The Immune Response to Mycobacterium tuberculosis in HIV-1-Coinfected Persons.

Globally, about 36.7 million people were living with HIV infection at the end of 2015. The most frequent infection co-occurring with HIV-1 is Mycobacterium tuberculosis-374,000 deaths per annum are attributable to HIV-tuberculosis, 75% of those occurring in Africa. HIV-1 infection increases the risk of tuberculosis by a factor of up to 26 and alters its clinical presentation, complicates diagnosis and treatment, and worsens outcome. Although HIV-1-induced depletion of CD4+ T cells underlies all these effects, more widespread immune deficits also contribute to susceptibility and pathogenesis. These defects present a challenge to understand and ameliorate, but also an opportunity to learn and optimize mechanisms that normally protect people against tuberculosis. The most effective means to prevent and ameliorate tuberculosis in HIV-1-infected people is antiretroviral therapy, but this may be complicated by pathological immune deterioration that in turn requires more effective host-directed anti-inflammatory therapies to be derived.

Transcriptomics for child and adolescent tuberculosis.

Tuberculosis (TB) in humans is caused by Mycobacterium tuberculosis (Mtb). It is estimated that 70 million children (<15 years) are currently infected with Mtb, with 1.2 million each year progressing to disease. Of these, a quarter die. The risk of progression from Mtb infection to disease and from disease to death is dependent on multiple pathogen and host factors. Age is a central component in all these transitions. The natural history of TB in children and adolescents is different to adults, leading to unique challenges in the development of diagnostics, therapeutics, and vaccines. The quantification of RNA transcripts in specific cells or in the peripheral blood, using high-throughput methods, such as microarray analysis or RNA-Sequencing, can shed light into the host immune response to Mtb during infection and disease, as well as understanding treatment response, disease severity, and vaccination, in a global hypothesis-free manner. Additionally, gene expression profiling can be used for biomarker discovery, to diagnose disease, predict future disease progression and to monitor response to treatment. Here, we review the role of transcriptomics in children and adolescents, focused mainly on work done in blood, to understand disease biology, and to discriminate disease states to assist clinical decision-making. In recent years, studies with a specific pediatric and adolescent focus have identified blood gene expression markers with diagnostic or prognostic potential that meet or exceed the current sensitivity and specificity targets for diagnostic tools. Diagnostic and prognostic gene expression signatures identified through high-throughput methods are currently being translated into diagnostic tests.

Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies.

BACKGROUND: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. METHODS AND FINDINGS: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. CONCLUSIONS: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.

PRMT5 epigenetically regulates the E3 ubiquitin ligase ITCH to influence lipid accumulation during mycobacterial infection.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), triggers enhanced accumulation of lipids to generate foamy macrophages (FMs). This process has been often attributed to the surge in the expression of lipid influx genes with a concomitant decrease in those involved in lipid efflux. Here, we define an Mtb-orchestrated modulation of the ubiquitination of lipid accumulation markers to enhance lipid accretion during infection. We find that Mtb infection represses the expression of the E3 ubiquitin ligase, ITCH, resulting in the sustenance of key lipid accrual molecules viz. ADRP and CD36, that are otherwise targeted by ITCH for proteasomal degradation. In line, overexpressing ITCH in Mtb-infected cells was found to suppress Mtb-induced lipid accumulation. Molecular analyses including loss-of-function and ChIP assays demonstrated a role for the concerted action of the transcription factor YY1 and the arginine methyl transferase PRMT5 in restricting the expression of Itch gene by conferring repressive symmetrical H4R3me2 marks on its promoter. Consequently, siRNA-mediated depletion of YY1 or PRMT5 rescued ITCH expression, thereby compromising the levels of Mtb-induced ADRP and CD36 and limiting FM formation during infection. Accumulation of lipids within the host has been implicated as a pro-mycobacterial process that aids in pathogen persistence and dormancy. In line, we found that perturbation of PRMT5 enzyme activity resulted in compromised lipid levels and reduced mycobacterial survival in mouse peritoneal macrophages (ex vivo) and in a therapeutic mouse model of TB infection (in vivo). These findings provide new insights into the role of PRMT5 and YY1 in augmenting mycobacterial pathogenesis. Thus, we posit that our observations could help design novel adjunct therapies and combinatorial drug regimen for effective anti-TB strategies.

Ensuring universal access to quality care for persons with presumed tuberculosis reaching the private sector: lessons from Kerala.

BACKGROUND: More than half of the people with Tuberculosis (TB) symptoms in India seek care from the private sector. People with TB getting treatment from private sector in India are considered to be at a higher risk for receiving suboptimal quality of care in terms of incorrect diagnosis and treatment, lack of treatment adherence support with a high loss to follow-up rate that could eventually increase their risk of drug resistance. The current study aims at documenting the approach and efforts taken by the Kerala state to partner with the private health care delivery providers for ensuring quality TB care to the people with presumed TB reaching them. METHODS: A case study approach was adopted with review of all available literature followed by five Key Informant Interviews to understand the case through a primary descriptive exploration. Grounded theory approach was used to generating the single theory of the case itself that explains it. RESULTS: Kerala state has taken a variety of interventions to ensure universal access to TB care for citizens reaching the private sector with documented improvement in the quality of TB care. Key learnings from these initiatives were (i) patients need to be at the centre of partnerships, (ii) good governance is essential for ensuring Universal Health Coverage in a mixed health system, (iii) data intelligence is required to guide partnerships, (iv) identification of the correct 'problems' is crucial for effective design of partnerships and (v) a platform for meaningful dialogue of key stakeholders is needed. CONCLUSION: Kerala experience demonstrated that if governments take a proactive role in engaging the private sector, in an informed and evidence-based way, they can leverage the advantages of the private sector while protecting the public health interest.

A multi-cohort study of the immune factors associated with M. tuberculosis infection outcomes.

Most infections with Mycobacterium tuberculosis (Mtb) manifest as a clinically asymptomatic, contained state, known as latent tuberculosis infection, that affects approximately one-quarter of the global population1. Although fewer than one in ten individuals eventually progress to active disease2, tuberculosis is a leading cause of death from infectious disease worldwide3. Despite intense efforts, immune factors that influence the infection outcomes remain poorly defined. Here we used integrated analyses of multiple cohorts to identify stage-specific host responses to Mtb infection. First, using high-dimensional mass cytometry analyses and functional assays of a cohort of South African adolescents, we show that latent tuberculosis is associated with enhanced cytotoxic responses, which are mostly mediated by CD16 (also known as FcγRIIIa) and natural killer cells, and continuous inflammation coupled with immune deviations in both T and B cell compartments. Next, using cell-type deconvolution of transcriptomic data from several cohorts of different ages, genetic backgrounds, geographical locations and infection stages, we show that although deviations in peripheral B and T cell compartments generally start at latency, they are heterogeneous across cohorts. However, an increase in the abundance of circulating natural killer cells in tuberculosis latency, with a corresponding decrease during active disease and a return to baseline levels upon clinical cure are features that are common to all cohorts. Furthermore, by analysing three longitudinal cohorts, we find that changes in peripheral levels of natural killer cells can inform disease progression and treatment responses, and inversely correlate with the inflammatory state of the lungs of patients with active tuberculosis. Together, our findings offer crucial insights into the underlying pathophysiology of tuberculosis latency, and identify factors that may influence infection outcomes.

Depression care integration in tuberculosis services: A feasibility assessment in Pakistan.

BACKGROUND: The co-occurrence of depression among tuberculosis (TB) patients is a critical issue, contributing to poor treatment outcomes, prolonged hospitalisations and increased healthcare expenses. OBJECTIVE: The objective of this study was to assess the feasibility of delivering a co-designed depression care pathway within TB services in Pakistan. DESIGN: Mixed-method study. SETTING AND PARTICIPANTS: Routine depression screening for TB patients was conducted at three TB facilities in Peshawar, Pakistan, encompassing primary, secondary and tertiary care settings. All patients aged 18 or above (male and female) attending the three TB facilities between November 2021 and February 2022 were included in the study using the consecutive sampling technique. RESULTS: A total of 301 people with confirmed TB, within the past 4 weeks, visited the three TB care facilities; 191/301 patients were screened for depression. Approximately 35% of the 191 TB patients screened positive for depression, with varying severity levels. Qualitative findings highlighted the acceptability of integrated depression care, emphasising the importance of open communication and empathetic attitudes. Barriers to integration include stigma, logistical challenges, patient noncompliance and cost burdens. Facilitators included the empathetic attitude of healthcare providers and the availability of mental health services within the same facility. CONCLUSION: There is a high burden of depression in patients with TB, highlighting the pressing need for mental health support in this population. Acceptability of integrated care was evident, with factors such as co-located mental health services, training healthcare providers and provider empathetic attitudes playing a crucial role. Further research is required to evaluate the effectiveness of the integrated TB-depression screening systems towards improved health outcomes, implementation, scalability and impact on the broader healthcare system. PATIENT AND PUBLIC CONTRIBUTION: To create a more inclusive and comprehensive TB and depression care pathway, we gathered input from both service providers and service users (TB patients, their carers). Reflective meetings with community leaders, social activists and health professionals from various sectors were also conducted during pathway delivery to get their insights. Power, gender and age imbalances were addressed by encouraging participation of patients and carers across gender and age groups. This approach ensured that the perspectives of all stakeholders were considered in the development of the care pathway.

The collaborative framework for the management of tuberculosis and type 2 diabetes syndemic in low- and middle-income countries: a rapid review.

INTRODUCTION: Given the absence of international guidelines on the joint management and control of tuberculosis (TB) and type 2 diabetes mellitus (T2D), the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (The Union) launched in 2011 a policy framework to address the growing syndemic burden of TB-T2D. This review aimed at mapping the available evidence on the implementation of the Union-WHO Framework, explicitly, or bi-directional TB-T2D health programs as an initiative for co-management in patients in low- and middle-income countries (LMIC). METHODS: A rapid review was performed based on a systematic search in PubMed and Web of Science electronic databases for peer-reviewed articles on The Union-WHO Framework and bi-directional interventions of TB and T2D in LMIC. The search was restricted to English language articles and from 01/08/2011 to 20/05/2022. RESULTS: A total of 24 articles from 16 LMIC met the inclusion criteria. Four described the implementation of The Union-WHO Framework and 20 on the bi-directional interventions of TB and T2D. Bi-directional activities were found valuable, feasible and effective following the Union-WHO recommendations. Limited knowledge and awareness on TB-T2D comorbidity was identified as one of the barriers to ensure a functional and effective integration of services. CONCLUSIONS: This review revealed that it is valuable, feasible and effective to implement bi-directional TB and T2D activities (screening and management) according to the Union-WHO Framework recommendations, especially in countries that face TB-T2D syndemic. Additionally, it was apparent that gaps still exist in research aimed at providing evidence of costs to implement collaborative activities. There is need for TB and T2D services integration that should be done through the well-stablished TB programme. This integration of two vertical programmes, could ensure patient-centeredness, continuum of care and ultimately contribute for health systems strengthening.

Impact of the COVID-19 pandemic on quality of tuberculosis care in private facilities in Bandung, Indonesia: a repeated cross-sectional standardized patients study.

BACKGROUND: Indonesia has the second highest incidence of tuberculosis in the world. While 74% of people with tuberculosis in Indonesia first accessed the private health sector when seeking care for their symptoms, only 18% of tuberculosis notifications originate in the private sector. Little is known about the impact of the COVID-19 pandemic on the private sector. Using unannounced standardized patient visits to private providers, we aimed to measure quality of tuberculosis care during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted using standardized patients in Bandung City, West Java, Indonesia. Ten standardized patients completed 292 visits with private providers between 9 July 2021 and 21 January 2022, wherein standardized patients presented a presumptive tuberculosis case. Results were compared to standardized patients surveys conducted in the same geographical area before the onset of COVID-19. RESULTS: Overall, 35% (95% confidence interval (CI): 29.2-40.4%) of visits were managed correctly according to national tuberculosis guidelines. There were no significant differences in the clinical management of presumptive tuberculosis patients before and during the COVID-19 pandemic, apart from an increase in temperature checks (adjusted odds ratio (aOR): 8.05, 95% CI: 2.96-21.9, p < 0.001) and a decrease in throat examinations (aOR 0.16, 95% CI: 0.06-0.41, p = 0.002) conducted during the pandemic. CONCLUSIONS: Results indicate that providers successfully identify tuberculosis in their patients yet do not manage them according to national guidelines. There were no major changes found in quality of tuberculosis care due to the COVID-19 pandemic. As tuberculosis notifications have declined in Indonesia due to the COVID-19 pandemic, there remains an urgent need to increase private provider engagement in Indonesia and improve quality of care.

Availability and readiness of health facilities providing services for other infectious diseases to treat neglected tropical diseases in Ethiopia: implications for service integration in high burden areas.

BACKGROUND: The burden of neglected tropical diseases (NTDs), HIV/AIDS, tuberculosis, and malaria pose significant public health challenges in Ethiopia. This study aimed to the explore service availability and readiness for NTD care among Ethiopian health facilities treating tuberculosis (TB), HIV/AIDS, and/or malaria. METHODS: This study utilized secondary data from the Ethiopian Service Provision Assessment 2021-22 survey. The availability of services was calculated as the percentage of HIV/AIDS, tuberculosis, or malaria facilities providing NTD services. Facilities were considered highly prepared to manage any type of NTD if they scored at least half (> 50%) of the tracer items listed in each of the three domains (staff training and guidelines, equipment, and essential medicines). Descriptive statistics and logistic regression models were employed to present the study findings and analyze factors influencing facility readiness, respectively. RESULTS: Out of 403 health facilities providing NTD care nationally, 179, 183, and 197 also offer TB, HIV/AIDS, and malaria services, respectively. The majority of TB (90.1%), HIV/AIDS (89.6%), and malaria (90.9%) facilities offer soil-transmitted helminth services, followed by trachoma (range 87-90%). The percentages of the aforementioned facilities with at least one trained staff member for any type of NTD were 87.2%, 88.4%, and 82.1%, respectively. The percentage of facilities with guidelines for any type of NTD was relatively low (range 3.7-4.1%). Mebendazole was the most widely available essential medicine, ranging from 69 to 70%. The overall readiness analysis indicated that none of the included facilities (TB = 11.9%; HIV/AIDS = 11.6%; and malaria = 10.6%) were ready to offer NTD care. Specifically, a higher level of readiness was observed only in the domain of medicines across these facilities. Hospitals had better readiness to offer NTD care than did health centers and clinics. Furthermore, a significant associations were observed between facility readiness and factors such as facility type, region, presence of routine management meetings, types of NTD services provided, and fixed costs for services. CONCLUSIONS: Ethiopian health facilities treating TB, HIV/AIDS, and malaria had an unsatisfactory overall service availability and a lack of readiness to provide NTD care. Given the existing epidemiological risks and high burden of TB, HIV/AIDS, malaria, and NTDs in Ethiopia, there is an urgent need to consider preparing and implementing a collaborative infectious disease care plan to integrate NTD services in these facilities.

Patient level barriers to accessing TB care services during the COVID-19 pandemic in Uganda, a mixed methods study.

INTRODUCTION: Lockdown measure has been utilized widely to mitigate COVID-19 pandemic transmission and recently during the 2022 Sudan Ebola Virus Disease outbreak in Uganda. These have setback effects on the continuity of essential health services such as tuberculosis (TB) care, reversing progress made in the fight against tuberculosis (TB) over the past decade. We set out to understand patient-reported barriers to accessing TB care services during the COVID-19 pandemic in Uganda. METHODS: Mixed methods study involving review of medical records of TB patients who received TB care from January to September 2020. We used quantitative and qualitative methods including phone questionnaires and in-depth interviews. We carried out descriptive statistics, a chi-square test and conducted a thematic analysis. RESULTS: We carried out phone interviews with 672 participants. The majority (60%) were male and with an average of 35 years (SD:11). A significantly higher proportion of patients reported a barrier to TB care access during the COVID-19 lockdown than pre-lockdown (79.9% vs. 68.1% p = 0.027). We carried out in-depth interviews with 28 participants (54% (15/28): male). Barriers experienced by these participants included lack of a means of transport to reach the health facility, lack of money to pay the transport fares, long distances to the facility, fear of COVID-19 infection, stigma due to overlap between TB and COVID-19 symptoms, and few health care workers available during the lockdown period. CONCLUSION: Lockdown measures instituted to mitigate the transmission of COVID1-19 affected access to TB care services in Uganda. Uganda is at risk of future emerging and re-emerging diseases of epidemic potential. Therefore, there should be measures to ensure the continuity of essential services such as tuberculosis care during the implementation of future epidemic response interventions such as a lockdown.

Impact of an innovative bundled payment to TB health care providers in China: an economic simulation analysis.

BACKGROUND: Tuberculosis is the second most deadly infectious disease after COVID-19 and the 13th leading cause of death worldwide. Among the 30 countries with a high burden of TB, China ranks third in the estimated number of TB cases. China is in the top four of 75 countries with a deficit in funding for TB strategic plans. To reduce costs and improve the effectiveness of TB treatment in China, the NHSA developed an innovative BP method. This study aimed to simulate the effects of this payment approach on different stakeholders, reduce the economic burden on TB patients, improve the quality of medical services, facilitate policy optimization, and offer a model for health care payment reforms that can be referenced by other regions throughout the world. METHODS: We developed a simulation model based on a decision tree analysis to project the expected effects of the payment method on the potential financial impacts on different stakeholders. Our analysis mainly focused on comparing changes in health care costs before and after receiving BPs for TB patients with Medicare in the pilot areas. The data that were used for the analysis included the TB service claim records for 2019-2021 from the health insurance agency, TB prevalence data from the local Centre for Disease Control, and health care facilities' revenue and expenditure data from the Statistic Yearbook. A Monte Carlo randomized simulation model was used to estimate the results. RESULTS: After adopting the innovative BP method, for each TB patient per year, the total annual expenditure was estimated to decrease from $2,523.28 to $2,088.89, which is a reduction of $434.39 (17.22%). The TB patient out-of-pocket expenditure was expected to decrease from $1,249.02 to $1,034.00, which is a reduction of $215.02 (17.22%). The health care provider's revenue decreased from $2,523.28 to $2,308.26, but the health care provider/institution's revenue-expenditure ratio increased from -6.09% to 9.50%. CONCLUSIONS: This study highlights the potential of BPs to improve medical outcomes and control the costs associated with TB treatment. It demonstrates its feasibility and advantages in enhancing the coordination and sustainability of medical services, thus offering valuable insights for global health care payment reform.

Assessing the impact of COVID-19 management on the workload of human resources working in India's National Tuberculosis Elimination Program.

BACKGROUND: In 1993, WHO declared tuberculosis (TB) as a global health emergency considering 10 million people are battling TB, of which 30% are undiagnosed annually. In 2020 the COVID-19 pandemic took an unprecedented toll on health systems in every country. Public health staff already engaged in TB control and numerous other departments were additionally tasked with managing COVID-19, stretching human resource (HR) capacity beyond its limits. As part of an assessment of HR involved in TB control in India, The World Bank Group and partners conducted an analysis of the impact of COVID-19 on TB human resources for health (HRH) workloads, with the objective of describing the extent to which TB-related activities could be fulfilled and hypothesizing on future HR requirements to meet those needs. METHODS: The study team conducted a Workload Indicators and Staffing Needs (WISN) analysis according to standard WHO methodology to classify the workloads of priority cadres directly or indirectly involved in TB control activities as over-, adequately or under-worked, in 18 districts across seven states in India. Data collection was done via telephone interviews, and questions were added regarding the proportion of time dedicated to COVID-19 related tasks. We carried out quantitative analysis to describe the time allocated to COVID-19 which otherwise would have been spent on TB activities. We also conducted key informant interviews (KII) with key TB program staff about HRH planning and task-shifting from TB to COVID-19. RESULTS: Workload data were collected from 377 respondents working in or together with India's Central TB Division (CTD). 73% of all respondents (n = 270) reported carrying out COVID-19 tasks. The average time spent on COVID-19 tasks was 4 h / day (n = 72 respondents). Multiple cadres highly instrumental in TB screening and diagnosis, in particular community outreach (ASHA) workers and CBNAAT/TrueNAAT laboratory technicians working at peripheral, block and district levels, were overworked, and spending more than 50% of their time on COVID-19 tasks, reducing time for TB case-finding. Qualitative interviews with laboratory technicians revealed that PCR machines previously used for TB testing were repurposed for COVID-19 testing. CONCLUSIONS: The devastating impact of COVID-19 on HR capacity to conduct TB case-finding in India, as in other settings, cannot be overstated. Our findings provide clear evidence that NTEP human resources did not have time or essential material resources to carry out TB tasks during the COVID pandemic without doing substantial overtime and/or compromising on TB service delivery. To minimize disruptions to routine health services such as TB amidst future emerging infectious diseases, we would do well, during periods of relative calm and stability, to strategically map out how HRH lab staff, public health resources, such as India's Health and Wellness Centers and public health cadre, and public-private sector collaboration can most optimally absorb shocks to the health system.

Towards universal health coverage in Vietnam: a mixed-method case study of enrolling people with tuberculosis into social health insurance.

BACKGROUND: Vietnam's primary mechanism of achieving sustainable funding for universal health coverage (UHC) and financial protection has been through its social health insurance (SHI) scheme. Steady progress towards access has been made and by 2020, over 90% of the population were enrolled in SHI. In 2022, as part of a larger transition towards the increased domestic financing of healthcare, tuberculosis (TB) services were integrated into SHI. This change required people with TB to use SHI for treatment at district-level facilities or to pay out of pocket for services. This study was conducted in preparation for this transition. It aimed to understand more about uninsured people with TB, assess the feasibility of enrolling them into SHI, and identify the barriers they faced in this process. METHODS: A mixed-method case study was conducted using a convergent parallel design between November 2018 and January 2022 in ten districts of Hanoi and Ho Chi Minh City, Vietnam. Quantitative data were collected through a pilot intervention that aimed to facilitate SHI enrollment for uninsured individuals with TB. Descriptive statistics were calculated. Qualitative interviews were conducted with 34 participants, who were purposively sampled for maximum variation. Qualitative data were analyzed through an inductive approach and themes were identified through framework analysis. Quantitative and qualitative data sources were triangulated. RESULTS: We attempted to enroll 115 uninsured people with TB into SHI; 76.5% were able to enroll. On average, it took 34.5 days to obtain a SHI card and it cost USD 66 per household. The themes indicated that a lack of knowledge, high costs for annual premiums, and the household-based registration requirement were barriers to SHI enrollment. Participants indicated that alternative enrolment mechanisms and greater procedural flexibility, particularly for undocumented people, is required to achieve full population coverage with SHI in urban centers. CONCLUSIONS: Significant addressable barriers to SHI enrolment for people affected by TB were identified. A quarter of individuals remained unable to enroll after receiving enhanced support due to lack of required documentation. The experience gained during this health financing transition is relevant for other middle-income countries as they address the provision of financial protection for the treatment of infectious diseases.

Exploring the Potential of Exosomes as Biomarkers in Tuberculosis and Other Diseases.

Tuberculosis (TB) is a major cause of morbidity and mortality and remains an important public health issue in developing countries worldwide. The existing methods and techniques available for the diagnosis of TB are based on combinations of laboratory (chemical and biological), radiological, and clinical tests. These methods are sophisticated and laborious and have limitations in terms of sensitivity, specificity, and accuracy. Clinical settings need improved diagnostic biomarkers to accurately detect biological changes due to pathogen invasion and pharmacological responses. Exosomes are membrane-bound vesicles and mediators of intercellular signaling processes that play a significant role in the pathogenesis of various diseases, such as tuberculosis, and can act as promising biomarkers for the monitoring of TB infection. Compared to conventional biomarkers, exosome-derived biomarkers are advantageous because they are easier to detect in different biofluids, are more sensitive and specific, and may be useful in tracking patients' reactions to therapy. This review provides insights into the types of biomarkers, methods of exosome isolation, and roles of the cargo (proteins) present in exosomes isolated from patients through omics studies, such as proteomics. These findings will aid in developing new prognostic and diagnostic biomarkers and could lead to the identification of new therapeutic targets in the clinical setting.

[Expert recommendations for internet medical care treatment of tuberculosis].

Tuberculosis, a chronic infectious disease caused by Mycobacterium tuberculosis, has long posed significant challenges to both medical professionals and patients in its diagnosis and treatment. The need for regular follow-up visits has resulted in a significant economic and logistical burden for patients and a strain on healthcare resources. However, the recent rapid development of Internet technology has significantly enhanced the role of telemedicine in the health care of tuberculosis. This proposal aims to provide a comprehensive overview of the various aspects of telemedicine in the management of tuberculosis. It covers functional positioning, medical qualifications, scope of application, management team, operational model, medical standards, medication evaluation, precautions, risk management. It is intended to serve as a reference for healthcare professionals in the practical application of telemedicine in tuberculosis care.【Expert Recommendation 1】: To provide the further online services for tuberculosis patients who have already had a face-to-face consultation and been diagnosed with tuberculosis. Telemedicine in tuberculosis care includes confirmation of diagnosis, treatment, health counseling, management, educational initiatives, and the initial assessment and management of new symptoms and signs.【Expert Recommendation 2】: The qualifications for telemedicine in tuberculosis care require that the attending physician has a valid medical license and has at least three years of clinical experience in tuberculosis.【Expert Recommendation 3】: The primary target group for online tuberculosis care are patients who are undergoing routine follow-up visits. Certain examinations and test results are mutually recognized within certain regions.【Expert Recommendation 4】: The management team for telemedicine in tuberculosis care is consist of specialist physicians from tuberculosis medical institutions or third-party internet medical organizations, together with information technology staff.【Expert Recommendation 5】: The informatization framework for telemedicine in tuberculosis care includes referrals between higher and lower-level institutions, as well as online and offline referrals. Methods for online follow-up consultations include text-based and video consultations.【Expert Recommendation 6】: Standards for telemedicine in tuberculosis care must be in line with government documents. Regular monitoring and evaluation of the safety and efficacy of anti-tuberculosis therapy is needed, with guidance for patients to seek further treatment at an offline medical institution if necessary.【Expert Recommendation 7】: The attending physician must comply with regulations when documenting patient care and issuing prescriptions, which are valid only after review and approval by a pharmacist.【Expert Recommendation 8】: Healthcare providers are encouraged to use digital platforms, including social media, short video platforms, and mini-programs, to disseminate health information to patients and their families.【Expert Recommendation 9】: If the attending physician discovers adverse events in internet medical treatment, it is necessary to report them immediately to the adverse reaction reporting system of the hospital relying on internet medical treatment.【Expert Recommendation 10】: The attending physician should handle any disputes or complaints about online diagnosis and treatment in accordance with applicable laws, regulations, and guidelines.【Expert Recommendation 11】: Strict confidentiality of patient information must be maintained in online tuberculosis care, and patient consent before data can be used for educational or research purposes.【Expert Recommendation 12】: For primary care facilities that do not have the necessary resources for online diagnosis and treatment, we recommend establishing satellite centers, implementing simplified remote care systems, and utilizing mobile devices in collaboration with nearby hospitals that can provide remote care. This approach aims to increase the capacity of primary care facilities to provide telemedicine service.

[Rigid bronchoscopy combined with flexible bronchoscopy for treatment of central airway stenosis caused by tuberculous tracheobronchial fistula: report of 2 cases].

Tuberculous tracheobronchial fistulas are caused by mediastinal or hilar tuberculous lymph nodes ulcerating into the trachea or bronchus. Patients usually require flexible bronchoscopic interventional procedures in addition to systemic anti-tuberculosis chemotherapy in the ulceration phase. In this paper, we reported 2 cases of central airway stenosis caused by tuberculous tracheobronchial fistula, which had poor treatment results after flexible bronchoscopy. According to the patients' condition, the airway lesions were treated by rigid bronchoscopy combined with flexible bronchoscopy, cryotherapy, argon plasma coagulation, and so on. The central airway stenosis was resolved quickly, and the caseating lymph node tissue was removed as much as possible under the premise of ensuring safety, which shortened the recovery time of tuberculous fistula.

[Retrospective analysis of diagnosis and treatment of tuberculosis in designated medical institutions in China from 2017 to 2022].

Objective: To understand the status of tuberculosis diagnosis and treatment capacity and the development and changes of tuberculosis diagnosis and treatment in provincial and municipal designated medical institutions in China from 2017 to 2022, so as to provide a basis for the formulation of relevant policies for the improvement and development of designated medical institutions for tuberculosis and the tuberculosis prevention and treatment service system, and to provide reasonable support for further strengthening the capacity of designated medical institutions for tuberculosis. Methods: This study was initiated and carried out by Beijing Chest Hospital affiliated to Capital Medical University/Clinical Center for Tuberculosis Prevention and Control of China CDC (hereinafter referred to as "Clinical Center") by means of questionnaire survey, and the investigation was carried out from March to November 2023. During this period, the clinical center distributed questionnaires to the hospital member units of "Beijing Tuberculosis Diagnosis and Treatment Technology Innovation Alliance", retrospectively collected their tuberculosis-related diagnosis and treatment data from 2017 to 2022, and used descriptive statistical methods to analyze the number of tuberculosis beds, outpatients and hospitalizations in medical institutions. The results were expressed in absolute numbers (percentages), and three-line tables, bar charts and line charts were drawn to describe the analysis results and changing trends. Results: The 54 medical institutions surveyed in this survey included 21 provincial-level designated medical institutions and 33 prefecture-level designated medical institutions. Most medical institutions have set up clinical departments, auxiliary departments and functional departments to undertake public health tasks of infectious diseases. The tuberculosis laboratory in the hospital has a comprehensive ability and has the detection technology needed for most tuberculosis diagnosis; The number of tuberculosis beds, children's tuberculosis beds and ICU beds all showed an increasing trend from 2017 to 2022. The proportion of tuberculosis beds in the hospital decreased slightly, from 39.31% in 2017 to 34.76% in 2022, showing a slight downward trend. Compared with the hospital surveyed, the number of tuberculosis outpatients in 2019 was 562 029, and the number of outpatients in 2020-2022 was 462 328, 519 630 and 424 069 respectively, which was significantly lower than that in 2019. The number of tuberculosis outpatients in medical institutions decreased significantly from 2020 to 2022. By analyzing the proportion of patients with different types of tuberculosis, the proportion of sensitive tuberculosis outpatients in 2017-2022 decreased from 84.49% in 2017 to 78.05% in 2022, showing a downward trend year by year. The proportion of patients with multidrug-resistant/ rifampin-resistant tuberculosis increased from 2.03% in 2017 to 7.18% in 2022. From 2017 to 2019, the total number of inpatients with tuberculosis showed an upward trend. Compared with 2019, the number of inpatients in 2020, 2021 and 2022 showed a downward trend, and the decline in 2020 was large (down 14.94% compared with 2019). Among the inpatients, the absolute number and proportion of patients with sensitive pulmonary tuberculosis remained relatively stable, and the number and proportion of inpatients with multidrug-resistant/rifampin-resistant pulmonary tuberculosis increased year by year. Conclusions: Most medical institutions have the capacity to carry out routine diagnosis and treatment of tuberculosis, but the public health function needs to be strengthened. The transformation of medical institutions requires proper guidance and adequate support. During 2019-2022, most medical institutions were affected by the COVID-19 epidemic, and their tuberculosis diagnosis and treatment work also changed to varying degrees. During this period, hospitals took various measures to overcome difficulties and tried their best to maintain the normal development of tuberculosis diagnosis and treatment, and the tuberculosis diagnosis and treatment work of various institutions gradually resumed in 2022.

Challenges and Barriers Faced by People with TB and Healthcare Workers Providing TB Care and Management - A Qualitative Study.

BACKGROUND: In tuberculosis (TB) care and management, there are practical challenges existing at the patient-provider level leading to implementation barriers at the primary care level. OBJECTIVES: The objective of the study is to explore the challenges and barriers faced by people with TB and health-care workers in TB care and management. MATERIALS AND METHODS: This study was done as a part of a community intervention study between November 2021 and December 2022. Twenty interviews were taken with treatment for TB (n = 7) and health-care personnel (n = 13). Health-care personnel include nursing staff, medical officers, laboratory technicians, community health workers, and medical personnel from tertiary care hospital. Participants were recruited across all levels of health-care systems. Interviews were carried out in the Hindi language, audio recorded, and translated to English. Participants were asked about their experiences of challenges and barriers faced during TB care and management. Qualitative data were coded, and thematic analysis was done manually. RESULTS: The challenges and barriers at the level of people with TB were issues with communication between providers and people with TB, out-of-pocket expenditure, poor adherence to medicines, lack of proper diet, gender issues, and stigma. The challenges and barriers at the level of health-care providers were a lack of infrastructure and logistics, lack of awareness, COVID-19-related issues, lack of workforce, and technical issues. CONCLUSION: Communication between providers and people with TB must be improved to improve the drug adherence and satisfaction of the end user. Proper funding must be provided for the TB programs. People with TB must be counseled properly regarding the free health care services available near their homes to prevent out-of-pocket expenditure. These will help in fast-tracking the elimination of TB.

Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis.

Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during antituberculosis treatment to support hemoglobin (Hb) recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, as well as changes in inflammation and iron metabolism indices. In a 26-week prospective study, Tanzanian adults with tuberculosis (N = 18) were studied before treatment and then every 2 weeks during treatment; oral and intravenous iron tracers were administered before treatment and after intensive phase (8/12 weeks) and complete treatment (24 weeks). No iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (∼80%), and iron absorption was negligible (<1%). During treatment, hepcidin and interleukin-6 levels decreased ∼70% after only 2 weeks (P< .001); in contrast, ERFE did not significantly decrease until 8 weeks (P< .05). ERFE and interleukin-6 were the main opposing determinants of hepcidin (P< .05), and greater ERFE was associated with reticulocytosis and Hb repletion (P< .01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (P< .01), indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ∼20-fold (P< .001), and Hb increased ∼25% (P< .001). In tuberculosis-associated anemia of inflammation, our findings suggest that elevated ERFE is unable to suppress hepcidin, and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well absorbed only after tuberculosis treatment, and supplementation should be reserved for patients remaining anemic after treatment. This trial was registered at www.clinicaltrials.gov as #NCT02176772.