Sixteenth meeting of the technical advisory group on leprosy, New Delhi, India 28-29 November 2019

SIXTEENTH MEETING OF THE TECHNICAL ADVISORY GROUP ON LEPROSY New Delhi, India 28 -29 November 2019 SEA-GLP-2019-2 Meeting Report 1 Sixteenth Meeting of the Technical Advisory Group on Leprosy SEA-GLP-2019-2 © World Health Organization 2019 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO license (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this license, 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. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons license. 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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. 2 Contents Abbreviations .......................................................................................................................................... 3 Executive summary ............................................................................................................................ 4 1. Inaugural session.......................................................................................................................... 6 Opening address by the Regional Director ....................................................................................... 6 Welcome remarks by the Chair of TAG-Leprosy .............................................................................. 6 Objectives and expected outcomes of the Sixteenth meeting of TAG-Leprosy............................... 7 2. Follow-up on recommendations of the Fifteenth meeting of TAG-Leprosy ...................... 8 3. Business session ......................................................................................................................... 11 3.1. Update on global leprosy situation ....................................................................................... 11 3.2. Independent evaluation of National Leprosy Eradication Programme in India ................... 12 3.3. Roadmap for NTDs 2021-2030 and Post-2020 Global Leprosy Strategy .............................. 13 3.4. Zero Leprosy Roadmap of Maldives ...................................................................................... 14 3.5. Enhanced surveillance in situations with post-elimination .................................................. 15 3.6. Assistive devices in improving functionality of persons with disabilities due to leprosy ..... 16 3.7. Anti-microbial resistance in leprosy: next steps ................................................................... 17 3.8. Single-dose rifampicin chemoprophylaxis ............................................................................ 18 3.9. Global Leprosy/Hansen Disease Forum: Conclusions and recommendations ..................... 19 3.10. Reactions and neuritis .......................................................................................................... 20 3.11. Research in leprosy ............................................................................................................... 21 3.12. Pharmacovigilance: monitoring of side-effects and adverse events .................................... 22 3.13. Vaccines: Report of expert consultation on LepVax ............................................................. 23 3.14. Any other business ............................................................................................................... 24 4. Concluding session ..................................................................................................................... 25 4.1. Conclusions ........................................................................................................................... 25 4.2. Recommendations ................................................................................................................ 26 Annexes Annex 1: List of participants ................................................................................................................. 28 Annex 2: Programme ............................................................................................................................ 30 Annex 3: Inaugural address by the Regional Director .......................................................................... 32 3 Abbreviations AMR anti-microbial resistance BCG bacille Calmette-Guérin ENL erythema nodosum leprosum GLP Global Leprosy Programme GPZL Global Partnership for Zero Leprosy G2D grade-2 disability HQ WHO headquarters ICMR Indian Council of Medical Research LRI Leprosy Research Initiative ILEP International Federation of Anti-Leprosy Associations LPEP Leprosy Post-Exposure Prophylaxis (feasibility study) MB multi-bacillary MCR micro-cellular rubber MDT multidrug therapy NGO nongovernmental organization NLP national leprosy programme NTD neglected tropical disease PB pauci-bacillary PEP post-exposure prophylaxis SDR single-dose rifampicin SEARO WHO Regional Office for South-East Asia TAG-Leprosy Technical and Advisory Group on Leprosy UHC universal health coverage WHO World Health Organization 4 Executive summary The Sixteenth meeting of the Technical and Advisory Group on Leprosy (TAG-Leprosy) started with the opening address, read out by the Director Programme Management on behalf of the Regional Director, South-East Asia Region of the World Health Organization (WHO). Occurrence of new cases, including children and/or with visible deformities continue to be reported. The paradigm shift of moving towards interruption of transmission of leprosy infection in the post-2020 era was highlighted and the need to develop tools for confirming interruption of transmission was emphasized by the Regional Director. TAG-Leprosy reviewed progress in implementation of recommendations that emanated during the previous TAG meeting; it also assessed the progress in global leprosy control, and especially the data of 2018. TAG-Leprosy further appreciated research agenda developed by the Leprosy Research Initiative (LRI) and the Global Partnership for Zero Leprosy (GPZL) as well as the progress made in vaccine development. The Zero Leprosy Framework for Maldives 2019‒2030 was also highlighted as an example for other countries. TAG-Leprosy also discussed and welcomed the conclusions and recommendations made by the Global Leprosy/Hansen Disease Forum which took place in September 2019. Recommendations from the Independent evaluation of India’s National Leprosy Eradication Programme were presented to TAG-Leprosy. TAG appreciated the efforts of WHO in developing e-learning modules on leprosy and advised to use these and other innovative methods to sustain clinical and programmatic expertise on leprosy, complementing regular training programmes. TAG-Leprosy was informed about the possible stock-out of multidrug therapy (MDT) drugs and made suggestions on how to mitigate such situation. The roadmap for addressing neglected tropical diseases (NTDs), protocols for validation or verification of elimination of leprosy, anti-microbial resistance (AMR) monitoring, post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR) for the prevention of leprosy and the technical guidance on treatment of reactions were discussed in detail. Recommendations were made with special emphasis on moving forward, improving uptake of PEP, verification of interruption of transmission, developing technical guidance documents on treatment of reactions and pharmacovigilance. In its Sixteenth meeting, TAG-Leprosy recommended:  to link the Global Leprosy Strategy 2021‒2030 with relevant Sustainable Development Goals (SDGs), the Global Action Plan for Universal Health Coverage (UHC) and targets of the NTD roadmap 2021‒2030 and refine it further to be more pragmatic in consultation with Member countries and partners;  to continue to advocate for increased domestic and international funding to achieve zero leprosy;  to prioritize the following two groups of countries: (i) current global priority countries (characterized by high endemicity or transmission); and (ii) countries which are close to interruption of transmission; 5  to design mechanisms for validation of elimination of leprosy as a public health problem and undertake such validation exercise on request; as well as for verification of interruption of transmission. It also suggested considering developing criteria for awarding the status of “zero leprosy” to be used at national or subnational level.  to Identify candidate countries for verification of interruption of transmission of leprosy infection based on at least the following indicators for the last ten years despite effective surveillance for detecting new cases: number of new autochthonous leprosy cases; new child cases; grade-2 disability (G2D) among new cases.  to advocate with the wider disability community for quality care and development of customized, protective, user-friendly devices/assistive technology products for persons with disabilities due to leprosy, based on the need and demand. It also recommended line-listing all cases with disabilities to facilitate access to assistive products, services, benefits and entitlements.  to include leprosy in the global AMR surveillance agenda with support from partner organizations and in line with the Guide for AMR surveillance in leprosy (2017 update).  to sustain expertise in the health workforce at all levels through traditional and innovative approaches including e-learning opportunities and the Skin NTD guide.  TAG-Leprosy reiterated the recommendation to use SDR for PEP and requested WHO to produce an operational manual, support countries to roll out SDR PEP, and to continue negotiations for drug donation;  to develop pharmacovigilance guidance through a systems approach for monitoring side effects and adverse events for the drugs used in management of leprosy, leprosy reactions and PEP as well as vaccines. 6 1. Inaugural session Opening address by the Regional Director Dr Pem Namgyal, Director Programme Management, read out the opening remarks on behalf of Dr Poonam Khetrapal Singh, Regional Director, WHO South-East Asia Region. In her opening remarks, the Regional Director observed that, in spite of a decline in global leprosy burden, still more than 200 000 new cases continue to be detected each year, including significant proportions of children and persons with visible deformities. She highlighted the importance of the current Global Leprosy Strategy which aims at maximally rolling out currently available approaches. The strategy has provided a boost to many leprosy programmes in different countries because of its innovative interventions. She also shared the salient findings of the independent review conducted in India. She further expressed her concerns about the slow uptake of some of the changes included in the Guidelines for the diagnosis, treatment and prevention of leprosy. Looking to the future, the Regional Director highlighted the paradigm shift, moving from elimination as a public health problem to true elimination linked to interruption of transmission. This is elaborated in the draft 2021-2030 Roadmap for NTDs as well as draft post-2020 Global Leprosy Strategy. She also mentioned the need to respond to requests from especially medium- and low-burden countries to develop a tool for confirming the low burden status and even interruption of transmission. Within the WHO South-East Asia Region, Maldives may show the way hereto. The Regional Director further reiterated that leprosy is linked to several of the Regional flagship programmes: universal health coverage, control of NTDs and anti-microbial resistance. While heavily focusing on disease control aspects, she urged all not to forget that a holistic approach including addressing stigma and discrimination remains important in leprosy. Respecting and capitalizing on the comparative advantage of different stakeholders and in the spirit of true partnership, collaboration can be further enhanced in the areas of service delivery, research, surveillance and resource mobilization. Welcome remarks by the Chair of TAG-Leprosy Dr Vijay Kumar Pannikar, Chair of TAG-Leprosy, in his welcome remarks highlighted some important challenges as well as opportunities. He cautioned that current and especially future leprosy control will need to address the challenges linked to the transition from elimination of leprosy as a public health problem to elimination in the epidemiological sense. In the endgame of leprosy, he also warned about the current limited 7 knowledge and impact of leprosy as a zoonotic disease as well as the role other mycobacteria (such as Mycobacterium lepromatosum) could play in transmission. For many years the principal strategy has focused on detecting cases and treating them promptly with MDT. This has shown a significant impact but may have reached the maximum of its potential. He, therefore, urged to embrace new tools such as PEP with single-dose rifampicin (SDR) and, in future, vaccines. Without these, bending the leprosy curve will unlikely happen. He also stressed the importance in properly communicating progress in leprosy control to policy makers and other stakeholders. The achievement of elimination as a public health problem was a crucial milestone but not the end point and that the generation of scientific evidence and introduction of new tools will be paramount for further success in global leprosy control. Objectives and expected outcomes of the Sixteenth meeting of TAG-Leprosy As this was the first meeting of TAG-Leprosy since its reconstitution in mid-2019, Dr Erwin Cooreman, Team Leader of WHO’s Global Leprosy Programme (GLP), recapitulated the terms of reference of TAG-Leprosy, being the principal advisory committee on global leprosy control and reporting to the Regional Director of the WHO South-East Asia Region. The 14 TAG members include experts from around the world in the fields of epidemiology, public health, infectious diseases, management, health care administration, laboratory and social sciences. They belong to different professional affiliations (academia, research institute, governmental body, affected persons). All members, though, have been nominated in personal capacity. The objectives of the Sixteenth meeting were: (i) to review progress in leprosy control, particularly in India, Indonesia, Brazil and monitoring and evaluation of leprosy programmes; (ii) to review trends of leprosy data and contribute towards monitoring progress towards newly set targets; (iii) to review the current situation with regard to normative guidance provided by GLP and advise on future important normative documents; and (iv) to discuss benchmarks for measuring reduction in disease burden and transmission of leprosy. As immediate outcomes of this Sixteenth meeting, GLP expects: - Feedback on (i) Roadmap for NTDs (especially its leprosy section); (ii) Zero leprosy roadmap for Maldives; (iii) Global Leprosy Forum; and (iv) independent evaluation of the National Leprosy Eradication Programme of India; - Sound advice, with special emphasis on moving forward, on: (i) validation/verification of interruption of transmission; (ii) AMR in leprosy; (iii) uptake of the change in regimen for pauci-bacillary (PB) leprosy; (iv) uptake of SDR chemoprophylaxis; (v) treatment of reactions and nerve involvement; (vi) pharmacovigilance; and (vii) vaccine development. 8 2. Follow-up on recommendations of the Fifteenth meeting of TAG-Leprosy Dr VRR Pemmaraju, Technical Officer GLP, provided an overview of the actions taken based on the recommendations formulated during the Fifteenth meeting of TAG-Leprosy, which took place in New Delhi from 21-22 June 2019. They are listed below. 1. TAG-Leprosy appreciated the progress made in implementing the Global Leprosy Strategy 2016‒ 2020 in countries for the past one and a half year Recommendation/ Action point Action taken Leprosy programme reviews to focus on assessing the status of implementation of the Global Leprosy Strategy 2016‒2020 Leprosy programme reviews were carried out in six global priority countries – India, Myanmar, Nepal, the Philippines, Somalia and Sri Lanka where progress in implementation of Global Leprosy Strategy was observed. The 2018 annual leprosy statistics were received from national leprosy programmes and analyzed. Zero child G2D cases was reached in 72 countries. 89 countries reported at least one new child cases with G2D. 77 countries have reported a G2D rate of <1 per million population 2. TAG-Leprosy recommended developing a mechanism for surveillance, management and providing long-term care for persons with disabilities due to leprosy. Opportunities for integrating with existing functional platforms such as morbidity management programmes of lymphatic filariasis or diabetes mellitus in noncommunicable diseases. Recommendation/ Action point Action taken Developing a mechanism for surveillance, management and long-term care for persons with disabilities due to leprosy Integration with lymphatic filariasis and diabetes mellitus and noncommunicable diseases To facilitate continuum of care for patients with disabilities due to leprosy the following approaches were introduced in national leprosy programmes (NLPs): (i) disability register for G2D cases; (ii) data on patients developing G2D during MDT; (iii) line-listing of persons with G2D after completion of MDT and patients eligible for reconstructive surgery; (iv) use of assistive devices to improve functionality of persons affected by leprosy was advocated and NLPs are encouraged to establish linkages with Departments of physical rehabilitation. Integrated disability care is yet to be introduced in NLPs. 3. TAG-Leprosy suggested to promote the use of existing tools for the elimination of stigma and discrimination used in other programmes (e.g. mental health, NTDs) be shared with the United Nations Human Rights Council. New toolkits should be developed as necessary to address existing gaps, e.g. in counselling. 9 Recommendation/ Action point Action taken Promote existing tools for elimination of stigma E-learning modules were developed for counselling with inputs from the NTD and Mental Health units and the Schieffelin Institute of Health Research and Leprosy Centre, Karigiri, India to address discrimination by persons affected by leprosy. Development of counselling toolkit in coordination with the International Federation of Anti-Leprosy Associations (ILEP) (work in progress). All discriminatory laws in India were enlisted with the help of a civil society organization involved in discriminatory laws in leprosy. The status of discriminatory laws (as reported by national programmes) was shared with the United Nations Special Rapporteur on the elimination of discrimination against persons affected by leprosy and their family members to contribute to the report to United Nations High Commissioner for Human Rights. 4. TAG-Leprosy suggested that, as management of reactions is a core component of leprosy control, WHO organizes a consultation on reactions, neuritis and disability care. Recommendation/ Action point Action taken Consultation on treatment of reactions, neuritis and prevention of disabilities An Informal Consultation on treatment of reactions and neuritis was organized in Chennai, India in December 2018. The conclusions and recommendations of this consultation were further disseminated with national programme managers in April 2019. The consultation findings were further reviewed and will be presented to the Sixteenth meeting of TAG-Leprosy for inputs and advice on further steps. 5. TAG-Leprosy advised GLP to participate in the working groups of LRI and GPZL and advise on the research agendas. Recommendation/ Action point Action taken Advise on research agenda in meetings and working groups of LRI and GPZL WHO participated in Leadership Team meetings of GPZL and during discussions on its research agenda. WHO also contributed to the development of the GPZL Country Model for zero leprosy. Reviews of NLPs were jointly undertaken by WHO and GPZL. GLP has provided inputs in the Research Agenda, finalized by GPZL. This agenda is scheduled to be published soon in Leprosy Review as well as a commentary in The Lancet Infectious Diseases. 6. TAG-Leprosy notes the merits of the modelling exercises developed to predict future trends in different scenarios and encourages to fine-tune and apply such models in different contexts. 10 Recommendation/ Action point Action taken Modelling exercises to predict future trends in different scenarios Modelling exercises are used in planning chemoprophylaxis in different countries (e.g. Kiribati). India Independent review: includes a recommendation to conduct a modelling exercise for chemoprophylaxis to build up an economic case for the next ten years. 7. TAG-Leprosy noted the inclusion of leprosy in the Integrated NTD skin pictorial guide and therefore encourages promotion and use of this tool. Recommendation/ Action point Action taken Promotion of Integrated NTD skin pictorial guide The Integrated NTD skin pictorial guide was discussed with national programme managers during field visits to use it as a tool to train health staff in order to identify leprosy along with other skin diseases. 8. TAG-Leprosy noted that the Guidelines for the diagnosis, treatment and prevention of leprosy has been approved by WHO’s Guidelines Review Committee and advised to collect further evidence in these areas while rolling it out, including on the management of drug resistance. Recommendation/ Action point Action taken Rolling out of the WHO Guidelines for the diagnosis, treatment and prevention of leprosy The guidelines were discussed with NLP managers during the Global Training of NLP managers held in Bangkok, Thailand in April 2019. The recommendations were endorsed. The MDT request forms were modified to include changes in treatment regimens. Discussions were held with Novartis on relabeling blister packs; rifampicin donation; clofazimine (100 mg and 50 mg) for erythema nodosum leprosum (ENL). Research in these areas are encouraged. New evidence will be reviewed when available. 9. TAG-Leprosy advised GLP to consider evaluation methodologies as followed by other NTD programmes for mid-term evaluation of the Global Leprosy Strategy 2016−2020. Recommendation/ Action point Action taken Mid-term evaluation of Global Leprosy Strategy 2016‒2020 A tool for assessing progress in implementation of the Global Leprosy Strategy 2016‒2020 was finalized. Data were collected from all global priority countries in 2019 to assess progress in implementing Global Leprosy Strategy 2016‒2020 10. TAG-Leprosy advised GLP to define a roadmap for progression towards already defined and future programme end goals. 11 Recommendation/ Action point Action taken Defining Roadmap for GLP future activities GLP contributed to the development of the NTD Roadmap 2021‒2030. GLP drafted Global Leprosy Strategy 2021‒2030 in consultation with national programme managers, partners and donor agencies. 11. TAG-Leprosy advised GLP to set up a task force involving WHO collaborating centres and the Department of Control of NTDs (HQ) to define a mechanism for certifying/validating interruption of transmission or elimination. Recommendation/ Action point Action taken Defining mechanism for verifying interruption of transmission of leprosy An Informal Consultation on defining mechanisms for verification of elimination of leprosy at national and sub-national level is planned by GLP in Mexico City in February 2020. WHO collaborating centres will be invited. 12. TAG-Leprosy suggested that leprosy should be adequately reflected in the post-2020 strategy of NTDs and aligned with the UHC agenda and the SDG targets set for 2030. Recommendation/ Action point Action taken Reflect leprosy adequately in the post-2020 NTD strategy GLP provided key inputs in the leprosy sections of the NTD Roadmap 2021‒2030 including setting of targets for 2030 and interim milestones. The NTD Roadmap will be discussed in the Sixteenth meeting of TAG- Leprosy. 3. Business session 3.1. Update on global leprosy situation Dr Erwin Cooreman provided an overview of the current global leprosy situation, both in terms of the global leprosy burden as well as the key activities that took place at global level since the previous TAG meeting. For 2018, data were submitted to WHO from a record 161 Member states and territories from all WHO regions, likely capturing >99% of the global case load. Twenty-two countries contributed 96% of the leprosy burden (absolute number of new cases) while another 106 countries reported at least one case (and are therefore considered as endemic). India accounted for 57.7% of the global case load (down from >62% few years ago), followed by Brazil (13.7%), the African Region (9.9%) and Indonesia (8.2%) with lower shares in the remaining countries and regions. Over the last 12 years, the overall trend is a slow decline in most regions and globally while it is increasing in the Americas, Eastern Mediterranean and Western Pacific Regions. 12 The increase in some regions and nivellation in other regions is attributed to more complete reporting as well as the impact of active case detection done in many countries rather than a true increase in cases. Progress is also made towards reducing the G2D rate, which stands at 1.5 per million in 2018, down from 2.2 in 2007 against a target of <1 by 2020. Several other epidemiological indicators were also elaborated. As part of the programmatic update since the previous TAG meeting, Dr Cooreman highlighted the development and work-in-progress on the NTD Roadmap and Global Leprosy Strategy, covering the period 2021-2030, the leprosy guidance documents in pipeline, the guidance documents produced by partners (including Toolkit of best practices and Research agenda by GPZL), e-training modules by SEARO. On different occasions, leprosy was advocated for. Important events included the Ninth and Tenth meetings of the NTD NGO Network, the annual conference of the Indian Association of Dermatologists, Venereologists and Leprologists, the annual Global Appeal and the Twentieth International Leprosy Congress. The agenda for 2020 was also presented with normative work focusing on developing mechanisms for assessing low disease burden (validation of elimination as a public health problem and verification of elimination); pharmacovigilance and AMR surveillance. 3.2. Independent evaluation of National Leprosy Eradication Programme in India Dr Rashmi Shukla, National Professional Officer (NTDs), WHO Country Office for India, presented some of the recommendations of the recently conducted independent evaluation of National Leprosy Eradication Programme of India. Out of the country’s 708 districts, 361 (51%) have a G2D rate of <1 per million population. The evaluation has recommended the need for a national roadmap for leprosy, a plan to roll out PEP with SDR, AMR surveillance and pharmacovigilance. The country needs to invest in a more robust system of reporting, recording, monitoring and supervision. It should constitute a Central Task Force for periodic (at least once or twice a year) evaluation of the programme. Evaluators have emphasized that India requires a special plan for urban leprosy control, continue to implement enhanced case detection measures, map out hot spots, build effective partnerships with agreed roles and responsibilities and sustain expertise. Recommendations also emphasized that India should continue to repeal the remaining discriminatory laws at national and state levels. 13 3.3. Roadmap for NTDs 2021-2030 and Post-2020 Global Leprosy Strategy Roadmap for NTDs, 2021-2030 Development of this Roadmap was coordinated by HQ. In comparison to the current Roadmap which covers the period 2012-2020, the leprosy profile is much more substantial. The key change is the elevation of leprosy from a disease targeted for elimination as a public health problem to a disease targeted for elimination (interruption of transmission). The framework of the Roadmap was presented as well as the detailed leprosy profile. As the document is already in final draft and forwarded to the Executive Board secretariat, there is no room for substantial changes. The draft version was earlier circulated to all TAG members and their inputs were incorporated. During the Sixteenth meeting of TAG-Leprosy, the leprosy section was well received. TAG-Leprosy suggested for minor improvements only. A population-at-risk was defined through the modeling work for estimating the number of persons that could benefit from prophylactic interventions. Other impacting factors such as economic progress or vaccines are already directly or indirectly included in this model. While the model was based on currently available data, it can be adjusted and finetuned as the future will evolve. During the discussion, TAG-Leprosy also highlighted the need to fully integrate leprosy in the UHC agenda, which should also include disabilities and rehabilitation. The different scenarios should be taken into consideration with at two ends of a spectrum the high burden settings and the areas close to elimination. TAG-Leprosy also suggested to provide maps of areas where there is geographic overlap of two or more NTDs or other diseases of public health importance. Post-2020 Global Leprosy Strategy While some stakeholders questioned the need for a stand-alone Global Leprosy Strategy in view of a much more elaborate NTD Roadmap, TAG-Leprosy agreed that such strategy would provide much more visibility to leprosy. Caution should be taken though that it is fully in line with the NTD Roadmap. Dr Cooreman presented the work-in-progress on the post-2020 Global Leprosy Strategy. Possible ambitious yet realistic targets were solicited through a global online questionnaire which had a high response rate. These key targets served as ultimate reference point for development of the strategy. As it was developed, the work-in-progress was shared during events over the past year, including First International Dermacon, held in Bengaluru in January 2019; ILEP and GPZL meetings; Global training of NLP managers from priority leprosy-endemic countries (Bangkok, April 2019); International leprosy training course for developing countries (Tai’an, China, June 2019) and Training of NLP managers of hyper-endemic island countries (Pohnpei, Federated States of Micronesia, November 2019). The document is envisaged as a succinct broad strategic document, linked to the wider development agenda, SDGs and UHC. A top-10 of the many challenges has been defined which will be the main 14 focus of the strategy. TAG-Leprosy amended this list during its Sixteenth meeting by including nerve damage and attention for care-after-cure. Aiming for zero catastrophic health expenditure should also be included. Vision and goal and key targets are copied from the leprosy section in the NTD Roadmap. Four strategic pillars have been identified, building on the current (2016‒2020) Strategy and expanding on one key innovation. They are: (i) Country-owned zero leprosy roadmaps in all endemic countries; (ii) Scale up preventive chemotherapy programmes alongside active case detection; (iii) Manage complications and prevent new disability; and (iv) Combat stigma and discrimination. As part of next steps, GLP will lead the detailed write-up of the Strategy and plan for a next round of inputs during a Global NLP managers meeting (including partners). During the discussions, TAG-Leprosy reiterated the need to prioritize, in addition to high burden countries, also countries with very low burden that can move to zero in the next ten years. This will reinforce the need for sustained political will, resources and introduction of new tools. 3.4. Zero Leprosy Roadmap of Maldives Dr VRR Pemmaraju presented the Zero Leprosy Roadmap of Maldives. This document showcases the commitment of the Government to galvanize efforts for ending leprosy. Maldives reached the target of elimination as a public health problem in 1997. All new cases since then (and even before) were coming from few islands. No child cases were reported since 2011. Grade-2 disabilities have also been absent for many years. Leprosy treatment is provided from the country’s tuberculosis clinics. The timing of developing a zero-leprosy roadmap is opportune for mobilizing high political commitment, strengthen health systems. The country has experience in eliminating malaria and lymphatic filariasis. The stigma of leprosy is limited. Chemoprophylaxis can also be introduced. Attaining zero leprosy in the near future should be possible due to convergence of epidemiological, operational and contextual factors; the latter ones include high literacy rate and inclusive social protection schemes. Important challenges, however, are still there, such as: difficult geography, highly mobile population across islands (with risk of transmission between islands or reintroduction of leprosy in islands where leprosy has disappeared) and internationally (richer people seeking health care overseas and migrant workers from endemic countries); technical capacity and sustained financial commitment by the Government (in the absence of external partners apart from WHO or donors). The roadmap envisages declaring zero leprosy by island and nationally when no new leprosy cases are detected among autochthonous populations for at least ten years (twice the average incubation time) on the premise that a strong surveillance system remains in place. 15 TAG-Leprosy was very much impressed by this initiative and recommended to publish it and be used as an example for other countries that have reached a similar level of endemicity and that have comparable contexts. A close monitoring of PEP (including determining the number of rounds required for elimination) can inform global policy on chemoprophylaxis in future. 3.5. Enhanced surveillance in situations with post-elimination Dr Vijay Kumar Pannikar introduced the subject by recapitulating the sequence of epidemiological concepts and their assessment mechanisms. They include: - “Control”: reducing the burden compared to previous period. - “Elimination as a public health problem”: reducing the burden to such a level that it is considered no longer to be a problem of public health. “Validation” is the process to ascertain its achievement. - “Elimination”: absence of new disease as a result of interruption of transmission. It still allows for import of new cases, which are not the result of local transmission. Its ascertainment is called “verification”. - “Eradication”: absence of new disease worldwide implying the absence of the causative organism in nature. Eradication is ascertained through “certification”. - “Extinction”: implies that the disease-causing organism is also absent from laboratories. With regard to leprosy, these levels of epidemiology have several implications. Elimination as a public health problem is determined by the choice of indicator. In the case of leprosy, “registered prevalence at the end of year” was chosen with a target of less than 1 per 10 000 population. This was based on the assumption that transmission would stop with such low levels of prevalence. However, this assumption was not based on any scientific evidence. Reaching the target is influenced by operational factors such as programme coverage or duration of treatment. Reaching the target at national level does not mean that it is also reached at sub-national level in view of the clustered occurrence of the disease. Choosing another indicator (e.g. G2D rate with target of less than 1 per million population) is another way of looking to elimination as a public health problem but may yield different results, hence elimination as a public health problem is not an absolute epidemiological benchmark in contrast to elimination or eradication. To declare “zero new cases” in a sustained way may also become arbitrary in view of the long incubation time of leprosy. Even if ten years (twice the average incubation time) is considered as pragmatic, sporadic cases can still occur beyond that time requiring sustained post-elimination surveillance. Verification for interruption of transmission requires proper documentation (such as a “dossier”) based on stringent criteria and independently assessed. Such tools are currently not in place for leprosy. In view of the above-mentioned possibility of sporadic cases, elimination can be reversible, and verification can be undone. 16 For eradication, not only absence of disease in humans is to be assessed but also presence of the causative organism in animals or other environmental samples (water, sea weeds, etc.). In view of the known animal reservoir, pursuing eradication is currently not on the agenda. Dr Cooreman informed TAG-Leprosy that a dedicated informal consultation will be convened in February 2020 to define criteria for verification of elimination. TAG-Leprosy discussed some of the potential benefits for countries of being verified as disease-free. They include political advocacy, opportunity for strengthening health systems or support to a country’s development agenda. Strong surveillance systems are paramount, even after elimination is achieved. Verification of elimination could be conceived for a time-limited period requiring a country to be reassessed after a number of years to document sustained elimination. It will also require motivating countries which have not reported leprosy for prolonged time to go through such rigorous verification process. TAG-Leprosy suggested to already identify candidate countries for verification. TAG-Leprosy concluded there is no need for actively pursuing countries to validate their status of elimination as a public health problem, but on a case-by-case basis, countries can be supported in such validation exercise. 3.6. Assistive devices in improving functionality of persons with disabilities due to leprosy In his presentation, Dr Patanjali Dev Nayar, WHO Consultant, highlighted the importance of including persons affected by leprosy in disability programmes in countries. Due to stigma they may not reveal their disabilities or seek support and therefore forego entitlements given to other persons with disabilities. During the independent review of the Indian leprosy programme, it was found that provision of footwear with micro-cellular rubber (MCR) was inadequate. Though considered the gold standard from medical viewpoint, its positive impact is undermined by the low acceptability (MCR footwear generally not accepted for cosmetic reasons) or low availability. Assistive technologies should be based on (i) actual need; (ii) demand; and (iii) supply. At global level assistive technology for leprosy patients has not been discussed adequately. The presenter proposed that some TAG members participate in the global disability meeting and draw special attention from the global partners. It was also highlighted to have an indicator to monitor disability support in any leprosy validation exercise. Rehabilitation at early stages is key to prevent progressive disability. Assistive devices can play an important role in improving the quality of life of affected persons – which is much more than providing cure – but need to be acceptable, tailored and available. The leprosy community therefore needs to better inform the disability community on its specific requirements. 17 3.7. Anti-microbial resistance in leprosy: next steps Anti-microbial resistance is based on identification of mutations associated with drug resistance in specific genomic loci of M. leprae. Detection of gene mutations through polymerase chain reaction and gene sequencing for folP1 for dapsone, rpoB for rifampicin and gyrA for ofloxacin was the basis for conferring resistance to dapsone, rifampicin and ofloxacin, respectively. Surveillance for AMR was initially supported by The Nippon Foundation and later by ILEP. WHO facilitated a network of sentinel laboratories which can support testing for AMR in 2006. Fifteen sentinel centres joined the network covering 21 countries. In 2009, WHO developed guidelines for global surveillance of drug resistance in leprosy keeping the focus on relapses. Progress and outcomes of the AMR surveillance were first published in the WHO Weekly epidemiological record (Weekly epidemiol rec 2011; 23 (86): 233-4). A World Health Assembly resolution on AMR in 2015 gave more impetus to the initiative. WHO continued to collect data from NLPs and from the data received in 2016, resistance to rifampicin in relapses was 5.2% while resistance in new cases was 2.1%. A Guide for surveillance of AMR in leprosy (2017 update) was developed and direct support was provided to high endemic countries such as India (2018) and Indonesia (2019). It was discussed to identify testing laboratories and linking to reference laboratory; sample collection, documentation and reporting were also discussed. National programmes have identified gaps with regard to laboratory capacity and linkages with leprosy facilities in the field and with reference laboratories for quality assurance. Advocacy is also to be enhanced at global level for merging AMR surveillance for leprosy with the wider AMR agenda and dito partners for greater support and investments in establishing the systems and at national level to ensure AMR surveillance is included in the national programme agenda. During the discussions, Professor Emmanuelle Cambau clarified operational issues such as type of samples to be collected (biopsies are superior to smear but less acceptable to patients) and need for including AMR data in regular monitoring and for publishing the data available. Examining nasal swabs can be useful for diagnosis for leprosy (on suspects) but plays no role in AMR assessment (which is done on confirmed cases). TAG-Leprosy advised WHO to provide further support for linking up with reference laboratories and collect data from countries with regard to both primary and secondary resistance levels for rifampicin, dapsone and ofloxacin. Dissemination of information about second-line treatment for those patients with drug-resistant leprosy was also emphasized by TAG-Leprosy. 18 3.8. Single-dose rifampicin chemoprophylaxis Next steps with regard to technical guidance The WHO Guidelines for the diagnosis, treatment and prevention of leprosy recommend SDR as preventive treatment for contacts of leprosy patients. The recommendation was based mainly on the COLEP study, a single-centre, cluster-randomized, double-blind, placebo-controlled trial in Bangladesh, which was conducted during 2001-2009 and valued as high quality. The study proved that SDR given to leprosy contacts reduces the incidence of leprosy with 57% during the first two years. There was no rebound effect after four years, thus there is no evidence of SDR postponing leprosy. Vaccination with bacille Calmette-Guérin (BCG) (at birth) and SDR have cumulative protective effects of 80%. The study was not enough powered for additional sub-analyses (such as effect on contacts of multi-bacillary (MB) index cases or household versus social contacts). Professor J H Richardus presented the results of a feasibility study – Leprosy Post-Exposure Prophylaxis (LPEP) – using SDR. The study started in 2015 and was conducted in eight countries: Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and the United Republic of Tanzania. In various settings, different contact definitions were applied depending on resources and presumed acceptance of the intervention. The implementation toolkit was created to facilitate the transition of the LPEP programme into routine leprosy control activities in participating countries. A total of 9186 index cases were enrolled with 179 769 contacts (about 20 contacts per index case). Of them, 174 782 (97%) were screened for leprosy: 810 persons were diagnosed with leprosy and received a full treatment while 151 928 contacts (87%) received SDR; less than 1% of eligible contacts refused SDR. Adverse drug events among those who took SDR remained very low. The overall results showed that PEP is feasible under programmatic conditions, is well accepted in the community and was demonstrated as a safe intervention. The delivery through the primary health care system is essential for better coverage, quality and cost-effectiveness. There are many collateral benefits such as an increase in case detection and rise in motivation and capacity of the programme staff. An implementation plan with clear workflows and monitoring and evaluation is important. Reaching social contacts was found challenging in certain settings. Though acceptance was high in the study population, stigma was assumed to be a major factor for refusal. Patient’s consent and confidentiality are also important elements in implementation. As the efficacy of SDR is modest, impact can be increased by maximizing coverage. A drug donation for rifampicin – currently under negotiation with Novartis – may further enhance implementation. MALTALEP trial The MALTALEP trial was a single-centre, cluster-randomized controlled trial conducted in Bangladesh. Its aim was (i) to assess the effectiveness of SDR given soon after BCG vaccination in 19 preventing leprosy in household contacts; and (ii) to determine whether possible excess cases (“precipitation”) during the first year after BCG could be prevented by SDR. A total of 14 988 contacts of 1552 new leprosy patients were randomized in an SDR‒ arm (i.e. BCG only, 7379 contacts) and an SDR+ arm (BCG vaccination followed by SDR 8-12 weeks later, 7609 contacts). Both arms yielded an almost similar number of contacts developing leprosy after two years of follow-up. There was a statistically non-significant reduction of 42% in the SDR+ arm after one year of follow-up. Of all new cases, 34% appeared within 8-12 weeks after BCG. More MB cases arose than in the BCG only group. There were no adverse events reported attributable to SDR and only 0.34% had adverse events after BCG. The results can be considered statistically non-significant due to the lower number of cases and smaller households compared to before. The large proportion of new cases during the first three months was comparable to a Brazilian trial. BCG accelerates pro-inflammatory T-helper 1 immunity to M. leprae antigens, which could be the reason for new cases arising soon after BCG and bactericidal effect of SDR was too late and therefore less prominent. Since BCG is a live vaccine, the presenter suggested that SDR should not be given simultaneously with BCG. TAG-Leprosy concluded that BCG protects against leprosy and has a potential positive impact on accelerating bacteriological clearance and reducing number and intensity of reactions and neuritis. TAG-Leprosy reconfirmed the use of SDR plus BCG at birth. The MALTALEP trial has no bearing on the current WHO guideline on SDR. 3.9. Global Leprosy/Hansen Disease Forum: Conclusions and recommendations The Global Forum of People’s Organizations of Hansen Disease was held in Manila, the Philippines from 7-10 September 2019. This event brought together 80 representatives of People’s Organizations from 23 countries, including observers and resource persons. It followed three regional assemblies held in Africa, Asia and Latin America. It addressed several themes identified as important in terms of organizational capability, sustainability, ability to fulfil the role as advocacy organizations and meet the expectations of the people they represent. Group discussions and plenary sessions were held on human rights, sustainability and public health where it underscored that Hansen Disease is not just a health issue but also an issue of human rights causing social and economic consequences. The continuing stigma has been a barrier to case detection and treatment. Inclusion requires new models to manage social aspects of the disease and obtain greater commitment from governments, academic institutions and industries. Leprosy services must include psychological, social and economic rehabilitation. All remaining discriminatory laws and practices must be abolished with full participation of People’s Organizations in policy- making processes concerning Hansen Disease. The forum also included trainings on social business, fundraising, management and networking. Most participants agreed to the adoption of “Hansen Disease” in place of leprosy as a step toward reducing stigma and discrimination. 20 TAG members welcomed the recommendations of the forum and highlighted that “Hansen Disease” is already a valid alternative word for “leprosy”. TAG-Leprosy however cautioned that phasing out “leprosy” in favour of “Hansen Disease” is a complex issue and would require the involvement anthropologists. It would also go against the current trend of no longer naming diseases by individual persons. Other words with potentially negative connotation such as “control”, “defaulter”, “suspect” or “elimination” should only be used in an appropriate (epidemiological) context. TAG- Leprosy prefers to concentrate efforts on eliminating the disease instead. 3.10. Reactions and neuritis Dr Paul Saunderson highlighted the work-in-progress of the technical guidance document that is being developed following the Informal consultation on treatment of reactions in leprosy (December 2018). Reactions and neuritis occur together and often cause nerve function impairment leading to G2D. These deformities progress in several patients causing disabilities and warrant care for life. To prevent disability in leprosy, it is essential that health workers have clear understanding on assessing nerve function. Many leprosy patients receive MDT in clinical settings without adequate capacity to manage reactions on the spot; patients with symptoms suggestive of reaction are referred to a secondary- or even tertiary-level hospital. In some health care settings patients are managed by health care workers who are able to use basic tools to assess nerve function and even give treatment with steroids. In referral hospitals, health staff use more sophisticated and precise tools, including nylon monofilaments, allowing nerve damage to be identified at an earlier stage. Considering the feasibility in the field and practicality of introducing periodic screening of all patients for reactions and managing those identified with reactions, three levels of care will be explained in the technical guide. The following table depicts three levels of care and characteristics of clinical setting. Table: Levels of care and characteristics of clinical setting Clinical setting Level of care Level 1 Identify possible reactions and refer Level 2 Use simple tools to assess the patient and initiate treatment Level 3 Use more complex and precise tools for early detection of neuritis Staff have the time, training and equipment (nylon monofilaments) for more accurate assessment Use available tools to check for early nerve damage and treat with prednisolone Prednisolone is available; nylon mono- filaments are not available Use a ballpoint pen to test for sensory loss; treat new episodes of neuritis with prednisolone 21 Prednisolone and albendazole are not routinely available Understand the symptoms and signs of reactions and neuritis; consult and refer Technical guidance will be under the following four headings: (i) recognizing a reaction; (ii) testing nerve function; (iii) treating certain cases with steroids; (iv) follow-up of patients. Six simple algorithms will be drafted for easy understanding by health workers. The algorithms can also be used as quick reference for the health workers in the field. Standardized treatment regimens will be prepared for guidance to health workers both for Type 1 (reversal reaction) and Type 2 reaction (ENL). Deworming when initiating treatment with steroids will be emphasized. Use of clofazimine in treating Type 2 reactions and use of thalidomide in steroid-dependent patients was flagged up as part of discussions. Based on available evidence, standardized treatment regimens with steroids, clofazimine and other drugs will be presented in the technical guidance document. Protocols for use of thalidomide and documentation procedures will be elaborated in detail in the technical guide. Reporting systems will consider the potential use of DHIS2 for capturing data on actual number of patients with reactions at national level and will be explained in the guide. TAG-Leprosy agreed with the structure of the technical guide. It was decided to circulate the final draft of the technical guide on reactions to all members of TAG-Leprosy. 3.11. Research in leprosy The topic of research was also introduced by Dr Paul Saunderson. Research activities on leprosy in general seek to understand the underlying science in leprosy, to prove the effectiveness of the interventions and accurately measure and analyse data on leprosy. The four priority areas of leprosy research agenda include several subheadings of priority research activities under transmission, disability, stigma and cross-cutting issues. The priority areas of research under the transmission heading (epidemiologic modelling, diagnostic, PEP and vaccines) include how and when transmission occur, how to reduce or stop transmission and how to measure the level of transmission. Under the disability heading, the priority research areas include implementation research on how to prevent disability in leprosy, improve the management of reactions and neuritis and measuring the burden and importance of leprosy related disability. Perceptions and cultural determinants underlying stigma, improving the participation and well-being of people affected by leprosy and monitoring the level of stigma and discrimination in leprosy are the priority research needs under the stigma heading. The cross-cutting research areas focus on digital tools (diagnostic aids, software and devices for mapping, point-of-care data collection and tools for consultation, referral and training; and operational research on mapping, health system strengthening and active case finding. 22 TAG-Leprosy also noted that there is an element of perceived stigma that is affecting early detection. TAG-Leprosy discussed that stigma occurs not only in the general community but also very much among health personnel. It advised to document principles that can provide insight into addressing stigma with relevance for other programmes. 3.12. Pharmacovigilance: monitoring of side-effects and adverse events Side effects to the constituent drugs of MDT were identified for each drug. The side effects are also mentioned in the manuals of national leprosy programmes of many countries and are included in the training curriculum of health staff working in the leprosy programme. Routine systems for monitoring side effects and adverse events were, however, not introduced into the leprosy programme as a routine activity. An adverse event is an undesired occurrence that results from taking a medication correctly. The event can either be a type A or a type B reaction. Type A reactions are predictable adverse events which are commonly dose dependent and can be mild, moderate or severe. Type B reactions are completely unpredictable and have nothing to do with doses. A side effect is an undesired effect that occurs when the medication is administered regardless of the dose. Unlike adverse events, side effects are mostly foreseen by the physician and the patient is told to be aware of the effects that could happen while on the therapy. Side effects differ from adverse events and later resolve on their own with time after taking the medication for several weeks. As of now reports on side effects or adverse events are not received from national programmes. Data are available from literature search and anecdotes noted during field visits. Dapsone hypersensitivity reactions were observed following introduction of MDT from 0.3% to 3.6%. (Richardus JH, Smith TC. Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy; Lepr Rev 1989, 60: 267-273). Dapsone hypersensitivity is noted in 1.4% of the patients receiving the drug as part of MDT and 1% were found to be fatal complications. (M Lorenz, G Wozwel, J Schmitt. Hypersensitivity reactions to dapsone – a systematic review; Acta Derm Ven 2012). Many case reports were also found in the search of the literature, including agranulocytosis. Flu syndrome was found to be the most common adverse event due to rifampicin (eight patients out of 176 patient cards reviewed) and gastro-intestinal symptoms for clofazimine (16 out of 176 patients) as per the study conducted in Chhattisgarh tribal health care centre (Singh H, Nel B, Dey V et al. Adverse effects of multidrug therapy in leprosy, a two years' experience (2006-2008) in a tertiary health care centre in the tribal region of Chhattisgarh State (Bastar, Jagdalpur); Lepr Rev 2011, 82(1): 17-24. TAG-Leprosy advised to develop a monitoring guide in consultation with the Department of Pharmacovigilance and develop recording and reporting systems for monitoring side effects and adverse events due to MDT and other drugs used in the management of leprosy and its complications as well as in prophylaxis. 23 3.13. Vaccines: Report of expert consultation on LepVax Dr Jerry Joshua reported on the meeting of experts that took place on 27 November 2019 which discussed the status of different vaccines for leprosy and possibilities of expansion of Phase 1a and Phase 2 trials for LepVax, the leprosy vaccine being developed by the Infectious Diseases Research Institute (IDRI) in the United States of America. MDT was introduced in 1983 to address emerging resistance to dapsone and to improve treatment effectiveness. MDT showed very high cure rates and allowed to reduce the duration of treatment considerably. As a result, the registered prevalence of leprosy reduced with more than 99% globally. The milestone of elimination of leprosy as a public health problem at global level was reached in 2000. New case detection, however, is decreasing more slowly (about 2-3% per year). To eliminate transmission of infection new tools – chemo- and immunoprophylaxis – in addition to MDT are needed to interrupt the chain of transmission. Single dose rifampicin prophylaxis is promising with nearly 57% protection but for interruption of transmission of infection vaccines are considered the only answer. Experts in the meeting reviewed the status of the three available vaccines. BCG, which includes different strains of attenuated Mycobacterium bovis, shows some protective effect against tuberculosis as well as leprosy. The BCG trials demonstrating lepromin conversion carried out in India (1939), Uganda (1989) and New Guinea showed efficacy varying from 50% to 80%. In Myanmar (1985) the efficacy demonstrated was low at 20% and similarly the unpublished data from South India also showed an efficacy of 24%. Another study conducted in Kanpur, North India with four arms using BCG, BCG and killed M. Leprae, ICRC vacine and M.w has shown precipitation of cases (i.e. an increased number of new cases of leprosy shortly after application of the vaccine followed by a reduction of cases subsequently). Mycobacterium indicum Pranii (MiP), a non-pathogenic mycobacterium formerly known as M. w, is fast growing and easily cultivable; it is an ancestor of M. tuberculosis, M. leprae and M. avium- intracellulare complex. Its protective efficacy was 68.6% in the first year and the cumulative efficacy was reduced to 39.3% in the third year. Precipitation of new cases was seen in the study population. LepVax, an antigenic complex of specific antigens of M. leprae and an antigenic protein adjuvant. Its expected therapeutic outcome includes reduced frequency of reaction episodes (up to 50%) and expected prophylactic outcome includes reduced incidence of leprosy. Lepromin conversion remains the main marker to assess the efficacy of vaccines and in addition the test for diagnosis which is in the process of finalization would help in measuring the efficacy of vaccines also. Adverse events should be rare. The Phase 1a study has been completed in healthy volunteers in the United States of America. This trial in a non-endemic setting was to determine safety and immunogenicity. The next phase (Phase 1b) is proposed among healthy volunteers in a leprosy-endemic area (Brazil). The design would be randomized, double-blind, placebo-controlled. The opinion of experts 24 supported the idea of carrying out Phase 1b trials in India as well. However, in the absence of representatives from the Indian Council of Medical Research (ICMR) and the Central Leprosy Division, discussions could not proceed. It was decided to try to get the collaboration of these agencies through updating them on the proceedings of this meeting. TAG recommended to take further steps in carrying out studies using LepVax in consultation with NLPs (Brazil and India), ICMR, Gennova Biopharmaceuticals Ltd. (a private company which has the capacity to produce the vaccine and would be committed to do so on a non-profit basis) and ILEP agencies. 3.14. Any other business Treatment of leprosy without dapsone GLP was informed that Scanpharm, the company producing dapsone (for inclusion in MDT), was no longer allowed by the Danish Regulatory Authority to produce medical products due to issues related to non-adherence to good manufacturing practice criteria. Novartis, the company that donates MDT blisters worldwide had immediately halted the supply of MDT from Sandoz, its subsidiary production (packing) site of MDT blisters in Kalwe, India. Internal quality controls conducted by Sandoz have indicated that all blister packs supplied from its site are fully safe. This has short-term repercussions on global MDT supply as the November and likely December planned shipments from Kalwe could not take place, affecting mostly some of the larger countries. Smaller countries are supplied from an MDT stock maintained by WHO in Geneva. These supplies could take place as planned but this stock was almost depleted and depends also no fresh supply from Kalwe. Novartis is in dialogue with the Indian Health Authority in order to receive a green light for resupply from its site in Kalwe and obtaining a waiver from the ban on production of dapsone by Scanpharm. TAG-Leprosy confirmed that, technically, leprosy can be treated without dapsone. The WHO recommendation for treating leprosy in case of dapsone intolerance remains valid in a situation without dapsone also. MB leprosy can be treated with two drugs, i.e. the same regimen but omitting dapsone; while for the treatment of PB leprosy, dapsone can be substituted by clofazimine. This however is rather a theoretical option. At the time of the Sixteenth TAG meeting, Novartis was hopeful for a quick restart of blister supply from the Sandoz plant in Kalwe. As most countries have a (limited) buffer stock, interruption of treatments of individual patients can likely be avoided by in-country management of available stocks. 25 Maintaining leprosy expertise TAG-Leprosy acknowledges the dwindling expertise in leprosy in many countries due to the disease becoming more rare, the phasing out of old leprosy experts and the lack of enthusiasm among young professionals to take interest in leprosy. This poses major challenges and will need to be addressed through adequately planning of human resources, training and supervision. In addition to traditional training approaches, new approaches should be more embraced, capitalizing on digital health. This includes development and use of e-modules (with possible linking to programmes for continuous medical education), e-health (with linking peripheral facilities to centers of excellence), use of smartphone technology (including WhatsApp groups), etc. Sub-national data collection and monitoring As leprosy is moving towards elimination, it will become necessary at global level to monitor disease trends not only at national level but also at sub-national level. This is being done also for other diseases targeted for elimination. It implies mapping of remaining focal areas and identifying areas for verification of cessation of transmission. 4. Concluding session 4.1. Conclusions In conclusion, TAG-Leprosy:  appreciated the progress made in implementing the Global Leprosy Strategy 2016‒2020 by NLPs in collaboration with partners;  appreciated GLP’s contribution in developing the NTD Roadmap 2021‒2030 and suggested finetuning a few points in the leprosy section;  appreciated the efforts by WHO in developing the draft Global Leprosy Strategy 2021‒2030 with the new focus on interruption of transmission;  welcomed the summary conclusions and recommendations from the meeting of the Global Forum of People’s Organizations on Hansen Disease, held in Manila in September 2019;  appreciated the efforts of Maldives in developing the pioneering Zero Leprosy Framework for Maldives and suggested publishing it and promoting it as a good example for other countries with similar contextual factors;  reviewed the status of the technical guidance for the management of reactions and neuritis and made recommendation for the final version;  appreciated and supported the research agenda developed by LRI and GPZL as a crucial contribution in terms of evidence generation towards elimination of leprosy;  Reiterated the need to sustain expertise in the health workforce at all levels; 26  supported conducting Phase1b and phase2 trials of LepVax vaccine developed by IDRI as a tool for prevention and management of leprosy and seek further guidance from SAGE. TAG- Leprosy acknowledged the potential occurrence of leprosy reactions linked to vaccination and recommended vigilance. 4.2. Recommendations In its Sixteenth meeting, TAG-Leprosy recommended:  to link the Global Leprosy Strategy 2021‒2030 with relevant SDGs, the Global Action Plan for UHC and targets of the NTD roadmap and refine it further to be more pragmatic in consultation with Member countries and partners;  to continue to advocate for increased domestic and international funding to achieve zero leprosy;  to prioritize the following two groups of countries: (i) current global priority countries (characterized by high endemicity or transmission); and (ii) countries which are close to interruption of transmission;  to design mechanisms for validation of elimination of leprosy as a public health problem and undertake such validation exercise on request; as well as for verification of interruption of transmission. It also suggested considering developing criteria for awarding the status of “zero leprosy” to be used at national or subnational level.  to Identify candidate countries for verification of interruption of transmission of leprosy infection based on at least the following indicators for the last ten years despite effective surveillance for detecting new cases: number of new autochthonous leprosy cases; new child cases; G2D among new cases.  to advocate with the wider disability community for quality care and development of customized, protective, user-friendly devices/assistive technology products for persons with disabilities due to leprosy, based on need and demand. It also recommended line-listing all cases with disabilities to facilitate access to assistive products, services, benefits and entitlements.  to include leprosy in the global AMR surveillance agenda with support from partner organizations and in line with the Guide for surveillance of AMR in leprosy (2017 update).  to sustain expertise in the health workforce at all levels through traditional and innovative approaches including e-learning opportunities and the Skin NTD guide.  TAG-Leprosy reiterated the recommendation to use SDR for PEP and requested WHO to produce an operational manual, support countries to roll out SDR PEP, and to continue negotiations for drug donation.  to develop pharmacovigilance guidance through a systems approach for monitoring side effects and adverse events for the drugs used in management of leprosy, leprosy reactions and PEP as well as vaccines. 27 28 Annex 1: List of participants TAG members 1. Dr Yasin Al-Qubati (unable to attend) Taiz Republic of Yemen 2. Professor Emanuelle Cambau (through skype) Paris France 3. Dr Maria Da Palma Caldas Luanda Angola 4. Dr Joshua Jerry Karigiri India 5. Dr Mauricio Nobre Sao Paulo Brazil 6. Dr Vijaykumar Pannikar (Chair) Hosuru India 7. Dr Mirta Roses Periago Buenos Aires Argentina 8. Professor Jan Hendrik Richardus Rotterdam The Netherlands 9. Dr Yotsu Rie Nagasaki Japan 10. Dr Lily Banonah Rivai (unable to attend) Jakarta Indonesia 11. Dr Silatham Sermrittirong Bangkok Thailand 12. Mr Tesfaye Tadesse Addis Ababa Ethiopia 13. Dr Paul Saunderson, Chair ITC (through skype) Ålesund Norway 14. Dr Benedict Okoe Quao Sakumono Ghana WHO Secretariat 1. Dr Pem Namgyal Director Programme Management WHO Regional Office for South-East Asia 2. Dr Erwin Cooreman, Team Leader Global Leprosy Programme WHO Regional Office for South-East Asia 3. Dr V R R Pemmaraju Technical Officer Global Leprosy Programme WHO Regional Office for South-East Asia 4. Dr Patanjali Dev Nayar Consultant Department of Noncommunicable Diseases and Environmental Health WHO Regional Office for South-East Asia 5. Dr Abate Mulugeta Beshah Acting Medical Officer (leprosy, Buruli ulcer, human African trypanosomiasis) WHO Regional Office for Africa 6. Dr Isabelle Roger (unable to attend) Regional Adviser, Neglected Infectious Diseases and Leprosy PAHO/WHO Country Office for Brazil 29 7. Dr Supriya Warusavithana Regional Adviser (NTDs) WHO Regional Office for the Eastern Mediterranean 8. Dr Md. Jamsheed Ahmed (unable to attend) Regional Adviser (NTDs) WHO Regional Office for South-East Asia 9. Dr Zaw Lin Technical Officer (NTDs) WHO Regional Office for South-East Asia 10. Dr Rashmi Shukla National Professional Officer (NTDs) WHO Country Office for India 11. Dr Kalpeshsinh Rahevar Medical Officer (End TB and Leprosy) WHO Regional Office for the Western Pacific 12. Ms Indu Arya Gulhar Executive Assistant Global Leprosy Programme WHO Regional Office for South-East Asia 30 Annex 2: Programme Day 1 – Thursday 28 November 2019 09:00 – 09:30 hrs INAUGURAL SESSION Opening address – Regional Director, WHO South-East Asia Region Welcome remarks – Chair of TAG Objectives and expected outcomes – Team Leader GLP 09:45 – 10:15 hrs FOLLOW UP ON RECOMMENDATIONS OF FIFTEENTH MEETING OF TAG- LEPROSY – Technical Officer GLP 10:15 – 10:45 hrs BUSINESS SESSION Update on global leprosy control – Team Leader GLP 10:45 – 11:00 hrs Salient findings of Independent evaluation of the National Leprosy Eradication Programme of India – NPO (NTDs), WHO Country Office for India 11:30 – 12:30 hrs Roadmap for NTDs 2021‒2030 and Post-2020 Global Leprosy Strategy – Team Leader GLP 12:30 – 13:00 hrs Assistive devices in improving functionality of persons with disabilities due to leprosy – Dr Patanjali Dev Nayar, WHO Consultant 13:00 – 13:30 hrs Zero Leprosy Roadmap for Maldives – Technical Officer GLP 14:30 – 15:30 hrs Enhanced surveillance in situations with post-elimination; parameters for certification/validation of elimination of leprosy or interruption of transmission – Dr Vijay Kumar Pannikar 16:00 – 16:30 hrs Anti-microbial resistance in leprosy – Technical Officer GLP Day 2 – Friday 29 November 2019 09:00 – 10:00 hrs Single-dose rifampicin prophylaxis: technical guidance to national leprosy programmes – Professor Jan H. Richardus 10:00 – 10:30 hrs Results of the MALTALEP trial – Professor Jan H. Richardus 11:00 – 11:30 hrs Anti-microbial resistance surveillance – Professor Emmanuelle Cambau 11:30 – 12:30 hrs Treatment of reactions and neuritis – Dr Paul Saunderson 12:30 – 13:00 hrs Research priorities – Dr Paul Saunderson 31 14:00 – 14:30 hrs Global Leprosy/Hansen Disease Forum: Conclusions and recommendations – Mr Tadesse Tesfaye 14:30 – 15:30 hrs Pharmacovigilance – Technical Officer GLP 15:30 – 16:00 hrs Report of Expert consultation on LepVax – Dr Jerry Joshua 16:00 – 16:30 hrs Any other business 17:00 – 18:00 hrs CLOSING SESSION Conclusions and recommendations 32 Annex 3: Inaugural address by the Regional Director A very good morning and welcome to this Sixteenth meeting of the WHO Technical and Advisory Group on Leprosy. Although our Regional Director, Dr Poonam Khetrapal Singh, would have liked to attend this important meeting, she is unable to due to prior commitments. It is my pleasure to deliver this message on her behalf. The Regional Director is pleased that the global burden of leprosy is declining. She nevertheless observes that more than 200 000 new cases are still reported annually. She notes that among the new cases is a significant proportion of child disabilities and grade-2 disabilities. This points to ongoing transmission and late case detection. The current Global Leprosy Strategy 2016−2020 was accepted by most endemic countries. The strategy is based on the maximum roll-out of currently available approaches – in particular, on enhancing case detection and prompt treatment. The strategy has provided a boost to national leprosy programmes, especially in active case detection, mapping, care after cure and stigma reduction. Electronic reporting is also expanding, in line with other disease control programmes. It will be of increasing importance for surveillance, especially when leprosy becomes very rare. The Regional Director is pleased that India recently completed an independent review of its national leprosy progamme. Salient findings include the need for approaches tailored to the local epidemiology – state, district or even below. She says that further programme integration is needed, as is ensuring a critical mass of competent human resources. We must further engage partners and communities, in addition to the private sector and dermatologists. As you appreciate, guidelines for diagnosis, treatment and prevention were formulated as per the WHO GRADE approach, which assessed all available evidence. The regimen changes are nevertheless being adopted slowly for several reasons, including lengthy in-country processes for policy change. Keeping in mind the limited efficacy of single dose rifampicin as a prophylactic tool, impact can be enhanced by ensuring maximum coverage of eligible contacts. This will be given utmost prominence in the next Global Leprosy Strategy. The Regional Director notes that the 2021-2030 NTD Roadmap, which is now almost finalized, includes a chapter on leprosy. Leprosy has been reclassified from a disease that we aim to eliminate as a public health problem to a disease that we aim to eliminate. She says that more countries, especially medium- and low-burden countries, are now requesting WHO to come up with a mechanism or tool to confirm their low-burden status, and if possible a tool to confirm the interruption of transmission. She is pleased that in this Region Maldives has developed a Zero-Leprosy Roadmap, which aims to eliminate autochthonous cases by 2030 or earlier. She notes that both NTDs and antimicrobial resistance are among the Region’s Flagship Priority programmes. Though resistance in leprosy control is not a menace today, strengthening vigilance is required. The Regional Director says that addressing the needs of leprosy-affected persons with permanent disabilities in a holistic way, as well as further addressing stigma and discrimination, remain important. The support of partners is needed in these areas. 33 The Regional Director notes with satisfaction that the Global Partnership for Zero Leprosy is increasingly recognized as a crucial global partner. She looks forward to further collaboration with the Partnership. The Regional Director reiterates WHO’s commitment to promoting good quality research and innovation as together we strive to sustain our achievements and accelerate progress to eliminate leprosy. She wishes you an engaging meeting and looks forward to being apprised of the outcomes. I echo that sentiment and wish you a comfortable stay in New Delhi. 34 The Sixteenth meeting of the Technical and Advisory Group on Leprosy (TAG-Leprosy) reviewed the progress in global leprosy control, and especially the data of 2018. The paradigm shift of moving towards interruption of transmission of leprosy infection in the post-2020 era was highlighted and the need to develop tools for confirming interruption of transmission was emphasized by the Regional Director. it also assessed TAG-Leprosy further appreciated research agenda developed by the Leprosy Research Initiative (LRI) and the Global Partnership for Zero Leprosy (GPZL) as well as the progress made in vaccine development. The Zero Leprosy Framework for Maldives 2019‒2030 was also highlighted as an example for other countries. TAG-Leprosy also discussed and welcomed the conclusions and recommendations made by the Global Leprosy/Hansen Disease Forum which took place in September 2019. Recommendations from the Independent evaluation of India’s National Leprosy Eradication Programme were presented to TAG-Leprosy. TAG appreciated the efforts of WHO in developing e-learning modules on leprosy and advised to use these and other innovative methods to sustain clinical and programmatic expertise on leprosy, complementing regular training programmes. TAG-Leprosy was informed about the possible stock-out of multidrug therapy (MDT) drugs and made suggestions on how to mitigate such situation. The roadmap for addressing neglected tropical diseases (NTDs), protocols for validation or verification of elimination of leprosy, anti-microbial resistance (AMR) monitoring, post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR) for the prevention of leprosy and the technical guidance on treatment of reactions were discussed in detail. Recommendations were made with special emphasis on moving forward, improving uptake of PEP, verification of interruption of transmission, developing technical guidance documents on treatment of reactions and pharmacovigilance.