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Introduction: Tuberculosis (TB) is still a major contributor to the global health burden. Pulmonary TB can lead to life-threatening respiratory failure necessitating extracorporeal membrane oxygenation (ECMO) therapy. However, data on ECMO experience in the management of TB patients are scarce., Methods: We conducted a systematic review of the literature using the search terms ECMO, extracorporeal membrane oxygenation, TB and tuberculosis in three databases (Medline, Web of Science and EMBASE). Clinical data were extracted by two independent investigators. Clinical parameters, such as mode of ECMO therapy, duration of treatment and clinical outcomes, were assessed., Results: Overall, 43 patients from 15 countries were included in the analysis. The age ranged from 0 to 65 years, 39.5% were male, and 60.5% were female. The majority of patients suffered from ARDS (83.4%), with a mean Horovitz quotient of 68.1 (range 30.0-131.0). 83.7% received VV-ECMO, and 24.3% received VA-ECMO. Coinfections and complications were frequently observed (45.5% and 48.6% respectively). At the end of the respective observation period, the overall outcome was excellent, with 81.4% survival., Discussion: ECMO therapy in TB patients appears to be a feasible therapeutic option, providing a bridge until antimycobacterial therapy takes effect. As the underlying cause is reversible, we advocate for the evaluation of ECMO usage in these patients with acute cardiac or respiratory failure., (© 2024. The Author(s).)

Post Tuberculosis lung disease (PTLD) and post tuberculosis sequelae is a global and poorly recognized problem, amplified by social factors and immunocompromising conditions, inadequate treatment, lack of effective prevention of tuberculosis (TB) infection and disease. As a disease, it remained until recently poorly defined, with studies heterogenous with regards to regions, population demographics, risk factors, cohort sizes, and methods. Pathophysiologically, even successfully treated pulmonary TB disease has sequelae i.e. involving central and peripheral airways, lung parenchyma and pleura, resulting in airway narrowing and dilatation, fibrocavitation and emphysema, pulmonary vascular changes as well as pleural fibrosis. Functionally patients have airflow limitation, restrictive disease or a mixture of both not rarely associated with respiratory, or even ventilatory failure. Quality of life is often impaired through disability, TB relapse, superinfections and through increased susceptibility to reinfection and persistent inflammation, leading to progressive lung function decline and an increased risk of cardiovascular disease and cancer. Premature mortality due to PTLD is very likely, but poorly described., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Introduction: Pulmonary infections, such as tuberculosis, can result in numerous pleural complications including empyemas, pneumothoraces with broncho-pleural fistulas, and persistent air leak (PAL). While definitive surgical interventions are often initially considered, management of these complications can be particularly challenging if a patient has an active infection and is not a surgical candidate., Case Presentation: Autologous blood patch pleurodesis and endobronchial valve placement have both been described in remedying PALs effectively and safely. PALs due to broncho-pleural fistulas in active pulmonary disease are rare, and we present two such cases that were managed with autologous blood patch pleurodesis and endobronchial valves., Conclusion: The two cases presented illustrate the complexities of PAL management and discuss the treatment options that can be applied to individual patients., (© 2024 S. Karger AG, Basel.)

Introduction: Lymphobronchial tuberculosis (TB) is common in children with primary TB and enlarged lymph nodes can cause airway compression of the large airways. If not treated correctly, airway compression can result in persistent and permanent parenchymal pathology, as well as irreversible lung destruction. Bronchoscopy was originally used to collect diagnostic samples; however, its role has evolved, and it is now used as an interventional tool in the diagnosis and management of complicated airway disease. Endoscopic treatment guidelines for children with TB are scarce., Areas Covered: The role of interventional bronchoscopy in the diagnosis and management of complicated pulmonary TB will be discussed. This review will provide practical insights into how and when to perform interventional procedures in children with complicated TB for both diagnostic and therapeutic purposes. This discussion incorporates current scientific evidence and refers to adult literature, as some of the interventions have only been done in adults but may have a role in children. Limitations and future perspectives will be examined., Expert Opinion: Pediatric pulmonary TB lends itself to endoscopic interventions as it is a disease with a good outcome if treated correctly. However, interventions must be limited to safeguard the parenchyma and prevent permanent damage.

With the ageing of the population, the incidence of pulmonary tuberculosis in the elderly has peaked. Elderly patients with pulmonary tuberculosis are easily misdiagnosed. In terms of treatment, the elderly are characterized by low success rate of treatment and high mortality. In particular, elderly pulmonary tuberculosis patients who are not detected in time and treated effectively, are the source of infection in places where people congregate, such as nursing homes and hospitals. The seriousness of pulmonary tuberculosis in elderly deserves greater recognition from the medical staff, especially respiratory physicians, infectious disease physicians and geriatricians. It is important to formulate and implement expert consensus on diagnosis and treatment of elderly pulmonary tuberculosis in accordance with China's national conditions in order to improve the early diagnosis rate of elderly pulmonary tuberculosis in China, standardize the treatment plan, improve the treatment outcome and to reduce the risk of transmission. This consensus covers the definition, epidemiology, immune status, risk factors, diagnosis and treatment of pulmonary tuberculosis in the elderly, and provides 20 recommendations for clinicians.

Objectives: To evaluate the outcomes of bronchial artery embolization (BAE) for the treatment of massive hemoptysis in patients with pulmonary tuberculosis and identify risk factors that influence recurrence., Methods: A total of 81 patients with massive hemoptysis who underwent BAE between January 2014 and December 2017 were retrospectively reviewed. All of the patients had either a history of pulmonary tuberculosis or a current diagnosis of pulmonary tuberculosis. Follow-up ranged from 18 to 66 months., Results: Hemoptysis was stopped or markedly decreased, with subsequent clinical improvement in 73 patients, while 11 patients experienced recurrence during the follow-up period. Systemic-pulmonary shunts and clinical failure showed a statistically significant correlation with the recurrence rate. The cumulative non-recurrence rate was 95.3% for 3 months and 81.9% for more than 24 months. Complications were common (12.5%), but self-limiting., Conclusions: BAE is a safe and effective treatment option for the control of massive hemoptysis in pulmonary tuberculosis patients. Systemic-pulmonary shunts and clinical failure are the risk factors for recurrence., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Anxiety and depression are two common psychological disorders in patients with pulmonary tuberculosis. We aimed to explore the effects of cognitive-behavioral therapy (CBT) on psychological stress and quality of life in patients with pulmonary tuberculosis., Methods: From September 2018 to November 2018, 20 communities (461 participants in total) were randomly assigned in an intervention or control group following a two-level cluster random design. The intervention group underwent CBT for 2 months, whereas the control group received routine follow-up. Anxiety, depression, and quality of life were assessed using the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder questionnaire (GAD-7), and 36-Item Short-Form Health Survey (SF-36) scales, respectively. Comparisons between the two groups were conducted using independent samples t-tests, and differences between the two groups before and after treatment were analyzed using paired samples t-tests., Results: There were a total of 454 participants in the final analysis. After 2 months of CBT intervention, the CBT group had a GAD-7 score that was 1.72 lower than the control group (1.47-1.99, p < 0.001), a PHQ-9 score of the CBT group that was 2.05 lower than that of the control group (1.74-2.37, p < 0.001). The CBT group had a total SF-36 score that was 10.7 lower than that of the control group (95% CI: 7.9-13.5, p < 0.001). In patients with different degrees of anxiety and depression, only those in the intervention group who had mild and moderate anxiety and depression symptoms showed a significant reduction in anxiety and depression scores following the intervention., Conclusions: CBT can relieve anxiety, and depression symptoms and increase the quality of life in subjects with pulmonary tuberculosis., Trials Registration: ChiCTR-TRC-12001958 Date of Registration: 22/02/2012., (© 2022. The Author(s).)

Objective: To analyze the medical care seeking of local and non-local pulmonary tuberculosis (TB) patients in Beijing from 2016 to 2021 and provide evidence for TB prevention and control in Beijing. Methods: The reported pulmonary TB data from 2016 to 2021 were collected from tuberculosis management information system and standard code management system of Chinese information system for disease control and prevention. The map data were obtained from the Institute of Geographic Sciences and Natural Resources Research. Excel 2016, SPSS 19.0, Python 3.9 and ArcGIS 10.6 softwares were used for data analysis and visualization for the inter-provincial mobility and inter-district mobility of pulmonary TB patient's medical care seeking in Beijing. Results: Among the reported pulmonary TB patients in Beijing from 2016 to 2021, 35.27%(24 307/68 926) were from 30 provinces (autonomous regions, municipalities) and Xinjiang Production and Construction Corps. The top 5 provinces with pulmonary TB patients medical care seeking in Beijing were Hebei (39.58%,9 620/24 307), Shanxi (8.82%,2 145/24 307), Inner Mongolia Autonomous Region (8.66%,2 105/24 307), Heilongjiang (6.95%,1 690/24 307) and Henan (6.88%,1 672/24 307). Patients from these 5 provinces accounted for 70.89% (17 232/24 307) of total pulmonary TB patients from other provinces. The pulmonary TB patients from other provinces mainly flowed to Tongzhou district of Beijing, accounting for 46.72% (11 356/24 307). These pulmonary TB patients mainly visited grade Ⅲ (A) hospitals, such as Beijing Chest Hospital of Capital Medical University with the highest proportion of 44.76% (10 880/24 307). Among pulmonary TB patients with current residence in Beijing, those sought medical care in other districts accounted for 55.06% (24 566/44 619). The outflow and inflow of TB cases' medical care seeking occurred in 16 districts of Beijing. The median proportion of cross district medical care seeking in 16 districts was 59.30% (56.05%, 65.13%). The inflow of the medical care seeking in Tongzhou, Haidian and Xicheng district was greater than the outflow, and the outflow was greater than the inflow in the other 13 districts. The pulmonary TB patients in Beijing mainly went to Beijing Chest Hospital in Tongzhou for medical care seeking, accounting for 42.18%(18 822/44 619). Conclusions: The proportions of non-local pulmonary TB patients seeking medical care in Beijing from 2016 to 2021 and local pulmonary TB patients seeking medical care in other districts in Beijing were high, and the hospitals where non-local pulmonary TB patients and local pulmonary TB patients sought medical care respectively belonged to grade Ⅲ (A) and municipal designated medical institutions of TB.

Tuberculosis (TB) has been for many years a major public health problem since treatment is long and sometimes ineffective favoring the increase of multidrug-resistant mycobacteria (MDR-TB). Gene therapy is a novel and effective tool to regulate immune responses. In this study we evaluated the therapeutic effect of an adenoviral vector codifying osteopontin (AdOPN), a molecule known for their roles to favor Th1 and Th17 type-cytokine expression which are crucial in TB containment. A single dose of AdOPN administration in BALB/c mice suffering late progressive pulmonary MDR-TB produced significant lower bacterial load and pneumonia, due to higher expression of IFN-γ, IL-12, and IL-17 in coexistence with increase of granulomas in number and size, resulting in higher survival, in contrast with mice treated with the control adenovirus that codify the green fluorescent protein (AdGFP). Combined therapy of AdOPN with a regimen of second line antibiotics produced a better control of bacterial load in lung during the first days of treatment, suggesting that AdOPN can shorten chemotherapy. Taken together, gene therapy with AdOPN leads to higher immune responses against TB infection, resulting in a new potential treatment against pulmonary TB that can co-adjuvant chemotherapy.

Hemoptysis is a crucial entity taking into account its morbidity and mortality. Pulmonary tuberculosis is the leading cause for massive hemoptysis in our part of the world, which if left untreated may be life threatening. We present a case of a 37-year-old male patient with pulmonary tuberculosis with concurrent pulmonary thromboembolism presenting with massive hemoptysis, which was successfully managed with Bronchial Artery Embolization. This case represents that this measure can be a viable therapeutic choice for a patient with a severe lifethreatening hemoptysis, particularly when other treatment options are unavailable or ineffective.

Background: Tuberculosis (TB) diagnosis and treatment delays increase the period of infectiousness, making TB control difficult and increasing the fatality rates. This study aimed to determine the evolution of health care service delay (time between the patient's first contact with the health service and the diagnosis/start of treatment) and patient delay (time between onset symptoms date and the date of first contact with health services) for Pulmonary Tuberculosis (PTB) in Portugal between 2008 and 2017 across different regions, age groups and gender., Methods: An exploratory analysis was performed, trends of both delays were studied, and 36 months forecasts were generated. We used the permutation test to test differences between groups and the Seasonal and Trend decomposition using Loess (STL) method and Autoregressive Integrated Moving Average (ARIMA) models for forecasting for both Health and Patient delays. We used data from notified PTB cases in mainland Portugal between 2008 and 2017, provided by the national surveillance system., Results: Health delays remained relatively constant while patient delays increased. Females had significantly higher health delays in some regions. Individuals older than 64 had higher health delays than younger individuals, while patient delay for working-age individuals between 15 and 64 years old, presents higher patient delay., Conclusions: Forecasts presage that the upward trend of the delays is unlikely to fall in the coming years. It is important to understand the evolution of the delays and predict how these will evolve. Our understanding of the delays behaviours will contribute to better health policies and resources allocation., (© 2022. The Author(s).)

This study evaluated the effects of simulated laughter therapy on physical symptoms, pulmonary function, depression, and health-related quality of life (HRQOL) among pulmonary tuberculosis patients. This quasi-experimental study assigned tuberculosis patients of hospital A to a laughter group (n = 26) and those of hospital B to a control group (n = 26). The eight-week laughter therapy, held twice a week in a 60-min group session, included laughter, entertainment, music-related chorusing, breathing exercises, and meditation. The values of physical symptoms, pulmonary function, depression, and HRQOL from before and after the therapy were analyzed using the paired t-test and the Mann−Whitney U-test. To verify group differences between the experiment and control group, the Wilcoxon signed-rank test and the analysis of covariance (ANCOVA) were employed. Unlike the control group, laughter therapy decreased physical symptoms (t = 7.30, p < 0.01) and increased pulmonary function (t = −3.77, p < 0.01). Psychological health also improved, including depression (t = 10.46, p < 0.01) and HRQOL (t = −9.31, p < 0.01) in the experimental group but not in the control group. Group differences of changes in physical symptoms, pulmonary function, depression, and HRQOL were also significant. Simulated laughter therapy can help moderate depression and physical symptoms and enhance pulmonary function among tuberculosis patients.

Background: Improving the health self-management level of patients with tuberculosis (TB) is significant for reducing drug resistance, improving the cure rate, and controlling the prevalence of TB. Mobile health (mHealth) interventions based on behavioral science theories may be promising to achieve this goal., Objective: This study aims to explore and conduct an mHealth intervention based on the Integrated Theory of Health Behavior Change (ITHBC) in patients with pulmonary TB to increase their ability of self-care management., Methods: A prospective randomized controlled study was conducted from May to November 2020. A total of 114 patients who were admitted consecutively to the TB clinic of Harbin Chest Hospital, China from May 2020 to August 2020 were recruited by convenience sampling. Patients were divided into the control group and intervention group, and all received a 3-month intervention. Patients in the intervention group and the control group received routine medical and nursing care in the TB clinic, including the supervision of their medications. In addition, pharmacist-assisted mHealth (WeChat) intervention based on the ITHBC theory about TB management was provided to the intervention group. The primary outcome was self-management behavior, while the secondary outcomes were TB awareness, self-efficacy, social support, and degree of satisfaction with health education. The outcomes were measured using web-based self-designed and standard questionnaires administered at baseline and at the end point of the study. Intergroup data were assessed using the Mann-Whitney U test, whereas intragroup data were assessed with the Wilcoxon test (for paired samples)., Results: A total of 112 patients (59 in intervention group and 53 in control group) completed the study. After the intervention, a statistically significant increase was noted in the scores of each item of self-care management behaviors compared with the scores at the baseline (P<.001) in the intervention group. The scores of all self-care management behaviors of the control group were lower than those of all self-care management behaviors in the intervention group (all P<.05), except for the item "cover your mouth and nose when coughing or sneezing" (P=.23) and item "wash hands properly" (P=.60), which had no statistically significant difference from those in the intervention group. Compared with those at baseline, TB knowledge awareness, self-efficacy, social support, and degree of satisfaction with health education in the intervention group increased significantly (P<.001), and the intervention group had significantly higher scores than the control group (P<.001)., Conclusions: mHealth intervention for TB self-management based on ITHBC could deepen the understanding of patients with TB about their disease and improve their objective initiative and self-care management behaviors, which were beneficial for promoting compliance behavior and quality of prevention and control for pulmonary TB., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200055557; https://tinyurl.com/4ray3xnw., (©Yuhan Bao, Chunxiang Wang, Haiping Xu, Yongjie Lai, Yupei Yan, Yuanyuan Ma, Ting Yu, Yibo Wu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 14.07.2022.)

Background: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea., Methods: We systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as 'before-pandemic' and 'during-pandemic' based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment., Results: Proportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715-1.094)., Conclusion: The COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic's impact on the national TB control project., Competing Interests: All authors have no potential conflicts of interest., (© 2022 The Korean Academy of Medical Sciences.)

Background: People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest., Design and Methods: An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation., Discussion: Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV., Competing Interests: The authors have declared that no competing interests exist.

Background: Understanding health delivery service from a patient´s perspective, including factors influencing healthcare seeking behaviour, is crucial when treating diseases, particularly infectious ones, like tuberculosis. This study aims to trace and contextualise the trajectories patients pursued towards diagnosis and treatment, while discussing key factors associated with treatment delays. Tuberculosis patients' pathways may serve as indicator of the difficulties the more vulnerable sections of society experience in obtaining adequate care., Methods: We conducted 27 semi-structured interviews with tuberculosis patients attending a treatment centre in a suburban area of Lisbon. We invited nationals and migrant patients in active treatment to participate by sharing their illness experiences since the onset of symptoms until the present. The Health Belief Model was used as a reference framework to consolidate the qualitative findings., Results: By inductive analysis of all interviews, we categorised participants' healthcare seeking behaviour into 4 main types, related to the time participants took to actively search for healthcare (patient delay) and time the health system spent to diagnose and initiate treatment (health system delay). Each type of healthcare seeking behaviour identified (inhibited, timely, prolonged, and absent) expressed a mindset influencing the way participants sought healthcare. The emergency room was the main entry point where diagnostic care cascade was initiated. Primary Health Care was underused by participants., Conclusions: The findings support that healthcare seeking behaviour is not homogeneous and influences diagnostic delays. If diagnostic delays are to be reduced, the identification of behavioural patterns should be considered when designing measures to improve health services' delivery. Healthcare professionals should be sensitised and perform continuous capacity development training to deal with patients´ needs. Inhibited and prolonged healthcare seeking behaviour contributes significantly to diagnostic delays. These behaviours should be detected and reverted. Timely responses, from patients and the healthcare system, should be promoted., Competing Interests: The authors have declared that no competing interests exist.

Background: Loss to follow-up (LTFU) among pulmonary tuberculosis (PTB) patients is a significant challenge for TB control. However, there is a dearth of information about the factors leading to LTFU among marginalized communities. This study highlights the factors associated with LTFU in Saharia, a tribe of Madhya Pradesh having high tuberculosis (TB) prevalence., Methods: A qualitative study was carried out during January-April 2020 among twenty-two pulmonary TB patients, recorded as LTFU in NIKSHAY, with ten treatment supporters and ten patient's family members. Semi-structured personal interview tools were used to collect the information on the history of anti-tuberculosis treatment, adverse drug events (ADE), social cognitive, behaviors, myths, and misbeliefs. The interviews were transcribed and thematically analysed to examine underlying themes., Results: The study explored various social, behavioral factors leading to loss to follow-up among PTB patients. Drug side effects, alcoholism, social stigma, lack of awareness of the seriousness of the diseases and poor counseling are the main barriers to treatment adherence in this community., Conclusions: The study highlights the need to address the issues related to LTFU during TB treatment. The enhanced efforts of treatment supporters, health staff, and family & community persons must motivate and support the patients., Competing Interests: The authors have declared that no competing interests exist.

The WHO's "Global tuberculosis report 2020" lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 10 8 ) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo , regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy., Clinical Trial Registration: (https://clinicaltrials.gov/ct2/results?cond=&term=NCT03575299&cntry=&state=&city=&dist=) ( NCT03575299)., Competing Interests: The authors ML and LiL were employed by Guangdong GD Kongming Biotech Ltd. The remaining 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 © 2021 Liang, Fu, Li, Chen, Wang, Lin, Zhang, Xu, Qin, Liu, Wang, Hao, Liu, Zhang, Lin, Alnaggar, Zhou, Zhou, Guo, Wang, Liu, Deng, Zhang, Wu and Yin.)

Introduction: To investigate the effectiveness of the case management mode on the application of smear-positive pulmonary tuberculosis patients., Methodology: This was a randomized control trial. A total of 70 newly diagnosed smear-positive pulmonary tuberculosis patients were recruited and been randomly divided into experimental group and control group, with 35 participants in each group. In the experimental group, patients received the tuberculosis case management mode based on the conventional management mode. In the control group, patients received the routine management mode. We compared the knowledge, attitude, and practice score; sputum-negative conversion rate, effective imaging rate of the two groups at the time of initial admission, discharge, and one month after discharge., Results: The results showed that there was no significant difference in baseline data between the two groups (p > 0.05); at the time of discharge and one month after discharge, the knowledge, belief, behavior, sputum-negative conversion rate, and imaging examination effective rate of the experimental group were higher than those of the control group (p < 0.05)., Conclusions: The case management mode can improve the knowledge, attitude, and practice level; sputum-negative conversion rate; and imaging efficiency of newly treated smear-positive pulmonary tuberculosis patients., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 YanLing Li, Ying Wang, GaiJing Wang, YiLin Wang, YanQing Tian, SiWei Zhu, Jiao Chen, LiLi Diao.)

Background A computer-aided detection (CAD) system may help surveillance for pulmonary metastasis at chest radiography in situations where there is limited access to CT. Purpose To evaluate whether a deep learning (DL)-based CAD system can improve diagnostic yield for newly visible lung metastasis on chest radiographs in patients with cancer. Materials and Methods A regulatory-approved CAD system for lung nodules was implemented to interpret chest radiographs from patients referred by the medical oncology department in clinical practice. In this retrospective diagnostic cohort study, chest radiographs interpreted with assistance from a CAD system after the implementation (January to April 2019, CAD-assisted interpretation group) and those interpreted before the implementation (September to December 2018, conventional interpretation group) of the CAD system were consecutively included. The diagnostic yield (frequency of true-positive detections) and false-referral rate (frequency of false-positive detections) of formal reports of chest radiographs for newly visible lung metastasis were compared between the two groups using generalized estimating equations. Propensity score matching was performed between the two groups for age, sex, and primary cancer. Results A total of 2916 chest radiographs from 1521 patients (1546 men, 1370 women; mean age, 62 years) and 5681 chest radiographs from 3456 patients (2941 men, 2740 women; mean age, 62 years) were analyzed in the CAD-assisted interpretation and conventional interpretation groups, respectively. The diagnostic yield for newly visible metastasis was higher in the CAD-assisted interpretation group (0.86%, 25 of 2916 [95% CI: 0.58, 1.3] vs 0.32%, 18 of 568 [95% CI: 0.20, 0.50%]; P = . 004). The false-referral rate in the CAD-assisted interpretation group (0.34%, 10 of 2916 [95% CI: 0.19, 0.64]) was not inferior to that in the conventional interpretation group (0.25%, 14 of 5681 [95% CI: 0.15, 0.42]) at the noninferiority margin of 0.5% (95% CI of difference: -0.15, 0.35). Conclusion A deep learning-based computer-aided detection system improved the diagnostic yield for newly visible metastasis on chest radiographs in patients with cancer with a similar false-referral rate. © RSNA, 2021 Online supplemental material is available for this article.

Objective: To investigate the effects of health education combined with dietary guidance on nutritional indicators, immune level, and quality of life of patients with pulmonary tuberculosis., Method: A total of 123 patients with pulmonary tuberculosis who were hospitalized to our hospital between October 2019 and October 2020 were chosen for the study and were separated into 60 control cases and 63 observation cases based on the ward they were assigned to. Patients in the two groups were compared in terms of nutritional risk, nutritional indicator levels in serum, immunological function, treatment compliance, sputum culture conversion rate, and quality of life., Result: With the prolongation of patients' illness, the total NRS 2002 score gradually increased in both groups and the total NRS 2002 score of patients in the control group was higher than that of patients in the observation group at the same time point after discharge. The difference between the total NRS 2002 score of patients in both groups was significant at 3 and 6 months after discharge. After the intervention, the Hb, ALB, CD4+, and CD4+/CD8+ levels of patients in both groups were higher than those at the time of admission, and the CD8+ levels were lower than those at the time of admission. At 6 months after discharge, the Hb, ALB, CD4+, and CD4+/CD8+ levels of patients in the observation group were significantly higher than those in the control group, and the CD8+ levels were significantly lower than those in the control group. The treatment compliance rate of patients in the observation group (96.83%) was significantly higher than that of the control group (75%), and the negative sputum culture transfer rate (85.71%) was significantly higher than that in the control group (60%). The overall quality of life scores of patients in the observation group was significantly higher than that in the control group., Conclusion: Health education combined with dietary guidance for patients with pulmonary tuberculosis can deepen patients' understanding of disease and nutritional knowledge, improve treatment compliance, improve their nutritional status, enhance their immune function, accelerate sputum bacterial conversion, enhance treatment effect, and improve their quality of life., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Baojuan Hu et al.)

Competing Interests: Competing interests The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests are here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

Abstract: Smear-positive pulmonary tuberculosis (SPPTB) is the major contributor to the spread of tuberculosis (TB) infection, and it creates high morbidity and mortality worldwide. The objective of this study was to determine the predictors of delayed sputum smear conversion at the end of the intensive phase of TB treatment in Kota Kinabalu, Malaysia.This retrospective study was conducted utilising data of SPPTB patients treated in 5 TB treatment centres located in Kota Kinabalu, Malaysia from 2013 to 2018. Pulmonary TB (PTB) patients included in the study were those who had at least completed the intensive phase of anti-TB treatment with sputum smear results at the end of the 2nd month of treatment. The factors associated with delayed sputum smear conversion were analyzed using multiple logistic regression analysis. Predictors of sputum smear conversion at the end of intensive phase were evaluated.A total of 2641 patients from the 2013 to 2018 periods were included in this study. One hundred eighty nine (7.2%) patients were identified as having delayed sputum smear conversion at the end of the intensive phase treatment. Factors of moderate (advanced odd ratio [aOR]: 1.7) and advanced (aOR: 2.7) chest X-ray findings at diagnosis, age range of >60 (aOR: 2.1), year of enrolment 2016 (aOR: 2.8), 2017 (aOR: 3.9), and 2018 (aOR: 2.8), smokers (aOR: 1.5), no directly observed treatment short-course (DOTS) supervisor (aOR: 6.9), non-Malaysian citizens (aOR: 1.5), and suburban home locations (aOR: 1.6) were associated with delayed sputum smear conversion at the end of the intensive phase of the treatment.To improve sputum smear conversion success rate, the early detection of PTB cases has to be fine-tuned so as to reduce late or severe case presentation during diagnosis. Efforts must also be in place to encourage PTB patients to quit smoking. The percentage of patients assigned with DOTS supervisors should be increased while at the same time ensuring that vulnerable groups such as those residing in suburban localities, the elderly and migrant TB patients are provided with proper follow-up treatment and management., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Delayed tuberculosis diagnosis and treatment increase morbidity, mortality, expenditure, and transmission in the community. Early diagnosis and initiation of treatment are essential for effective TB control. Therefore, the main objective of this study was to assess the magnitude and factors associated with patient delay among tuberculosis patients in Gamo Zone, Southern Ethiopia., Methods: A cross-sectional study was conducted in Gamo Zone, Southern Ethiopia from February to April 2019. Fifteen health facilities of the study area were selected randomly and 255 TB patients who were ≥18 years of age were included. Data were collected using a questionnaire through face-to-face interviews and analyzed using SPSS version 20.0. Patient delay was analyzed using the median as the cut-off value. Multivariable logistic regression analysis was fitted to identify factors associated with patient delay. A p-value of ≤ 0.05 with 95% CI was considered to declare a statistically significant association., Results: The median (inter-quartile range) of the patient delay was 30 (15-60) days. About 56.9% of patients had prolonged patients' delay. Patient whose first contact were informal provider (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI] 1.29, 3.86), presenting with weight loss (AOR: 2.53; 95%CI: 1.35, 4.74) and fatigue (AOR: 2.38; 95%CI: 1.36, 4.17) and body mass index (BMI) categories of underweight (AOR: 1.74; 95%CI: 1.01, 3.00) were independently associated with increased odds of patient delay. However, having good knowledge about TB (AOR: 0.44; 95% CI: 0.26, 0.76) significantly reduce patients' delay., Conclusion: In this study, a significant proportion of patients experienced more than the acceptable level for the patient delay. Knowledge about TB, the first action to illness, presenting symptoms, and BMI status were identified factors associated with patient delay. Hence, raising public awareness, regular training, and re-training of private and public healthcare providers, involving informal providers, and maintenance of a high index of suspicion for tuberculosis in the vulnerable population could reduce long delays in the management of TB., Competing Interests: The authors have declared that no competing interests exist.

There is a crucial need for non-sputum-based TB tests. Here, we evaluate the performance of RISK6, a human-blood transcriptomic signature, for TB screening, triage and treatment monitoring. RISK6 performance was also compared to that of two IGRAs: one based on RD1 antigens (QuantiFERON-TB Gold Plus, QFT-P, Qiagen) and one on recombinant M. tuberculosis HBHA expressed in Mycobacterium smegmatis (IGRA-rmsHBHA). In this multicenter prospective nested case-control study conducted in Bangladesh, Georgia, Lebanon and Madagascar, adult non-immunocompromised patients with bacteriologically confirmed active pulmonary TB (ATB), latent TB infection (LTBI) and healthy donors (HD) were enrolled. ATB patients were followed-up during and after treatment. Blood RISK6 scores were assessed using quantitative real-time PCR and evaluated by area under the receiver-operating characteristic curve (ROC AUC). RISK6 performance to discriminate ATB from HD reached an AUC of 0.94 (95% CI 0.89-0.99), with 90.9% sensitivity and 87.8% specificity, thus achieving the minimal WHO target product profile for a non-sputum-based TB screening test. Besides, RISK6 yielded an AUC of 0.93 (95% CI 0.85-1) with 90.9% sensitivity and 88.5% specificity for discriminating ATB from LTBI. Moreover, RISK6 showed higher performance (AUC 0.90, 95% CI 0.85-0.94) than IGRA-rmsHBHA (AUC 0.75, 95% CI 0.69-0.82) to differentiate TB infection stages. Finally, RISK6 signature scores significantly decreased after 2 months of TB treatment and continued to decrease gradually until the end of treatment reaching scores obtained in HD. We confirmed the performance of RISK6 signature as a triage TB test and its utility for treatment monitoring.

Background: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4 + T cells ("CD27 - CD4 + " and "CD27 - IFN-γ + CD4 + ") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27 - IFN-γ + CD4 + " cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27 - IFN-γ + CD4 + " cells by Spearman statistical analysis., Results: We observed that the percentages of "CD27 - IFN-γ + CD4 + " cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27 - IFN-γ + CD4 + " cells was negatively correlated with WBC (white blood cell count) (r = - 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27 - IFN-γ + CD4 + " cells were significantly decreased, especially in the > 50 years group, after clinical treatment., Conclusion: The present results demonstrated that the percentage of "CD27 - IFN-γ + CD4 + " cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.

Background: A rapid, blood-based triage test that allows targeted investigation for tuberculosis at the point of care could shorten the time to tuberculosis treatment and reduce mortality. We aimed to test the performance of a host blood transcriptomic signature (RISK11) in diagnosing tuberculosis and predicting progression to active pulmonary disease (prognosis) in people with HIV in a community setting., Methods: In this prospective diagnostic and prognostic accuracy study, adults (aged 18-59 years) with HIV were recruited from five communities in South Africa. Individuals with a history of tuberculosis or household exposure to multidrug-resistant tuberculosis within the past 3 years, comorbid risk factors for tuberculosis, or any condition that would interfere with the study were excluded. RISK11 status was assessed at baseline by real-time PCR; participants and study staff were masked to the result. Participants underwent active surveillance for microbiologically confirmed tuberculosis by providing spontaneously expectorated sputum samples at baseline, if symptomatic during 15 months of follow-up, and at 15 months (the end of the study). The coprimary outcomes were the prevalence and cumulative incidence of tuberculosis disease confirmed by a positive Xpert MTB/RIF, Xpert Ultra, or Mycobacteria Growth Indicator Tube culture, or a combination of such, on at least two separate sputum samples collected within any 30-day period., Findings: Between March 22, 2017, and May 15, 2018, 963 participants were assessed for eligibility and 861 were enrolled. Among 820 participants with valid RISK11 results, eight (1%) had prevalent tuberculosis at baseline: seven (2·5%; 95% CI 1·2-5·0) of 285 RISK11-positive participants and one (0·2%; 0·0-1·1) of 535 RISK11-negative participants. The relative risk (RR) of prevalent tuberculosis was 13·1 times (95% CI 2·1-81·6) greater in RISK11-positive participants than in RISK11-negative participants. RISK11 had a diagnostic area under the receiver operating characteristic curve (AUC) of 88·2% (95% CI 77·6-96·7), and a sensitivity of 87·5% (58·3-100·0) and specificity of 65·8% (62·5-69·0) at a predefined score threshold (60%). Of those with RISK11 results, eight had primary endpoint incident tuberculosis during 15 months of follow-up. Tuberculosis incidence was 2·5 per 100 person-years (95% CI 0·7-4·4) in the RISK11-positive group and 0·2 per 100 person-years (0·0-0·5) in the RISK11-negative group. The probability of primary endpoint incident tuberculosis was greater in the RISK11-positive group than in the RISK11-negative group (cumulative incidence ratio 16·0 [95% CI 2·0-129·5]). RISK11 had a prognostic AUC of 80·0% (95% CI 70·6-86·9), and a sensitivity of 88·6% (43·5-98·7) and a specificity of 68·9% (65·3-72·3) for incident tuberculosis at the 60% threshold., Interpretation: RISK11 identified prevalent tuberculosis and predicted risk of progression to incident tuberculosis within 15 months in ambulant people living with HIV. RISK11's performance approached, but did not meet, WHO's target product profile benchmarks for screening and prognostic tests for tuberculosis., Funding: Bill & Melinda Gates Foundation and the South African Medical Research Council., Competing Interests: Declaration of interests AP-N, GW, GC, TJS, and MH report grants from the Bill & Melinda Gates Foundation during the conduct of the study. AP-N and GW report grants from the South African Medical Research Council during the conduct of the study. GW and TJS report grants from the South African National Research Foundation during the conduct of the study. AP-N and TJS have patents of the RISK11 and RISK6 signatures pending. GW has had a patent (tuberculosis diagnostic markers; PCT/IB2013/054377) issued and a patent (method for diagnosing tuberculosis; PCT/IB2017/052142) pending. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. ATRA treatment decreases MDSC frequency, but fails to mature MDSCs to non-suppressive, terminally differentiated myeloid cells and does not restore T-cell function or cytokine production in the presence of MDSCs. The impact of ATRA treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Increased intake of vegetables and fruits has been associated with reduced risk of tuberculosis infection. Vegetables and fruits exert immunoregulatory effects; however, it is not clear whether vegetables and fruits have an adjuvant treatment effect on tuberculosis. Between 2009 and 2013, a hospital-based cohort study was conducted in Linyi, Shandong Province, China. Treatment outcome was ascertained by sputum smear and chest computerised tomography, and dietary intake was assessed by a semi-quantitative FFQ. The dietary questionnaire was conducted at the end of month 2 of treatment initiation. Participants recalled their dietary intake of the previous 2 months. A total of 2309 patients were enrolled in this study. After 6 months of treatment, 2099 patients were successfully treated and 210 were uncured. In multivariate models, higher intake of total vegetables and fruits (OR 0·70; 95 % CI 0·49, 0·99), total vegetables (OR 0·68; 95 % CI 0·48, 0·97), dark-coloured vegetables (OR 0·61; 95 % CI 0·43, 0·86) and light-coloured vegetables (OR 0·67; 95 % CI 0·48, 0·95) were associated with reduced failure rate of tuberculosis treatment. No association was found between total fruit intake and reduced failure rate of tuberculosis treatment (OR 0·98; 95 % CI 0·70, 1·37). High intake of total vegetables and fruits, especially vegetables, is associated with lower risk of failure of tuberculosis treatment in pulmonary tuberculosis patients. The results provide important information for dietary guidelines during tuberculosis treatment.

No previous studies have examined Mycobacterium avium complex pulmonary disease (MAC-PD) in only elderly patients ⩾75 years old. Here, we investigated the exacerbating factors of MAC-PD in elderly patients and clarified cases that can be followed up without MAC medication. From April 2011 to March 2019, 126 advanced aged patients at our institute were newly diagnosed with MAC-PD, and could be observed based on radiological findings for over a year. Their medical records were retrospectively examined for clinical and radiological findings at the time of diagnosis and 1 year later. To identify the predictors of exacerbation, clinical characteristics of 109 treatment-naïve patients were compared between exacerbated and unchanged groups. Additionally, the unchanged group was followed for one more year. In the current study, positive acid-fast bacilli smears from the sputum test, the presence of cavitary lesions and extensive radiological findings, particularly abnormal shadows in ⩾3 lobes, were predictive of exacerbation among treatment-naïve elderly MAC-PD patients. In the unchanged group, <10% showed exacerbation of radiological findings within the subsequent year. In conclusion, if the sputum smear is negative, no cavitary lesions are present, and abnormal shadows are restricted to ⩽2 lobes, elderly patients with MAC-PD may remain untreated for a few years.

Background: Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment., Methods and Findings: For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness-including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments-was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%-24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%-86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%-14%, N = 2), increasing to 88% at 2 months (95% CI 84%-92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%-16%, N = 1) and 59% (95% CI 47%-70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation., Conclusions: This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment., Trial Registration: Systematic review registration: PROSPERO 85226., Competing Interests: The authors have declared that no competing interests exist.

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.

Background: A therapeutic vaccine that prevents recurrent tuberculosis would be a major advance in the development of shorter treatment regimens. We aimed to assess the safety and immunogenicity of the ID93 + GLA-SE vaccine at various doses and injection schedules in patients with previously treated tuberculosis., Methods: This randomised, double-blind, placebo-controlled, phase 2a trial was conducted at three clinical sites near Cape Town, South Africa. Patients were recruited at local clinics after receiving 4 months of tuberculosis treatment, and screened for eligibility after providing written informed consent. Participants were aged 18-60 years, BCG-vaccinated, HIV-uninfected, and diagnosed with drug-sensitive pulmonary tuberculosis. Eligible patients had completed standard treatment for pulmonary tuberculosis in the past 28 days. Participants were enrolled after completing standard treatment and randomly assigned sequentially to receive vaccine or placebo in three cohorts: 2 μg intramuscular ID93 + 2 μg GLA-SE on days 0 and 56 (cohort 1); 10 μg ID93 + 2 μg GLA-SE on days 0 and 56 (cohort 2); 2 μg ID93 + 5 μg GLA-SE on days 0 and 56 and placebo on day 28 (cohort 3); 2 μg ID93 + 5 μg GLA-SE on days 0, 28, and 56 (cohort 3); or placebo on days 0 and 56 (cohorts 1 and 2), with the placebo group for cohort 3 receiving an additional injection on day 28. Randomisation was in a ratio of 3:1 for ID93 + GLA-SE and saline placebo in cohorts 1 and 2, and in a ratio of 3:3:1 for (2 ×) ID93 + GLA-SE, (3 ×) ID93 + GLA-SE, and placebo in cohort 3. The primary outcomes were safety and immunogenicity (vaccine-specific antibody response and T-cell response). For the safety outcome, participants were observed for 30 min after each injection, injection site reactions and systemic adverse events were monitored until day 84, and serious adverse events and adverse events of special interest were monitored for 6 months after the last injection. Vaccine-specific antibody responses were measured by serum ELISA, and T-cell responses after stimulation with vaccine antigens were measured in cryopreserved peripheral blood mononuclear cells specimens using intracellular cytokine staining followed by flow cytometry. This study is registered with ClinicalTrials.gov, number NCT02465216., Findings: Between June 17, 2015, and May 30, 2016, we assessed 177 patients for inclusion. 61 eligible patients were randomly assigned to receive: saline placebo (n=5) or (2 ×) 2 μg ID93 + 2 μg GLA-SE (n=15) on days 0 and 56 (cohort 1); saline placebo (n=2) or (2 ×) 10 μg ID93 + 2 μg GLA-SE (n=5) on days 0 and 56 (cohort 2); saline placebo (n=5) on days 0, 28 and 56, or 2 μg ID93 + 5 μg GLA-SE (n=15) on days 0 and 56 and placebo injection on day 28, or (3 ×) 2 μg ID93 + 5 μg GLA-SE (n=14) on days 0, 28, and 56 (cohort 3). ID93 + GLA-SE induced robust and durable antibody responses and specific, polyfunctional CD4 T-cell responses to vaccine antigens. Two injections of the 2 μg ID93 + 5 μg GLA-SE dose induced antigen-specific IgG and CD4 T-cell responses that were significantly higher than those with placebo and persisted for the 6-month study duration. Mild to moderate injection site pain was reported after vaccination across all dose combinations, and induration and erythema in patients given 2 μg ID93 + 5 μg GLA-SE in two or three doses. One participant had grade 3 erythema and induration at the injection site. No vaccine-related serious adverse events were observed., Interpretation: Vaccination with ID93 + GLA-SE was safe and immunogenic for all tested regimens. These data support further evaluation of ID93 + GLA-SE in therapeutic vaccination strategies to improve tuberculosis treatment outcomes., Funding: Wellcome Trust (102028/Z/13/Z)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5-71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by - 0.85% (- 0.19 to - 0.52) (p ≤ 0.0001) and - 14% (- 28.22 to - 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05-1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome.

Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are currently the two main causes of death among infectious diseases. There is an increasing number of studies trying to elucidate the interactions between Mycobacterium tuberculosis and SARS-CoV-2. Some of the first case reports point to a worsening of respiratory symptoms in co-infected TB/COVID-19 individuals. However, data from the cohort studies has shown some conflicting results. This study proposes to conduct a systematic review on the current literature on TB/COVID-19 co-infection cohorts, evaluating clinical and epidemiological data, focusing on its implications to the immune system. From an immunological perspective, the TB/COVID-19 co-infection has the potential to converge in a "perfect storm". The disorders induced by each pathogen to the immunomodulation tend to induce an unbalanced inflammatory response, which can promote the progression and worsening of both diseases. Understanding the nature of the interactions between M. tuberculosis and SARS-CoV-2 will be crucial for the development of therapeutic strategies against co-infection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The association of human immunodeficiency virus (HIV) infection with Burkitt lymphoma is related to the presence of Epstein Barr virus infection and the impact of the HIV antigen on the expansion of B-polyclonal cells. In Southeast Europe, the association is rare, and recognizing this is important in the therapeutic decision to increase patient survival rate. The association of HIV with Burkitt lymphoma and tuberculosis is even more rarely described in the literature., Patient Concerns: We present the case of a 40-year-old patient who presented with a 3-week history of fever (max. 38.7 °C), painful axillary swelling on the right side, lumbar pain, gait disorders, headache, and night sweats. Clinical manifestations included marked weight loss (about 30 kg in the last 2 months before his admission)., Diagnosis: A LyCD4 count of 38/μL and a HIV1 viral load of 384,000/mm3, classified the patient into a C3 stage. A biopsy of the right axillary lymph node was performed for suspected ganglionic tuberculosis due to immunodeficiency. Histopathological examination confirmed the diagnosis of Burkitt lymphoma. Cultures on Löwenstein-Jensen medium from sputum harvested at first admission were positive for Mycobacterium tuberculosis., Interventions: Highly active antiretroviral therapy, chemotherapeutic agents for Burkitt lymphoma, anti-tuberculous drug therapy, neurosurgical intervention of spinal cord decompression, and antibiotic therapy of the associated bacterial infection., Outcome: Burkitt lymphoma disseminated rapidly, with central nervous system, spinal cord, osteomuscular, adrenal, and spleen involvement. The evolution under treatment was unfavorable, with patient death occurring 6 months after diagnosis., Conclusions: The association of HIV infection with Burkitt lymphoma and tuberculosis is rare in the highly active antiretroviral therapy (HAART) era, posing prompt and multidisciplinary therapeutic management issues. Similar cases of HIV-TB and Burkitt lymphoma association have been described, but none of the other cases showed the involvement of the central nervous system or of the bilateral adrenal glands., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Micro-nutrients are closely related to pulmonary tuberculosis (PTB). Most patients with PTB suffer from micro-nutrients deficiency. We aimed to evaluate the efficacy of micro-nutrients support on clinical therapy and chronic inflammation in patients with PTB., Methods: We searched Pubmed, Springer link, Web of Science, Cochrane, Wan Fang and CNKI databases for randomised controlled trials (RCTs). The patients with anti-TB treatments were divided into two groups, the control group with nutritional advice or placebo, and the experimental group with micro-nutrients support for more than 2 weeks. Two reviewers conducted data extraction and quality assessment of the studies independently, and ReviewManager 5.2 software was used to input and analyse the data. The dichotomous variable was expressed in the risk ratios (RRS) and 95% CI, the continuous data were expressed in the mean difference (MD) and 95% CI, and the heterogeneity of subgroup was evaluated by I (Kerantzas and Jacobs, Jr., 2017) [2] test., Results: A total of 13 trials (2847 participants) were included. First, micro-nutrients improved sputum smears or culture negative conversion rates (OR 0.16 0.03-0.77, 2.29; MD -2.36, -4.72~-0.01, z = 1.97). Meanwhile, micro-nutrients support increased lymphocytes and decreased leukocytes, neutrophils, CRP and ESR (MD 0.20, 0.06-0.35, z = 2.78; MD -0.42, -0.65~-0.18, z = 3.48; MD -0.66, -1.12~-0.20, z = 2.82). However it had not impact on body weight, MUAC, haemoglobin, albumin or monocytes (p > 0.05)., Conclusion: Micro-nutrients support can reduce chronic inflammation and improve sputum smears or culture conversions to contribute to anti-TB treatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the pattern of tuberculosis (TB) care initiation and risk factors for TB diagnostic delay in The Gambia., Methods: In this cross-sectional study, adult patients diagnosed with pulmonary TB (pTB) in public facilities in the Greater Banjul Area of The Gambia were consecutively recruited from October 2016 to March 2017. Diagnostic delay was defined as >21 days from the onset of at least one symptom suggestive of pTB to diagnosis. Logistic regression analyses were used to investigate risk factors for diagnostic delay., Results: Overall, 216 pTB patients were included in the study; the median (Interquartile Range (IQR)) age was 30 (23-39) years and 167 (77%) were male patients. Of the 216 patients, 110 (50.9%) of them initiated care-seeking in the formal and informal private sector and 181/216 (83.8%) had TB diagnostic delay. The median (IQR) duration from the onset of symptoms to TB diagnosis was 34 (28-56) days. Age groups 18-29 years (aOR 3.2; 95% CI 1.2-8.8 [p = 0.02]) and 30-49 years (aOR 5.1; 95% CI 1.6-16.2 [p = 0.006]) and being employed (aOR 4.2; 95% CI 1.7-10.5 [p = 0.002]) were independent risk factors for TB diagnostic delay., Conclusion: There is considerable TB diagnostic delay in The Gambia, and this is likely to be worsened by the COVID-19 pandemic., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study is aimed at evaluating the clinical application value of RNA simultaneous amplification and testing method for Mycobacterium tuberculosis (SAT-TB) combined with acid-fast staining in the diagnosis and treatment of pulmonary tuberculosis (PTB)., Methods: This paper included 168 suspected and confirmed PTB sufferers admitted to The Sixth People's Hospital of Wenzhou from December 2018 to December 2019, whose sputum was collected and tested using SAT-TB, smear acid-fast staining method, and the BACTEC MGIT 960 system. With the MGIT 960 culture test method as the gold standard, the application value of SAT-TB, acid-fast staining, or SAT-TB combined with acid-fast staining in the diagnosis and treatment of PTB was assessed., Results: With the MGIT 960 culture as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of SAT-TB for the diagnosis of PTB were 57.3%, 92.5%, 84.3%, and 73.5%, respectively. The conformity was 76.8%, and the Kappa value was 0.515, suggesting a statistically significant difference ( χ 2 = 7.314, p < 0.05) and a general consistency degree. Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value of SAT-TB combined with sputum smear acid-fast staining were 81.3%, 86.0%, 88.4%, and 80.8%, respectively, with the MGIT 960 culture still the gold standard. The conformity and Kappa value were 83.9% and 0.672, respectively, showing no statistically significant difference ( χ 2 = 0.438, p > 0.05) and a relatively high consistency degree., Conclusion: SAT-TB combined with acid-fast staining had a similar detection rate to that of the MGIT 960 culture test with a high consistency degree, which could be applied in the diagnosis of PTB efficiently and accurately., Competing Interests: The authors declare that they have no potential conflicts of interest., (Copyright © 2020 Chaochao Qiu et al.)

COVID-19, designated as SARS-CoV-2, has caused millions of infections worldwide, including in patients with concomitant infections. Here, we report two unusual cases of patients with triple infections of SARS-CoV-2, Mycobacterium tuberculosis , and HIV. Both cases were confirmed through microbiological and immunological studies. The acute respiratory phase in both patients was treated with supplemental oxygen. Antituberculosis and antiretroviral therapies were started simultaneously. In 2 weeks, both patients demonstrated clinical improvement and recovery from COVID-19. Our findings suggest that even in cases of triple infection, clinical management together with respiratory therapy contributes to patient survival.

This research mainly aims to develop a generalized cure rate model, estimate the proportion of cured patients and their survival rate, and identify the risk factors associated with infectious diseases. The generalized cure rate model is based on bounded cumulative hazard function, which is a non-mixture model, and is developed using a two-parameter Weibull distribution as the baseline distribution, to estimate the cure rate using maximum likelihood method and real data with R and STATA software. The results showed that the cure rate of tuberculosis (TB) patients was 26.3%, which was higher than that of TB patients coinfected with human immunodeficiency virus (HIV; 23.1%). The non-parametric median survival time of TB patients was 51 months, while that of TB patients co-infected with HIV was 33 months. Moreover, no risk factors were associated with TB patients co-infected with HIV, while age was a significant risk factor for TB patients among the suspected risk factors considered. Furthermore, the bounded cumulative hazard function was extended to accommodate infectious diseases with co-infections by deriving an appropriate probability density function, determining the distribution, and using real data. Governments and related health authorities are also encouraged to take appropriate actions to combat infectious diseases with possible co-infections., Competing Interests: The authors have declared that no competing interest exist.

Background: The co-morbidity of cardiometabolic diseases in patients with Tuberculosis adds a significant burden in current health systems in developing countries including Nepal. The main objective of this study was to explore cardiometabolic risk factors among patients with Tuberculosis., Methods: This was a cross-sectional study conducted among patients with tuberculosis in 12 tuberculosis treatment centers from eight districts of Nepal between May and July 2017. Interviews with participants were conducted using a structured questionnaire and were supplemented by anthropometric measurements and on-site blood glucose tests. Data were analyzed using descriptive and inferential statistics., Results: Among 221 study participants, 138 (62.4%) had new smear-positive pulmonary tuberculosis, 24 (10.9%) had new smear-negative pulmonary tuberculosis and 34 (15.4%) had new extra- pulmonary tuberculosis. Overall, 43.1% of the patients with tuberculosis had at least one cardiometabolic risk factor. The prevalence of at least one cardiometabolic risk factor was more in male than female (47.8% versus 33.8%). Prevalence of tobacco (18.9% versus 4.8%), and alcohol (12.6% versus 6.5%) use was proportionately higher in male compared to female. The prevalence of hypertension (17% vs. 21%) and obesity (11.9% vs. 12.9%) was lower in male compared to females. Female (AOR = 0.47; CI: 0.23-0.94), those from Gandaki Province (AOR = 0.32; CI: 0.13-0.79) and literate (AOR = 0.49; CI: 0.25-0.96) had reduced risk of cardiometabolic disease risk factors., Conclusions: This study highlights the role of gender and socio-demographic characteristics associated with the risk of cardiometabolic diseases in patients with Tuberculosis. The findings from this study can guide medical practitioners and policy makers to consider clinical suspicion, diagnosis and treatment. National treatment guideline can benefit by integrating the management of non-communicable diseases in Tuberculosis treatment centers.

Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrug-resistant and extensively drug-resistant TB is making control of TB more difficult. Mycobacterium bovis bacillus Calmette-Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection. Therefore, TB control may benefit on novel therapeutic options beyond antimicrobial treatment. Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfection. In the last years, the use of donor lymphocytes after hematopoietic stem cell transplantation has emerged as a new strategy in the cure of hematologic malignancies in order to induce graft-versus leukemia and graft-versus-infection effects. Moreover, adoptive therapy has proven to be effective in controlling cytomegalovirus and Epstein-Barr virus reactivation in immunocompromised patients with ex vivo expanded viral antigen-specific T cells. Unconventional T cells are a heterogeneous group of T lymphocytes with limited diversity. One of their characteristics is that antigen recognition is not restricted by the classical major histocompatibility complex (MHC). They include CD1 (cluster of differentiation 1)-restricted T cells, MHC-related protein-1-restricted mucosal-associated invariant T (MAIT) cells, MHC class Ib-reactive T cells, and γδ T cells. Because these T cells are genotype-independent, they are also termed "donor unrestricted" T cells. The combined features of low donor diversity and the lack of genetic restriction make these cells suitable candidates for T cell-based immunotherapy of TB., (Copyright © 2020 La Manna, Orlando, Tamburini, Badami, Dieli and Caccamo.)