Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise.

The current active-latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.

"As a patient I do not belong to the clinic, I belong to the community." Co-developing a multi-level, person-centred tuberculosis stigma intervention in Cape Town, South Africa.

Background: Anticipated, internal, and enacted stigma are major barriers to TB care engagement, and directly impact patient well-being. Unfortunately, targeted stigma interventions are lacking. We aimed to co-develop a person-centred stigma intervention with TB-affected community members and health workers in South Africa. Methods: Using a community-based participatory research approach, we conducted ten group discussions with people diagnosed with TB (past or present), caregivers, and health workers (total n=87) in Khayelitsha, Cape Town. Group discussions were facilitated by TB survivors. Discussion guides explored experiences and drivers of stigma and used human-centred design principles to co-develop solutions. Recordings were transcribed, coded, thematically analysed and then further interpreted using the socio-ecological model. Results: Intervention components across socio-ecological levels shared common behaviour change strategies, namely education, empowerment, engagement, and innovation. At the individual level, participants recommended counselling to improve TB knowledge and provide ongoing support. TB survivors can guide messaging to nurture stigma resilience by highlighting that TB can affect anyone and is curable, and provide lived experiences of TB to decrease internal stigma. At the interpersonal level, support clubs and family-centred counselling were suggested to dispel TB-related myths and foster support. At the institutional level, health worker stigma reduction training informed by TB survivor perspectives was recommended. Consideration of how integration of TB/HIV care services may exacerbate TB/HIV intersectional stigma and ideas for restructured service delivery models were suggested to decrease anticipated and enacted stigma. At the community level, participants recommended awareness-raising events led by TB survivors, including TB information in school curricula. At the policy level, solutions focused on reducing the visibility generated by a TB diagnosis and resultant stigma in health facilities and shifting tasks to community health workers. Conclusions: Decreasing TB stigma requires a multi-level approach. Co-developing a person-centred intervention with affected communities is feasible and generates stigma intervention components that are directed and implementable. Such community-informed intervention components should be prioritised by TB programs, including integrated TB/HIV care services.

"This is an illness. No one is supposed to be treated badly": Community-based stigma assessments in South Africa to inform TB stigma intervention design.

Background: Though TB-related stigma is a recognized barrier to care, interventions are lacking and gaps remain in understanding the drivers and experiences of TB-related stigma. We undertook community-based mixed methods stigma assessments to inform stigma intervention design. Methods: We adapted the Stop TB Partnership stigma assessment tool, and trained three peer research associates (PRAs; two TB survivors, one community health worker) to conduct surveys with people with TB (PWTB, n=93) and caregivers of children with TB (n=24) at peri-urban and rural clinic sites in Khayelitsha, Western Cape, and Hammanskraal, Gauteng Province, South Africa. We descriptively analyzed responses for each stigma experience (anticipated, internal, and enacted), calculated stigma scores, and undertook generalized linear regression analysis. We further conducted 25 in-depth interviews with PWTB (n=22) and caregivers TB (n=3). Using inductive thematic analysis, we performed open coding to identify emergent themes, and selective coding to identify relevant quotes. Themes were organised using the CARD (Constraints, Actions, Risks and Desires) framework. Results: Surveys revealed at least one-third of PWTB and one-quarter of caregivers report experiences of anticipated, internal, and/or enacted stigma, which affected engagement throughout the care cascade. Participants in rural locations (compared to peri-urban) reported higher anticipated, internal, and enacted stigma (ß-coefficient 0.72, 0.71, and 0.74). Interview participants described how stigma experiences, including HIV intersectional stigma, act individually and in concert as key constraints to impede care, and underpins failure to disclose a TB diagnosis, isolation, and exclusion. Stigma resilience arose through understanding that TB can affect anyone and should not diminish self-worth. Risks of stigma, driven by fears related to disease severity and infectiousness, led to care disengagement and impaired psychological wellbeing. Participants desired counselling, identifying a specific role for TB survivors as peer counsellors, and community education. Conclusions: Stigma is highly prevalent and negatively impacts TB care and the well-being of PWTB, warranting its assessment as a primary outcome indicator rather than intermediary contributor to poor cascade outcomes. Multicomponent stigma interventions are needed, including counselling for PWTB and education for health workers and communities. Such interventions must incorporate contextual differences based on gender or setting, and use survivor-guided messaging to foster stigma resilience.

The role of counselling in tuberculosis diagnostic evaluation and contact tracing: scoping review and stakeholder consultation of knowledge and research gaps.

BACKGROUND: Tuberculosis (TB) care cascade analyses show large gaps at early stages, including care-seeking and diagnostic evaluation, where promising interventions to decrease attrition are urgently needed. Person-centered care is prioritized in the World Health Organization's End TB strategy; yet little is known about how it is delivered and can be optimized. Recommendations for counselling, a core component of person-centered care, are largely limited to its role in improving TB treatment adherence. The role of counselling to close key diagnostic gaps in the care cascade is poorly understood. METHODS: We conducted a scoping review to identify evidence on the use of counselling at TB diagnosis, for both people with presumptive TB and index patients to promote patient retention and contact tracing. Using search terms for TB, diagnosis and counselling, we systematically searched PubMed, EMBASE and Web of Science. Two independent reviewers screened all abstracts, full-texts, extracted data and conducted a quality assessment. We used thematic analysis to identify key themes. RESULTS: After screening 1785 articles, we extracted data from 15 studies and determined that the major themes best corresponded to the following gaps in the TB care cascade: care-seeking, pre-diagnosis, and pre-treatment. Studies were conducted across varied settings including pharmacies, primary health centres, and clinics, primarily in high TB incidence countries. No study directly evaluated the impact of counselling on outcomes such as treatment initiation or retention in care. Included studies suggested counselling may play an important role in improving the uptake of diagnostic testing and contact tracing. Barriers to counselling included time and personnel requirements. Stakeholder consultation emphasized the importance of high-quality counselling as a core tenet of TB care. CONCLUSION: Data on the impact of counselling to improve TB case detection are absent from the literature. The shift towards person-centred care for TB presents an opportunity to incorporate counselling during earlier stages of the TB care cascade; however, evidence-based approaches are needed. Implementation research is needed to operationalize and evaluate counselling to strengthen high-quality TB care delivery.

Analysing interventions designed to reduce tuberculosis-related stigma: A scoping review.

Stigma is a critical barrier for TB care delivery; yet data on stigma reduction interventions is limited. This review maps the available literature on TB stigma reduction interventions, using the Health Stigma and Discrimination framework and an implementation analysis to identify research gaps and inform intervention design. Using search terms for TB and stigma, we systematically searched PubMed, EMBASE and Web of Science. Two independent reviewers screened all abstracts, full-texts, extracted data, conducted a quality assessment, and assessed implementation. Results were categorized by socio-ecological level, then sub-categorized by the stigma driver or manifestation targeted. After screening 1865 articles, we extracted data from nine. Three studies were implemented at the individual and interpersonal level using a combination of TB clubs and interpersonal support to target internal and anticipated stigma among persons with TB. Two studies were implemented at the interpersonal level using counselling or a video based informational tool delivered to households to reduce stigma drivers and manifestations. Three studies were implemented at the organizational level, targeting drivers of stigma among healthcare workers (HW) and enacted stigma among HWs. One study was implemented at the community level using an educational campaign for community members. Stakeholder consultation emphasized the importance of policy level interventions and education on the universality of risk to destigmatize TB. Review findings suggest that internal and anticipated TB stigma may be addressed effectively with interventions targeted towards individuals using counselling or support groups. In contrast, enacted TB stigma may be better addressed with information-based interventions implemented at the organizational or community level. Policy level interventions were absent but identified as critical by stakeholders. Implementation barriers included the lack of high-quality training and integration with mental health services. Three key gaps must be addressed in future research: consistent stigma definitions, standardized stigma measurement, and measurement of implementation outcomes.

Access to new medications for the treatment of drug-resistant tuberculosis: patient, provider and community perspectives.

Multidrug-resistant tuberculosis (MDR-TB) is on the rise, and is difficult to treat. The approval of two new drugs, bedaquiline and delamanid, and growing evidence for the use of linezolid, offer renewed hope for addressing MDR-TB. However, access to these medicines remains a significant challenge. These drugs have not been registered for TB in most settings; barriers to preapproval access persist; and high pricing and intellectual property restrictions limit access. Many unanswered research questions about optimal use of these drugs also limit access, particularly for vulnerable populations. This review outlines challenges in accessing drugs encountered from the perspective of clinicians, patients and affected communities, and offers potential solutions.