UNASSIGNED: To effectively control tuberculosis (TB), it is crucial to distinguish between active TB disease and latent TB infection (LTBI) to provide appropriate treatment. However, no such tests are currently available. Immune responses associated with active TB and LTBI are dynamic and exhibit distinct patterns. Comparing these differences is crucial for developing new diagnostic methods and understanding the etiology of TB. This study aimed to investigate the relationship between pro- and anti-inflammatory CD4+ cytokine production following stimulation with two types of latency-associated Mycobacterium tuberculosis (M.tb) antigens to allow differentiation between active TB and LTBI.
UNASSIGNED: Cryopreserved PBMCs from patients with active TB disease or LTBI were stimulated overnight with replication-related antigen [ESAT-6/CFP-10 (E/C)] or two latency-associated antigens [heparin-binding hemagglutinin (HBHA) and alpha-crystallin-like protein (Acr)]. Responses were analyzed using multiparameter flow cytometry: active TB disease (n=15), LTBI (n=15) and ELISA: active TB disease (n=26) or LTBI (n=27).
UNASSIGNED: CD4+ central memory T cells (Tcm) specific to E/C and CD4+ effector memory T cells specific to Acr and HBHA were higher in LTBI than in TB patients. IFN-γ+Tcm and IL-17+ Tem cells was higher in the LTBI group (p= 0.012 and p=0.029 respectively), but IL-10+ Tcm was higher in the active TB group (p= 0.029) following HBHA stimulation. Additionally, following stimulation with HBHA, IL-10 production from CD4+ T cells was significantly elevated in patients with active TB compared to those with LTBI (p= 0.0038), while CD4+ T cell production of IL-17 and IFN-γ was significantly elevated in LTBI compared to active TB (p= 0.0076, p< 0.0001, respectively). HBHA also induced more CCR6+IL-17+CD4Tcells and IL-17+FoxP3+CD25+CD4Tcells in LTBI than in TB patients (P=0.026 and P=0.04, respectively). HBHA also induced higher levels of IFN-γ+IL-10+CD4+ T cells in patients with active TB (Pp=0.03) and higher levels of IFN-γ+IL-17+ CD4+ T cells in those with LTBI (p=0.04). HBHA-specific cytokine production measured using ELISA showed higher levels of IFN-γ in participants with LTBI (P=0.004) and higher levels of IL-10 in those with active TB (P=0.04).
UNASSIGNED: Stimulation with HBHA and measurement of CD4+ T cell production of IFN-γ, IL-10, and IL-17 could potentially differentiate active TB from LTBI. The characteristics of cytokine-expressing cells induced by HBHA also differed between participants with active TB and LTBI.

To reach the millions of people with tuberculosis (TB) undiagnosed each year, there is an important need to provide people-centered screening and testing services. Despite people-centered care being a key pillar of the WHO END-TB Strategy, there have been few attempts to formally characterize and integrate the preferences of people most affected by TB - including those who have increased exposure to TB, limited access to services, and/or are at increased risk for TB - into new tools and strategies to improve screening and diagnosis. This perspective emphasizes the importance of preference research among people most affected by TB, provides an overview of qualitative preference exploration and quantitative preference elicitation research methods, and outlines how preferences can be applied to improve the acceptability, accessibility, and appropriateness of TB screening and testing services via four key opportunities. These include the following: (1) Defining the most preferred features of novel screening, triage, and diagnostic tools, (2) exploring and prioritizing setting-specific barriers and facilitators to screening and testing, (3) understanding what features of community- and facility-based strategies for improving TB detection and treatment are most valued, and (4) identifying the most relevant and resonant communication strategies to increase individual- and community-level awareness and demand. Preference research studies and translation of their findings into policy/guidance and operationalization have enormous potential to close the existing gaps in detection in high burden settings by enhancing the people-centeredness and reach of screening and diagnostic services to people most affected by TB who are currently being missed and left behind.

METHODS: Daru Island in Papua New Guinea (PNG) has a high prevalence of TB and multidrug-resistant TB (MDR-TB).
OBJECTIVE: To evaluate the early implementation of a community-wide project to detect and treat TB disease and infection, outline the decision-making processes, and change the model of care.
METHODS: A continuous quality improvement (CQI) initiative used a plan-do-study-act (PDSA) framework for prospective implementation. Care cascades were analysed for case detection, treatment, and TB preventive treatment (TPT) initiation.
RESULTS: Of 3,263 people screened for TB between June and December 2023, 13.7% (447/3,263) screened positive (CAD4TB or symptoms), 77.9% (348/447) had Xpert Ultra testing, 6.9% (24/348) were diagnosed with TB and all initiated treatment. For 5-34-year-olds without active TB (n = 1,928), 82.0% (1,581/1,928) had tuberculin skin testing (TST), 96.1% (1,519/1,581) had TST read, 23.0% (350/1,519) were TST-positive, 95.4% (334/350) were TPT eligible, and 78.7% (263/334) initiated TPT. Three PDSA review cycles informed adjustments to the model of care, including CAD4TB threshold and TPT criteria. Key challenges identified were meeting screening targets, sputum unavailability from asymptomatic individuals with high CAD4TB scores, and consumable stock-outs.
CONCLUSIONS: CQI improved project implementation by increasing the detection of TB disease and infection and accelerating the pace of screening needed to achieve timely community-wide coverage.
BACKGROUND: L\'île de Daru en Papouasie-Nouvelle-Guinée (PNG) présente une forte prévalence de la TB et de la TB multirésistante (MDR-TB).
OBJECTIVE: Évaluer la mise en œuvre précoce d\'un projet à l\'échelle de la communauté pour détecter et traiter la TB et l\'infection, décrire les processus de prise de décision et changer le modèle de soins.
UNASSIGNED: Une initiative d\'amélioration continue de la qualité (CQI, pour l’anglais « continuous quality improvement ») a utilisé un cadre de planification, d\'action, d\'étude, d\'action (PDSA, pour l’anglais «plan-do-study-act ») pour la mise en œuvre prospective. Les cascades de soins ont été analysées pour la détection des cas, le traitement et l\'initiation du traitement préventif de la TB.
UNASSIGNED: Sur 3 263 personnes dépistées pour la TB entre juin et décembre 2023, 13,7% (447/3 263) ont été dépistées positives (CAD4TB ou symptômes), 77,9% (348/447) ont subi un test Xpert Ultra, 6,9% (24/348) ont reçu un diagnostic de TB et toutes ont commencé un traitement. Chez les 5 à 34 ans sans TB active (n = 1 928), 82,0% (1 581/1 928) ont subi un test cutané à la tuberculine (TCT), 96,1% (1 519/1 581) ont eu un test de dépistage du TCT, 23,0% (350/1 519) étaient positifs au TCT, 95,4% (334/350) étaient éligibles au TPT et 78,7% (263/334) ont initié le TPT. Trois cycles d\'examen PDSA ont permis d\'ajuster le modèle de soins, y compris le seuil CAD4TB et les critères TPT. Les principaux défis identifiés étaient l\'atteinte des objectifs de dépistage, l\'indisponibilité des expectorations chez les personnes asymptomatiques avec des scores CAD4TB élevés et les ruptures de stock de consommables.
CONCLUSIONS: L\'ACQ a amélioré la mise en œuvre du projet en augmentant la détection de la TB et de l\'infection et en accélérant le rythme de dépistage nécessaire pour atteindre une couverture à l\'échelle de la communauté en temps opportun.

BACKGROUND: India\'s National TB Elimination Programme (NTEP) aims to eliminate TB-related catastrophic expenditure by offering free diagnosis and treatment. However, 3.9% of TB patients have drug-resistant TB (DR-TB) and are facing higher costs.
OBJECTIVE: To assess DR-TB patients\' diagnosis and pre-treatment evaluation costs, catastrophic cost incidence, and its relation to patient characteristics.
METHODS: The study included DR-TB patients from three District Drug-Resistant TB Centres in Delhi and Faridabad (October 2021-June 2022). Socio-economic and clinical characteristics and direct medical and non-medical costs from drug susceptibility testing eligibility to the start of DR-TB treatment were collected using patient interviews and records. Indirect costs were calculated via the human capital approach, defining catastrophic costs as expenses over 20% of household annual income. Multivariable regression was used to estimate the effects of patient characteristics on catastrophic costs.
RESULTS: Of 158 patients, 37.3% were aged 19-30 years, and 55.7% were women. Median total cost was USD326.6 (IQR 132.7-666.7), with 48.2% for diagnosis and 66.0% indirect. 32% faced catastrophic costs, with manual labourers at higher risk (adjusted OR 4.4).
CONCLUSIONS: Despite free diagnosis and treatment, a significant portion of DR-TB households in India incur catastrophic costs, mainly from indirect expenses, indicating a need for targeted policy and programme interventions.
BACKGROUND: Le Programme national Indien d\'élimination de la TB (NTEP) a pour objectif de réduire les dépenses catastrophiques liées à la TB en offrant un diagnostic et un traitement gratuits. Cependant, 3,9% des patients atteints de TB présentent une TB résistante aux médicaments (DR-TB) et doivent faire face à des coûts plus élevés.
OBJECTIVE: Évaluer les coûts de diagnostic et d\'évaluation pré-thérapeutique chez les patients atteints de DR-TB, ainsi que l\'impact des coûts catastrophiques et leur corrélation avec les caractéristiques des patients.
UNASSIGNED: L\'étude a porté sur les patients atteints de DR-TB provenant de trois Centres de lutte contre la TB résistante aux médicaments des districts de Delhi et de Faridabad, Inde (octobre 2021–juin 2022). Les données relatives aux caractéristiques socio-économiques et cliniques, ainsi qu\'aux coûts directs médicaux et non médicaux, ont été collectées lors de l\'évaluation de l\'éligibilité à l\'antibiogramme au début du traitement de la DR-TB, à travers des entretiens avec les patients et l\'analyse des dossiers. Les coûts indirects ont été évalués en utilisant l\'approche du capital humain, définissant les coûts catastrophiques comme dépassant 20 % du revenu annuel du ménage. Une régression multivariable a été réalisée pour estimer l\'impact des caractéristiques des patients sur les coûts catastrophiques.
UNASSIGNED: Sur un échantillon de 158 patients, 37,3% avaient entre 19 et 30 ans et 55,7% étaient des femmes. Le coût médian total s\'élevait à 326,6 USD (IQR 132,7–666,7), dont 48,2% pour le diagnostic et 66,0% pour les coûts indirects. En outre, 32% des patients ont été confrontés à des coûts catastrophiques, les travailleurs manuels étant les plus touchés (OR ajusté 4,4).
CONCLUSIONS: Bien que le diagnostic et le traitement soient gratuits, de nombreux ménages indiens touchés par la DR-TB doivent faire face à des coûts élevés, en particulier des dépenses indirectes, soulignant ainsi le besoin d\'interventions politiques et programmatiques ciblées.

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden. Efforts to find novel vaccines are hampered due to the need for large-scale, prolonged, and costly clinical trials. Controlled human infection models (CHIMs) for TB may be used to accelerate vaccine development by ensuring only the most promising vaccine candidates are selected for phase 3 trials, but it is not currently possible to give participants Mycobacterium tuberculosis as a challenge agent. This study aims to replicate and refine an established BCG CHIM at the Liverpool School of Tropical Medicine. Participants will receive an intradermal injection with licensed BCG vaccine (Statens Serum Institut strain). In phase A, participants will undergo punch biopsy two weeks after administration, paired with minimally invasive methods of skin sampling (skin swab, microbiopsy, skin scrape). BCG detection by classical culture and molecular methods will be compared between these techniques and gold standard punch biopsy. Techniques meeting our pre-defined sensitivity and specificity criteria will be applied in Phase B to longitudinally assess intradermal BCG growth two, seven and fourteen days after administration. We will also measure compartmental immune responses in skin, blood and respiratory mucosa in Phase B. This feasibility study will transfer and refine an existing and safe model of BCG controlled human infection. Longitudinal BCG quantification has the potential to increase model sensitivity to detect vaccine and therapeutic responses. If successful, we aim to transfer the model to Malawi in future studies, a setting with endemic TB disease, to accelerate development of vaccines and therapeutics relevant for underserved populations who stand to benefit the most. Registration: ISRCTN: ISRCTN94098600 and ClinicalTrials.gov: NCT05820594.

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Applied behaviour science\'s focus on individual-level behaviours has led to overestimation of and reliance on biases and heuristics in understanding behaviour and behaviour change. Behaviour-change interventions experience difficulties such as effect sizes, validity, scale-up, and long-term sustainability. One such area where we need to re-examine underlying assumptions for behavioural interventions in Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) prevention, which seek population-level benefits and sustained, measurable impact. This requires taking a \"Big Leap.\" In our view, taking the big leap refers to using a behavioural science-informed approach to overcome the chasms due to misaligned assumptions, tunnel focus, and overweighting immediate benefits, which can limit the effectiveness and efficiency of public health programmes and interventions. Crossing these chasms means that decision-makers should develop a system of interventions, promote end-user agency, build choice infrastructure, embrace heterogeneity, recognise social and temporal dynamics, and champion sustainability. Taking the big leap toward a more holistic approach means that policymakers, programme planners, and funding bodies should \"Ask\" pertinent questions to evaluate interventions to ensure they are well informed and designed.

BACKGROUND: Artificial intelligence (AI) based computer-aided detection devices are recommended for screening and triaging of pulmonary tuberculosis (TB) using digital chest x-ray (CXR) images (soft copies). Most AI algorithms are trained using input data from digital CXR Digital Imaging and Communications in Medicine (DICOM) files. There can be scenarios when only digital CXR films (hard copies) are available for interpretation. A smartphone-captured photo of the digital CXR film may be used for AI to process in such a scenario. There is a gap in the literature investigating if there is a significant difference in the performance of AI algorithms when digital CXR DICOM files are used as input for AI to process as opposed to photos of the digital CXR films being used as input.
OBJECTIVE: The primary objective was to compare the agreement of AI in detecting radiological signs of TB when using DICOM files (denoted as CXRd) as input versus when using smartphone-captured photos of digital CXR films (denoted as CXRp) with human readers.
METHODS: Pairs of CXRd and CXRp images were obtained retrospectively from patients screened for TB. AI results were obtained using both the CXRd and CXRp files. The majority consensus on the presence or absence of TB in CXR pairs was obtained from a panel of 3 independent radiologists. The positive and negative percent agreement of AI in detecting radiological signs of TB in CXRd and CXRp were estimated by comparing with the majority consensus. The distribution of AI probability scores was also compared.
RESULTS: A total of 1278 CXR pairs were analyzed. The positive percent agreement of AI was found to be 92.22% (95% CI 89.94-94.12) and 90.75% (95% CI 88.32-92.82), respectively, for CXRd and CXRp images (P=.09). The negative percent agreement of AI was 82.08% (95% CI 78.76-85.07) and 79.23% (95% CI 75.75-82.42), respectively, for CXRd and CXRp images (P=.06). The median of the AI probability score was 0.72 (IQR 0.11-0.97) in CXRd and 0.72 (IQR 0.14-0.96) in CXRp images (P=.75).
CONCLUSIONS: We did not observe any statistically significant differences in the output of AI in digital CXRs and photos of digital CXR films.

UNASSIGNED: Voluntary counseling and testing for HIV has proven to be a highly effective and cost-efficient approach in many locations, yielding excellent results. It serves as a gateway to a range of HIV-related services, including the provision of antiretroviral drugs. Therefore, this study was aimed to assess the willingness toward VCT and associated factors among TB infected patients at Public Hospitals in Addis Ababa, Ethiopia; 2023.
UNASSIGNED: A facility-based cross-sectional study was undertaken at public hospitals in Addis Ababa from 1st to 30th of March 2023 with 235 participants using systematic random sampling. Trained data collectors employed a pretested data extraction tool for information gathering. Variables with p-value less than 0.05 in the multivariable logistic regression were considered statistically significant.
UNASSIGNED: The prevalence of willingness toward VCT among TB infected patients was (78.3, 95%CI: 72.8, 83.4). Individuals with a primary education level (AOR: 6.32; 95%CI: 1.65, 24.25), government employees (AOR: 5.85; 95%CI: 1.78, 19.22) and private employees (AOR: 3.35; 95%CI: 1.12, 10.01), good knowledge of VCT (AOR: 3.12; 95%CI: 1.36, 7.16), perceived a higher risk (AOR: 6.58; 95%CI: 2.44, 17.73) and perceived stigma (AOR: 14.95; 95%CI: 4.98, 44.91) were factors associated with willingness toward VCT.
UNASSIGNED: The proportion of Tuberculosis infected patients expressing willingness toward Voluntary Counseling and Testing in this study was higher than in previous studies, it falls below the UNAIDS target of 90% of people knowing their HIV status. Notably, factors such as level of education, occupation, knowledge, perceived risk, and perceived stigma emerged as independent factors significantly associated with the willingness of TB-infected patients to undergo VCT. These findings underscore the importance of considering socio-demographic characteristics, knowledge levels, and psychosocial factors in designing strategies to enhance VCT acceptance among TB-infected individuals.

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