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Background: India, with the highest global burden of tuberculosis (TB) and drug-resistant TB, aims to eliminate TB by 2025. Yet, limited evidence exists on drug resistance patterns and retreatment among patients with silico-tuberculosis. This study explores these patterns and assesses the impact of silicosis on TB retreatment in India. Methods: This secondary data analysis stems from a larger retrospective cohort study conducted in Khambhat, Gujarat, between January 2006 and February 2022. It included 138 patients with silico-tuberculosis and 2,610 TB patients without silicosis. Data from the Nikshay TB information portal were linked with silicosis diagnosis reports from the Pneumoconiosis Board using the unique Nikshay ID as the linking variable. Drug-resistant TB was defined as resistance to any anti-TB drug recorded in Nikshay. Retreatment refers to TB patients who have previously undergone anti-TB treatment for one month or more and need further treatment. Recurrent TB denotes patients who were previously declared cured or had completed treatment but later tested positive for microbiologically confirmed TB. Multivariable logistic regression was used to determine the impact of co-prevalent silicosis on drug resistance and retreatment. Results: Patients with silico-tuberculosis showed a higher proportion of retreatment compared to those without silicosis (55% vs. 23%, p < 0.001). Notably, 28% of patients with silico-tuberculosis were recurrent TB cases, compared to 11% among those without silicosis. Regarding drug resistance, the silico-tuberculosis group exhibited a higher rate (6% vs. 3%), largely due to rifampicin resistance (5% vs. 2%, p = 0.022). Co-prevalent silicosis was associated with a 2.5 times greater risk of drug-resistant TB (adjusted OR 2.5, 95% CI, 1.1–5.3; p = 0.021). Additionally, patients with silico-tuberculosis had a fourfold increased risk of retreatment for TB (adjusted OR 4, 95% CI, 3–6; p < 0.001). Conclusions: Co-prevalent silicosis significantly elevates the risk of drug resistance, recurrence, and retreatment among TB patients in India. This study indicates a need for improved treatment protocols and suggests that future research should focus on randomized controlled trials to evaluate appropriate anti-TB regimen and duration of therapy for this high-risk group. Given India's goal to eliminate TB by 2025, addressing the challenges posed by silico-tuberculosis is critical. [ABSTRACT FROM AUTHOR]

Objective To investigate the determinants of linezolid-associated neurological adverse reactions in patients with multidrug-resistant tuberculosis and develop a risk prediction model for such adverse events. Methods A prospective cohort study design was employed to select 120 patients with drug-resistant pulmonary tuberculosis who received a chemotherapy regimen containing linezolid at Guangzhou Chest Hospital from April 2023 to January 2024 as the study population. Clinical data, adverse reactions, and plasma concentration of linezolid were collected during fasting and at 2 hours post-medication. Univariate analysis and multivariate logistic regression were conducted to identify factors influencing linezolid-related neurological adverse reactions. Furthermore, a prediction model for such adverse reactions was developed, and its predictive efficacy and calibration ability were evaluated using ROC analysis. Results Re-treatment (OR = 2.540, P =0.028), coexistence of cavities (OR = 4.092, P = 0.021), anemia (OR = 10.921,P = 0.005), and Cmin 5 0.7665 mg/L (OR = 6.813,P < 0.001) are independent risk factors for the occurrence of linezolid-related neurological adverse reactions. The prediction model, based on these four factors, exhibits an AUC of 0.851 (95% CI:0.774 ~ 0.929), accompanied by a Youden index of 0.590, a sensitivity of 66.7%, and a specificity of 92.3%. Moreover, the prediction model demonstrates excellent calibration ability. (Hosmer-lemeshow X² = 8.719, P = 0.273). Conclusion In MDR/RR-TB patients, the presence of cavitation, retreatment, and anemia may confer a heightened risk of linezolid-related neurological adverse reactions. A risk prediction model incorporating these four indicators demonstrates significant predictive value for the occurrence of such adverse events. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization predicted 10.6 million new tuberculosis cases and 1.5 million deaths in 2022. Tuberculous meningitis, affecting 1% of active TB cases, is challenging to diagnose due to sudden onset, vague symptoms, and limited laboratory tests. Nanopore-targeted sequencing (NTS) is an emerging third-generation sequencing technology known for its sequencing capabilities. We compared its detection efficiency with Xpert, MTB culture, PCR, and AFB smear in cerebrospinal fluid samples to highlight the substantial potential of NTS in detecting intracranial tuberculosis. Methods: This study included 122 patients suspected of having intracranial tuberculosis at the Second Hospital of Nanjing in Jiangsu Province, China, between January 2021 and January 2024. The Univariate logistic regression and random forest regression identified risk factors and clinical markers. A chi-square test evaluated diagnostic accuracy for different image types of intracranial tuberculosis. Results: The research involved 100 patients with intracranial tuberculosis. Among them, 41 had tuberculous meningitis, 27 had cerebral parenchymal tuberculosis, and 32 had mixed intracranial tuberculosis. Besides, 22 patients were diagnosed with other brain conditions. In diagnosing intracranial tuberculosis, NTS demonstrated a sensitivity of 60.0% (95% CI: 49.7-69.5%) and a specificity of 95.5% (95% CI:75.1-99.8%), with an AUC value of 0.78 (95% CI: 0.71 to 0.84), whose overall performance was significantly better than other detection methods. There was no notable difference (P > 0.05) in diagnostic accuracy between NTS and the final diagnosis for intracranial tuberculosis patients with varying imaging types. Furthermore, patients who tested positive had a 31.500 (95% CI: 6.205-575.913) times higher risk of having intracranial tuberculosis compared to those with negative results. Conclusion: Due to its convenience, efficiency, quick turnaround time, and real-time sequencing analysis, NTS might become a promising and reliable method for providing microbiological diagnoses for patients with intracranial tuberculosis and for screening populations at risk. [ABSTRACT FROM AUTHOR]

Despite the achievements of modern medicine, tuberculosis remains one of the leading causes of mortality globally. The difficulties in differential diagnosis have particular relevance in the case of suspicion of tuberculosis with other granulomatous diseases. The most similar clinical and radiologic changes are sarcoidosis. The aim of this study is to apply mathematical modeling to determine diagnostically significant immunological parameters and an algorithm for the differential diagnosis of tuberculosis and sarcoidosis. Materials and methods: The serum samples of patients with sarcoidosis (SD) (n = 29), patients with pulmonary tuberculosis (TB) (n = 32) and the control group (n = 31) (healthy subjects) collected from 2017 to 2022 (the average age 43.4 ± 5.3 years) were examined. Circulating 'polarized' T-helper cell subsets were analyzed by multicolor flow cytometry. A symbolic regression method was used to find general mathematical relations between cell concentrations and diagnosis. The parameters of the selected model were finally fitted through multi-objective optimization applied to two conflicting indices: sensitivity to sarcoidosis and sensitivity to tuberculosis. Results: The difference in Bm2 and CD5−CD27− concentrations was found to be more significant for the differential diagnosis of sarcoidosis and tuberculosis than any individual concentrations: the combined feature Bm2 − [CD5−CD27−] differentiates sarcoidosis and tuberculosis with p < 0.00001 and AUC = 0.823. An algorithm for differential diagnosis was developed. It is based on the linear model with two variables: the first variable is the difference Bm2 − [CD5−CD27−] mentioned above, and the second is the naïve-Tregs concentration. The algorithm uses the model twice and returns "dubious" in 26.7% of cases for patients with sarcoidosis and in 16.1% of cases for patients with tuberculosis. For the remaining patients with one of these two diagnoses, its sensitivity to sarcoidosis is 90.5%, and its sensitivity to tuberculosis is 88.5%. Conclusions: A simple algorithm was developed that can distinguish, by certain immunological features, the cases in which sarcoidosis is likely to be present instead of tuberculosis. Such cases may be further investigated to rule out tuberculosis conclusively. The mathematical model underlying the algorithm is based on the analysis of "naive" T-regulatory cells and "naive" B-cells. This may be a promising approach for differential diagnosis between pulmonary sarcoidosis and pulmonary tuberculosis. The findings may be useful in the absence of clear differential diagnostic criteria between pulmonary tuberculosis and sarcoidosis. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to determine the incidence of TB among immigrants and non-immigrants in Sanliurfa, Türkiye between 2018 and 2022 and to examine the effect of COVID-19 on the incidence, location, and drug resistance patterns of tuberculosis. Methods: This study was a retrospective review of patients diagnosed with tuberculosis in Şanlıurfa Tuberculosis Dispensary between January-2018 and May-2022. Patients were assessed in terms of age, sex, site of tuberculosis, and drug resistance profiles before and during the COVID-19 pandemic. Results: A total of 887 patients with TB were included in the study. The mean age of patients diagnosed with tuberculosis was 40.63 ± 17.50 years. Of the total number of patients diagnosed, 50.7% were women, 85.8% were Turkish citizens, and 91.9% were new cases. Comparing the rate of positive cultures between the pre-COVID-19 and COVID-19 periods revealed a statistically significant rate of positive culture during the COVID-19 period (p < 0.001). In terms of mortality, the mean age of the patients who died was 60.2 ± 18.4 years and that of the survivors was 39.1 ± 16.6 years; these values were statistically significant (p < 0.001). Among the patients who survived, the rate of pulmonary tuberculosis was statistically significantly higher than that of extrapulmonary tuberculosis (p < 0.001). Conclusion: The prevalence of pulmonary TB is high and the proportion of women is increasing. During the COVID-19 period, the number of patients diagnosed with TB decreased, but interestingly, the rate of positive cultures remained high, and the rate of resistance to INH also decreased. The results revealed rates similar to those reported by the World Health Organization. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is leading cause of morbidity and mortality worldwide. However, this endemic disease rarely involves heart. Cardiac TB can involve any structure of heart with pericarditis is most frequent manifestation. Methods: This retrospective study was conducted at Department of Pathology from January 2012 to December 2020. Autopsy records of all cases suggestive of tuberculosis in any part of heart were selected and slides were reviewed. Results: A total of 11 cases of cardiac TB were recorded on autopsy, including 6 cases of isolated myocarditis, 2 cases of myopericarditis 2 cases of isolated pericarditis and one case of necrotizing arteritis in left coronary artery. Concomitant pulmonary TB was present in 72.7% cases. Conclusion: This study highlights that in all patients of pulmonary tuberculosis with appearance of any cardiovascular sign or symptom, cardiac TB should be suspected as one of the differentials. [ABSTRACT FROM AUTHOR]

Providing social support to tuberculosis (TB) patients is a recommended strategy as households having TB patients find themselves in a spiral of poverty because of high cost, huge income loss and several other economic consequences associated with TB treatment. However, there are few examples of social support globally. The Indian government introduced the 'Nikshay Poshan Yojana' scheme in 2018 to provide nutritional support for all registered TB patients. A financial incentive of 500 Indian Rupee (6 United States Dollars) per month was proposed to be transferred directly to the registered beneficiaries' validated bank accounts. We examined the reach, timing, amount of benefit receipt and the extent to which the benefit alleviated catastrophic costs (used as a proxy to measure the impact on permanent economic welfare as catastrophic cost is the level of cost that is likely to result in a permanent negative economic impact on households) by interviewing 1482 adult drug-susceptible TB patients from 16 districts of four states during 2019 to 2023, using the methods recommended by the World Health Organization for estimating household costs of TB nationally. We also estimated the potential amount of social support required to achieve a zero catastrophic cost target. At the end of treatment, 31–54% of study participants received the benefit. In all, 34–60% of TB patients experienced catastrophic costs using different estimation methods and the benefit helped 2% of study participants to remain below the catastrophic cost threshold. A uniform benefit amount of Indian Rupee 10 000 (127 United States Dollars) for 6 months of treatment could reduce the incidence of catastrophic costs by 43%. To improve the economic welfare of TB patients, levels of benefit need to be substantially increased, which will have considerable budgetary impact on the TB programme. Hence, a targeted rather than universal approach may be considered. To maximize impact, at least half of the revised amount should be given immediately after treatment registration. [ABSTRACT FROM AUTHOR]

We describe a 19-year-old indigenous male with no relevant medical history who presented with chronic symptoms of headache, fever, weight loss, blurred vision, and conjunctival mass who was diagnosed with disseminated tuberculosis (TB). Extensive ocular involvement, including multifocal choroiditis and nodular episcleritis, in addition to brain, spinal cord, lung, and gastrointestinal tract involvement were identified. Ocular tuberculosis (OTB) is a rare presentation of extrapulmonary manifestations, with choroiditis being the most common. Nodular episcleritis has been rarely reported in some cases in the literature. This case highlights the importance of suspecting tuberculosis in immunocompetent patients, from endemic countries, with a history of contact with a confirmed case of TB, with associated pulmonary involvement or prolonged episcleritis. [ABSTRACT FROM AUTHOR]

Backgrounds: Most significant findings from the Global Tuberculosis (TB) Report 2023 indicate that India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the Democratic Republic of the Congo (DRC) collectively contribute to approximately two-thirds of global TB cases. This study aims to provide crucial data-driven insights and references to improve TB control measures through a comprehensive analysis of these eight high-burden countries. Methods: The eight high-burden TB countries analyzed in this study include India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the DRC. Age-standardized incidence rates (ASIR) of TB were derived from the Global Burden of Diseases Study 2021 data. Temporal trends were analyzed using Joinpoint regression. An age-period-cohort model was applied to examine the risk ratios (RR) of TB across diverse age groups, periods, and birth cohorts. A Bayesian age-period-cohort framework was employed to predict the ASIR of TB by 2030. Results: The study found that the Philippines (average annual percentage change = 3.1%, P < 0.001) exhibited an upward trend from 1990 to 2021. In India, the Philippines, Pakistan, and Bangladesh, the RR of TB incidence exceeded 1 after individuals reached 25 years old. Notably, the RR has shown a consistent upward trend since 2001, peaking during the period of 2017–2021 with an estimated RR of 1.5 (P < 0.001) in the Philippines. Similarly, the highest RR was observed during the period of 2017–2021 reaching 1.1 (P < 0.001) in the DRC. In the Philippines, the markedly increasing RR values for TB have been observed among individuals born after 1997–2001. Projections suggest that the ASIR of TB is expected to follow a continued upward trajectory, with an estimated rate of 392.9 per 100,000 by 2030 in the Philippines; India and Indonesia are projected to achieve less than 20.0% of the target set by the World Health Organization (WHO). Conclusions: Among the eight high-burden countries, the Philippines, India and Indonesia are diverging from the goals set by the WHO, and the risk of TB in the Philippines and the DRC shows a trend toward affecting younger populations, which suggests that the management strategies for TB patients need to be further strengthened. [ABSTRACT FROM AUTHOR]

Background: Rifampicin-resistant pulmonary tuberculosis (RR-PTB) presents a significant threat to global public health security. China bears a substantial burden of RR-PTB cases globally, with Guizhou Province experiencing particularly alarming trends, marked by a continual increase in patient numbers. Understanding the population characteristics and treatment modalities for RR-PTB is crucial for mitigating morbidity and mortality associated with this disease. Methods: We gathered epidemiological, diagnostic, and treatment data of all RR-PTB cases recorded in Guizhou Province from January 1, 2017 to December 31, 2023. Utilizing composition ratios as the analytical metric, we employed Chi-square tests to examine the spatiotemporal distribution patterns of RR-PTB patients and the evolving trends among different patient classifications over the study period. Results: In our study, 3396 cases of RR-PTB were analyzed, with an average age of 45 years. The number of RR-PTB patients rose significantly from 176 in 2017 to 960 in 2023, peaking notably among individuals aged 23–28 and 44–54, with a rising proportion in the 51–80 age group (P < 0.001). Since 2021, there has been a notable increase in the proportion of female patients. While individuals of Han ethnic group comprised the largest group, their proportion decreased over time (P < 0.001). Conversely, the Miao ethnicity showed an increasing trend (P < 0.05). The majority of patients were farmers, with their proportion showing an upward trajectory (P < 0.001), while students represented 4.33% of the cases. Geographically, most patients were registered in Guiyang and Zunyi, with a declining trend (P < 0.001), yet household addresses primarily clustered in Bijie, Tongren, and Zunyi. The proportion of floating population patients gradually decreased, alongside an increase in newly treated patients and those without prior anti-tuberculosis therapy. Additionally, there was a notable rise in molecular biological diagnostic drug sensitivity (real-time PCR and melting curve analysis) (P < 0.001). However, the cure rate declined, coupled with an increasing proportion of RR-PTB patients lost to follow-up and untreated (P < 0.05). Conclusions: Enhanced surveillance is crucial for detecting tuberculosis patients aged 23–28 and 44–54 years. The distribution of cases varies among nationalities and occupations, potentially influenced by cultural and environmental factors. Regional patterns in RR-PTB incidence suggest tailored prevention and control strategies are necessary. Despite molecular tests advances, challenges persist with low cure rates and high loss to follow-up. Strengthening long-term management, resource allocation, and social support systems for RR-PTB patients is essential. [ABSTRACT FROM AUTHOR]

Background: Pyrazinamide (PZA) usage has been associated with adverse drug reactions, prompting its avoidance in treating elderly tuberculosis (TB) patients. This study aims to examine whether the administration of PZA is associated with poor outcomes during TB treatment among elderly individuals. Methods: A retrospective analysis was undertaken on data collected from a prospective cohort conducted between July 2019 and June 2023, which involved tuberculosis patients from 18 institutions across the Republic of Korea. The study aimed to assess the impact of PZA on the incidence of serious adverse events (SAEs), medication interruptions, and becoming loss to follow-up (LTFU) during standard short courses of TB treatment in elderly (≥65 years old) patients. Results: PZA was administered to 356 of 390 elderly patients (91.3%), and 98 of the 390 (25.1%) experienced SAEs. Treatment success was significantly lower in patients not treated with PZA compared to those who received PZA (64.7% vs 89.9%, p < 0.001). The incidence of SAEs, medication interruption, or LTFU was higher in patients not given PZA compared those who received PZA (52.9% vs. 27.2%, p = 0.002). A multivariate logistic regression analysis, factoring in covariates such as age, comorbidities, and baseline laboratory data, revealed that PZA was not a risk factor for SAEs, medication interruption, or LTFU in TB treatment (odds ratio [OR] 0.457, 95% confidence interval [CI] 0.201–1.041). Conclusion: Treating elderly TB patients with PZA did not increase the incidence of SAEs, medication interruptions, or LTFU during the standard short course of TB treatment. Therefore, considering its potential advantages, incorporating PZA into the treatment regimen for elderly TB patients may be advisable. [ABSTRACT FROM AUTHOR]

Background: SQ109 is a promising candidate drug for the treatment of patients with drug-resistant tuberculosis (DR-TB). The purpose of this study was to investigate the activity of SQ109 against clinical isolates of Mycobacterium tuberculosis (MTB) from patients with multidrug-resistant TB (MDR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB), and to explore new drug-resistant mechanisms of SQ109. Methods: We evaluated the in vitro activity of SQ109 against clinical isolates from patients with MDR-TB and pre-XDR-TB using minimal inhibitory concentration (MIC) assay. The drug-resistant gene, mmpL3 of SQ109-resistant strains was sequenced, and a quantitative real-time PCR assay was used to analyze 28 efflux pump genes in SQ109-resistant strains without mmpL3 mutations. The role of candidate efflux pumps mmpL5 and mmpL7 on the MIC of SQ109 was evaluated using recombinantly cloned MmpL5 and MmpL7 expressed in Mycobacterium smegmatis. Results: The MIC90, MIC95 and MIC99 values of SQ109 for 225 clinical isolates of MTB were 0.25 mg/L, 0.5 mg/L and 1.0 mg/L, respectively. Among the pre-XDR strains, six showed resistance to SQ109 despite the absence of gene mutations in mmpL3. In six resistant pre-XDR strains, the MIC of SQ109 decreased with the use of an efflux pump inhibitor, and there was significant upregulation of mmpL5 and mmpL7 in two strains after exposure to SQ109. The presence of MmpL7 in Mycobacterium smegmatis resulted in decreased susceptibility to SQ109, with the MIC increasing from 16 mg/L to 32 mg/L. Conclusions: Our data demonstrated that SQ109 exhibited excellent levels of in vitro activity against MTB. MmpL7 may be a potential gene for MTB resistance to SQ109, providing a useful target for detecting SQ109 resistance in MTB. [ABSTRACT FROM AUTHOR]

Background: Endometrial Tuberculosis is one of the most common gynecological problems known to have serious implications for the quality of life like infertility. The commonly practiced histopathology solely relies on the suggestive feature of Tuberculosis (TB) with low specificity. Regarding the alternative bacteriological and molecular detection tools, little evidence was generated on their utility in the diagnosis of endometrial tuberculosis in Ethiopia. Therefore, we aim to investigate the detection rate of molecular and bacteriological detection methods on formalin-fixed paraffin-embedded biopsy samples for the diagnosis of endometrial and lymph node TB. Methods: A retrospective cross-sectional study was conducted on 90 formalin fixed paraffin embedded biopsy samples from patients with gynecologic and lymph problems collected between 2018 and 2022 at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. SPSS version 26 was used for statistical analysis. The diagnostic performance was calculated using the histopathology method as the reference standard. Cohen's Kappa value was used to measure the level of agreement. A test with a P-value of < 0.05 was considered statistically significant. Results: A total of 90 samples were analyzed in the current study. Auramine O, GeneXpert MTB/RIF assay, and Real-Time PCR tests have shown a detection rate of 32/90 (36%), 43/90 (47.8%), and 54/90 (60%) respectively (P ≤ 0.01). The sensitivity and specificity of AO were 38.1% and 95% respectively. RT PCR showed superior sensitivity followed by GeneXpert MTB/RIF assay, 70% and 58.6%. AO and molecular methods have shown a similarly low level of agreement with histopathology (Kappa value = 0.2). Conclusions: In a resource-limited setting, the selection of diagnostic tools needs careful attention. Putting the patients on anti-TB treatments based solely on histopathological findings may lead to undesired and adverse complications. Therefore, applying molecular and bacteriological detection methods along with histopathology, could help minimize inappropriate antimicrobial use. [ABSTRACT FROM AUTHOR]

Objective This study assesses the status and determinants of treatment delays among patients with rifampicin-resistant tuberculosis (RR-TB) in Guizhou Province, 2016-2022, aiming to inform the development of RR-TB control strategies in the region. Methods Data on RR-TB patients from 2016 to 2022 were extracted from the "Tuberculosis Management Information System," a subsystem of the "China Disease Prevention and Control Information System." The trend in treatment delay rates over time was analyzed using Trend chi-square test, while logistic regression models were used to examine the factors influencing these delays. Results From 2016 to 2022, Guizhou Province reported 513 cases of treatment delays among patients with rifampicin-resistant tuberculosis (RR-TB), resulting in a treatment delay rate of 23.29%. The rate of treatment delays decreased from 2016 to 2019 (Trend chi-square test = 9.099, P = 0.003), reaching its lowest in 2018 at 10.53%. However, from 2020 to 2022, the rate of treatment delays exhibited an upward trend (Trend chi-square test = 5.937, P = 0.015), peaking in 2021 at 31.62%. Multivariable analysis indicated that compared to migrant populations, patients undergoing initial treatment, and those tested with molecular biological drug sensitivity tests, non-migrant patients (OR = 1.496, 95%CI = 1.198 to 1.867), new patients (OR = 1.774, 95%CI = 1.344 to 2.342), patients with relapse (OR = 1.494, 95%CI = 1.110 to 2.011), and those tested using traditional drug sensitivity methods (OR = 2.985, 95%CI = 2.323 to 3.834) were at higher risk for treatment delays. Conclusion From 2016 to 2022, the overall trend of treatment delays in rifampicin-resistant tuberculosis (RR-TB) patients in Guizhou Province showed a decline. However, there was an increasing trend during the COVID-19 pandemic. This suggests a need to enhance the prevention and control of drug-resistant tuberculosis in key areas such as Bijie City. There is also a need to intensify health education for patients with drug resistance, implement patient-centered care systems for those patients, expand the application of molecular biological drug sensitivity testing techniques, and strengthen the referral and admission mechanisms for RR-TB patients. [ABSTRACT FROM AUTHOR]

Background: microRNAs (miRNAs) were recognized as a promising source of diagnostic biomarker. Herein, we aim to evaluate the performance of an ultrasensitive method for detecting serum miRNAs using single molecule arrays (Simoa). Methods: In this study, candidate miRNAs were trained and tested by RT-qPCR in a cohort of PTB patients. Besides that, ultrasensitive serum miRNA detection were developed using the Single Molecule Array (Simoa) platform. In this ultrasensitive sandwich assay, two target-specific LNA-modified oligonucleotide probes can be simply designed to be complementary to the half-sequence of the target miRNA respectively. We characterized its analytical performance and measured miRNAs in the serum of patients with pulmonary tuberculosis and healthy individuals. Results: We identified a five signature including three upregulated (miR-101, miR-196b, miR-29a) and two downregulated (miR-320b, miR-99b) miRNAs for distinguishing PTB patients from HCs, and validated in our 104 PTB patients. On the basis of Simoa technology, we developed a novel, fully automated digital analyser, which can be used to directly detect miRNAs in serum samples without pre-amplification. We successfully detected miRNAs at femtomolar concentrations (with limits of detection [LODs] ranging from 0.449 to 1.889 fM). Simoa-determined serum miR-29a and miR-99b concentrations in patients with PTB ((median 6.06 fM [range 0.00-75.22]), (median 2.53 fM [range 0.00-24.95]), respectively) were significantly higher than those in HCs ((median 2.42 fM [range 0.00-28.64]) (P < 0.05), (median 0.54 fM [range 0.00-9.12] (P < 0.0001), respectively). Serum levels of miR-320b were significantly reduced in patients with PTB (median 2.11 fM [range 0.00-39.30]) compared with those in the HCs (median 4.76 fM [range 0.00-25.10]) (P < 0.001). A combination of three miRNAs (miR-29a, miR-99b, and miR-320b) exhibited a good capacity to distinguish PTB from HCs, with an area under the curve (AUC) of 0.818 (sensitivity: 83.9%; specificity: 79.7%). Conclusions: This study benchmarks the role of Simoa as a promising tool for monitoring miRNAs in serum and offers considerable potential as a non-invasive platform for the early diagnosis of PTB. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) morbidity and mortality are significantly increasing in the elderly worldwide. Their optimal health outcomes are hampered by medication related burden (MRB) and poor treatment adherence. Understanding th e MRB status from patients’ perspectives and its association with adherence among elderly TB patients will help achieve the End TB targets. Thus, we aimed to identify the incidence of MRB and nonadherence among elderly TB patients in Guizhou, and determine their association. Methods: A cross-sectional study was conducted in three prefectures with high TB notifications in Guizhou in 2022. The data were collected via face-to-face structured interviews. MRB was measured using the Living with Medicines Questionnaire version 3 (LMQ-3), which consists of eight domains. Nonadherence was assessed by treatment interruption, which was defined as any interruption lasting at least 1 day at any time within the last 3 months. A binary unconditional logistic regression model was used to determine the association between variables. Results: Of the 405 elderly TB patients enrolled, 49.4% and 42.7% of the respondents perceived suffering from moderate and high MRB, respectively. The incidence of nonadherence among patients was 33.6%. Patients with higher scores in domain 2 (practical difficulties) [ORadj = 1.19; 95% CI (1.11–1.28)] and domain 4 (side effects burden of prescribed medications) [ORadj = 1.16; 95% CI (1.06–1.27)] were more likely to experience nonadherence. But, patients with higher scores in domain 8 (control/ autonomy of medicine use) [ORadj = 0.70; 95% CI (0.61, 0.81)] were more likely to occur adherence. Patients with a high education level [ORadj = 0.29; 95% CI (0.08, 0.92)] had a decreased risk of nonadherence, but those with a living expense from a retirement salary [ORadj = 2.55; 95% CI (1.16, 5.71)] had an increased risk of nonadherence. Discussion: The incidence of MRB and medication nonadherence is high among elderly TB patients in Guizhou. The significant associations between the three domains of MRB and nonadherence highlight that measuring MRB in multiple dimensions using the LMQ-3 in elderly TB patients could assist clinicians in providing patient-centered care, and multifaceted interventions targeting the identified problems should be implemented to reduce MRB and nonadherence among elderly TB patients in Guizhou. [ABSTRACT FROM AUTHOR]

Background: Respiratory microbiota is closely related to tuberculosis (TB) initiation and progression. However, the dynamic changes of respiratory microbiota during treatment and its association with TB progression remains unclear. Methods: A total of 16 healthy individuals and 16 TB patients (10 drug-sensitive TB (DS-TB) and 6 drug-resistant TB (DR-TB)) were recruited. Sputum samples were collected at baseline for all anticipants and after anti-TB treatment at Month-6 for TB patients. High throughput 16 S RNA sequencing was used to characterize the respiratory microbiota composition. Results: Compared to the healthy individuals, TB patients exhibited lower respiratory microbiota diversity (p < 0.05). This disruption was alleviated after anti-TB treatment, especially for DS-TB patients. Parvimonas spp. numbers significantly increased after six months of anti-TB treatment in both DS-TB and DR-TB patients (p < 0.05). Rothia spp. increase during treatment was associated with longer sputum-culture conversion time and worse pulmonary lesion absorption (p < 0.05). Besides, Moraxella spp. prevalence was associated with longer sputum-culture conversion time, while Gemella spp. increase was associated with worsening resolving of pulmonary lesions (p < 0.05). Conclusion: Dynamic changes of respiratory microbiota during anti-TB treatment is closely related to TB progression. The involvement of critical microorganisms, such as Parvimonas spp., Rothia spp., Moraxella, and Gemella spp., appears to be associated with pulmonary inflammatory conditions, particularly among DR-TB. These microorganisms could potentially serve as biomarkers or even as targets for therapeutic intervention to enhance the prognosis of tuberculosis patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. Methods: Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon β (IFN-β) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. Results: The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P < 0.05), in patients with active lesions than in patients with stable lesions. The serum concentration of IFN-β was significantly higher in patients with active lesions (P = 0.028). Compared with healthy individuals, the expression level of the cGAS-STING pathway was elevated in PBMCs of TB patients (P < 0.05), and the difference in the expression level of IFN-β was not statistically significant (P > 0.05), and the serum IFN-β concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-β in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively. Conclusions: The expression level of TBK1 and IRF3 in PBMCs, and IFN-β in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-β in serum has higher sensitivity when used to differentiate between patients with active and stable lesions. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75–89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease. [ABSTRACT FROM AUTHOR]

Background: Patients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients. Methods: The 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed. Results: Compared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively. Conclusion: Our study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity. [ABSTRACT FROM AUTHOR]

Pulmonary Tuberculosis (TB) is one of the leading causes of death globally, including in Indonesia. TB patients often experience anxiety, frustration, irritability, and guilt, influenced by their knowledge, attitudes, beliefs, work, and primarily psychospiritual factors. One form of support provided to these patients is the Psycho-Spiritual and Spiritual Emotional Freedom Technique (PS-SEFT). This research aimed to determine the effect of e-counseling combined with PS-SEFT on anxiety levels and motivation for recovery in TB patients. The study used an experimental, correlational analytical method, with a random sample of 14 respondents suffering from pulmonary tuberculosis. The independent variable was the provision of e-counseling combined with PS-SEFT, and the dependent variables were the levels of anxiety and motivation to recover from TB. Data collection instruments included questionnaires, the HARZ scale, and medical records. Data were processed using various analyses, including the paired t-test and Wilcoxon test. The results showed a significant decrease in anxiety levels after the PS-SEFT intervention, with anxiety reducing by 35.7% from a previously very severe level. Motivation to recover increased significantly, with all 14 patients (100%) showing improvement from moderate to high levels. The Wilcoxon test results indicated a significant difference in the anxiety levels of TB patients before and after the PS-SEFT intervention (p-value=0.005), with the HARZ score decreasing from 95.00 to 32.00. The paired t-test results also showed a significant difference in patient motivation to recover before and after the PS-SEFT intervention (p-value=0.000), with the motivation score increasing from 91.25 to 98.75. Routine PS-SEFT practice by TB patients enhances their ability to manage anxiety and motivates them to recover. The success of these patients must be supported and accompanied by their families. [ABSTRACT FROM AUTHOR]

Objective To investigate the trajectory of insomnia symptoms and the influence of psychosocial factors in newly-treated tuberculosis patients. Methods From October 2022 to January 2023, a convenience sampling method was employed to select eligible participants for a six-month longitudinal follow-up at three tertiary hospitals. Assessments were conducted on the day of treatment (T1), at the end of the first month (T2), at the end of the second month (T3), and at the end of the sixth month (T4) using the Pittsburgh Sleep Quality Index (PSQI), Perceived Stress Scale (PSS), Generalized Anxiety Disorder 7-item scale (GAD-7), Tuberculosis Related Stigma Scale (TRSS), and Social Support Rating Scale (SSRS) to evaluate insomnia, stress, anxiety, stigma, and social support dynamically. Mplus 8.3 was used to construct three types of latent growth models to explore the development trajectory of insomnia in patients and further analyze the impact of various psychosocial factors, particularly stigma and social support, on this trajectory. Results A total of 266 participants were included, with the insomnia detection rate in newly-treated tuberculosis patients decreasing from 57.9% to 36.8%. The results of the latent growth model indicated that the nonlinear fitting index was optimal, with PSQI scores showing a downward trend that gradually slowed (intercept=3.987, slope=-2.466, curve slope=0.453, P<0.05). There was significant individual variation in development changes, which were significantly negatively correlated with the initial level (r=-0.266, P<0.05). Additionally, social support had a significant negative predictive effect on the rate of insomnia development (β=-0.023, P<0.05), while stigma during the T1 to T4 period significantly positively influenced insomnia (β=0.088-0.453, P<0.05). Stress and anxiety during the T1 to T3 period also significantly positively influenced insomnia (β=0.070-0.143, P<0.05). Conclusion The development of insomnia in newly-treated tuberculosis patients over the first six months exhibited a nonlinear decreasing trend influenced by the initial level. The effects of stress and anxiety on insomnia were primarily concentrated during the intensification period, while the impact of stigma persisted throughout the treatment process. Good social support can facilitate the improvement of insomnia. [ABSTRACT FROM AUTHOR]

We asked if SARS-CoV-2 seropositivity in HIV/TB co-infected patients plays a role in precipitating active tuberculosis in HIV-infected individuals and alters inflammatory status. A prospective study was conducted on HIV/TB co-infected patients presenting with pulmonary (n = 20) or extrapulmonary (n = 12) tuberculosis. Abbott SARS-CoV-2 IgG kits assessed the presence of anti-nucleoprotein antibodies. Inflammatory markers viz. osteopontin, total and full-length galectin-9, and C-reactive protein were tested at baseline and the end of antituberculosis treatment. The inflammatory score (INS) was assessed based on the percentage of reduction in the inflammatory markers' levels at the end of the treatment. Anti-SARS-CoV-2 antibodies were detected in five male patients diagnosed with pulmonary (n = 2) and extrapulmonary (n = 3) TB. None of them reported symptomatic COVID-19. Inflammatory marker levels did not differ significantly at baseline compared to those in seronegative patients. However, the INS correlated negatively with SARS-CoV-2 seropositivity (r = −0.386, p = 0.039), indicating persistently raised inflammatory markers in these patients at the end of the treatment compared to seronegative individuals. Among the four markers studied, total galectin-9 levels failed to decrease significantly in these patients (p = 0.030). The majority of HIV/TB co-infected patients enrolled in our study (84.5%) were SARS-CoV-2-seronegative, indicating that SARS-CoV-2 infection might not have played a role in precipitating TB reactivation. [ABSTRACT FROM AUTHOR]

Background In the healthcare domain, the indispensable role of caregivers in patient support is utmost. The family plays a crucial role in the care of a mentally and chronically ill patient. As these conditions can significantly impact the lives of patients, they also exert a profound influence on those who provide care, affecting their burden and quality of life. Aim This study aimed to evaluate the burden and Quality of Life among caregivers of Bipolar Disorder and Tuberculosis Patients. Methods This cross-sectional study involved primary caregivers of patients diagnosed with Bipolar Affective Disorder according to ICD-10 guidelines and of chronic medical conditions such as Refractory tuberculosis, and Drug-Resistant Tuberculosis. The study took place at the Department of Psychiatry, Rama Medical College, Hospital, and Research Centre, Kanpur. The sample was calculated using scientific statistical tools. The patient's caregivers were recruited from the Department of Psychiatry and the Department of TB & Chest till the required sample size was met and were categorized into two groups: Group 1 comprised 40 caregivers of bipolar patients, and Group 2 included caregivers of tuberculosis. Sociodemographic information was obtained through a semi-structured questionnaire. The Montgomery Borgatta Caregiver Burden Scale and Quality of Life WHOQOL-BREF were administered to both groups to assess the burden and their Quality of life. Results and discussion According to the burden scale caregivers of Group 1 face more burden compared to Group 2 caregivers and their Quality of Life is also more affected in all the four domains. The result is statistically significant in all the dimensions. Conclusion Our study concluded that caregivers in both groups experience significant burden that adversely affect their quality of life. Therefore, strategies should be developed to support and psychoeducating caregivers to help them cope better and enhance their Quality of life. [ABSTRACT FROM AUTHOR]

Globally, tuberculosis is a leading cause of infectious disease deaths. China ranks third among the 30 high‐burden countries for tuberculosis and accounts for approximately 7.4% of the cases reported worldwide. Since very few studies have investigated the age difference in tuberculosis prevalence in mainland China, therefore, the preliminary characterisation of age differences in tuberculosis patients is not well understood. The data of reported sputum smear‐positive, tuberculosis and sputum smear‐negative cases in 340 prefectures from mainland China were extracted from the China Information System for Disease Control and Prevention from January 2009 to December 2018. Multiple statistical analysis and GIS techniques were used to investigate the temporal trend and identify the spatial distribution of sputum smear‐positive, tuberculosis and sputum smear‐negative cases in the study area. The results showed that the incidence of sputum smear‐positive and tuberculosis has dropped to a stable level, while sputum smear‐negative exhibited a rising trend. Additionally, sputum smear‐positive, tuberculosis and sputum smear‐negative are still highly prevalent in northwestern and southwestern regions of China. Interestingly, the young adult group (20–50 age) and elder group (>50 age) are more susceptible to being infected with tuberculosis, while lower infection levels were recorded in the juvenile group (<20 age). The present study investigated the temporal–spatial distribution of sputum smear‐positive, tuberculosis and sputum smear‐negative cases in mainland China before the COVID‐19 pandemic breakout, which would help the government agency establish an effective mechanism of tuberculosis prevention in high‐risk periods and high‐risk areas in the study region. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes has been related to higher risk and poor prognosis of patients with tuberculosis, while the influence of prediabetes on the treatment outcome of patients with tuberculosis remains not determined. A meta‐analysis was performed to evaluate the influence of prediabetes on treatment outcome of patients with tuberculosis. Methods: Relevant cohort studies were acquired through a search of Medline, Embase, and Web of Science databases. To minimise the influence of between‐study heterogeneity, a randomised‐effects model was used to pool the results. Results: Eight prospective cohort studies including 3001 patients with tuberculosis were available for the meta‐analysis. Among them, 752 (25.1%) were with prediabetes at baseline, and the patients were followed for a mean duration of 17.7 months. It was shown that compared to patients with normoglycemia, those with prediabetes were associated with a higher incidence of unfavourable treatment outcome (risk ratio [RR]: 1.41, 95% confidence interval [CI]: 1.02 to 1.96, p = 0.04; I2 = 56%). Subgroup analysis did not support that difference in study country (Asian or non‐Asian), diagnosis (pulmonary tuberculosis only or also with extrapulmonary tuberculosis), mean age, follow‐up duration, or study quality score had significant influence on the results (p for subgroup difference all >0.05). However, prediabetes at baseline was not associated with an increased risk of all‐cause mortality during follow‐up (RR: 1.59, 95% CI: 0.75 to 3.38, p = 0.23; I2 = 54%). Conclusions: Patients with tuberculosis and prediabetes may have a higher risk of unfavourable treatment outcome compared to patients with normoglycemia. [ABSTRACT FROM AUTHOR]

Limited information is currently available on the prevalence of and risk factors for tuberculosis infection (TBI) among close contacts of patients with pulmonary TB (PTB) in China. In this study, we estimated the burden of TBI among close contacts using QuantiFERON-TB Gold In-Tube assay (QFT) and identified factors associated with TB transmission among this high-risk population. From January 1, 2018 to August 31, 2020, we identified laboratory-confirmed patients with PTB from a population-based, multicentered, cluster-randomized control trial for tuberculosis preventive treatment. Close contacts of these patients were identified, interviewed, and tested using the QFT assay. We estimated TBI prevalence and calculated ORs and 95% CIs for TBI risk factors. A total of 3138 index cases and 8117 close contacts were identified. Of these contacts, 36 had PTB (a prevalence of 443.51 cases/100 000 population). Among the remaining 7986 close contacts; 3124 (39.12%) reported a positive QFT result. QFT positivity was significantly associated with older age (adjusted OR, 1.77; [95% CI, 1.27–2.47], 2.20; [95% CI, 1.59–3.05], and 2.74; [95% CI, 1.96–3.82]) for age groups: 35–44, 45–54, and 55–64, respectively) when compared with a younger age group: 5–14; longer contact duration (adjusted OR, 1.44; 95% CI, 1.22–1.69); and sharing of a bedroom (adjusted OR, 1.39; 95% CI, 1.18–1.65). Our findings indicate a high TBI burden among the close contacts of PTB. The results also highlighted that contact tracing and investigation for TBI are necessary and beneficial, particularly for those who are older, have had a longer contact duration, and share a bedroom. [ABSTRACT FROM AUTHOR]

Few studies have characterized the respiratory microbiota of tuberculosis disease, with inconclusive results. Our aim was to compare the microbial ecosystem of the sputum between Tuberculosis patients and patients with moderate lung disease of asthma, Chronic Obstructive Pulmonary Disease, bronchiectasis, and lung fibrosis using metagenomic profiling techniques. In particular, we assessed the common, overlapping communities of Tuberculosis patients. The Bacterial communities in the sputum of pulmonary tuberculosis patients within a cohort of patients in Saudi Arabia were identified using amplicon sequencing. Forty sputum samples were collected from patients admitted to King Fahad Armed Forces Hospital from (2019-2020). 16S rRNA V3-V4 hypervariable regions were sequenced using Illumina technology and analyzed using a pipeline of standard bioinformatics techniques to identify unique and common patterns of microbial communities. Our results demonstrated that the microbiota of the sputum of pulmonary tuberculosis patients was similar to that of the sputum of control participants at the phylum and genus levels. Additionally, we observed heterogeneity of taxa at the individual level. At the family level, the abundance of Mycobacteriaceae did not differ between anti-tuberculosis-treated and untreated cases. In contrast, the Corynebacteriaceae and Lactobacillaceae families differed significantly under the antibiotic and anti-TB regimens, respectively. This study provides insights into the microbial communities found in sputum samples from individuals with tuberculosis (TB) and the potential alterations that may occur as a result of antituberculosis treatment. [ABSTRACT FROM AUTHOR]

Background: In 2012, the World Health Organization recommended screening and investigation of contacts of index tuberculosis patients as a strategy to accelerate detection of tuberculosis (TB) cases. Nine years after the adoption of this recommendation, coverage of TB contact investigations in Uganda remains low. The objective of this study was to examine health care providers' perceptions of factors influencing coverage of TB contact investigations in three selected rural health facilities in Mbarara district, southwestern Uganda. Methods: This study identified provider opinions on the barriers and facilitators to implementation of TB contact investigation using the Consolidated Framework for Implementation Research. Using an exploratory qualitative study design, semi-structured interviews with 19 health workers involved in the TB program at district, health facility and community levels were conducted from April 2020 and July 2020. Analysis was conducted inductively using reflexive thematic analysis in six iterative steps: familiarizing with the data, creating initial codes, searching for themes, reviewing themes, developing theme definitions, and writing the report. Results: Nineteen health care workers participated in this study which translates to a 100% response rate. These included two district TB and leprosy supervisors, five nurses, five clinical officers, six village health team members and one laboratory technician. The three themes that emerged from the analysis were intervention-related, health system and contextual factors. Health system-related barriers included inadequate or delayed government funding for the TB program, shortage of human resources, insufficient personal protective equipment, and a stock-out of supplies such as Xpert MTB cartridges. Contextual barriers included steep terrain, poverty or low income, and the stigma associated with TB and COVID-19. Facilitators comprised increased knowledge and understanding of the intervention, performance review and on-the-job training of health workers. Conclusions: This study found that most of the factors affecting TB contact investigations in this rural community were related to health system constraints such as inadequate or delayed funding and human resource shortages. This can be addressed by strengthening the foundational elements of the health system - health financing and human resources - to establish a comprehensive TB control program that will enable the efficient identification of missing TB patients. [ABSTRACT FROM AUTHOR]

Background: Despite readiness for hospital discharge widespread popularity since readiness for hospital discharge introduction in 1979 and extensive study, readiness for hospital discharge among pulmonary tuberculosis (PTB) patients has not yet been investigated. Moreover, the factors influencing this process remain unclear. Objective: The objective of this study was to investigate the factors influencing readiness for hospital discharge in initially treated PTB patients using the capability, opportunity, motivation-behavior (COM-B) model. Methods: This phenomenological study was conducted from December 2023 to March 2024. Face-to-face individual interviews were conducted with 18 initially treated patients with PTB according to a semistructured interview guide developed on the basis of the COM-B model. The interview data were subjected to analysis using NVivo 14 software and Colaizzi's method. Results: As a result, 6 themes and 14 subthemes were identified. Physical capability for readiness for hospital discharge (subthemes included poor health status, early acquisition of adequate knowledge about PTB, inadequate knowledge about readiness for hospital discharge), psychological capability for readiness for hospital discharge(subthemes included false perceptions about readiness for hospital discharge, high treatment adherence), physical opportunity for readiness for hospital discharge (subthemes included high continuity of transition healthcare, insufficient financial support, insufficient informational support), social opportunity for readiness for hospital discharge (subthemes included stigmatization, inadequate emotional support), reflective motivation for readiness for hospital discharge (subthemes included lack of reflection on coping with difficulties, intention to develop a readiness for hospital discharge plan), and automatic motivation for readiness for hospital discharge (subthemes included strong desire to be cured, negative emotions). Conclusion: We established factors related to readiness for hospital discharge in initially treated PTB patients in terms of capability, opportunity and motivation, which can inform the future development of readiness for hospital discharge plans. To improve patients' readiness for hospital discharge, patients need to be motivated to plan and desire readiness for hospital discharge, patients' knowledge and treatment adherence should be improved, and patients' transition healthcare continuity and emotional support should be focused on. Moreover, the quality of readiness for hospital discharge and discharge education should be assessed in a timely manner to identify impeding factors and provide interventions. [ABSTRACT FROM AUTHOR]

Background: Comorbidity of diabetes mellitus and tuberculosis (TB) is a major public health concern in low- and middle-income countries including Bangladesh. An integrated approach is required for adequate management of diabetes mellitus and TB. The objective of the present study was to investigate the availability and readiness of the TB care centers of Bangladesh toward diabetic patients' management. Methods: The present study was conducted based on existing data obtained from the Bangladesh Health Facility Survey (BHFS) 2017. Data collected from a total of 303 facilities providing TB services were retrieved. The outcome variables of the present study were availability and readiness of the TB health facilities for providing diabetes mellitus service. Readiness was measured for four domains: staff and guidelines, equipment, diagnostic facility and basic medicine. The independent variables were: facility level, management authority and location of the facility. Binary and multiple logistic regression models were constructed for both the outcome variables (availability and readiness) to find out their predictors. Results: Services for diabetes mellitus were available in 68% of the TB facilities while high readiness was present in 36% of the facilities. For domain-specific readiness index, readiness for the domains of staff and guidelines, equipment, diagnostic facility and basic medicine was reported in 46%, 96%, 38% and 25% facilities respectively. In the logistic regression model, availability of diabetes mellitus services was better in primary level (aOR 2.62, 95% CI 1.78–4.77) and secondary level (aOR 3.26, 95% CI 1.82–9.05) facilities than community facilities. Similarly, readiness of diabetes mellitus care was also better in these facilities (aOR 2.55, 95% CI 1.05–4.71 for primary and aOR 2.75, 95% CI 1.80–4.32 for secondary facilities). Besides, private TB facilities had better availability (aOR 2.84, 95% CI 1.75–5.89) and readiness (aOR 2.52, 95% CI 1.32–4.29) for diabetes mellitus care. Conclusion: Availability and readiness for providing diabetes mellitus services in TB care providing facilities in Bangladesh is inadequate. [ABSTRACT FROM AUTHOR]

Background: Limited research exists on the comorbidity of pulmonary tuberculosis with non-communicable diseases (NCDs) and its implications for healthcare utilization in Indonesia. The lack of investigation into NCD comorbidity among pulmonary tuberculosis patients could adversely affect both the healthcare system and the national health insurance scheme. Understanding the NCD comorbidity among pulmonary tuberculosis patients, associated factors, and healthcare utilization is crucial for ensuring the effective and efficient delivery of health services. Method: This study utilized an observational cross-sectional design based on anonymized sample data from tuberculosis cases covered by Indonesia's National Health Insurance in 2021. Chi-square tests were employed to analyze dependent and independent variables, while unadjusted and adjusted logistic regressions were used to explore further associations. Results: The prevalence of NCD comorbidity in tuberculosis patients was 11.81%. Aged over 60 (aOR 5.16; [CI] 4.23—6.3), married (aOR 1.19; [CI] 1.05—1.34), and unemployed (aOR 1.27; [CI] 1.08—1.49) were associated with the NCD comorbidity in pulmonary tuberculosis patients. Factors associated with increased inpatient service utilization among pulmonary tuberculosis patients included aged over 60 (aOR 5.69; [CI] 4.81—6.74), male (aOR 1.32; [CI] 1.23—1.40), self-employment (aOR 1.42; [CI] 1.29—1.56), having insurance subsidized by central government (aOR 1.89; [CI] 1.73—2.08) or local government funds (aOR 1.75; [CI] 1.58—1.93), and having comorbidity non-communicable diseases (aOR 1.80; [CI] 1.66—1.96). Conclusion: Pulmonary tuberculosis patients exhibit a significant prevalence of NCD comorbidity, which substantially impacts healthcare utilization. Early detection and management of these conditions are critical to mitigate burdens on both the healthcare system and the financial sustainability of the national health insurance scheme. Integrating health services for tuberculosis and NCDs through bidirectional screening is essential for comprehensive patient care. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant tuberculosis (MDR-TB) presents persistent global health challenges, characterized by low treatment success rates among patients enrolled for treatment. The World Health Organization recommends decentralization to improve outcomes. This study aims to assess predictors of mortality among MDR-TB patients after decentralization of services in Tanzania. This was a retrospective cohort study involving all MDR-TB patients enrolled in treatment in all 31 regions in Tanzania from 2017 to 2019. The overall mortality rate among MDR-TB patients was calculated using the incidence rate. Additionally, independent factors of MDR-TB mortality were determined using multivariable cox proportional hazards models. Results: The study followed 985 patients for a total of 12,929 months. During this time, it found that approximately 12 out of every 1000 patients died each month. Specifically, the death rates were about 18 out of 1000 patients at 6 months, 8 out of 1000 at 12 months, and 7 out of 1000 at 24 months. Patients who had both MDR-TB and HIV, as well as those who were malnourished, had a lower chance of surviving at 6, 12, and 24 months. Malnourished patients had almost three times the risk of dying [adjusted hazard ratio (aHR) 2.96, with a 95% confidence interval (CI) of 2.10–4.19], while those with HIV had nearly double the risk [aHR 1.91, with a 95% CI of 1.37–2.65]. Conclusion: In summary, our study on MDR-TB patient outcomes in Tanzania between 2017 and 2019 reveals a pattern of high mortality rates within the first 6 months of treatment. Furthermore, malnutrition and HIV co-infection were found to be significant predictors of mortality. To decrease mortality, it is crucial to closely monitor patients during the initial 6 months of treatment, especially those who are malnourished or co-infected with HIV, and ensure they receive appropriate and timely care. Additionally, further investigation is needed to find out what may be contributing to possible rise in mortality rate. [ABSTRACT FROM AUTHOR]

Background: This dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB). Methods: A total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance. Results: In both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB. Conclusion: Isoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate serum chitotriosidase level in tuberculosis patients, its relationship with microbiological and clinical parameters, and response to treatment. Materials and methods: This longitudinal panel study included 149 patients with confirmed TB disease. Serum chitotriosidase activity was measured at the beginning and the end of treatment. Factors associated with chitotriosidase activity were explored using univariate and multivariable logistic regression analysis. Results: Out of 149 study participants, 71(47.7%) were female. The mean age was 53.0 (SD = 18.2). Majority of cases were new 118(79.2), predominantly 145 (97.3%) having pulmonary tuberculosis. More than half of the patients were sputum smear positive 91 (61.1%) while culture positive in 146 (98%) of them. According to radiological findings, cavitary lesions were found in 92 (63.4%) patients. Anti TB treatment was associated with significant decrease in serum chitotriosidase level (< 0.001). New TB treatment (OR = 4.41%;95% CI = 1.20–9.89), and cavitary lesions (OR = 3.86;95%CI = 0,59-26.57) were found to be significantly associated with decrease of chitotriosidase activity. Conclusions: The results of our study showed that serum chitotriosidase values are strong biomarkers for starting anti TB treatment and for treatment monitoring, since decrease in serum chitotriosidase level can predict favorable treatment response in patients with tuberculosis. Further studies are needed to explore these, and other factors associated with chitotriosidase activity among tuberculosis patients. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical and laboratory characteristics and to identify predictors of moderate to severe anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with tuberculosis. Methods: This prospective study enrolled Tuberculosis (TB) patients treated with first-line anti-tuberculosis drugs at the Affiliated Hospital of Zunyi Medical University between May 2022 and June 2023. The occurrence of ATB-DILI was monitored, and demographic and clinical data were gathered. We analyzed risk factors for the development of moderate to severe ATB-DILI. Results: ATB-DILI was detected in 120 (10.7%) of the patients, with moderate to severe ATB-DILI occurring in 23 (2.0%) of the 1,124 patients treated with antituberculosis treatment. Multivariate cox regression analysis identified malnutrition (HR = 4.564, 95% CI: 1.029-20.251, p = 0.046) and hemoglobin levels <120 g/L (HR = 2.825, 95% CI: 1.268-11.540, p = 0.017) as independent risk factors for moderate to severe ATB-DILI. Conclusion: The incidence of moderate to severe ATB-DILI was found to be 2.0%. Malnutrition and hemoglobin levels below 120 g/L emerged as significant independent risk factors for the occurrence of moderate to severe ATB-DILI in this patient population. [ABSTRACT FROM AUTHOR]

Objective: To investigate the epidemiological characteristics of pulmonary tuberculosis in Xuzhou from 2019 to 2021, and construct a logistic regression prediction model for influencing factors. Methods: 788 cases of pulmonary tuberculosis registered in Xuzhou from January 1, 2019 to December 30, 2021 were selected as the study subjects. Observed the epidemiological characteristics of pulmonary tuberculosis in Xuzhou from 2019 to 2021, and used univariate and multivariate logistic regression analysis to analyze the influencing factors of pulmonary tuberculosis incidence. Constructed a Log P regression prediction model and analyzed its predictive performance. Results: Epidemiological statistics showed that from 2019 to 2021, the majority of pulmonary tuberculosis patients in Xuzhou were male, aged ≥ 60 years old, residing in rural areas, and married, the number of patients in the disease course and education level classification group was relatively close. Univariate analysis showed that the incidence of pulmonary tuberculosis was related to contact history of pulmonary tuberculosis, drinking history, tuberculosis health education, gender, average monthly income of per person in family, age, occupation, smoking history, BCG vaccination history, and residence (P<0.05). The results of multivariate logistic regression analysis showed that residing in rural areas, smoking history, gender as male, drinking history, average monthly income of per person in family <3000 yuan, age ≥ 60 years old, occupation as a farmer or worker, and contact history of pulmonary tuberculosis were risk factors for pulmonary tuberculosis, while BCG vaccination history was a protective factor (P<0.05). The corresponding Log P model, after ROC analysis, it showed that this prediction model had good predictive performance for the incidence of pulmonary tuberculosis, with an ROC-AUC (0.95CI) of 0.881 (0.817-0.928) and an accuracy of 86.5%. Conclusion: Xuzhou should focus on population affected by pulmonary tuberculosis of male, elderly, residing in rural areas, smoking history, drinking history, low average monthly income of per person in family, farmers or workers, and contact history of pulmonary tuberculosis, and should actively carry out the vaccination of BCG vaccine. In addition, the prediction model constructed through influencing factors has good predictive performance on the incidence of pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

Objective To analyze the drug resistance of Mycobacterium tuberculosis in Qinghai Province, to provide scientific basis for the diagnosis, treatment, and prevention and control of tuberculosis in Qinghai Province. Methods A total of 1 836 culture-positive strains in pulmonary tuberculosis patients from eight cities (prefectures) in Qinghai Province from 2017 to 2021 were selected for drug resistance testing using the proportion method for isoniazid (I), rifampicin (R), streptomycin (S), ethambutol (E), ofloxacin (0), and kanamycin (K). Results Among the tested strains, 462 were found to be drug-resistant, with an overall drug resistance rate of 25.16%. The primary drug resistance rate was 23.84%, and the acquired drug resistance rate was 38.89%. The rate of extensively drug-resistant tuberculosis was 5.85%. The drug resistance rates of the six anti-tuberculosis drugs from high to low were as follows: I (15.74%), S (12.58%), R (9.15%), E (5.56%), 0 (4.74%), and K (1.63%). The rate of multi-drug resistant tuberculosis (MDR-TB) was 7.46%, with a primary MDR rate of 5.97% and an acquired MDR rate of 22.84%. There were differences in drug resistance rates (光2=25.645, P<0.001) and MDR rates (光2=13.578; P=0.009) in different years, as well as differences in drug resistance rates (%2=16,865, PcO.001) and MDR rates (x2=7.068, P-0.029) among urban, agricultural, and pastoral areas. Conclusion The drug resistance rates of Mycobacterium tuberculosis isolated in Qinghai Province, especially the rates of primary drug resistance and MDR-TB, are relatively high, showing an increasing trend year by year. The drug resistance rates are particularly high in pastoral areas. This suggests the need to strengthen standardized treatment for tuberculosis patients, as well as the standardized use of second-line drugs and patient follow-up management. [ABSTRACT FROM AUTHOR]

Guidelines generally recommend a combination of immunological assays and chest X-ray imaging (CXR) when screening for latent tuberculosis infection (LTBI) prior to biologic treatment in inflammatory bowel disease (IBD). To investigate whether CXR identify patients with suspected LTBI/TB who were not identified with QuantiFERON tests (QFT) when screening for LTBI/TB before starting biologic treatment in IBD patients. Single-center, retrospective cohort study of patients with inflammatory bowel disease who had a QFT and a CXR prior to initiation of biologic treatment in a 5-year period (October 1st, 2017 to September 30th, 2022). 520 patients (56% female, mean age 40.1 years) were included. The majority had none or few risk factors for TB (as reflected by the demographic characteristics) but some risk factors for having false negative QFT results (concurrent glucocorticoid treatment and inflammatory activity). QFT results were positive in 8 patients (1.5%), inconclusive in 18 (3.5%) and negative in 494 (95.0%). Only 1 patient (0.19%) had CXR findings suspicious of LTBI. This patient also had a positive QFT and was subsequently diagnosed with active TB. All patients with negative or inconclusive QFT had CXR without any findings suggesting LTBI/TB. One patient developed active TB after having initiated biologic treatment in spite of having negative QFT and a normal CXR at screening. In a population with low risk of TB, the benefits of supplementing the QFT with a CXR are limited and are unlikely to outweigh the cost in both patient test-burden, radioactive exposure, and economic resources. [ABSTRACT FROM AUTHOR]

In Indonesia, 2.4% of all new tuberculosis patients had multi-drug resistant disease (MDR-TB); an estimated 24,000 incidences. Historical case series of MDR-TB described a high frequency of cavitation and poor prognosis. The diagnosis of chronic pulmonary aspergillosis (CPA) relies on raised levels of Aspergillus IgG antibodies, and detectable Histoplasma IgG antibodies are suspicious for chronic pulmonary histoplasmosis (CPH). We investigated whether MDR-TB patients might have concurrent CPH or CPA. This was a cross-sectional study with 50 MDR-TB patients. ELISA was used to detect Histoplasma IgG antibodies and lateral flow assay was used to detect Aspergillus IgG/IgM antibodies. Several other possible disease determinants were assessed by multivariate analysis. Of the 50 MDR-TB patients, 14 (28%) and 16 (32%) had positive Histoplasma or Aspergillus serology; six patients (12%) had dual antibody reactivity. Radiological abnormalities in positive patients included diffuse or local infiltrates, nodules, consolidation, and apical cavities, consistent with CPH and CPA. Patients with detectable fungal antibodies tended to have worse disease, and 4 of 26 (15.3%) died in the first 5 months of dual infection (p = 0.11 compared with no deaths in those with only MDR-TB). The criteria for the diagnosis of CPH and CPA were fulfilled in those with moderately and far advanced disease (13 of 14 or 93%) and 12 of 16 (75%), respectively. Damp housing was the only determinant associated with Histoplasma antibodies (PR 2.01; 95%CI 0.56–7.19), while pets were associated with the Aspergillus antibody (PR 18.024; 95%CI 1.594–203.744). CPA or CPH are probably frequent in MDR-TB patients in Indonesia and may carry a worse prognosis. [ABSTRACT FROM AUTHOR]

The present study aims to characterise the pharmacokinetics of rifampicin (RIF) in tuberculosis (TB) patients with and without HIV co-infection, considering the formation of 25-O-desacetyl-rifampicin (desRIF). It is hypothesised that the metabolite formation, HIV co-infection and drug formulation may further explain the interindividual variation in the exposure to RIF. Pharmacokinetic, clinical, and demographic data from TB patients with (TB-HIV+ group; n = 18) or without HIV (TB-HIV− group; n = 15) who were receiving RIF as part of a four-drug fixed-dose combination (FDC) regimen (RIF, isoniazid, pyrazinamide, and ethambutol) were analysed, along with the published literature data on the relative bioavailability of different formulations. A population pharmacokinetic model, including the formation of desRIF, was developed and compared to a model based solely on the parent drug. HIV co-infection does not alter the plasma exposure to RIF and the desRIF formation does not contribute to the observed variability in the RIF disposition. The relative bioavailability and RIF plasma exposure were significantly lower than previously reported for the standard regimen with FDC tablets. Furthermore, participants weighting less than 50 kg do not reach the same RIF plasma exposure as compared to those weighting >50 kg. In conclusion, as no covariate was identified other than body weight on CL/F and Vd/F, low systemic exposure to RIF is likely to be caused by the low bioavailability of the formulation. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study evaluated the efficacy of the TrueLab™ Real Time mini-PCR system in providing rapid and accurate diagnostic results for tuberculosis (TB) detection in India. The goal is to improve case detection and accelerate treatment in settings with limited resources. Materials and Methods: This prospective study was conducted by the Department of Microbiology on 120 patients, age ranging from >=15 years with at least two clinical symptoms of pulmonary TB. Molbio and Universal Cartridge Based Sample Prep were the 2 methods used for processing sputum samples. The diagnosis was based on the MTB Real Time PCR test, which has a detection limit of 100 CFU/mL. Patients under 15 years, samples lacking clinical background, saliva specimens or extra-pulmonary TB cases were excluded from the study. Results: A total of 44.17% samples were positive for TB with maximum positivity in the age group 31-45 years. Positivity rate was found to be higher in females. In 4.17% of cases there was rifampicin resistance, which was significantly high in previously treated cases. Comparison of Truenat with Ziehl-Neelsen and fluorescent method revealed that it was more sensitive and less time consuming. Conclusion: Truenat MTB/RIF is a sensitive detection system for TB with rapid results, which serves as an important tool in the early management of tuberculosis patients and drug-resistant-TB cases. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This article reports a case of mediastinal lymph node tuberculosis with no obvious symptoms and a concealed focus. This patient, a 33‐year‐old male, suffered from pain behind the sternum after eating. He underwent three gastroscopic examinations and two fine needle punctures guided by ultrasound gastroscopy but was not diagnosed. Chest‐enhanced CT revealed a mediastinal mass compressing the adjacent esophagus, suggesting the possibility of enlarged lymph nodes. Furthermore, T cells from patients infected with tuberculosis tested positive. Ultrasound bronchoscopy revealed enlarged lymph nodes in area 7, and then EBUS‐TBNA was performed in that region. Only a few scattered lymphocytes and necrotic tissue were found under the biopsy microscope. The EBUS‐TBNA biopsy Xpert MTB/RIF showed low positive results, and the EBUS‐TBNA puncture fluid Xpert MTB/RIF was positive. Therefore, he was diagnosed with mediastinal lymph node tuberculosis. After antituberculosis treatment with the 2HREZ/10HRE regimen, the patient's pain behind the sternum gradually alleviated, and the enlarged mediastinal lymph nodes gradually narrowed. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is uncertainty about the risk of TB relapse in patients with TB and comorbidities requiring treatment with these agents. To assess the risk of TB relapse in patients (re-)started on TNF antagonists or JAK inhibitors. Systematic review. PubMed and Cochrane Library databases until 11 December 2023. Randomized control trials, prospective and retrospective cohort studies, case reports and case series. Patients with current or previous TB who were (re-)started on TNF antagonists or JAK inhibitors. (Re-)introduction of TNF antagonists and JAK inhibitors. All studies meeting entry criteria were included regardless of quality. Categorical data are presented as frequencies and percentages. For non-normally distributed aggregated data, we calculated the pooled weighted median with 95% CI. For individual patient data, the median and interquartile range (IQR) were calculated. Of 5018 articles screened for eligibility, 67 publications reporting on 368 TB patients who (re-)initiated treatment with TNF antagonists for underlying diseases were included. The median age was 42.5 years (95% CI: 40.4–42.5) and the proportion of female patients was 36.6% (n = 74) of patients whose sex was reported. A total of 14 patients (3.8%, 95% CI: 2.1–6.3%) developed TB relapse after a median of 8.5 months (interquartile range, 6.8–14.8 months) following (re-)initiation of anti-TNF treatment. Furthermore, among 251 articles screened for eligibility, 11 reports on TB patients who were (re-)started on JAK inhibitors for underlying diseases were identified. The median age was 62 years (interquartile range, 48.5–68.5 years) and 45.5% (n = 5) were female. Only one patient (9.1%; 95% CI: 0.2–41.3%) had TB reactivation 10 months after starting treatment with ruxolitinib. In addition, 94 patients who were treated with TNF antagonists and two patients temporarily treated with JAK inhibitors for the prevention or treatment of paradoxical reactions were analysed. None of the publications reported microbiological failure or worsening of TB-related symptoms. (Re-)initiation of TNF antagonists and JAK inhibitors may be relatively safe in patients with current or previous TB and the need for further treatment of underlying diseases. [ABSTRACT FROM AUTHOR]

Tuberculosis is still an endemic in many parts of the world. Vascular complications have been described in patients with tuberculosis and in aggressive chest infections such as actinomycoses. Etiology of internal mammary artery pseudoaneurysms includes iatrogenic causes or a complication of infection (mycotic aneurysm). Early diagnosis and treatment of these aneurysms are key to prevent complications such as hemorrhage, hemothorax, and hemorrhagic shock. In this case report, we describe the presentation and management of a 11-year-old patient with tuberculosis, who developed an internal mammary artery pseudoaneurysm during the course of treatment. We describe the case of a 11-year-old girl with known tuberculosis who developed a left internal mammary artery pseudoaneurysm, and treated with percutaneous ultrasound-guided glue embolization. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis often presents on imaging in the form of a solitary nodule, sometimes accompanied by elevated CEA, which is clinically difficult to differentiate from lung cancer and prone to misdiagnosis. Methods: Lung tissue taken by lung biopsy and sent for NGS and Xpert MTB/RIF finally led to the definitive diagnosis of nodular foci in the upper lobe of the left lung caused by tuberculosis. Results: Enhanced CT of the chest showed nodular foci in the upper lobe of the left lung. Initially the nodules were thought to be malignant, but after a series of tests, were finally confirmed to be tuberculosis. Conclusions: In patients with lung disease, when chest imaging reveals a space-occupying lesion accompanied by an elevated CEA level, a comprehensive analysis of the type of lung disease, the patient's age, and comorbidities should be performed before final diagnosis to avoid misdiagnosis and delay in appropriate treatment. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) was the leading cause of death from a single infectious agent before the coronavirus pandemic. Therefore, it is important to search for severity biomarkers and devise appropriate therapies. A total of 139 pulmonary TB (PTB) patients and 80 healthy controls (HCs) were recruited for plasma soluble CD137 (sCD137) detection through ELISA. Moreover, pleural effusion sCD137 levels were measured in 85 TB patients and 36 untreated lung cancer patients. The plasma cytokine levels in 64 patients with PTB and blood immune cell subpopulations in 68 patients with PTB were analysed via flow cytometry. Blood sCD137 levels were higher in PTB patients (p = 0.012) and correlated with disease severity (p = 0.0056). The level of sCD137 in tuberculous pleurisy effusion (TPE) was markedly higher than that in malignant pleurisy effusion (p = 0.018). Several blood cytokines, such as IL‐6 (p = 0.0147), IL‐8 (p = 0.0477), IP‐10 (p ≤ 0.0001) and MCP‐1 (p = 0.0057), and some laboratory indices were significantly elevated in severe PTB (SE) patients, but the percentages of total lymphocytes (p = 0.002) and cytotoxic T cells (p = 0.036) were significantly lower in SE patients than in non‐SE patients. In addition, the sCD137 level was negatively correlated with the percentage of total lymphocytes (p = 0.0008) and cytotoxic T cells (p = 0.0021), and PTB patients with higher plasma sCD137 levels had significantly shorter survival times (p = 0.0041). An increase in sCD137 is a potential biomarker for severe TB and indicates a poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary tuberculosis (PTB) remains a life-threatening disease in Tanzania, with negative physical, financial, economic and psychosocial consequences to individuals and the society. It mainly lowers the quality of life of patients, survivors and their families, especially those in the poorest and socially deprived categories. Objectives: To report and discuss a qualitative study that assessed the nature of social support desired and received by PTB patients and survivors. Participants were given a chance to share their experiences and their perceptions on whether the social support they desired had an impact on their treatmentseeking behaviour and treatment adherence. Methods: Face-to-face interviews were conducted with the three aforementioned groups, purposively selected at a TB clinic between October 2020 and March 2021. The questions covered topics related to the types of social support desired and the sources of support during and after treatment, if any. Interviews were concluded until no new information was obtained. Data analysis was facilitated using NVivo 12 software. Results: Participants pointed out a need for psychosocial, financial, and material support during and after treatment. However, they sometimes miss support from family/household members or the rest of the community. Because of this experience, they lived with difficulties, facing hardships when required to pay out of pocket for transport during the care-seeking. Survivors testified experience of a denial of support by even their close relatives who regarded them as no longer needing it after recovering. Patients and survivors also reported experience of social isolation as they were believed able to transmit PTB infections. Limited psychological support at the contacted TB clinics was another experience reported. TB clinic staff's experiences confirmed almost all the experiences shared by their clients. With limited support, resilience and self-care were identified as key mechanisms for coping. Conclusion: Complete recovery from PTB is possible, but reverting to a normal life is difficult without social support. Policies and programs need to increase opportunities for social support for TB patients and survivors. Doing so is likely to improve TB-related treatment, care-seeking practices, and adherence. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal‐associated invariant T (MAIT) cells play an important role in early anti‐TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non‐MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti‐TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4−CD8− cells, and very few were CD4+ cells. After BCG infecting autologous antigen‐presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1‐specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti‐TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti‐TB immunotherapy. [ABSTRACT FROM AUTHOR]