to LC screening, the detection rate of LC by CXR was lower, approximately 50%, than the expected rate (41.0 per 100,000 persons) of LC morbidity based on the age-sex distribution of this study population. However, the role of CXR for LC screening cannot be mentioned based on this result, because assessment of mortality reduction is essential to evaluate the role.

New approaches to prophylactic radiological examinations in the active detection of tuberculosis and non-respiratory diseases in the current conditions

Prophylactic radiological examinations were performed on the population of 54893 people from risk groups and increased vigilance for tuberculosis in different administrative territories of the Republic of Moldova. The structure of the medico-social unfavorable factors in 18223 persons was evaluated. Out of 357 patients with evolutionary pulmonary tuberculosis, with prophylactic purpose, 176 patients were detected, most of them in 95 or 54.0% cases — within this project with the mobile digital radiodiagnostic complexes shipped to different administrative territories of the Republic of Moldova.

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB.

The relevance of household contacts tracing among child contacts of patients with multidrug-resistant tuberculosis

BACKGROUND. The World Health Organization (WHO) reports an unknown contact history of pediatric tuberculosis (TB), especially in children younger than 5 years old. Tracing pediatric household contacts of patients with multidrug-resistant TB (MDR-TB) is considered to be a highly effective intervention for detection of new cases of chemoresistant TB in children and timely prevention of its transmission. OBJECTIVE. To study the nature of TB process manifestations and concordance of mycobacterium tuberculosis (MBT) drug resistance profiles in household child contacts of patients with MDR-TB. MATERIALS AND METHODS. The nature of TB process manifestations and concordance of MBT drug resistance profiles in 12 household child contacts of patients with MDR-TB in 6 households (6 adult MDR-TB index patients, IP) were studied. Adults and children were examined and treated in the Pulmonary Tuberculosis Department No 3 and in the Pediatric Department of the Clinical Base of the Department of Phthisiology and Pulmonology of Zaporizhzhia State Medical University at the Municipal Institution “Zaporizhzhia Regional Tuberculosis Clinical Dispensary”. RESULTS AND DISCUSSION. The tracing of children who were household contacts of the MDR-TB IP revealed the following features. The incidence of child TB was 2 times higher than that of contact adults (44 % vs. 20 %). Moreover, the incidence among children younger than 2 years of age was almost 3 times higher than in children across other age groups (54.5 % vs. 18.2 % in children younger than 5 years of age and 18.2 % in children aged 5 years and older). The children were non-BCG vaccinated in 63.6 % of cases. There was an alarmingly high rate of non-BCG vaccinated children, namely 83.3 % among individuals younger than 2 years of age and all of those younger than 5 years of age (100 %). The children mostly presented small clinical forms of non-destructive TB: intrathoracic lymph node TB (36.4 %), MBT complex (36.4 %) and focal TB (18.2 %). Most of the children (63.6 %) who developed TB were detected within the first year of IP with MDR-TB follow-up, and it is worthy of note that in the majority of cases (4 households; 66.6 %). With respect to the concordance of MBT drug resistance profiles between the children and MDR-TB IP in the households, diagnosis in children was microbiologically confirmed in only 3 cases (3 households) demonstrating the complete concordance of profiles in each one. At the same time, the complete concordance of MBT drug resistance profiles between adult household contacts and the MDR-TB IP was also recorded in 3 cases. As is evident, across the household contacts group aged between 0 and 18 years who were exposed to the MDR-TB IP, the most susceptible to develop TB were non-BCG vaccinated children younger than 2 years. More worryingly is that among 3 microbiologically conformed individuals of this age group, 2 children younger than 2 years were found to have their own drug resistant MTB isolates. CONCLUSIONS. Tracing household child contacts of MDR-TB IP is particularly effective for timely detection of active TB within the first year of MDR-TB IP follow-up. Non-BCG vaccinated children younger than 2 years of age are at the highest risk for MDR-TB followed by non-BCG vaccinated children younger than 5 years of age. The early detection and timely antimycobacterial therapy initiation based on drug susceptibility test results of a MDR-TB IP is a guarantee not only for an effective treatment but also for a reduction in the MDR-TB transmission to other persons.

Strategies for active detection of tuberculosis in Ukraine: Comparative effectiveness amongst key populations (2014-2018).

Ukraine has gaps in Tuberculosis (TB) service coverage, especially in key populations (KPs). We compared effectiveness of three different strategies for active TB detection among KPs and their linkage to TB treatment during three time periods. The KPs included people who inject drugs (PWID), sex workers (SW), men who have sex with men (MSM) and groups at-risk of TB (ex-prisoners, Roma and homeless). The active case finding included decentralized symptom screening and specimen collection (2014, strategy-1), decentralized screening with patient referred for specimen collection (2015-2017, strategy-2) and strategy-2 plus GeneXpert (2018, strategy-3). In total 680,760 KPs were screened, of whom 68% were PWID. TB case detection per 100,000 populations was 1,191 in strategy-1, 302 in strategy-2, and 235 in strategy-3. The number needed to screen (NNS) to identify one case was respectively 84, 332, and 425. TB detection was highest among homeless (range: 1,839-2,297 per 100,000 population). The lowest detection was among the MSM and SW. Between 2014 and 2018, 82-94% of all diagnosed TB patients in KPs started TB treatment. The active case finding in KPs increased detection of TB cases in Ukraine, and the majority of diagnosed KPs initiated TB treatment. Centralization of diagnosis reduced the effectiveness of TB screening. Each region in Ukraine should assess the composition and the needs of KPs which will allow for adoption of specific strategies to detect TB among KPs with high TB prevalence.

Active detection of tuberculosis: tackling the problem head on in the remote area of Andaman and Nicobar Islands

Background: Community based active case finding for tuberculosis (TB) is an essential step in the fight forward for eliminating TB. One of the steps in targeting TB intervention is early diagnosis and treatment of patients by reducing the reservoir of infection in the community. Active case finding (ACF) targeting the entire population by house to house survey was done in Nicobar district of these islands.Methods: A community-based, cross-sectional, descriptive study was conducted with the trained mobile teams from 17.07.2017 to 31.07.2017 in the Nicobar District. The algorithm of the case detection included screening patients by symptoms, then by sputum microscopy for confirmation. X-ray was done in patients who were symptomatic but sputum negative. If both smear and chest X-ray results were negative but still symptomatic, then cartridge-based nucleic acid amplification test (CBNAAT) was done.Results: A total population of 18526 was mapped of which 14784 (79.8) could be screened. A total of 209 people were identified by the mobile teams with symptoms who were examined by sputum microscopy. Among them 7 cases were identified to be sputum smear positive, 2 X-ray positive and 2 were diagnosed by CBNAAT.Conclusions: This study shows that the active case finding method is feasible and acceptable by the community. The results obtained are encouraging for the implementation of ACF through mobile team activity in all these islands in order to meet the target of WHO’s End TB Strategy.

The characteristic of the tuberculosis of lungs detected for the first time in various periods of time in territory with low level of morbidity

The article presents results of comparative evaluation of age-sex, social and clinical structure of patients with tuberculosis of lungs, primarily detected in Zheleznogorsk in 1993-2000 and 2008-2013. The average indicator of tuberculosis morbidity in these two periods amounted to 29.8 per 100 000 of population and indicator of mortality amounted to 1.8 and 4.7 per 100 000 of population correspondingly. It is established that despite significantly lower epidemiological indicators as compared with average national indicators, the manifestations of negative pathomorphosis were revealed: deterioration of structure of clinical forms and characteristics of specific process; manifestation of cases of tuberculosis combined with HIV-infection; increasing of epidemiological danger for ill patients against the background of deterioration of their social structure at the expense of persons having no family, no job, residing in unfavorable housing conditions, homeless, and persons with harmful habits and drug addicted. It is proposed to take into account established aggravating factors while organizing check-up fluorography of population for tuberculosis. The conclusion is made about necessity of increasing of quality of activities concerning active detection of tuberculosis in population, especially the categories whose significance increased in formation of indicator of morbidity. Also, it is necessary to implement effective preventive activities with persons in contact with patients with tuberculosis.

The Application of T.SPOT-TB Assay for Early Diagnosis of Active Tuberculosis in Chronic Kidney Disease Patients Receiving Immunosuppressive Treatment

Background: The current study investigated the clinical application of the T-SPOT.TB assay for detecting tuberculosis (TB) infection in chronic kidney disease patients treated with immunosuppressive therapy. Methods: Clinical data from 91 patients were retrospectively analyzed. The rate of positive T-SPOT.TB results and spot numbers were compared before and after treatment. Clinical characteristics that may affect the test results were also investigated. Results: Two active TB cases were observed after immunosuppressive treatment, and eight patients with negative T-SPOT.TB results at baseline had positive results after treatment. No significant changes in spot numbers were observed for patients who were positive at baseline. Compared with pretreatment baseline, patients who received medium/high doses of corticosteroids had a greater number of T-SPOT.TB positive results (p = 0.016) and CFP-10 spots (p = 0.041) after treatment. For patients who received combination therapy with medium/high doses of corticosteroids, the T-SPOT.TB positive rate (p = 0.046) and CFP-10 spot number (p = 0.041) were increased after treatment, with no significant changes in the total number of spots or ESAT-6 spots. For those who received combination therapy with low doses of corticosteroids and those who received single immunosuppressive medication, there were no significant differences in the T-SPOT.TB positive rate, total spot number, or numbers of ESAT-6 and CFP-10 spots. Conclusion: The increase in positive T-SPOT.TB results was mainly associated with medium/high doses of glucocorticoids. The active TB cases might represent new infections. Regular monitoring using the T-SPOT.TB assay will help in the early detection of active TB.

Stigma against tuberculosis may hinder non-household contact investigation: a qualitative study in Thailand.

A northern province in Thailand. To explore experiences and perspectives on tuberculosis (TB) contact investigations in non-household contacts. Focus group discussions and in-depth interviews with eight groups: three groups of former TB patients (teachers, students and hospital staff) and five groups of representatives from congregate settings such as schools and workplaces. Data were analysed using the modified grounded theory. Annual health check-ups at the workplace contributed to the early detection of active TB in teachers. Former TB patients were highly exposed to non-household contacts, but contact investigations were limited to household contacts only. Barriers and facilitators for non-household contact investigations are associated with five factors, including information, awareness and knowledge about TB; stigma; empathy; health system response and informing non-household contacts about TB exposure. Stigma may be the main barrier to investigations among non-household contacts because TB patients tend to withhold information about their diagnosis from colleagues. Lack of knowledge and misperceptions regarding TB transmission contributed to stigma. Empathy with other people encouraged TB patients to inform non-household contacts. Non-household contact investigations are not performed despite the risk of TB transmission. To promote contact investigations in congregate settings, interventions to overcome TB stigma and improve public knowledge about TB transmission are required.

A systematic review of biomarkers to detect active tuberculosis.

Millions of cases of tuberculosis (TB) go undiagnosed each year. Better diagnostic tools are urgently needed. Biomarker-based or multiple marker biosignature-based tests, ideally performed on blood or urine, for the detection of active TB might help to meet target product profiles proposed by the World Health Organization for point-of-care testing. We conducted a systematic review to summarize evidence on proposed biomarkers and biosignatures and evaluate their quality and level of evidence. We screened the titles and abstracts of 7,631 citations and included 443 publications that fulfilled the inclusion criteria and were published in 2010-2017. The types of biomarkers identified included antibodies, cytokines, metabolic activity markers, mycobacterial antigens and volatile organic compounds. Only 47% of studies reported a culture-based reference standard and diagnostic sensitivity and specificity. Forty-four biomarkers (4%) were identified in high-quality studies and met the target product profile minimum criteria, of which two have been incorporated into commercial assays. Of the 44 highest-quality biomarkers, 24 (55%) were multiple marker biosignatures. No meta-analyses were performed owing to between-study heterogeneity. In conclusion, TB biomarker discovery studies are often poorly designed and findings are rarely confirmed in independent studies. Few markers progress to a further developmental stage. More validation studies that consider the intended diagnostic use cases and apply rigorous design are needed. The extracted data from this review are currently being used by FIND as the foundation of a dynamic database in which biomarker data and developmental status will be presented.

Diagnostic pathways and delay among tuberculosis patients in Stockholm, Sweden: a retrospective observational study

BackgroundAsylum seekers in Sweden are offered tuberculosis (TB) screening at a voluntary post-arrival health examination. The role of this screening in improving the TB diagnostic pathway has not been previously evaluated. The aim of this study was to determine diagnostic pathways for active TB cases and compare diagnostic delays between different pathways.MethodsRetrospective review of medical records of patients reported with active TB in Stockholm in 2015, using a structured and pre-coded form.ResultsSeventy-one percent of patients actively sought health care due to symptoms. As for source of referral to TB specialist clinic, 15% came from screening of eligible migrants, of whom the majority were asymptomatic. Among asylum seekers, 69% were identified through screening at a health examination (HE). The main sources of referral to TB clinics were emergency departments (27%) and primary health care centers (20%). Median health care provider delay was significantly longer in patients identified through migrant screening in health examination.ConclusionsScreening at a health examination was the main pathway of active TB detection among mainly asymptomatic and non-contagious asylum seekers but contributed modestly to total overall TB case detection. In these patients TB was diagnosed early in a non-contagious phase of the disease. Further research is required to assess the effectiveness and cost-effectiveness of HE TB screening as well as inclusion of other groups of migrants from high incidence countries in the screening program in terms of impact on delay, transmission and treatment outcomes.

The effect of combining QuantiFERON-TB Gold In-Tube test with tuberculin skin test on the detection of active tuberculosis.

Interferon-γ release assays (IGRAs) and tuberculin skin tests (TSTs) play an important role in the detection of tuberculosis (TB) infection. However, the interaction between these tests in detecting active pulmonary TB in adults has never been researched. A matched case-control study was conducted in Taiwan from 1 March 2012 to 31 December 2013 by enrolling 150 confirmed TB cases and 852 matched controls dwelling at the same area (stratified by low, medium and high incidence). Compared with a negative QuantiFERON-TB Gold In-Tube (QFT-GIT) test and a negative tuberculin skin test (TST), the effect size for detecting active pulmonary TB was highest for both a positive QFT-GIT and positive TST (adjusted odds ratio [aOR] 8.77 [95% confidence interval {CI} 4.51 to 17.05]), but the detectability was substantially attenuated in the absence of either a positive TST (aOR 1.59 [95% CI 0.70 to 3.63]) or positive QFT-GIT (aOR 1.15 [95% CI 0.48 to 2.71]) after controlling for age and gender. The joint effect of detecting active TB was positively synergistic according to a large positive value of relative excess risk due to interaction (7.05 [95% CI 2.48 to 11.61]). The administration of both the IGRA and TST for enhancing the detectability of active pulmonary TB in an area with a moderate prevalence of TB such as Taiwan is strongly suggested.