Strategic and Technical Advisory Group for Tuberculosis: annual meeting report, Geneva, Switzerland, 17-19 June 2024

Strategic and Technical Advisory Group for Tuberculosis Annual meeting report, Geneva, Switzerland 17–19 June 2024 Strategic and Technical Advisory Group for Tuberculosis Annual meeting report, Geneva, Switzerland 17–19 June 2024 Strategic and Technical Advisory Group for Tuberculosis: annual meeting report, Geneva, Switzerland, 17-19 June 2024 ISBN 978-92-4-010643-7 (electronic version) ISBN 978-92-4-010644-4 (print version) © World Health Organization 2025 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial- ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. 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Contents Abbreviations ........................................................................................................................................ iv 1. Introduction ........................................................................................................................................ 1 2. Progress updates ................................................................................................................................ 4 2.1 Background .................................................................................................................................. 4 2.2 STAG-TB comments...................................................................................................................... 4 2.3 STAG-TB recommendations ......................................................................................................... 5 3. TB and PHC and integrated approaches to lung health ................................................................... 6 3.1 Background .................................................................................................................................. 6 3.2 Topics covered.............................................................................................................................. 8 3.3 Questions to STAG-TB .................................................................................................................. 8 3.4 STAG-TB comments...................................................................................................................... 8 3.5 STAG-TB preamble ..................................................................................................................... 10 3.6 STAG-TB recommendations ....................................................................................................... 10 4. Addressing the intersection of TB and climate change .................................................................. 12 4.1 Background ................................................................................................................................ 12 4.2 Topics covered............................................................................................................................ 13 4.3 Questions to STAG-TB ................................................................................................................ 13 4.4 STAG-TB comments.................................................................................................................... 14 4.5 STAG-TB preamble ..................................................................................................................... 14 4.6 STAG-TB recommendations ....................................................................................................... 14 5. Closing the gap between clinical TB research and global implementation: streamlined, pragmatic and adaptive trial platform ................................................................................................ 16 5.1 Background ................................................................................................................................ 16 5.2 Topics covered............................................................................................................................ 18 5.3 Questions to STAG-TB ................................................................................................................ 19 5.4 STAG-TB comments.................................................................................................................... 19 5.5 STAG-TB preamble ..................................................................................................................... 21 5.6 STAG-TB recommendations ....................................................................................................... 21 6. Estimates of TB incidence and mortality required for assessment of progress towards the 2025 and 2030 milestones and targets from the End TB Strategy and the SDGs: data sources, analytical methods and process ........................................................................................................................... 23 6.1 Background ................................................................................................................................ 23 6.2 Topics covered............................................................................................................................ 23 6.3 Questions to STAG-TB ................................................................................................................ 26 6.4 STAG-TB comments.................................................................................................................... 27 6.5 STAG-TB preamble ..................................................................................................................... 28 6.6 STAG-TB recommendations ....................................................................................................... 29 7. On the road to TB elimination: key criteria, indicators and the validation governance process .. 30 7.1 Background ................................................................................................................................ 30 7.2 Topics covered............................................................................................................................ 31 7.3 Questions to STAG-TB ................................................................................................................ 31 7.4 STAG-TB comments.................................................................................................................... 32 7.5 STAG-TB preamble ..................................................................................................................... 32 7.6 STAG-TB recommendations ....................................................................................................... 32 8. Planning for the 2025 STAG-TB meeting ......................................................................................... 34 References ............................................................................................................................................ 35 Annex 1. Final STAG-TB 2024 meeting agenda.................................................................................... 37 Annex 2. STAG-TB 2024 list of participants ......................................................................................... 40 iv Abbreviations ACF active case finding AMR antimicrobial resistance CSTF-TB Civil Society Task Force on Tuberculosis CXR chest X-ray DR-TB drug-resistant tuberculosis GTB Global Tuberculosis Programme (WHO) HIV human immunodeficiency virus IPC infection prevention and control MoH ministry of health NTP national TB programme PAL practical approach to lung health PHC primary health care SCI service coverage index SDG Sustainable Development Goal STAG-TB Strategic and Technical Advisory Group for Tuberculosis TB tuberculosis UHC universal health coverage UN United Nations UNHLM United Nations General Assembly High-level Meeting UNHLM-TB United Nations General Assembly High-level Meeting on the fight against tuberculosis WHO World Health Organization 1 1. Introduction The World Health Organization (WHO), through its Global Tuberculosis Programme (GTB), leads and guides the global effort to end the tuberculosis (TB) epidemic. WHO does this using a human rights- based approach for universal access to people-centred prevention and care, multisectoral action and innovation. The major functions of the Global Tuberculosis Programme include: • providing global leadership to end TB through strategy development, political and multisectoral engagement, strengthening of reviews and accountability, and advocacy and partnership (including with civil society); • developing policies, norms and standards for TB prevention and care, and action on TB determinants, with support for their implementation; • shaping the TB research and innovation agenda, and stimulating the generation, translation and dissemination of knowledge; • providing specialised technical support for Member States and partners, and working with WHO regional and country offices to catalyse change and build sustainable capacity; and • monitoring, evaluation and reporting on the status of the TB epidemic and progress in the financing and implementation of the End TB Strategy. The Strategic and Technical Advisory Group for Tuberculosis (STAG-TB) is an expert advisory body that was established in 2001. STAG-TB’s mission is to contribute to ending the TB epidemic and eventually eliminating the disease by providing state-of-the-art scientific, strategic and technical guidance to WHO. Its functions are as follows: • to advise WHO on the prioritisation of WHO’s strategies and activities in TB prevention and care; • review, from a scientific and technical viewpoint, progress and challenges in WHO’s TB-related core functions, including the content, scope and dimensions of WHO’s: o development of TB policies, strategies and standards in TB prevention and care; o collaboration with, and support of, countries’ efforts to end TB, including the WHO provision of guidance, technical assistance and capacity-building on policies, strategies and standards; o TB epidemiological surveillance, monitoring, evaluation and operational research activities, their relevance to countries’ efforts to end the TB epidemic, and approaches to be adopted; o promotions and support of partnerships, advocacy and communications towards ending TB worldwide; • review and make recommendations on the establishment of committees, working groups, and other means through which scientific and technical matters are addressed; and 2 • advise on priorities for potential areas of collaboration within WHO, on activities related to TB prevention and care. As per the rules of procedures, members are appointed by the WHO Director-General, and the advisory group reports to the WHO Director-General. The full terms of reference for STAG-TB are provided on the WHO STAG-TB website (1). The 24th meeting of STAG-TB was held in person on 17–19 June 2024; it was organized by the Global Tuberculosis Programme, which acts as the Secretariat for the advisory body. The meeting was chaired by Dr Ethel Maciel, Secretary of Surveillance for Health and Environment, Ministry of Health, Brazil. Dr Maciel has been appointed by the WHO Director-General as STAG-TB Chair for the period 2024–2026. All 16 STAG-TB members were present in person and were required to sign a declaration of interest before attending the meeting. The declarations were assessed by the STAG-TB Secretariat and no significant conflicts of interest were identified. The agenda for the 24th annual STAG-TB meeting (Annex 1) included the following five sessions: • Session 1 – Progress report: o progress update from the Global Tuberculosis Programme o WHO regional TB advisors on efforts to make progress on targets and commitments from the United Nations General Assembly High-level Meeting on the fight against TB (UNHLM-TB); and o the WHO Civil Society Task Force on TB1 (CSTF-TB) – actions to advance uptake of targets and commitments from the UNHLM-TB. • Session 2 – From challenges to opportunities: harnessing primary health care (PHC) and integrated approaches, and other intersections for ending TB:2 o Session 2a – TB and PHC and integrated approaches to lung health; and o Session 2b – Addressing the intersection of TB and climate change. • Session 3 – Closing the gap between clinical TB research and global implementation: streamlined, pragmatic and adaptive trial platform. • Session 4 – Estimates of TB incidence and mortality required for the 2025 and 2030 milestones and target assessments from the End TB Strategy (3) and the Sustainable Development Goals (SDGs): data sources, analytical methods and process. • Session 5 – On the road to TB elimination: key criteria, indicators and the validation governance process. 1 The WHO CSTF-TB provides a platform for discussion and exchange with WHO, acting as an advisory body focusing on leveraging engagement with civil society and affected communities at all levels to accelerate progress towards ending TB, in line with the WHO End TB Strategy (2). 2 This session comprised two separate presentations and discussions that were complementary to the session topic. 3 Background documents – including key supporting reading material and questions to STAG-TB members – were shared in advance of the meetings. These documents were intended to inform discussions during the meeting and were considered confidential. Session 1 included a presentation from the Director of the Global Tuberculosis Programme, progress updates from the six WHO regional TB advisors and perspectives from the CSTF-TB. Sessions 2–6 each started with a presentation by the Global Tuberculosis Programme to introduce the topic and provide supporting evidence (Session 2a included a speaker from the Special Programme on Primary Health Care). The presentations were followed by commentaries from two STAG-TB discussants and a discussion with STAG-TB members where recommendations were made to WHO on the session topic. With the assistance of the WHO STAG-TB Secretariat, STAG-TB discussants developed draft recommendations for each session. All draft recommendations were reviewed and finalized in a plenary session on Day 3 by all STAG-TB members. This report summarizes the meeting sessions, focusing on comments and recommendations from STAG-TB members. All reports of STAG-TB meetings are submitted by the Chair of STAG-TB and the Director of WHO’s Global Tuberculosis Programme to the WHO Assistant Director-General of WHO’s Division of UHC/Communicable and Noncommunicable Diseases, the Deputy Director-General and the Director-General. The report is posted on the STAG-TB website (1) and is distributed widely through a newsletter. The complete list of participants for the 24th STAG-TB meeting is provided in Annex 2. 4 2. Progress updates 2.1 Background Dr Ethel Maciel, STAG-TB Chair, welcomed the new members of STAG-TB and set the stage for the meeting by emphasizing the importance of collaborative efforts in the fight against TB. Dr Tereza Kasaeva, Director of WHO’s Global Tuberculosis Programme, presented a global overview of key progress and actions towards reaching the targets and commitments made by world leaders in the political declaration of the second UNHLM-TB, held in September 2023 (4). WHO regional advisors on TB presented on progress in their regions, highlighting region-specific actions that are being prioritized to meet the End TB Strategy targets. Additionally, Mr Luan Vo and Ms Victoria James, nominated members of the CSTF-TB, joined the session to share the position of CSTF-TB to accelerate efforts to end TB. Particular emphasis was placed on the need to increase funding, empower communities, foster innovation, safeguard social protection and drive demand for new tools. At the onset of the meeting, the STAG-TB Secretariat, hosted by the Global Tuberculosis Programme, clarified the functions of STAG-TB, the roles and responsibilities of STAG-TB members and the STAG-TB Chair, and the requirement to complete declarations of interest. 2.2 STAG-TB comments STAG-TB members appreciated the updates and perspectives shared by speakers, and commended WHO for progress and achievements made regarding the implementation of the 2023 STAG-TB recommendations. STAG-TB members acknowledged global progress made towards the achievement of global targets set out in the End TB Strategy (3) and the targets and commitments included in the political declaration of the UNHLM-TB (4). However, they also shared concerns about global targets being off track, and funding for TB remaining stagnant and inadequate. STAG-TB members underscored the need for a comprehensive response to TB that is people- centred, makes optimal use of new tools and technologies, and seeks linkages with other programmes and sectors beyond health. In this regard, members acknowledged the importance of WHO in terms of providing strategic leadership, developing technical products, taking actions taken to shape the research and innovation agenda, undertaking monitoring and evaluation of the TB epidemic, and providing support directly to Member States. Also emphasized was WHO’s key role in facilitating a multisectoral collaboration and response, including civil society engagement, which is driven and supported by the highest government authorities within countries. STAG-TB members recognized WHO’s Global Tuberculosis Programme as being a pathfinder within WHO in multiple areas; for example, the release of rapid communications on its guidelines, the development of living TB guidelines, the establishment of a digital knowledge sharing platform, meaningful engagement of civil society through the CSTF-TB and the introduction of innovative technologies (e.g. full genome sequencing and clinical trial platforms). To facilitate an effective global TB response, STAG-TB members agreed with the identified need for WHO’s Global 5 Tuberculosis Programme to cover aspects that are beyond its current mandate, such as post-TB disease, TB-related disability, comorbidities and differential diagnostics, and other lung functions. STAG-TB members underscored the need for WHO’s senior leadership to maintain a strong focus on TB and to ensure the availability of financial resources across the three levels of the organization, to accelerate action and drive progress at country level. 2.3 STAG-TB recommendations STAG-TB recommended that: • WHO’s leadership and the three levels of WHO continue to support countries in line with the Director-General Flagship Initiative, the End TB Strategy, and targets and commitments included in the declaration of the UNHLM-TB to accelerate and drive action at country level; • WHO’s senior leadership ensure that WHO’s TB-related work is adequately and sustainably resourced at the three levels of the organization; • WHO’s leadership endorse work carried out by WHO’s Global TB Programme on other lung health related aspects in its mandate; and • WHO support countries and advocate for visibility and prioritization of combating drug- resistant TB (DR-TB) as part of the antimicrobial resistance (AMR) agenda, as set out in the political declaration of the 2024 UNHLM on AMR. 6 3. TB and PHC and integrated approaches to lung health 3.1 Background In a significant step towards the global health agenda, the 2023 UNHLM-TB represented a pivotal moment for international efforts to end TB (4). Ending the global TB epidemic requires all commitments made at the global level to be urgently translated into action at the country level, and all opportunities to be explored and seized through a sustainable system approach. The resulting political declaration underscores the imperative of advancing multisectoral efforts and community empowerment, to ensure equitable and affordable access to high-quality services. This, in turn, includes accelerating progress towards universal health coverage (UHC), emphasizing the importance of robust and sustainable PHC (5). In the context of global health targets, the importance of PHC as the foundation of strong health systems is emphasized by the global community. PHC centres around the provision of essential health services that are accessible, comprehensive and people-centred, addressing immediate health needs; it also calls our attention to addressing social determinants of health, contributing to better health outcomes and reducing health disparities. WHO advocates for a radical reorientation of health systems towards PHC as the vehicle for achieving UHC, recognizing that PHC is the most efficient and equitable approach to delivering health care services, leaving no one behind. This approach, in turn, requires sustainable health systems that are responsive to the health needs of populations, promote health equity and contribute to achieving the SDGs. The End TB Strategy offers a comprehensive approach to TB care and prevention, addressing the continuum of care between and across all levels of the health system, while placing people’s needs at the forefront of TB care delivery. The strategy aligns seamlessly with the three PHC components and the strategic and operational levers of the operational framework for PHC (6). Strengthening and leveraging longstanding programmes in which interventions are aligned with the PHC approach presents a strategic pathway to mutually reinforce the impact of PHC strategies to address other public health priorities (5). Within this context, leveraging the respective strengths of national TB programmes (NTPs) and the PHC approach emerges as an imperative. NTPs are often embedded in PHC to some extent across various settings. Moreover, they employ care models that engage communities and stakeholders from various sectors and foster collaboration with governmental counterparts, thereby facilitating cross-cutting initiatives. By capitalizing on these attributes, the synergies and opportunities that arise from aligning the TB response with the principles of PHC jointly advance their respective efforts to strengthen PHC and end TB as a public health threat. By leveraging the strengths of PHC, TB prevention, treatment and care can be enhanced, leading to more sustainable and equitable health outcomes, and ultimately to ending the TB epidemic. Vice versa, NTPs offer significant opportunities to enhance PHC-oriented health systems. They provide avenues for collaborative actions aimed at strengthening PHC, while reciprocally benefiting from the framework and TB services of PHC. Through this synergy, resources can be optimized, and health care delivery can become more efficient and effective, leading to 7 improved health outcomes across different disease spectra. This approach not only optimizes resource allocation but also enhances the overall resilience and responsiveness of health systems to evolving challenges (6). TB services have typically been administered as an integrated package encompassing infection prevention and control (IPC), case finding, screening, contact tracing, diagnosis and treatment. NTPs acknowledge the increased risk faced by people with specific risk factors and comorbid conditions, which can lead to unsuccessful outcomes from TB treatment and increased mortality. Consequently, the joint management of TB and specific conditions has been encouraged extensively, most notably in the case of TB/HIV and TB/diabetes. Although these efforts are not perfect, coordination and collaboration between various disease programmes has yielded favorable results (7). In most high TB burden settings, NTPs have established a broad-reaching infrastructure through PHC networks (both tangible and intangible elements), to effectively deliver TB services, albeit with imperfections. Over the years, these programmes have played a pivotal role in the development and implementation of crucial components such as IPC measures, screening protocols, diagnostic networks and referral systems integrated within the public health network. Furthermore, recent years have witnessed a notable political drive that has bolstered multisectoral action, fostering partnerships with diverse stakeholders to address the social determinants of health. This momentum has led to the establishment of community networks, empowering individuals and communities to actively engage in initiatives for TB prevention, treatment and support. One of the greatest examples of the positive effect of NTPs is that of the coronavirus disease (COVID- 19) pandemic. During that pandemic, NTPs demonstrated remarkable adaptability, showcasing how their expertise and experience could be effectively leveraged. This was exemplified by the rapid repurposing of TB laboratories for COVID-19 testing, tapping into established diagnostic capabilities, and using personnel skilled in laboratory techniques. Moreover, TB contact tracing methodologies were swiftly adapted for COVID-19 contact tracing, benefiting from pre-existing networks and protocols. The community-based approach inherent in NTPs also played a pivotal role in pandemic response efforts. Existing infrastructure and expertise facilitated outreach focused on COVID-19 prevention and mitigation strategies. Through established community networks, accurate information was disseminated, supporting public health interventions. This seamless integration of NTP resources and methodologies into the pandemic response underscored the importance of leveraging prior investments in health care infrastructure (e.g. investments in NTPs). Overall, the experience gained and infrastructure developed through TB control efforts significantly bolstered the capacity of health systems to effectively tackle the challenges posed by the COVID-19 pandemic. The practical approach to lung health (PAL) focuses on the management of the most prevalent lung diseases at primary care units while expanding high-quality TB diagnosis, treatment and care services to people and communities in need. This approach was envisioned to help establish linkages across and within services, to ensure that these services remained responsive and people- centred to attend to the needs of those affected by lung disease (8, 9). A fundamental characteristic 8 of PAL was that it sought to create efficiencies through the best use of existing services and facilitate the successful navigation of patients through the system, by coordinating service delivery and focusing on integrated care for lung disease. As new public health challenges continue to arise, and the global burden of disease is heavily compounded by lung diseases, re-envisioning integrated approaches to lung health will help in managing the fragmented, underfunded health system. In addition, by enhancing health access, collaboration, coordination and community involvement, people-centred services – particularly those that adopt integrated approaches to lung health – can help to mitigate vulnerabilities in service delivery and strengthen preparedness for pandemics caused by respiratory pathogens. 3.2 Topics covered The topics covered in this session included: • the rationale for focusing on the intersections, synergies and opportunities that arise from integrating TB in the PHC approach; • an explanation of the PHC approach and its central role in WHO’s agenda (10); • an illustration of the synergies between the three PHC components and the pillars of the End TB Strategy, and of the potential opportunities to strengthen the TB response using the PHC lens and vice versa; and • a description of the steps taken to date, including the scope and proposed outline of the policy brief. Key actions led and supported by WHO between June 2023 and June 2024 were as follows: • Quarter 2 to Quarter 3 (Q2–3) 2023: Establishment of a WHO internal steering committee and meetings of the steering group to define the scope of work and workplan. • Q3–4 2023: Conduct of a scoping review of the literature and case study of Kenya’s experience in delivering TB services through the PHC approach. • November 2023: Presentation of the topic and scope of work to representatives of high TB burden countries. • March 2024: Internal consultation with the steering committee on the policy brief. • May 2024: Global virtual consultation on the policy brief. 3.3 Questions to STAG-TB The following questions were posed to STAG-TB members: 1. What are STAG-TB’s recommendations to WHO to strengthen the synergies between TB and PHC, to progress towards the commitments made by all Member States in the 2023 political declaration to end TB? 2. What does STAG-TB propose to WHO to further the outlined workplan on integrated approaches to lung health, including its potential contribution to strengthening pandemic preparedness? 3.4 STAG-TB comments The discussants for this session were Dr Ya Diul Kukadi and Robert Makombe. 9 Both discussants underscored the importance of this topic and re-emphasized the points made in the presentation. They noted that progress in reaching the targets of the End TB Strategy has been slow, particularly with regards to DR-TB, TB mortality and quality of TB services, and that most high TB burden countries also have a low service coverage index (SCI), indicating a lack of progress towards UHC. Both discussants pointed to the urgent need to identify alternative approaches that can be adopted to end TB. They noted that PHC is the obvious answer because it can improve access to TB services, early detection, and adherence to treatment and preventive therapy, while decreasing TB-related costs. The discussants also highlighted the need to look at efficiency gains in TB service delivery, particularly in the current funding landscape (which remains stagnant); for example, making the TB response more effective by integrating it into a PHC-oriented health system. These comments built on the accounts provided by the regional advisors, who reported that reorienting the health system towards PHC is a priority in their setting. STAG-TB members emphasized the need to look at adaptations to the local context, and how NTP managers are going to be involved in this agenda going forward. They supported the development and publication of a concise policy brief that would bring a common understanding of the topic to all stakeholders. That policy brief should be followed by an implementation document and concrete actions at the local level, which could be informed by the lessons learned from the implementation of the HIV and PHC policy brief, and by other disease areas. Establishing the right financing arrangements is crucial to support the development of people- centred PHC that includes TB service delivery in an integrated fashion. As emphasized by the Director of the Special Programme on Primary Health Care, Dr Suraya Dalil, to answer the question of how to make these changes, it is necessary to go far beyond technical considerations. Fundamentally shifting a health system’s priorities (i.e. away from specialist-based and hospital-based services and towards PHC) involves political choices and creates numerous political challenges. Successfully reorienting a system towards PHC requires shrewd political leadership and long-term commitment, as well as proactive, adaptable strategies to engage with stakeholders at all levels that account for the social and economic contexts. STAG-TB members noted that WHO should play a strong advocacy role in this process. In relation to integrated approaches to lung health, STAG-TB members emphasized the need for a holistic and people-centred approach that prioritizes operational efficiency, sustainability and health system resilience, especially in preparing for future airborne pandemics. They noted that the effective delivery of integrated care approaches must leverage past experiences (e.g. those from countries implementing PAL), while addressing persistent gaps (e.g. in diagnostics) and ensuring long-term monitoring. Members agreed on the need to balance specialized TB care with integrated services, ensuring that critical resources and expertise are not diluted, particularly in high TB 10 burden settings. Advances in diagnostics, such as multidisease platforms and digital technologies, were seen as opportunities to improve overall outcomes on lung health. By incorporating lessons from the pandemic, STAG-TB members advocated for a resilient health care model that addresses the entire spectrum of lung health, from prevention to treatment, without compromising the quality of TB care. A thorough health policy analysis is needed, to illuminate past policy failures and successes, and identify synergies in current strategies. Members discussed leveraging TB as an entry point for other conditions, using TB screening methods (e.g. chest X-ray [CXR]) to identify other lung abnormalities, and integrating these practices into relevant and applicable primary care and community practices. 3.5 STAG-TB preamble STAG-TB: • acknowledges the interlinkages between the End TB Strategy’s pillars and the components and levers of the PHC approach (i.e. integrated people-centred care, community engagement and multisectoral action); • acknowledges that ending TB requires accelerating progress towards UHC, particularly through strong and sustainable PHC with an adequate health workforce; • recognizes that affordable and early access to high-quality, equitable health services through the PHC approach (which includes TB services) will help to address the gaps in the TB care cascade, improve treatment outcomes and uptake of TB preventive interventions, and reduce catastrophic costs; • recognizes that, despite notable progress, global TB targets (e.g. the UNHLM political declaration and the End TB Strategy) remain off track, that funding for TB remains stagnant, and that the UHC SCI has its lowest values among the most high TB burden countries; • recognizes TB as an integral part of the PHC and UHC agenda, and underlines the need to explore all avenues to jointly strengthen TB and PHC, to accelerate progress towards ending TB through PHC-oriented health systems that are sustainable and resilient; • commends WHO’s leadership role on advancing both agendas, for TB and PHC, and welcomes the continued engagement and collaboration between WHO’s Global Tuberculosis Programme and the Special Programme on Primary Health Care to identify synergies and opportunities; and • emphasizes the value of integrated approaches to lung health, and the critical need for strong, evidence-informed and patient-centred approaches, contributing to respiratory pathogen pandemic preparedness, and advancing efforts to address AMR. 3.6 STAG-TB recommendations STAG-TB recommends that WHO: • build on the commitments and actions outlined in the UNHLM-TB declaration to guide countries in strengthening the integration of TB services within the PHC approach based on local context; • continue to play a strong leadership role in convening policy dialogue among all relevant stakeholders and sectors for coordinated planning for system building towards ending TB, strengthening PHC and progressing towards UHC; 11 • engage in dialogue to ensure that health financing mechanisms support sustainable and resilient system building, which in turn supports efforts towards ending TB and achieving UHC; • develop a policy brief on the synergies and opportunities that arise from aligning the TB response with the PHC approach, which will provide an advocacy resource for key stakeholders who influence strengthening PHC and ending TB; • collect and share best practices and the outcome of research on implementing the TB response through a PHC-oriented health system, with the aim of developing operational guidance and a package of services; • develop a technical brief reflecting on past successes and challenges – in particular, based on known integrated approaches to lung health, such as PAL – to identify synergies and leverage points for integrated health approaches, ensuring their sustainability; and • develop and disseminate concise technical document(s) that can help in designing, operationalizing, optimizing and scaling up integrated approaches to lung health, considering local contexts, and based on outcomes of health policy analysis of successes and challenges. 12 4. Addressing the intersection of TB and climate change 4.1 Background Social, economic and environmental drivers of TB include inequalities, poverty, food insecurity, mass displacement, disruption of health systems, poor air ventilation and air pollution. These drivers heighten susceptibility to TB disease, increase people’s vulnerability to the clinical and financial consequences of TB, and contribute to fuel TB transmission globally (11, 12). Addressing these social determinants is a key component of WHO’s End TB Strategy, and was upheld in the UNHLM-TB in 2023 (4). Climate change exacerbates these challenges and can thus affect the global TB epidemic, both directly and indirectly. In 2022, for example, one in five estimated incident cases of TB were attributable to undernourishment (13) and more than 100 million people were forcibly displaced worldwide due to events that included climate-related disasters, social conflicts, food shortages, and economic and humanitarian crises (14). Burning fossil fuel drives climate change, one effect of which is poor air quality; WHO estimates that more than 90% of the world’s population live in neighbourhoods with polluted air (15). Besides the anticipated need to mitigate the effects of climate change on global health, it is necessary to consider the contribution that health care products and services are making to climate change. Key gaps and challenges • The ranking of countries most vulnerable to climate change according to the Notre Dame Global Adaptation Initiative (ND-GAIN) Country Index (16) shows a strong overlap between countries that are more likely to suffer the effects of climate change and those that make up a large proportion of the global burden of TB. It can be speculated that hazards related to climate change (e.g. extreme heat, floods, storms and drought) will continue to feed the local TB epidemics and hamper progress towards ending TB in these countries, mainly through disruption of health services and increased effects on the social determinants of TB. • Unitaid’s report From milligrams to megatons: a climate and nature assessment of ten key health products (17) indicates that health chains account for 6.4% of global carbon emissions; thus, they contribute significantly to climate change. TB care services are likely to play their role in this share of emissions; hence, the rapid decarbonization of TB products and services will contribute to meeting the targets of the Paris Agreement (18) and mitigate the impact of climate change on the TB epidemic. • Although the global TB community is now beginning to recognize climate change as a significant threat to the progress in ending TB and a potential future driver of the epidemic, there is currently limited evidence on how climate change will affect the TB epidemic and on the interventions needed to create a climate-resilient TB response. Addressing TB in the context of climate change has been constrained by a paucity of research exploring the interdependencies between climate and health dynamics. This gap underscores the urgent need for targeted research efforts to clarify these complexities and forge effective strategies for TB management under changing environmental conditions. 13 4.2 Topics covered 4.2.1 Policy steps to promote action on the nexus between TB and climate change Steps taken Global Tuberculosis Programme is currently working on the development of a policy brief on TB and climate change, which aims to raise awareness of this threat to the progress made in ending the TB epidemic. The brief will present and discuss potential interventions to mitigate the effects of climate change on TB through collaborative actions among NTPs, TB stakeholders and other sectors operating in the climate change arena, building on up-to-date WHO policies on climate change and health. Proposed future directions (2024–2025) Increasing awareness on TB and climate change will hopefully promote global, regional and national debates about the need to pursue research on progress towards ending the TB epidemic, and to identify policies that could mitigate the impact of climate change on TB operations (e.g. increased social protection) and reduce the carbon footprint of such operations. 4.2.2 Research to explore the nexus between TB and climate change Steps taken WHO is currently developing a comprehensive analytical framework to understand the potential relationship between the TB epidemic and climate change, drawing on literature reviews and expert consultation. This work includes identification of research domains to guide follow-on technical consultation on establishing a research agenda on the nexus between TB and climate change (Q3 2024). The research agenda will seek to expand knowledge on the adverse effects of climate change on the TB epidemic and its outcomes, and on strategies to address TB and climate change in an integrated manner, including infrastructures, technologies, human resources and other programming. Proposed future directions (2024–2025) WHO intends to use the upcoming technical consultation for research agenda setting to achieve consensus on climate risks that are aggravating the TB epidemic and its socioeconomic fallout. On this basis, WHO plans to commence work on estimating the impact of prioritized climate risks on the TB epidemic, and appraise economic losses associated with TB’s health and economic effects within specific time frames, retrospectively or prospectively (or both). These activities are anticipated to provide Member States, United Nations (UN) agencies, partners, civil society and other relevant stakeholders with actionable information about potential TB-related health and economic impacts of climate change, to raise awareness of the need to include TB and health in general as part of climate risk mitigation programmes, and climate-resilient funding and response mechanisms. 4.3 Questions to STAG-TB 4.3.1 Policy steps to promote a climate-resilient TB response 1. Could STAG-TB suggest a list of strategic actions that WHO’s Global Tuberculosis Programme should consider for a proper response to the threat posed by climate change to the progress made so far in ending the TB epidemic? 14 2. Does STAG-TB support the step being taken to raise awareness and, at a later stage, to develop technical guidance on TB and climate change to support NTPs to develop a climate-resilient TB response, while contributing to decarbonizing TB diagnostic, treatment and care services? 4.3.2 Research to explore the nexus between TB and climate change 1. Does STAG-TB have any suggestions as to how WHO can improve its research roadmap, including modelling efforts, to better explore the relationship between climate risks and the TB epidemic (including its socioeconomic ramifications)? 4.4 STAG-TB comments The discussants for this session were Dr Anurag Bhargava and Professor Helen Ayles. STAG-TB members agreed in the plenary session that all comments are adequately covered in the preamble. 4.5 STAG-TB preamble STAG-TB: • acknowledges that climate change and its impact on health and disease are emerging concerns in global health, and that TB is currently not well covered in the global debates but is a climate sensitive disease; • supports the steps being taken and planned by WHO’s Global Tuberculosis Programme to improve the understanding of the links between climate change and TB, and increase awareness among Member States on this emerging area of work; • recognizes that the vulnerability to effects of climate change is unequally distributed, with a significant overlap among populations, particularly in high TB burden countries; • recognizes that climate change can result in population displacement and adverse socioeconomic outcomes (including food insecurity), which are drivers of TB; it can also disrupt health system functioning, creating barriers to an effective TB response; • recognizes that further research is needed to improve understanding about the direct and indirect links between climate change and TB, particularly on the effects of climate change on TB determinants driving the TB epidemic in high TB burden countries; and • welcomes the efforts towards engaging the global TB community in the global climate change debates, and making policies to mitigate the effects of climate change on health, including the reduction of the carbon footprint of the response to TB. 4.6 STAG-TB recommendations STAG-TB recommends that WHO: • conduct a scoping review of evidence to inform development of a comprehensive TB-specific conceptual framework that describes the direct and indirect interactions between TB and climate change; • document good practices implemented by countries to mitigate the disruption of health care delivery caused by climate-related emergencies; • convene expert consultations to support the development of the proposed policy brief on TB and climate change, and the research roadmap on TB and climate change, with a focus on 15 implementation research and, where appropriate, specific modelling to support advocacy efforts; and • partner with the WHO Department of Environment, Climate Change and Health, and other relevant agencies to develop policies aimed at enabling Member States to mount a climate change resilient TB response. 16 5. Closing the gap between clinical TB research and global implementation: streamlined, pragmatic and adaptive trial platform 5.1 Background 5.1.1 Challenges with evidence that supports WHO TB guidelines The Global TB Programme regularly releases guidelines on various aspects of TB diagnosis, prevention and treatment. These guidelines serve as a vital resource, providing health care professionals in the Member States and beyond with invaluable insights on how to enhance treatment and care standards for people with TB. However, the strength of the recommendations in these guidelines and their uptake depends on the available evidence, and several challenges have been identified with evidence that supports WHO TB guidelines: • selection of interventions is often not sufficiently driven by the needs of high TB burden countries and affected communities, and is not coordinated at a global level; • trial goals are mostly focused on satisfying regulatory requirements, not on informing policy or implementation; and • restrictive eligibility criteria limit the people-centredness of the interventions and evidence generated. This situation has sometimes resulted in trials with small sample sizes, generated as part of tightly controlled trials that do not reflect programmatic realities; typically, such trials led to conditional recommendations. The limited involvement of high TB burden countries during prioritization and leadership of trials, combined with limited geographical involvement (partly due to the high cost and complexity of typical TB trials) has resulted in slow or limited uptake, or even repeat trials in certain countries. 5.1.2 WHO mandate in relation to TB and research At the second UNHLM-TB in 2023, world leaders approved a political declaration with ambitious new targets for the next 5 years, to advance the global efforts towards ending the TB epidemic. The declaration included commitments to substantially increase investments in TB research, and establish and build effective collaboration platforms to drive the development and rapid uptake of innovations (19). World Health Assembly resolution WHA75.8 – Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination (19) – calls on Member States “to coordinate clinical trials research priorities based on public health needs of Member States including collaborative and, as appropriate, multicountry and multiregional clinical trials when mutually beneficial, while avoiding unnecessary duplication of work.” These calls, as well as related discussions held in November 2023 at the first WHO Global Clinical Trials Forum (20) and key messages in WHO Guidance for best practices for clinical trials (21), resonated with the 17 challenges laid out above, and demonstrated that these challenges – and their possible solutions – are not unique to TB. Recently published target regimen profiles (22) and ongoing work to develop guidance on evidence generation on new regimens for TB treatment help to pave a clearer path towards prioritization in regimen selection and clarity on evidence needs. 5.1.3 Pipeline of new TB drugs, regimens, trials and consortia Today, the pipeline of novel TB drugs and regimens looks stronger than ever and promises to deliver multiple new treatment options over the coming years. Several large and well-funded trial consortia have been established to conduct Phase 2b/c trials to evaluate over a dozen new TB regimens. Some of these trials are designed as platform trials that will conduct multiple rounds of evaluation over at least 5 years, and will eventually generate Phase 2 level results on new regimens. Given the number of new drugs in the pipeline for TB and the newly established trial consortia, it is likely that several promising new regimen candidates and treatment approaches will emerge, requiring investigation in Phase 3 trials; however, as yet there are no clear plans to match the output from these mid-phase trials with evaluations in late-stage trials, covering all key populations, which would enable WHO policy recommendations and uptake by high TB burden countries. 5.1.4 Knowledge gaps with available regimens Despite the potential for advancements in TB treatment with the introduction of new drugs, there are still significant gaps and unanswered questions in optimizing current regimens. Dosage and duration adjustments, as well as simple substitutions in regimen components, hold promise for enhancing effectiveness and expanding therapeutic options using drugs and regimens that are already available. However, a major obstacle to addressing these questions is the prohibitive cost of conducting clinical trials under the current TB clinical trials paradigm, which is based on sequential, unconnected, explanatory1 one-off trials. This financial barrier underscores the importance of prioritizing research funding and resource allocation towards optimization of TB treatment. Collaborative efforts among researchers, policy-makers and funding agencies are essential in finding innovative solutions to reduce the costs associated with clinical trials. Additionally, exploring alternative trial designs (e.g. adaptive trials, streamlined trials and pragmatic trials) can offer more cost-effective approaches to generating evidence for optimizing TB treatment regimens. Key gaps and challenges 1. Currently, there are no mechanisms for prioritizing regimens to be investigated for late-stage trials that give a leading role to high TB burden countries and affected communities. 2. Traditional TB clinical trials are often slow, expensive, small in size, not inclusive of population groups and geographies, and conducted under conditions that do not represent real-world conditions, resulting in low certainty evidence, conditional recommendations, and low, slow or limited uptake. 1 An explanatory trial assesses the effectiveness of a treatment in a controlled environment, to study the direct effects of that treatment. 18 3. Several Phase 2b/c trials are underway, which may generate multiple highly promising candidate regimens; however, there is no plan for Phase 3 trials that will provide evidence for the inclusion of evaluated regimens into guidelines and adoption by high TB burden countries. 5.1.5 Proposed solution In response to the needs outlined above, STAG-TB members propose the establishment of a streamlined, multicountry, randomized, open-label, Phase 3/4, pragmatic and adaptive trial platform to evaluate the safety and effectiveness of TB treatment regimens and treatment-related interventions. Using innovative digital technologies and combining the strengths of emerging approaches – that is, large, simple (streamlined) trials; pragmatic trials; adaptive platform trials; and decentralized (point-of-care), people-centred trials – may be an efficient and effective way to address the following critical needs: • match the amount of initial (Phase 2b/c) evidence that will be emerging from the pipeline in the coming years with a suitable platform that can rapidly accommodate multiple late- stage studies; • generate high-certainty evidence that is suitable for use in the WHO policy development framework and has the potential to lead to strong recommendations with high certainty in the underlying evidence; and • facilitate the eventual adoption and implementation of the potential recommendations resulting from this work by: o working in close collaboration with ministries of health (MoHs), affected communities and other key stakeholders in high TB burden countries; o using a pragmatic approach in which clinical trial conduct is largely aligned with programmatic practice; and o focusing on addressing the needs of affected people and populations, including key populations such as children and adolescents. STAG-TB members propose that this platform trial be established under the aegis of WHO, in close collaboration with partners and MoHs of high TB burden countries. WHO is well positioned to lead the coordination of this work and ensure broad representation of key stakeholders and acceptance by high TB burden countries, and to support partners in conducting trial activities. 5.2 Topics covered Increased funding has been allocated for TB in general, with a specific focus on optimizing treatment. However, there are challenges with regards to prioritization and trial objectives. Often, priorities are established in countries with a low burden of TB, with the aim of obtaining approval for a new medication for the market, without considering public health policy. The idea is to establish a large, simple, decentralized (digital) trial that will augment the body of evidence. Randomized controlled trials (RCTs) provide the highest level of evidence. The proposed platform for TB treatment trials will allow for the collection of evidence and is expected to enhance the strength of recommendations. 19 The platform will focus on low- or medium-complexity and risk interventions, rather than registering new chemical entities. WHO will support the development of this platform. Additionally, a scientific advisory group and a community advisory board will be formed, comprising NTP managers, clinical trialists, trial methodologists, treating clinicians and community members. The community advisory board will be formed early in the development of the platform, to ensure person-centred care. A trial sponsor will be selected through a transparent request for proposal. The trial’s pragmatic nature is innovative, with the aim of including pregnant women and children if sufficient safety data are available. A digital solution for on-treatment and post-treatment follow-up could also be added. Anticipated challenges include securing buy-in from countries with a high TB burden and managing complexities in implementation. An acceptable governance structure will also need to be found, and securing funding for this concept will be a significant undertaking. However, the opportunities are immense. This trial has the potential to revolutionize evidence generation in TB treatment, leading to enhanced policy-making. It will also significantly strengthen research capacity, fostering the development of new competencies and resulting in more effective learning within the health system. WHO is the ideal organization to lead this trial, given its ability to convene countries and its well- recognized role in drafting normative guidelines. Its leadership will provide a sense of confidence and reassurance to all stakeholders involved. 5.3 Questions to STAG-TB 1. Does STAG-TB support a streamlined, pragmatic and adaptive trial platform under the aegis of WHO as part of the solution to the challenges to improving TB treatment globally? 2. How should trial governance and mechanisms for intervention selection be structured to ensure that priorities for people affected by TB, NTP and other key stakeholders are addressed? 5.4 STAG-TB comments The discussants for this topic were Dr Payam Nahid and Dr Fareed Abdullah. STAG-TB acknowledges the existence of a critical gap between research and implementation. This gap is driven by the current mechanisms for prioritization and by insufficient application of the principle of risk- proportionality in TB trials. The enthusiasm for the pragmatic clinical trial platform, as indicated by the discussants, reflects a growing recognition in the TB community of the importance of such a platform. Trials that occur after a drug has received regulatory approval are crucial for monitoring long-term safety and effectiveness in a broader patient population. They provide valuable data on real-world usage, which can lead to the optimization of treatment guidelines and ensure that the benefits of a drug continue to outweigh any risks. STAG-TB welcomes WHO engagement with high TB burden countries, research partners and civil society stakeholders while building the TB trial platform. The engagement leverages WHO’s convening capacity and its unique relationship with its Member States and health care authorities to address the complexities inherent in the design and conduct of TB trials. 20 STAG-TB welcomes the WHO TB trial platform initiative as a timely effort to facilitate late-phase and public health policy oriented research on medicines, regimens and implementation strategies or approaches in TB treatment that aim to obtain more precise estimates and more direct evidence on key questions related to TB treatment. Incorporating implementation science into clinical trials can significantly enhance their relevance to guideline development. By focusing on person-centred care and individual preferences, the trial can provide insights into how interventions can be tailored for maximum patient benefit. Moreover, integrating elements of cost–effectiveness and health economics will offer valuable data on the economic viability of interventions. Ensuring post-trial access to medications and interventions is also crucial, because it addresses the ethical considerations of trial conduct and supports the sustainability of health benefits in the participating countries. These enhancements will align the trial outcomes with real-world applications, facilitating the translation of research into practice. There are challenges that will need to be overcome when conducting pragmatic trials embedded in country programmes and routine care. These challenges include heterogeneity in health systems; differences in country guidelines, regulatory and ethics processes; and the need to find the substantial resources required for this endeavour. The challenges of TB clinical trial capacity and funding are significant, with a clear need for innovative approaches to expand and enhance research infrastructure. It is essential that new models for a clinical trial platform not only seek additional sites and funding, but also align with ongoing efforts in the field to ensure a cohesive and comprehensive approach to TB research. WHO, as a central figure in global health, should play a crucial role in coordinating these efforts and ensuring that new initiatives complement and support existing work, rather than compete with or detract from it. Explanatory clinical trials are essential for the development of new medical treatments, ensuring that they are both safe and effective. However, the traditional design of these trials often excludes key populations such as the elderly, pregnant women, children, those with advanced HIV and the undernourished. This exclusion can lead to a lack of data on how new treatments work in these groups. The trial platform would take on this risk, with trial protocols being adapted to include these populations, ensuring that their specific needs are met and risks are carefully managed. This approach will not only broaden the applicability of the research findings but also enhance the ethical aspect of clinical research, by providing potentially beneficial treatments to more diverse groups. In the context of the trial platform, it was decided to start with one trial and progressively build the platform. This approach aligns with best practices that suggest starting with a core set of interventions and then expanding to include more complex ones (e.g. new chemical entities) as the platform evolves. The development of generic templates and best practice tools supports this iterative process by providing guidance on the design, planning, implementation and conduct of integrated research trial platforms. By adopting this flexible and scalable approach, the platform can maintain momentum and adapt to emerging data and innovations, ensuring a more efficient and responsive research environment. 21 5.5 STAG-TB preamble STAG-TB: • showed unanimous support for the establishment of a global pragmatic TB trial platform as part of a solution to the challenges of improving TB care globally and closing the gap between research and implementation; • acknowledges the existence of a critical gap between research and implementation that is driven by current mechanisms for prioritization, and insufficient application of the principle of risk proportionality in TB trials; • welcomes the WHO TB trial platform initiative as a timely effort to facilitate late-phase and public health policy oriented research on medicines, regimens and implementation strategies or approaches in TB treatment, with the goal of attaining more precise estimates and more direct evidence on key questions related to TB treatment; • welcomes WHO engagement with high TB burden countries, research partners and civil society stakeholders while building the TB trial platform, which leverages the WHO convening capacity and its unique relationship with its Member States and health care authorities, to address the complexities inherent in the design and conduct of TB trials; and • highlights challenges that will need to be overcome when conducting pragmatic trials embedded in country programmes and routine care, including heterogeneity in health systems; differences in country guidelines, regulatory and ethics processes; and the need to find the substantial resources required for this endeavour. 5.6 STAG-TB recommendations STAG-TB: • advises WHO to identify clinical trial priorities and needs from the perspective of high TB burden countries, their technical partners, civil society and the research community; • asks WHO to further develop the TB trial platform and the mechanism to define and select priority questions for evaluation in this platform, along with associated optimal approaches to the design and conduct of trials, through consultation with clinical trialists, trial methodologists, NTPs, the research community and TB-affected communities; and • acknowledges that the pragmatic TB clinical trial platform is essential and holds significant potential, but also that its ambitious nature will require additional resources to be allocated to the Global Tuberculosis Programme to ensure successful implementation. STAG-TB recommends that WHO: • engage with potential donors and high TB burden countries; • focus on highly pragmatic research questions and trials, including elements of implementation and qualitative science in the framework of the TB trial platform; • develop a clear and inclusive governance structure that balances innovative ideas from cutting-edge research with practical constraints for implementable interventions sought by NTPs and the needs of TB patients, while providing leadership and strong public health orientation of the trials selected to run on the platform; 22 • engage with existing research expertise in countries, and contribute towards building additional trial capacity at the national level with the ultimate goal of working towards learning health systems; • put in place mechanisms that ensure post-trial access (at the country level) to evaluated drugs and other interventions; • ensure diverse geographical representation of the intended sites for this TB trial platform; • aim to include the collection of patient-reported outcomes, to capture more directly how interventions affect patients’ lives and experience; • use the trial platform to learn about optimal treatment in populations where evidence is currently scarce and clinical practice is not well supported by evidence (e.g. the inclusion of people with diabetes, pregnant women, children, elderly people and those with extrapulmonary TB or a high risk of mortality); and • once established, expand the scope to other areas of TB research beyond TB treatment. 23 6. Estimates of TB incidence and mortality required for assessment of progress towards the 2025 and 2030 milestones and targets from the End TB Strategy and the SDGs: data sources, analytical methods and process 6.1 Background To monitor and report on the 2025 and 2030 milestones and targets of the End TB Strategy and SDGs, the Global TB programme (GTB) publishes an annual global TB report. The report includes estimates of TB incidence and mortality at global, regional and country levels, up to the latest complete calendar year. These estimates are produced using data sources reported by Member States and analytical methods that are periodically reviewed by the WHO Global Task Force on TB Impact Measurement (23). The 2030 targets of the End TB Strategy and SDGs are only 6 years away, and an assessment of the status of progress with respect to the 2025 milestones of the End TB Strategy will be required in 2026. In this context, and in the wake of the COVID-19 pandemic, a thorough review is needed of the data sources, analytical methods and process to be used by WHO to produce estimates of TB incidence and mortality for the periods 2015–2025 and 2015–2030. Given the recognized limitations of the current methods that are used to produce TB incidence and mortality estimates, it is important to conduct periodic reviews of approaches that could improve these methods. In advance of a major review of existing and possible new options at the September 2024 meeting of the WHO Global Task Force on TB Impact Measurement, the STAG-TB meeting offered an opportunity for an early consultation on three of the new options under consideration for estimates of TB incidence. 6.2 Topics covered The three new options that were presented for discussion were: • the use of prevalence survey data for estimation of incidence that accounts for the latest literature on the natural history of TB (with particular attention to subclinical TB); • the use of data from active case finding (ACF) campaigns to estimate the prevalence of TB disease in the population (and, in turn, the incidence), or to inform assessment of trends in incidence; and • the systematic use of the UHC SCI to estimate TB incidence in two major groups of countries. 24 6.2.1 Use of prevalence survey data for estimation of incidence that accounts for the latest literature on the natural history of TB (with particular attention to subclinical TB) National TB prevalence surveys have consistently shown that a substantial proportion (a pooled average of about 50%) (24) of the people found to have bacteriologically confirmed pulmonary TB did not report symptoms suggestive of TB, when screened for symptoms as part of the survey. Such “subclinical” TB has been gaining renewed recognition in recent years (25, 26). A 2023 publication analysing data from longitudinal cohorts from the prechemotherapy era, along with prevalence surveys, highlighted subclinical TB as being just one part of a clinical spectrum of disease (25), with potential “undulation” between different disease states. Such a dynamic natural history presents new challenges in the interpretation of incidence. For example, an individual may experience multiple, distinct episodes of bacteriologically positive pulmonary TB disease; therefore, one question is whether incidence in a particular year should be conceptualized as the sum of such episodes at the population level, or as the number of individuals experiencing one or more such episodes. At present, the only evidence for this type of progression and regression is from historical cohorts from the prechemotherapy era: the extent to which this applies to populations in high TB burden countries today is unclear and, for ethical reasons, it cannot be studied. Moreover, a question remains as to whether incidence should be identified with the onset of bacteriologically positive status (i.e. including both subclinical and symptomatic TB), or with the onset of symptoms. Modelling analysis was presented in the context of an example of a country that highlighted the potential disparity between the incidence of “infectious” TB (i.e. all sputum bacteriologically positive forms, including subclinical pulmonary TB), and “symptomatic” TB. The latter is roughly consistent with incidence estimates currently reported by WHO, whereas the former could be substantially higher. 6.2.2 Use of data from ACF campaigns to estimate the prevalence of TB disease in the population (and, in turn, the incidence), or to inform assessment of trends in incidence In recent years, there has been particular interest in whether data from ACF for TB in the community could be used as a substitute for a national TB prevalence survey. ACF that includes use of CXR and questions about TB symptoms, followed by diagnostic testing for those who screen positive, to some extent resemble what is done in a national TB prevalence survey. However, the following need to be considered: • If ACF relies on questions about symptoms, then the only data available will be those related to the prevalence of symptomatic TB. National TB prevalence surveys have consistently found a substantial proportion of bacteriologically positive pulmonary TB without self-reported symptoms (on average, 44% in African countries and 62% in Asian countries). • If ACF relies only on symptom-based screening of the general population, a diagnostic testing algorithm based only on rapid molecular tests may result in more than half of positive test results being false positives (27). Hence, the latest WHO guidance on national TB prevalence surveys recommends confirmatory testing using liquid culture for all those with a positive Xpert® Ultra result. 25 • In line with current WHO guidelines for ACF (28), most ACF for TB focuses on settings such as prisons, slums or health care settings, which are not representative of the overall population. Therefore, estimation of TB burden in the general population would require assumptions about the relationship between TB prevalence in the target population and TB prevalence in the general population. A major, recent ACF initiative in Uganda offers an opportunity to examine the role of these factors. Known as CAST-TB (Community Awareness, Screening, Testing, Prevention and Treatment to End TB and Leprosy), this initiative began in 2022. Involving over 70 000 community health workers, it emphasizes raising community awareness of TB, and strengthening links between communities and facilities to improve treatment outcomes. Individuals were screened for symptoms, and those with symptoms suggestive of TB were referred for confirmation with Xpert Ultra. Overall, any burden estimates based on data from this intervention would need to make at least two corrections: one for the proportion of cases that report symptoms, and another for the excess risk of TB in the screened population relative to the general population. Incidence estimates based on the data from CAST-TB, accounting for both these sources of uncertainty, were presented. Based on ACF data alone, incidence estimates have substantially wider uncertainty than those based on prevalence survey data, even without including adjustment for the specificity of the confirmatory algorithm, which would further widen the uncertainty. Moreover, central estimates varied considerably from those derived from prevalence survey data. ACF efforts are typically not conducted in populations that are representative of the country and they rely on symptom screening; thus, overall, they introduce important uncertainties that render them less informative for incidence estimation than prevalence survey data. It is nonetheless important to explore the use of ACF data in combination with prevalence survey data, to inform estimation of trends. Moreover, given the sheer scale of CAST-TB, with minor adjustments in its design it may be possible for this initiative to have an impact on public health while simultaneously improving burden estimates (e.g. by “nesting” a prevalence survey within CAST-TB). 6.2.3 Systematic use of the UHC SCI to estimate TB incidence in specific countries The SDGs include a target to achieve UHC by 2030. The UHC SCI is one of two indicators used to measure UHC; it can have values from 0 (worst) to 100 (best). The SCI is calculated as the geometric mean of 14 “tracer” indicators for the coverage of health care. Estimates were first published by WHO and the World Bank in a UHC monitoring report in 2017 and the latest WHO report (published in September 2023) includes estimates for all WHO and UN Member States for 7 years: 2000, 2005, 2010, 2015, 2017, 2019 and 2021 (29). To date, WHO has published reports that include UHC SCI estimates every 2 years; the latest year for which estimates are published in each report is the report year minus 2 (e.g. the 2023 report includes estimates up to 2021). It is anticipated that reports with UHC SCI estimates for every WHO and UN Member State will continue to be published every 2 years until at least 2030; the next report is due for publication in 2025. Given the limitations of two of the main methods currently being used for incidence estimation, the UHC SCI could be used to directly inform TB treatment coverage in two major groups of countries: 26 a) Countries for which incidence estimates currently rely on notification data combined with expert opinion about underreporting, underdiagnosis and overdiagnosis (currently 39 countries). b) Countries for which incidence estimates currently rely on notification data combined with a standard upward adjustment that is based on expert opinion and on evidence about levels of underreporting and underdiagnosis in high-income countries (currently used for most high- income or low-burden countries, and some middle-income countries). For countries in (a), a proposed 2-step approach involves first using a statistical model to predict TB treatment coverage, using the UHC SCI profile over time in countries where at least one national TB prevalence survey was implemented between 2000 and 2021. The next step is to estimate TB incidence using TB case notification data (routinely reported to WHO by all Member States every year) that are upwardly adjusted according to the predicted TB treatment coverage in the first step. For countries in (b), the UHC SCI could be used directly, without any further adjustment, as an approximation of TB treatment coverage (defined as the percentage of incident TB cases that are notified and treated). As presented during the STAG-TB meeting, the proposed approach appears to be consistent with existing estimates, for both groups of countries. A strength of this approach is that it does not require any reliance on expert opinion and allows more country-specific adjustments (as opposed to the standard adjustment currently employed). 6.2.4 Process for finalization and implementation of options At the time of the STAG-TB meeting, a suggested process for the finalization and implementation of existing and new options to be used for the 2025 milestones and 2030 targets assessment was in development (for further discussion at the September 2024 meeting of the WHO Global Task Force on TB Impact Measurement). A high-level summary was presented during the STAG-TB meeting. 6.3 Questions to STAG-TB 1. What is STAG-TB’s advice related to the three new methods that have been presented? 2. Does STAG-TB have any suggestions related to the proposed timeline and associated activities for the finalization and implementation of new options? 27 6.4 STAG-TB comments 6.4.1 Subclinical TB STAG-TB supported the continuation of the existing work to consider the implications of subclinical TB for global estimates of TB incidence, including at the September 2024 meeting of the WHO Global Task Force on TB Impact Measurement, with attention to the following considerations: • Currently, there are limited data supporting the trajectories of subclinical TB, especially in relation to progression and reversion of symptom status, and how these might vary by country. The potential role of using consensus-based – “expert opinion” – approaches relying on the best available data was noted. • Estimates of symptomatic TB and bacteriologically positive TB should be reported separately because their relevance for programme priorities and approaches may be different. • Any updates to estimates should ensure consistency with estimates already published for the period since 2015; they should also ensure consistency between estimates for countries with prevalence survey data (which include people with sublinical TB) and estimates for countries without prevalence survey data. • Estimates should not double-count individuals who experience multiple episodes without intervening treatment. • Input should be obtained from country and civil society representatives. 6.4.2 Use of data from ACF campaigns to estimate the prevalence of TB disease in the population (and, in turn, the incidence), or to inform assessment of trends in incidence STAG-TB members suggested that the use of data from large-scale ACF campaigns be considered as a complement to, rather than a replacement for, other methods for estimating TB incidence. Several points were noted: • Such data, if obtained from repeated and consistently implemented campaigns, may be more useful for estimating trends than for estimating the absolute level of disease burden. • ACF campaigns may represent an opportunity to measure the absolute level of TB prevalence through nested studies or stratified sampling, if appropriate a priori attention is paid to the design. • Attention should be paid to the possibility of substantial bias in data from ACF campaigns if applied to generate estimates of TB incidence (e.g. estimates derived from the second round of CAST-TB in Uganda were exceeded by national case notifications, suggesting that these estimates were too low). • Attention should be paid to variation in the way that ACF is implemented across countries, and how this should be accounted for in burden estimates. • Several members of STAG-TB highlighted the ongoing value of prevalence surveys in providing the most reliable estimates of TB incidence. 6.4.3 Systematic use of the UHC SCI to estimate TB incidence in specific countries Pending review and approval by the WHO Global Task Force on TB Impact Measurement, STAG-TB recommended implementing the proposed method based on the UHC SCI for the two major groups of countries for which it was proposed. It was noted that: 28 • attention should be paid to concerns that any method using case notifications to estimate incidence may result in inappropriate trends when case notifications increase owing to improved case finding and diagnosis; and • use of laboratory-based data could be considered to help make adjustments for intensified approaches to testing and case finding (e.g. the percentage of Xpert tests that are positive, stratified by district). 6.4.4 Other estimates STAG-TB also suggested considering the generation of estimates of TB incidence and mortality for specific subgroups or areas, where appropriate data exist. Three specific examples were mentioned: individuals who are pregnant or postpartum, individuals deprived of liberty (in jails and prisons) and subnational areas. 6.4.5 Process for finalization and implementation of options STAG-TB supported the process proposed by the Global Tuberculosis Programme. It was also suggested that: • WHO’s Global Tuberculosis Programme should aim to provide estimates using any updated methods, once finalized, in the 2025 global TB report; • priority in the process should be given to countries with a large TB burden and for which concerns have been expressed regarding the current methods; and • civil society and country representatives should be engaged early in the process, including in the upcoming meeting of the WHO Global Task Force on TB Impact Measurement in September 2024. 6.5 STAG-TB preamble STAG-TB congratulates WHO for the impressive work done to consider alternative and improved approaches to estimate the burden of TB incidence and mortality. This includes the thoughtfulness behind the proposed approaches for estimating the burden of subclinical TB, using large-scale ACF campaigns to improve burden estimates, using the UHC SCI to refine case notification-based estimates of TB incidence, and developing a plan to finalize and implement options for revised burden estimates. 29 6.6 STAG-TB recommendations STAG-TB recommends that WHO: • continue ongoing work to refine estimates of TB incidence and mortality, including at the September 2024 meeting of the WHO Global Task Force on TB Impact Measurement, with particular attention to: o considering the implications of subclinical TB; o considering use of data from large-scale ACF campaigns as a complement to, or replacement for, existing methods to estimate incidence; o applying the proposed method based on UHC SCI to replace expert opinion and standard adjustment to estimate TB incidence from case notification data; • implement the process of updating TB burden estimates as suggested, with a view to using any updated methods that have been endorsed by the WHO Global Task Force on TB Impact Measurement in the 2025 global TB report; and • consider generating estimates of TB incidence and mortality for specific subgroups or areas, where appropriate data exist. 30 7. On the road to TB elimination: key criteria, indicators and the validation governance process 7.1 Background Commitments made by world leaders at the 2023 UNHLM-TB have galvanized countries to accelerate the TB response on the road to TB elimination (4, 30). This builds on the WHO End TB Strategy (3), which delineates a comprehensive framework for Member States to intensify and accelerate efforts towards ending TB; the strategy is underpinned by the overarching vision of a world free of TB. Despite this renewed political impetus and countries having made progress towards the operationalization of the above commitments, TB remains a significant public health challenge globally and one of the world’s deadliest infectious killers, with enormous impacts on families and communities. The ultimate goal of global TB efforts is the elimination of the disease. In the context of public health efforts, the traditional definition of disease elimination – understood as “the reduction to zero of the incidence of a particular disease in a defined geographical area as a result of deliberate efforts” (31) – is inadequate for TB owing to the substantial reservoir of TB infection. TB elimination is a continuation of the path for countries beyond the targets in the End TB Strategy. It entails further driving down incidence, with the aim of achieving an incidence rate of less than one case per million population (32). Currently, some countries have already reduced their burden of TB disease to fewer than 10 cases (pre-elimination) and less than one death per 100 000 population per year (13). However, even in settings with advanced health systems, robust public health infrastructure and sufficient resources, achieving pre-elimination in the next decade requires a dramatic acceleration of efforts. To expedite the TB response in settings with the potential for elimination, WHO released its TB elimination framework (32). The framework supports efforts at elimination, particularly in low-incidence1 countries. Ten years after the release of the framework, given the expanding and varying drivers of TB and changing needs, WHO initiated a process to expand its guidance for TB elimination beyond low TB burden countries (e.g. to tackle pockets of high TB burden that persist in these settings). The expansion aims to assist countries in addressing factors that continue to threaten progress; these factors could lead to missed opportunities for reaching global targets if action is not accelerated. Furthermore, the expansion helps in making progress on targets for achieving health equity and fulfilling the commitments made by Member States in the 2023 political declaration to end TB (4). Updating the TB elimination framework and linked operational guide The WHO TB elimination framework (32) delineated eight priority areas to advance the TB response in settings with the potential for elimination. It also emphasized the importance of collaboration between public health authorities, health care providers and community stakeholders to ensure a comprehensive and integrated approach to TB elimination. The current update will continue to 1 Low-incidence settings are those with an incidence of less than 100 TB cases (all forms) per million population. 31 stress the need to rapidly tackle the drivers of TB through targeted actions, optimization of evidence-based interventions aimed at populations at the highest risk, strengthened health systems and collaborative efforts. The forthcoming framework will be accompanied by an operational guide that will offer a systematic approach to initiating planning, preparation and implementation of interventions aimed at achieving elimination beyond the patient-care pathway. Crucially, the guide will outline the essential metrics and criteria for countries to evaluate their progress in eliminating TB, and the procedures for pursuing certification and maintaining TB elimination status. WHO initiated a series of consultations to discuss the considerations for accelerating progress, not only in low TB burden settings but also in supporting subnational efforts to eliminate TB in specific populations. Insights from an expert consultation in December 2023 in Istanbul shaped the preliminary work, particularly on identifying key metrics for monitoring TB elimination and the sustainability of those metrics. Another consultation in June 2024 reviewed progress on the metrics, indicators and governance processes to finalize the TB elimination framework and operational guide. Several key themes emerged during these initial consultations, highlighting both strategic approaches and ongoing challenges. For instance, participants observed that geopolitical issues and competing health priorities in various countries can hamper TB elimination efforts. However, they also noted that ambitious TB elimination targets could inspire countries and drive political engagement, with certification offering achievable short-term goals to motivate progress (33, 34). 7.2 Topics covered The topics covered were: • modelling to inform priorities for TB elimination; • proposed metrics for TB elimination, specifically elimination of TB in children, elimination of DR-TB, elimination of TB deaths, elimination of TB infection, elimination of TB in risk groups and vulnerabilities, and elimination of TB at the subnational level; • proposed validation governance structure and process, including a tiered approach to TB elimination; • core principles and preconditions to apply for certification; and • surveillance system considerations. 7.3 Questions to STAG-TB 1. What is STAG-TB’s advice to WHO on the scope of the proposed criteria and indicators on the path to TB elimination? 2. What does STAG-TB propose to WHO on the validation governance process presented on the TB elimination pathway and linked certification process, to streamline it and increase uptake? 32 7.4 STAG-TB comments STAG-TB members highlighted the importance of setting realistic and motivating targets for high TB burden countries, with a tiered structure (gold, silver and bronze) that includes achievable intermediate goals. The certification process should not only focus on incidence rates but also on the quality of health systems and the robustness of infrastructure, drawing lessons from other disease elimination efforts. Advocacy, political engagement and multisectoral action addressing socioeconomic determinants were emphasized as critical components of the TB elimination efforts. STAG-TB members noted the importance of ethical considerations, especially with regard to vulnerable populations; they also flagged the risks of overly ambitious targets and the potential for political pressures. To ensure the success of the TB elimination framework, they emphasized the need to maintain a balance between aspirational goals and practical targets, include quality care indicators, and actively involve civil society and patient perspectives. Continuous review and adaptation of the framework based on feedback and lessons learned from implementation will be essential to achieving and sustaining progress in TB elimination. 7.5 STAG-TB preamble STAG-TB: • commends WHO for its work on key criteria, indicators and validation governance processes on the path to TB elimination, including modelling of TB elimination indicators followed by an intensive consultative process, and emphasizes the need for this work as a motivator for countries on the path to elimination; STAG-TB urges WHO to build on lessons learned from other disease elimination efforts and avert risks; • recognizes the importance of the TB elimination framework and the proposed certification process as crucial drivers for countries to prioritize their TB response at the highest level, highlights the advantages (e.g. potential socioeconomic benefits) beyond health, and advocates for improved access to medicines and diagnostics; • notes the epidemiological diversity of countries on the path to elimination and the need for targeted achievable indicators with incentives for countries at every stage of the epidemic; • acknowledges the need for multisectoral collaboration and engagement, including with civil society and affected communities to tackle TB, its barriers (e.g. stigma) and its drivers on the path to elimination; and • recognizes that elimination is an ongoing process and needs to be sustained to ensure that there are no reversals in gains. 7.6 STAG-TB recommendations STAG-TB: • recommends that WHO develop a clear advocacy case for incorporation in the TB elimination framework, highlighting core incentives and quick gains to support countries in securing internal political commitments and resources for the TB response; • proposes that WHO expands the list of criteria in the certification tiers, ensuring a mix of coverage and impact targets, to give countries more achievable targets and quick wins or incentives, including for high TB burden countries (this includes indicators on mortality and 33 transmission, additional risk groups, quality of care and nonmedical indicators such as social protection and UHC); • asks WHO to outline a clear step-by-step process to guide countries on applying for certification, and urges WHO to streamline the validation and certification process, ensuring that it is not resource intensive and burdensome; • recommends that WHO strengthen coordination and collaboration with other sectors, civil society and affected communities, building on the multisectoral accountability framework to fast-track elimination; • strongly supports the need for targeting subnational elimination, and urges WHO to liaise with key stakeholders at national and local levels to seek inputs on including this in the elimination framework; • requests that WHO guides countries to prioritize relevant risk groups based on the setting, ensuring that human rights, equity and ethical considerations are mainstreamed; • asks WHO to explore the usefulness of proxies and methodologies to strengthen TB surveillance, learning lessons from other disease elimination efforts and the COVID-19 response; and • asks WHO’s leadership to engage with officials at the highest levels in countries to prioritize and accelerate TB elimination efforts, and participation in the certification process, following the launch of the TB elimination framework and operational guide. 34 8. Planning for the 2025 STAG-TB meeting The 25th annual meeting of STAG-TB is planned for June 2025. STAG-TB members provided a list of suggested agenda items to consider for the 2025 meeting. A proposed agenda will be drafted and discussed with the STAG-TB Chair. This will be shared with STAG-TB members well in advance of the meeting dates. 35 References 1 Strategic and Technical Advisory Group for Tuberculosis (STAG-TB) [website]. Geneva: World Health Organization; 2025 (https://www.who.int/groups/strategic-and-technical-advisory-group- for-tuberculosis/about). 2 WHO Civil Society Task Force on Tuberculosis [website]. Geneva: World Health Organization; 2025 (https://www.who.int/groups/civil-society-task-force-on-tb). 3 The End TB Strategy. Geneva: World Health Organization; 2015 (https://www.who.int/teams/global-tuberculosis-programme/the-end-tb-strategy). Licence: WHO/HTM/TB/2015.19. 4 Resolution 78/5: Political declaration of the second high-level meeting of the General Assembly on the fight against tuberculosis. New York: United Nations General Assembly; 2023 (https://digitallibrary.un.org/record/4025280?v=pdf). 5 Primary health care: report of the International Conference on Primary Health Care, Alma-Ata, USSR, 6–12 September 1978, jointly sponsored by the World Health Organization and the United Nations Children's Fund. Geneva: World Health Organization; 1978 (https://www.who.int/publications/i/item/9241800011). 6 World Health Organization, United Nations Children’s Fund. Operational framework for primary health care. Geneva: World Health Organization; 2020 (https://www.who.int/publications/i/item/9789240017832). 7 Framework for collaborative action on tuberculosis and comorbidities. Geneva: World Health Organization; 2022 (https://www.who.int/publications/i/item/9789240055056). 8 Practical approach to lung health: a primary health care strategy for the integrated management of respiratory conditions in people five years of age and over. Geneva: World Health Organization; 2005 (https://iris.who.int/bitstream/handle/10665/69035/WHO_HTM_TB_2005.351.pdf?sequence=1 &isAllowed=y). 9 Practical approach to lung health: manual on initiating PAL implementation. Geneva: World Health Organization; 2008 (https://iris.who.int/bitstream/handle/10665/69937/WHO_HTM_TB_2008.410_eng.pdf?sequen ce=1&isAllowed=y). 10 Primary health care [website]. Geneva: World Health Organization; 2025 (https://www.who.int/teams/primary-health-care). 11 Koltringer FA, Annerstedt KS, Boccia D, Carter DJ, Rudgard WE. The social determinants of national tuberculosis incidence rates in 116 countries: a longitudinal ecological study between 2005-2015. BMC Public Health. 2023;23:337 (https://doi.org/10.1186/s12889-023-15213-w). 12 Hargreaves JR, Boccia D, Evans CA, Adato M, Petticrew M, Porter JD. The social determinants of tuberculosis: from evidence to action. Am J Public Health. 2011;101:654-62 (https://doi.org/10.2105/AJPH.2010.199505). 13 Global tuberculosis report 2023. Geneva: World Health Organization; 2023 (https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis- report-2023). Licence: CC BY-NC-SA 3.0 IGO. 14 More than 100 million people are forcibly displaced [website]. Geneva: United Nations Refugee Agency; 2022 (https://www.unhcr.org/refugee-statistics/insights/explainers/100-million-forcibly- displaced.html). 15 Air pollution [website]. Geneva: World Health Organization; 2025 (https://www.who.int/health- topics/air-pollution#tab=tab_1). 16 Country rankings [website]. South Bend, IN: Notre Dame Global Adaptation Initiative (ND-GAIN); 2025 (https://gain.nd.edu/our-work/country-index/rankings/). 36 17 From milligrams to megatons: a climate and nature assessment of ten key health products. Geneva: Unitaid; 2023 (https://unitaid.org/uploads/Report_From-milligrams-to-megatons_A- climate-and-nature-assessment-of-ten-key-health-products.pdf). 18 The Paris Agreement [website]. Bonn: United Nations Climate Change; 2025 (https://unfccc.int/process-and-meetings/the-paris-agreement). 19 Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination (75th World Health Assembly: WHA75.8). Geneva: World Health Organization; 2022 (https://apps.who.int/gb/ebwha/pdf_files/wha75/a75_r8- en.pdf). 20 WHO Global Clinical Trials Forum, Geneva, 20–21 November 2023: summary of proceedings (WHO/SCI/RFH/2024.1). Geneva: World Health Organization; 2024 (https://www.who.int/thailand/publications/i/item/WHO-SCI-RFH-2024.1). 21 Guidance for best practices for clinical trials. Geneva: World Health Organization; 2024 (https://www.who.int/publications/i/item/9789240097711). Licence: CC BY-NC-SA 3.0 IGO. 22 Target regimen profiles for tuberculosis treatment, 2023 update. Geneva: World Health Organization; 2023 (https://www.who.int/publications/i/item/9789240081512). Licence: CC BY- NC-SA 3.0 IGO. 23 Global Task Force on TB Impact Measurement [website]. Geneva: World Health Organization; 2025 (https://www.who.int/groups/global-task-force-on-tb-impact-measurement). 24 National tuberculosis prevalence surveys 2007–2016. Geneva: World Health Organization; 2021 (https://www.who.int/publications/i/item/9789240022430). 25 Horton KC, Richards AS, Emery JC, Esmail H, Houben R. Reevaluating progression and pathways following Mycobacterium tuberculosis infection within the spectrum of tuberculosis. PNAS. 2023;120:e2221186120 (https://doi.org/10.1073/pnas.2221186120). 26 Ryckman TS, Dowdy DW, Kendall EA. Infectious and clinical tuberculosis trajectories: Bayesian modeling with case finding implications. PNAS. 2022;119:e2211045119 (https://doi.org/10.1073/pnas.2211045119). 27 National tuberculosis prevalence surveys: what diagnostic algorithms should be used in future? Geneva: World Health Organization; 2023 (https://www.who.int/publications/i/item/9789240073913). Licence: CC BY-NC-SA 3.0 IGO. 28 WHO operational handbook on tuberculosis. Module 2: Screening – systematic screening for tuberculosis disease. Geneva: World Health Organization; 2022 (https://www.who.int/publications/i/item/9789240022614). 29 Tracking universal health coverage: 2023 global monitoring report. Geneva: World Health Organization; 2023 (https://www.who.int/publications/i/item/9789240080379). Licence: CC BY- NC-SA 3.0 IGO. 30 Resolution 73/3: Political declaration of the high-level meeting of the United Nations General Assembly on the fight against tuberculosis. New York: United Nations General Assembly; 2018 (https://www.who.int/publications/m/item/political-declaration-of-the-un-general-assembly- high-level-meeting-on-the-fight-against-tuberculosis). 31 Dowdle WR. The principles of disease elimination and eradication. Bull World Health Organ. 1998;76 Suppl 2:22–5 (https://www.ncbi.nlm.nih.gov/pubmed/10063669). 32 Towards tuberculosis elimination: an action framework in low-incidence countries. Geneva: World Health Organization; 2014 (https://www.who.int/publications/i/item/9789241507707). 33 Development of metrics, criteria and processes for the validation of tuberculosis elimination: consultation report, 14–15 December 2023. Geneva: World Health Organization; 2024 (https://www.who.int/publications/b/76151). Licence: CC BY-NC-SA 3.0 IGO. 34 Development of metrics, criteria and processes for the validation of tuberculosis elimination: consultation report, 13–14 June 2024 Geneva: World Health Organization; 2024 (https://www.who.int/publications/b/76153). Licence: CC BY-NC-SA 3.0 IGO. 37 Annex 1. Final STAG-TB 2024 meeting agenda Day 1: Monday, 17 June 2024 Meeting opening and objectives 09:00 – 9:10 Welcome messages Ethel Maciel, Chair Tereza Kasaeva, GTB Director 9:10 – 9:25 Opening remarks and introductions (video) Jérôme Salomon, ADG, UCN 9:25 – 9:35 Meeting objectives, agenda and follow-up on STAG-TB 2023 Marek Lalli, GTB/TME Karine Halle, GTB/ODT 9:35 – 9:50 Global Tuberculosis Programme’s achievements (video) Hannah Monica Dias, GTB/ODT 9:50 – 10:00 Break Session 1: Progress report 10:00 – 10:30 Global Tuberculosis Programme’s progress updates Tereza Kasaeva, GTB Director 10:30 – 11:30 Regional offices’ efforts to advance UNHLM-TB targets and commitments WHO Regional TB Advisors: Jean-Louis Abena, AFR Pedro Avedillo, AMR Martin Van Den Boom, EMR Askar Yedilbayev, EUR Vineet Bhatia, SEAR Rajendra Yadav, WPR 11:30 – 11:40 WHO CSTF on TB: actions to advance uptake of UNHLM-TB targets and commitments CSTF Victoria James Luan Vo 11:40 – 12:30 Questions and comments STAG-TB members 12:30 – 13:30 Lunch break Session 2: From challenges to opportunities: harnessing PHC and integrated approaches, and other intersections for ending TB 13:30 – 15:30 TB and PHC and integrated approaches to lung health Tauhidul Islam, GTB/PCD Debora Pedrazzoli, GTB/PCD Licē González-Angulo, GTB/PCI Perspectives from the Special Programme on Primary Health Care on harnessing PHC, TB and integrated approaches Shams Syed PHC/PPU 38 Discussion and STAG-TB recommendations STAG-TB discussants Ya Diul Mukadi Robert Makombe 15:30 – 16:00 Break 16:00 – 17:00 Addressing the intersection of TB and climate change, through policy and research Ernesto Jaramillo, GTB/PCI Matteo Zignol, GTB/PCI Discussion and STAG-TB recommendations STAG-TB discussants: Anurag Bhargava Helen Ayles 17:00 – 17:15 Summary and wrap-up of Day 1 Ethel Maciel, Chair 17:30 Welcome reception Day 2: Tuesday, 18 June 2024 Session 3: TB platform trial 09:00 – 10:30 Closing the gap between clinical TB research and global implementation: streamlined, pragmatic and adaptive trial platform Francesca Conradie, GTB/PCI Samuel Schumacher, GTB/PCI Discussion and STAG-TB recommendations STAG-TB discussants: Payam Nahid Fareed Abdullah 10:30 – 11:00 Break Session 4: TB estimates for TB incidence and mortality 11:00 – 12:30 Estimates of TB incidence and mortality required for the 2025 and 2030 End TB Strategy and SDG milestones and targets assessment: data sources, analytical methods and process Nim Arinaminpathy, GTB/TME Mathieu Bastard, GTB/TME Discussion and STAG-TB recommendations STAG-TB discussants: David Dowdy Sarang Deo 12:30 – 13:30 Lunch break Session 5: On the road to TB elimination: key criteria, indicators and the validation governance process 13:30 – 15:00 TB elimination criteria and validation process Hannah Monica Dias, GTB/ODT Nim Arinaminpathy, GTB/TME Licē González-Angulo, GTB/PCI 39 Discussion and STAG-TB recommendations STAG-TB discussants: Mahshid Nasehi Gunta Dravniece 15:00 – 15:30 Break 15:30 – 17:00 TB elimination criteria and validation process (continued) Hannah Monica Dias, GTB/ODT Nim Arinaminpathy, GTB/TME Licē González-Angulo, GTB/PCI Discussion and STAG-TB recommendations STAG-TB discussants: Mahshid Nasehi Gunta Dravniece 17:00 – 17:15 Summary and wrap-up of Day 2 Ethel Maciel, Chair Day 3: Wednesday, 19 June 2024 Finalization of STAG-TB recommendations and meeting closure 09:00 – 10:40 Finalization of STAG-TB recommendations and meeting closure Ethel Maciel, Chair Session leads Rapporteurs STAG-TB members 10:40 – 11:00 Break 11:00 – 12:00 Next steps and closing remarks Ethel Maciel, Chair Tereza Kasaeva, GTB Director 12:00 Meeting closure ADG: Assistant Director General; AFR: WHO African Region; AMR: WHO Region of the Americas; EMR: WHO Eastern Mediterranean Region; EUR: WHO European Region; GTB: Global TB Programme; ODT: Office of the Director GTB (WHO/GTB); PCD: People-centred Services, Communities and Determinants Unit (WHO/GTB); PCI: TB Prevention, Diagnosis, Treatment, Care & Innovation Unit (WHO/GTB); PHC: Special programme on Primary Health Care (WHO); PPU: Policy and Partnerships Unit (WHO/PHC); SEAR: WHO South-East Asian Region; TME: TB Monitoring, Evaluation and Strategic Information Unit (WHO/GTB); UCN: Division of Universal Health Coverage/Communicable and Noncommunicable Diseases (WHO); WHO: World Health Organization; WPR: WHO Western-Pacific Region. 40 Annex 2. STAG-TB 2024 list of participants STAG-TB members 1. Ethel Leonor Maciel STAG-TB Chair Secretary of Surveillance for Health and Environment Ministry of Health Brasília Brazil 2. Fareed Abdullah Director Office of AIDS and TB Research South African Medical Research Council Pretoria South Africa 3. Helen Ayles Professor of Infectious Diseases and International Health London School of Hygiene & Tropical Medicine London United Kingdom of Great Britain and Northern Ireland 4. Anurag Bhargava Head Center for Nutrition Studies Yenepoya (Deemed to be University) Mangalore India 5. Erlina Burhan Professor of Respiratory Medicine Department of Pulmonology and Respiratory Medicine Faculty of Medicine Universitas Indonesia Persahabatan Hospital Jakarta Indonesia 6. Sarang Deo Professor of Operations Management and Deputy Dean, Faculty and Research School of Business Indian School of Business Hyderabad India 41 7. David Dowdy Professor and Executive Vice Dean for Academic Affairs Johns Hopkins Bloomberg School of Public Health Baltimore, M.D. United States of America 8. Gunta Dravniece Project Director PATH Riga Latvia 9. Robert Makombe Director TB FHI 360 Pretoria South Africa 10. Ziad Ahmed Memish Senior Consultant Infectious Diseases and Director for Research and Innovation Center King Saud Medical City Ministry of Health Riyadh Saudi Arabia 11. Ya Diul Mukadi Deputy Division Chief Infectious Disease Office/Tuberculosis Division Global Health Bureau United States Agency for International Development Washington, D.C. United States of America 12. Payam Nahid Professor of Pulmonary and Critical Care Medicine Director of UCSF Center for Tuberculosis Medical Director University of California, San Francisco San Francisco, C.A. United States of America 13. Mahshid Nasehi National Director of Tuberculosis and Leprosy Control Department Disease Control Department Ministry of Health and Medical Education Tehran Islamic Republic of Iran 42 14. Maria Imelda Quelapio Infectious Diseases Specialist Programmatic Management of Drug-resistant TB Cavite Philippines 15. Ingrid Schoeman Director Advocacy and Strategy TB Proof Cape Town South Africa 16. Jayne Sutherland Professor of Immunology and Head of the TB Research Group Medical Research Council Unit Gambia London School of Hygiene & Tropical Medicine Banjul Gambia Representatives of the WHO Civil Society Task Force 17. Victoria James Team lead New Dimension Consulting Harare Zimbabwe 18. Luan Vo President and Head of Viet Nam Project Office Friends for International Tuberculosis Relief Ha Noi Viet Nam Observers 19. Anand Date Chief Global TB United States Centers for Disease Control and Prevention Atlanta, G.A. United States of America 20. Mustapha Gidado Executive Director KNCV Tuberculosis Foundation The Hague Netherlands 43 21. Koura Kobto Director, TB Department International Union Against Tuberculosis and Lung Disease Paris France 22. Christian Lienhardt Director of Research French Institute for Research on Sustainable Development Montpellier France 23. Cherise Scott Senior Technical Manager, a.i. Strategy Team Unitaid Geneva Switzerland 24. Sahu Suvanand Deputy Executive Director Stop TB Partnership Geneva Switzerland 25. Eliud Wandwalo Head of Tuberculosis The Global Fund to Fight AIDS, Tuberculosis and Malaria Geneva Switzerland WHO regional offices African Region 26. Jean-Louis Abena Foe Medical Officer TB Communicable and Noncommunicable Diseases WHO Regional Office for Africa Brazzaville Congo Region of the Americas 27. Pedro Avedillo Regional Advisor, TB Pan American Health Organization / WHO Regional Office for the Americas Washington, D.C. United States of America 44 Eastern Mediterranean Region 28. Martin van den Boom Regional Advisor, TB Division of Communicable Disease Control WHO Regional Office for Eastern Mediterranean Cairo Egypt European Region 29. Askar Yedilbayev TB Unit Lead Joint TB, HIV, and Viral Hepatitis Programme WHO Regional Office for Europe Copenhagen Denmark South-East Asia Region 30. Vineet Bhatia Regional Advisor, TB Tuberculosis Control Department of Communicable Diseases WHO Regional Office for South-East Asia New Delhi India Western Pacific Region 31. Rajendra Yadav Coordinator Integrated Communicable Diseases WHO Regional Office for Western Pacific Manila Philippines WHO headquarters Division of UHC/Communicable and Noncommunicable Diseases 32. Jérôme Salomon Assistant Director-General Global Tuberculosis Programme 33. Tereza Kasaeva Director Office of the Director 34. Karina Halle Cross-cutting Specialist, Enhanced TB Collaboration for Country Impact 35. Hannah Monica Dias Cross-cutting Lead, Strategic Leadership and Multisectoral Engagement for TB 45 36. Karina Halle Cross-cutting Specialist, Enhanced TB Collaboration for Country Impact 37. Anna Stukalova Technical Officer 38. Michael Andrew Tabiszewski Assistant to Team Planning, Analysis and Risk Management 39. Michael McCullough Unit Head 40. Anne-laure Lameyre Programme Officer 41. Cassiana Tissot Assistant to Team 42. Sébastien Tefy Office Assistant TB Monitoring and Evaluation and Strategic Information 43. Katherine Floyd Unit Head 44. Nimalan Arinaminpathy Team Lead, Global TB Monitoring, Estimates and Projections 45. Mathieu Bastard Statistician 46. Marek Lalli Technical Officer 47. Nicole Degroot Assistant to Team TB Prevention, Diagnosis, Treatment, Care and Innovation 48. Matteo Zignol Unit Head 49. Dennis Falzon Team Lead, TB Prevention, Research and Innovation 50. Fuad Mirzayev Team Lead, TB Treatment 51. Licē González-Angulo Technical Officer 52. Samuel Schumacher Scientist 46 53. Francesca Conradie Technical Officer People-centred Services, Communities and Determinants 54. Farai Mavhunga Unit Head 55. Tauhidul Islam Team Lead, People-centred Care and Community Engagement 56. Kerri Viney Team Lead, Comorbidities, TB/HIV and Vulnerable Populations 57. Ernesto Jaramillo Medical Officer 58. Debora Pedrazzoli Technical Officer 59. Lana Syed Technical Officer