NETWORK OF WHO COLLABORATING CENTRES FOR
TRACHOMA
INCEPTION MEETING REPORT DECATUR, GA, USA, 19–20 FEBRUARY 2015
Cover photograph: © Dominic Nahr/Magnum/Sightsavers
Network of WHO Collaborating Centres for Trachoma Inception Meeting Report
Decatur, GA, USA, 19–20 February 2015
This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the World Health Organization.
WHO Library Cataloguing-in-Publication Data Network of WHO Collaborating Centres for Trachoma. Inception Meeting Report. Decatur, GA, USA, 19-20 February 2015 I.World Health Organization. ISBN 978 92 4 150896 4 Subject headings are available from WHO institutional repository
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Table of contents Abbreviations ....................................................................................................................iv Background ....................................................................................................................... 1 Opening of the meeting ..................................................................................................... 2 Introduction to WHO Collaborating Centres....................................................................... 2 Vision, aim and objectives of the Network ......................................................................... 4 Activities ............................................................................................................................ 5 Activities for objective A1: To plan and undertake collaborative research on the facial cleanliness and environmental improvement components of the SAFE strategy ......................................................................................................................... 5 Activities for objective A2: To plan and undertake collaborative research on the antibiotic component of the SAFE strategy, including research on co-administration of azithromycin with other drugs ................................................................................... 7 Activities for objective A3: To plan and undertake collaborative research on elimination thresholds and surveillance for trachoma .................................................. 11 Activities for objective A4: To plan and undertake collaborative research on the surgery component of the SAFE strategy .............................................................. 15 Activities for objective A5: To develop, and make accessible, quality-assured systems for measuring the prevalence of ocular CT infection, and of circulating anti-CT antibodies, for the purposes of research at programmatic scale ..................... 17 Activities for objective B: To plan and undertake capacity building and training initiatives to support trachoma elimination programmes .............................................. 18 Activities for objective C: To collaborate in the collection, collation and dissemination of information about trachoma elimination and reference substances relevant to trachoma elimination programmes ............................................................. 20 Activities for objective D: To help standardize the use of terminology and data about trachoma ........................................................................................................... 21 Activities for objective E: To coordinate efforts towards research and development; capacity building and training; collection, collation and dissemination of information and reference substances; and standardized use of terminology and data. ............................................................................................................................ 22 Annex 1: Inception meeting participants .......................................................................... 23 Annex 2: Inception meeting agenda ................................................................................ 24
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Abbreviations BMGF CDC CT DFID EDCTP GTMP HKI LSHTM KCCO MMDP NTD-SC SAFE TF TI TT UCSF USAID WHO WHOCC Bill & Melinda Gates Foundation Centers for Disease Control and Prevention Chlamydia trachomatis Department for International Development European & Developing Countries Clinical Trials Partnership Global Trachoma Mapping Project Helen Keller International London School of Hygiene & Tropical Medicine Kilimanjaro Centre for Community Ophthalmology Morbidity Management and Disability Prevention Neglected Tropical Diseases Support Center Surgery, antibiotics, facial cleanliness, environmental improvement Trachomatous inflammation—follicular Trachomatous inflammation—intense Trachomatous trichiasis University of California, San Francisco United States Agency for International Development World Health Organization World Health Organization Collaborating Centre
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Background There is international commitment, supported by World Health Assembly Resolution 51.11, to eliminate trachoma as a public health problem worldwide by the year 2020. Much work towards this goal has already been achieved, utilising mostly informal relationships between partners that include member states, the World Health Organization (WHO), academic institutions, donors and non-governmental organizations. Recognizing that we still have much to do, however, and that the 2020 target is rapidly approaching, in December 2014, the WHO Department of Control of Neglected Tropical Diseases suggested formalising partnerships with and between a number of academic institutions that have for many years helped WHO to implement its mandated trachoma work, by establishing a network of WHO Collaborating Centres (WHOCCs) for Trachoma. WHO believes that such formalised collaboration brings benefits to both parties. WHO gains access to top institutions worldwide and the institutional capacity to support its work. Institutions designated as WHOCCs gain increased visibility and recognition by national authorities, and greater attention from the public for the health issues on which they are active. Centres can also work together at international level via a formal WHO-led platform, facilitating better coordination and increased opportunities to mobilize resources from funding partners. This win–win relationship between WHO and its Collaborating Centres should make a difference to the prospects of trachoma elimination globally. To be considered for designation as a WHOCC, eligible institutions must fulfil all of the following criteria: a) high scientific and technical standing at national and international levels; b) prominent place in the country's health, scientific or educational structures; c) high quality of scientific and technical leadership, and sufficient number of staff with high-level qualifications; d) stability in terms of personnel, activity and funding; e) strong working relationship with other institutions in the country, and at intercountry, regional and global levels; f) clear ability, capacity and readiness to contribute, both individually and within networks, to WHO programme activities, whether in support of country programmes or through participation in international cooperative activities; g) clear technical and geographical relevance of both the institution and its activities to WHO's programme priorities; h) at least two years of previous collaboration with WHO in carrying out jointly planned activities. Institutions thought to meet these criteria for trachoma included (in alphabetical order): Dana Center for Preventive Ophthalmology, Johns Hopkins University, Baltimore – already a WHO Collaborating Centre for research in trachoma and age-related macular degeneration; re-designation due by 24 June 2015 Department of Global Health, Emory University, Atlanta Division of Parasitic Diseases, Centers for Disease Control and Prevention (CDC), Atlanta Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London Francis I. Proctor Foundation, University of California San Francisco (UCSF), San Francisco Kilimanjaro Centre for Community Ophthalmology (KCCO), University of Cape Town, Cape Town Wake Forest School of Medicine, Wake Forest University, Winston-Salem 1
To expedite the process of establishing the Network, to allow potential WHOCCs to discuss in detail what the Network might do, develop terms of reference and draft work plans, a two day meeting was held from 19-20 February 2015 at the International Trachoma Initiative, Decatur, GA.
Opening of the meeting The meeting was opened by Anthony Solomon, Medical Officer for Trachoma at WHO Geneva, and Secretary to the WHO Alliance for the Global Elimination of Trachoma by 2020. He expressed an enthusiastic welcome from the WHO Department of Neglected Tropical Diseases, thanked participants for devoting time to prepare for and attend the meeting, and noted that only 70 months and 11 days remained before December 31, 2020: the target for Global Elimination of Trachoma as a public health problem. Participants (Annex 1) introduced themselves, and the purpose, outcome and outputs of the meeting were agreed, as follows: Purpose: to accelerate the process of establishing a Network of WHOCCs for Trachoma, allow the proposed institutions to discuss in detail what the Network might do, develop terms of reference, and draft work plans. Outcome: a nascent Network, composed of a number of institutions working towards designation as WHOCCs for Trachoma, plus the Secretariat at WHO headquarters supported by the relevant regional offices. Outputs: a meeting report, draft terms of reference for each proposed Collaborating Centre, and draft work plans for each proposed Collaborating Centre. The Agenda (Annex 2) was adopted without amendment.
Introduction to WHO Collaborating Centres Beatriz Muñoz, Associate Professor of Ophthalmology, Dana Center for Preventive Ophthalmology, summarized the Dana Center’s experience of being a WHOCC, a designation that has been in place since 1983. During that long association with WHO, the Dana Center has contributed to work on trachoma, onchocerciasis, vitamin A deficiency, age-related macular degeneration, cataract and glaucoma, by undertaking research, training, knowledge dissemination, and meeting convening and write-up. Lessons learned have included: 1. WHO and the WHOCC must define a mutually-agreed set of activities over a defined time period, to • enable WHO and its regional offices to plan and set targets, and • enable the WHOCC to marshal resources and set aside time from other activities. 2. The WHOCC must understand whether funding is available from WHO for these activities, and what the financial commitment from the WHOCC will be. When WHO funding has been provided, often it has not included time reimbursement for WHOCC staff, and WHOCCs may therefore need to seek external funding.
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3. WHO and the WHOCC must agree on the outputs from the activities, to • enable the WHOCC to marshal appropriate resources for those outputs, and • clarify WHO expectations (e.g., recommendations versus published papers). 4. The WHOCC should involve WHO at all stages in carrying out the activity, to • enable mid-course correction if needed, and avoid misunderstandings, and • ensure the outputs are in formats acceptable for use by WHO and its regional offices. 5. The partnership needs interest and commitment from both sides. This is particularly true for WHOCC consortiums. 6. There needs to be common commitment to the goal, and not the glory. Anthony Solomon summarized some important aspects of the designation process for and functions of WHOCCs, and the motivations of the WHO Department of Control of Neglected Tropical Diseases in wishing to set up the Network. Designation is: • made with the agreement of the head of the establishment to which the institution is attached, and after consultation with the national government; • initially for a term of four years; • independent of financial support being given to the institution by WHO: grants may be made to any institution that is able to perform a specific task connected with WHO's programme, but this has no relevance to the eligibility or ineligibility of an institution for designation; and • not possible for working groups, programmes, non-governmental organizations, foundations, or professional associations, all of which are ineligible to become WHOCCs. Typical functions of WHOCCs include: a) collection, collation and dissemination of information; b) standardization of terminology and nomenclature, of technology, of diagnostic, therapeutic and prophylactic substances, and of methods and procedures; c) development of evidence-based technical guidance tools and resource materials on various topics; d) development and application of appropriate technology; e) provision of reference substances and other services; f) participation in collaborative research developed under WHO's leadership, including the planning, conducting, monitoring and evaluation of research; evaluation of WHO interventions in countries; and promotion of the application of the results of research; g) training, including research training; h) coordination of activities carried out by several institutions on a given subject; i) capacity-building work at country level; and/or j) provision of monitoring, preparedness and response services to deal with disease outbreaks and public health emergencies. These functions are intended to meet two main needs: implementing WHO's mandated work and programme objectives, and developing and strengthening institutional capacity in countries and regions.
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To help meet the second of these needs: 1. Some activities of each WHOCC should specifically aim to develop institutional capacity in target countries. 2. As a network, we should involve in activities some institutions which are located in trachoma-endemic countries and where developing institutional capacity may be a great asset to achieve the goals of the programme as a whole. 3. We should consider twinning arrangements between a WHOCC in a developed country and one or more institutions in developing countries to jointly develop and implement activities. The Department of Control of Neglected Tropical Diseases has no wish to: • take credit for the research or ideas of the WHOCCs; • dictate what research on trachoma should be undertaken; or • force all activity on trachoma to become a collaboration with WHO or between institutions.
Vision, aim and objectives of the Network Vision of the Network: Global elimination of trachoma as a public health problem by 2020 Aim of the Network: To facilitate coordinated action of designated academic institutions in their trachoma elimination area of work. Objectives of the WHOCCs, and of the Network as a whole: A: To plan and undertake collaborative research, and development and application of appropriate technology, relevant to trachoma elimination programmes A1: To plan and undertake collaborative research on the facial cleanliness and environmental improvement components of the SAFE strategy A2: To plan and undertake collaborative research on the antibiotic component of the SAFE strategy, including research on co-administration of azithromycin with other drugs A3: To plan and undertake collaborative research on elimination thresholds and surveillance for trachoma A4: To plan and undertake collaborative research on the surgery component of the SAFE strategy A5 To develop, and make accessible, quality-assured systems for measuring the prevalence of ocular Chlamydia trachomatis (CT) infection, and of circulating anti-CT antibodies, for the purposes of research at programmatic scale B: To plan and undertake capacity building and training initiatives to support trachoma elimination programmes C: To collaborate in the collection, collation and dissemination of information about trachoma elimination and reference substances relevant to trachoma elimination programmes D: To help standardize the use of terminology and data about trachoma E: To coordinate efforts towards research and development; capacity building and training; collection, collation and dissemination of information and reference substances; and standardized use of terminology and data.
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Activities Activities for objective A1: To plan and undertake collaborative research on the facial cleanliness and environmental improvement components of the SAFE strategy Questions that the activity should address (potential utility of answers) 1. At district / evaluation unit level, what are the water and sanitation correlates of high TF prevalence? (Hypothesis development for intervention studies) 2. What approaches to the F&E components of SAFE have been used by trachoma elimination programmes? Are there any unpublished data on outcomes? (Hypothesis development for intervention studies) 3. What are the major routes of transmission of ocular CT, and their behavioural determinants? Can contextually appropriate, targeted approaches be designed to interrupt them? Relevant previous and ongoing work Previous studies are of highly variable quality; explanatory variables, grading and survey design generally not standardized. To be determined through the activity Suggested approach (potential locations) Analysis of data from the Global Trachoma Mapping Project: will require ministries of health to contribute their data. Review of grey literature by graduate student. International Coalition for Trachoma Control (ICTC) members to be asked to search for reports on file, and liaise with in-country partners. STRONGER-SAFE (Ethiopia / Chad): (1) understand transmission - intensive observational studies, swab collection for PCR and CT sequencing; (2) interrupt transmission – small scale pilot studies; (3) cluster randomized trials Tentative cost (USD)1, possible funders 20K Nominated lead(s) to develop activity LSHTM (Brooker) and Emory (Freeman)
26K (WHO)
Emory (Freeman)
There is evidence that flies may be involved in transmission of ocular CT infection in some contexts. Fingers and fomites are believed to also play a role, but evidence is limited.
9000K
LSHTM (Burton/Cairncross)
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In this table, and the tables on the follow pages, amounts in green text are funds already secured; amounts in amber text are funds that have been requested and are under active consideration by one or more funding agencies; and amounts in red text have not yet been formally requested. 5
4. What approaches to the F&E components of SAFE lead to sustained changes in behaviour and access? Do these changes produce reductions in the prevalence of TF and/or ocular CT infection? (Guideline development and programme planning)
Previous: 1. West et al, Lancet 1995 2. Emerson et al, Lancet 1999 3. Emerson et al, Lancet 2004 4. West et al, Lancet 2006 Current: 1. LSHTM (Curtis) working on UNILEVER trial of school-based hygiene intervention, with trachoma as one of several endpoints 2. FASTRAC study (Amhara, Ethiopia) 3. SWIFT-WUHA study
Reprise the FASTRAC study: a community randomized trial, comparing antibiotic distribution alone to antibiotic distribution+F&E (Two sites, one of which should be Oromia, Ethiopia; the other selected from, e.g., Bijagos Islands, Guinea-Bissau; Karamoja, Uganda; and Amazonas, Colombia) Outcome measures: prevalence of TF, prevalence of ocular CT, prevalence of soil-transmitted helminths, growth markers, cost
500K already allocated for FASTRAC (World Bank) + proposal for 200K in review by 3ie. An additional 500K required for PCR and final year data collection. 4000K for two additional sites Queen Elizabeth Diamond Jubilee Trust and DFID (?to fund implementation of F&E) NTD-SC / USAID / EDCTP (research funds) 400K
Emory (Freeman/McFarland) and UCSF (Keenan)
5. What are the optimal strategies for delivery of F&E in populations where measuring impact on disease is difficult? (Guideline development and programme planning)
Limited
Work with 2-3 counties in which F&E is being implemented (as part of existing projects) to conduct a rigorous outcome evaluation. Develop a consistent evaluation framework (tools, indicators) and pilot, revise, and evaluate approaches to assess potential to change behavior, with input from behavioural scientists. 6
Emory (Freeman)
Activities for objective A2: To plan and undertake collaborative research on the antibiotic component of the SAFE strategy, including research on co-administration of azithromycin with other drugs Questions that the activity should address (potential utility of answers) 1. Does azithromycin coverage matter? If yes, how do we maximize demand, and optimally motivate distribution teams? (Guideline development and programme planning) Relevant previous and ongoing work 1. Harding-Esch et al, PLOS NTDs 2013 2. West et al, PLOS NTDs 2013 In programme practice, administrative coverage reports differ from coverage survey data. Coverage appears to be highly dependent on the distributor. People’s choice about participation seems to be more important than their availability. Donors are often unwilling to pay for coverage surveys, so they are done infrequently. Suggested approach (potential locations) Should consider whether coverage matters in the context of program impact – do areas of low compliance become ‘hot spots’ of infection? Tentative cost (USD), possible funders For “Does coverage matter?”, Dana Center has 15K (internal seed funding) for work in Kongwa, Tanzania; require an additional 10K. LSHTM partfunded (50K) by Wellcome Trust, 138K needed. Maximizing demand: In Malawi, LSHTM part-funded to look at this. Social scientists needed. For “How do we maximize demand?”, LSHTM has 29K (Economic and Social Research Council) Await literature review to determine whether further funding is required. Nominated lead(s) to develop proposal Dana Center (West)
LSHTM (Mtuy/Burton)
LSHTM (GuptaWright/Parker)
2. How should national programmes rapidly identify areas with poor coverage? (Guideline development and programme planning)
There is a significant literature on coverage estimation for various interventions. Data Quality Assessment
Review previous approaches used to evaluate coverage in mass administration of azithromycin and other interventions. ?Evaluate the “rapid monitoring of 7
KCCO (Courtright) / Emory (Haddad)
3. Is co-administration of azithromycin + albendazole (or mebendazole) safe? Is co-administration of azithromycin + ivermectin + albendazole safe? (Guideline development and programme planning) 4. Are there specific population subsets that should be targeted for antibiotic treatment, rather than undertaking mass drug administration? Should the target population for antibiotic mass drug administration remain the same throughout the whole program cycle, or should it change? Is it more effective or efficient (in terms of quantities of azithromycin and drug distribution costs) to use an intensive antibiotic “attack phase” and then maintain the gains made with less intensive intervention, rather than simply to conduct routine annual treatment
being developed by WHO (check administrative coverage reports, rapid monitoring assessment in areas where reported results are questionable). 1. Amsden et al, AJTMH 2007 2. El-Tahtawy et al, PLOS NTDs 2008 3. Coulibaly et al, PLOS NTDs 2013
coverage” approach (7 households × 30 clusters, undertaken within one month of mass drug administration) for azithromycin. Intensive safety monitoring of coadministration. Discuss with clinical pharmacologists and regulatory experts to determine the scale of data collection needed to provide assurance about the safety of coadministration (Colombia, Vanuatu, Solomon Islands) Publication of TANA2 and PRETNiger studies that compared targeting to children versus other strategies, including annual treatment of the entire community. Prepare a summary of relevant studies, which could be presented to decision makers. The “Enhanced MDA Study” is a programme-embedded community-randomized trial for Amhara, Ethiopia, that will examine the effect of giving children two extra rounds of antibiotic treatment in quick succession after whole-population MDA; it is already part-funded. Consider a community 8
Budget estimates being prepared. ITI has 150K available.
LSHTM (Marks)
Previous: 1. TANA – treating children only had a similar effect to treating the whole population. 2. Biannual versus annual treatment has been studied; very little evidence of advantage over annual treatment Ongoing: 1. Bijagos Islands study (LSHTM): 2nd treatment 1 week after 1st. Could suit difficult-toreach populations. 2. TANA2/TIRET: A childtargeted treatment arm, compared to ongoing annual mass treatment and stopped treatment
No funding required for dissemination and summary of current results.
UCSF (Lietman)
Enhanced MDA study: 600K already committed by ITI; additional 1400K required.
Emory (Emerson/Callahan)
Subsequent
rounds? Do the answers to these questions depend on the baseline TF prevalence? (Guideline development and programme planning)
3. PRET-Niger: A biannual child-treated arm compared to annual mass treatment
randomized trial undertaken in the context of programmes to assess antibiotic-sparing, sustainable treatment strategies, including: i) a single mass treatment followed by treatment targeted to children only ii) targeting treatment to a subset of individuals—the minimal core group identified by an initial survey to be responsible for transmission in the community. As a first step, form a committee to address how to perform randomized trials in the context of existing programs, at a reasonable cost. Longitudinal studies using sequencing in Tanzania (where many rounds of mass azithromycin treatment have been delivered in some places) and Guinea Bissau.
communityrandomized trials would cost a minimum of 1000K per site, unless substantial cost savings could occur in the context of an existing treatment program and a simple trial design.
5. What causes reemergence? Primary treatment failure? Persistent/latent infection? Local recrudescence? Reintroduction from outside? (Hypothesis generation for intervention studies)
Modeling suggests that the efficacy of treatment is ~70%. Treatment failures frequently occur in treatment of genital tract CT infections
LSHTM: part of STRONGERSAFE proposal (see objective A1, activity 3) For Tanzania: 65K needed to supplement 60K already in hand from NIH. Specific funds not needed.
LSHTM (Bailey/Thomson)
Dana Center (West/Quinn)
6. What is the optimal number of rounds of antibiotic distribution before conducting or repeating an impact survey? (Guideline development and programme
Reliable data are limited, in part due to the previous lack of international standardization of grader training and survey design
Ongoing analyses of routine programmatic data collected using Global Trachoma Mapping Project (GTMP) at baseline and standardized impact and surveillance survey protocols 9
LSHTM (Harding-Esch)
planning) 7. Are individuals in endemic communities receiving an ideal therapeutic dose? (Guideline development and programme planning)
People ≥15 years old receive 1g; anyone <15 years old should receive 20mg/kg, but evidence suggests they receive more than this; the heightbased dosing algorithm is designed to minimize under-dosing.
using certified graders. Collect data on height, weight, and 30K dose received, in multiple countries Revise the algorithm for the next Zithromax® Program Managers Guide
Emory (Emerson)
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Activities for objective A3: To plan and undertake collaborative research on elimination thresholds and surveillance for trachoma Questions that the activity should address (potential utility of answers) 1. Do internally-displaced people, refugees, indigenous populations, refugee camps, nomadic populations, prisoners have trachoma at prevalences indicating a public health problem? If yes, how do we best reach them with interventions? (Guideline development and programme planning) Relevant previous and ongoing work Populations not overseen by the United Nations High Commissioner for Refugees (generally internally-displaced people) are of greater potential concern than those living in established UNHCR camps. There are large refugee populations in the Eastern Mediterranean Region. Recent assessments in camps in Djibouti and Jordan reported no trachoma. There is a considerable literature on TT and age. Muñoz et al, TMIH 1997 found that the incidence appeared to increase with increasing age. Suggested approach (potential locations) GTMP should continue to work towards conducting these assessments where possible. CDC and ITI are very interested in this issue Tentative cost (USD), possible funders No additional funding needed at present: GTMP can support baseline population-based prevalence assessments in specific populations, where required Nominated lead(s) to develop proposal CDC (Martin)
2. The current TT elimination prevalence threshold is difficult to measure and use. Would another measure (e.g., TT prevalence in those aged ≥40 years) be more reliable, and more easily interpretable? (Indicator development) 3. What are the correct criteria (and terminology) to use for a TT case at the time of impact and surveillance surveys? Currently,
Analysis of baseline survey data (GTMP) and impact survey data
WHO 2010 (Report of the 3rd Global Scientific Meeting on Trachoma)
Use impact and surveillance survey data in Eritrea, Nepal, Tanzania, Vietnam, ?others Explore possibility of linking 11
36K (Sightsavers / Helen Keller International (HKI)’s USAID Morbidity Management and Disability Prevention (MMDP) grant) Emory have a 7K student travel grant; require a further 3K
LSHTM (Flueckiger) / KCCO (Courtright)
Emory (Haddad) to task MSc students going to Senegal and Uganda with investigating, at community level, what
individuals who have refused surgery, are listed for surgery but have not yet received it, or who have had surgery and now have post-operative TT (“recurrent cases”) are all considered cases “known to the system” and are not included in the backlog estimate. (Indicator development and programme planning) 4. The WHO simplified trachoma grading system is not designed for assessing TT in impact surveys. What is the effect on the measured TT prevalence of recording the presence or absence of trachomatous scarring in all cases of trichiasis? (Guideline development, indicator development, and programme planning) 5. How accurate is the prevalence of TT as assessed by trained antibiotic distributors? Could this be used as an alternative to dedicated TT surveys? (Guideline development) 6. The elimination threshold for active trachoma is a TF prevalence of <5% in 1-9 year-olds, but the prevalence
developed country and developing country students. KCCO (Courtright) / Dana Center (West) / Emory (Haddad) / WHO (Solomon) to agree on a basic question set. Review and discuss at time of the International Trachoma Initiative’s Trachoma Expert Committee meeting, summer 2015. Examine this question in Cameroon, Zambia, Guatemala, Ethiopia, Nigeria and Malawi impact surveys, and in the trichiasis screening work in Kongwa. An ophthalmologist or experienced ophthalmic nurse should ideally undertake the work. Dana Center have secured 5K from the Johns Hopkins University Dean’s Office and 5K from BMGF 10K (WHO)
services or advice people with TT have previously been offered. Dana Center (West) sending an MD student to Tanzania.
Rajak et al, IOVS 2011
KCCO (Lewallen) / LSHTM (Rajak/Burton) / Dana Center (West)
Ongoing work in Kongwa, Tanzania (Dana Center)
Compare TT prevalences determined by trained antibiotic distributors with TT prevalences determined by population-based prevalence surveys Collect data on TF, TI, CT infection and anti-CT antibodies in order to explore the relationship between them at individual and 12
There is an extensive literature on the disease/CT infection mismatch. Recent
10K in addition to partnership with the national programme and an NGO supporting an impact survey The Trachoma Alternative Indicators study has 350K support
Dana Center (West) / Wake Forest (Gower)
UCSF (Porco) / Emory (Emerson) / Dana Center (West) / LSHTM (Mabey)
of CT infection is often much lower than this. What is TF really telling us about CT infection? (Indicator development)
publications on serology: 1. Goodhew et al, PLoS NTDs 2012 2. Liu et al, PLoS NTDs 2013 3. Goodhew et al, BMC Infect Diseases 2014 4. Martin et al, PLoS NTDs 2015 Ongoing: 1. Trachoma Alternative Indicators study (Emory) 2. Pacific Enigma study (LSHTM) Previous: 1. Risk of TS is related to inflammatory scores rather than follicular scores (Dawson et al, ISHCI 1990) 2. West et al, Ophthal Epidemiol 2001 3. Wolle et al, Ophthalmol 2009 4. In individuals with established trachomatous conjunctival scarring, scarring progresses in the absence of ocular CT; progression is associated with episodes of conjunctival inflammation (Burton et al, PLoS NTD, in press).
evaluation-unit levels. Should include country and number of years of intervention as variables.
from USAID through the NTDSC The Pacific Enigma study has 205K support from the Fred Hollows Foundation, with an additional 1130K requested LSHTM (Mabey)
7. The elimination threshold for active trachoma is a TF prevalence of <5% in 1-9 year-olds, but the prevalence of CT infection is often much lower than this. Is infection or disease more important in predicting the risk of future conjunctival scarring? (Indicator development)
Cohort study in Tanzania
300K (funded by Wellcome Trust)
LSHTM (Burton)
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8. What would be the impact on the estimated TF prevalence of having TF diagnoses confirmed by a supervisor? What would the cost-benefit be? Could a cell phone or tablet photograph be used for supervision? 9. It is recommended that impact surveys be done 6-12 months after the final round of 1-5 rounds of mass drug administration. If TF prevalence <5% at this time point, what is the risk that TF will recrudesce?
Ongoing: cohort study in Tanzania GTMP systems used to MSc project. Would need photograph yaws lesions in supervisor review of a random the Solomon Islands sample of 5% of “no-TF” eyes, too, otherwise the only consequence of involving supervisors would be to reduce or maintain the prevalence estimate
10K (including publication costs) LSHTM Trust Funds / WHO 20K to support the photograph reading centre at UCSF 10K to compile datasets (research student required; a few months’ work)
LSHTM (HardingEsch/Butcher) / UCSF (Keenan)
UCSF (Lietman)
WHO 2014 (Technical consultation on trachoma surveillance)
Use data from existing datasets (PRET, ASANTE, TIRET) to assess TF and TI at 6 months and at 12 months to determine if 6 months simply measures the effect of the last MDA. Involve BMGF-funded modelling consortium. In Tanzania, resurvey communities with no disease every 6 months after MDA is discontinued.
Dana Center (Muñoz) / Emory (Callahan)
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Activities for objective A4: To plan and undertake collaborative research on the surgery component of the SAFE strategy Questions that the activity should address (potential utility of answers) 1. What is the relationship between the prevalence of TF and the prevalence of TT at presumed steady state? (Guideline and indicator development) 2. What is the ratio of TT prevalence in women to TT prevalence in men? Does this change with overall prevalence? (Advocacy, indicator development and programme planning) 3. After, or in spite of, mass drug administration, what causes scarring and trichiasis? (Indicator development) Relevant previous and ongoing work Most published data lack international grader standardization and do not use standardized survey or analysis protocols. Previous 1. West et al, BJO 2004 2. Cromwell et al, TRSTMH 2009 Suggested approach (potential locations) Analysis of data from the Global Trachoma Mapping Project: will require ministries of health to contribute their data. Analysis of data from the Global Trachoma Mapping Project: will require ministries of health to contribute their data. A University of Cape Town student will be given this task. Longitudinal studies of host gene expression, microbiota, and antiCT serological responses Tentative cost (USD), possible funders 5K (publication cost) GTMP can support publication costs 5K (plus 5K publication costs) GTMP can support publication costs 150K ? LSHTM (Holland) Nominated lead(s) to develop proposal LSHTM (Mabey) / KCCO (Courtright) / Wake Forest (Gower)
KCCO (Courtright) / LSHTM (Mabey)
In individuals with established trachomatous conjunctival scarring, scarring progresses in the absence of ocular CT; progression is associated with episodes of conjunctival inflammation (Burton et al, PLoS NTD, in press).
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4. How can surgery for trichiasis be optimized to maximize post-surgical outcomes? (Guideline development and programme planning) 5. Is TT surgery uptake and refusal equitable between males and females? (Guideline development and programme planning) 6. How can case finding and surgical uptake be made most effective and efficient? What is the value of integrated approaches (e.g., what additional eye health activities could be carried out at the same time as trachoma surveys or TT surgical services?) (Guideline development and programme planning) 7. Does providing good quality epilation forceps to individuals with TT reduce uptake of surgery? (Guideline development and programme planning)
Merbs et al, Ophthal Epidemiol 2015: lower post-operative scar height is associated with increased post-operative trichiasis 1 year after bilamellar tarsal rotation Habte et al, Ophthal Epidemiol 2008: no difference (Ethiopia)
A randomized controlled trial to compare high versus low incisions is planned
1500K NIH? (proposal submitted)
Dana Center (Merbs) / Wake Forest (Gower)
Bowman et al, TMIH 2000
Programme data from Queen Elizabeth Diamond Jubilee Trustsupported, DFID-supported and USAID Morbidity Management and Disability Prevention Projectsupported programmes Vaupes, Colombia; Tanzania Need input from health economists from the beginning Trials of different approaches to case encouragement: e.g., house to house v surgical camps v current standard of care, examining uptake and costs (Burkina Faso, Ethiopia, Mali, Niger, Senegal, Sudan, Tanzania) Multi-centre individual randomized controlled trial Sudan, Kenya Tanzania, Ethiopia, Cameroon, Burkina Faso, Uganda, Kenya
10K Queen Elizabeth Diamond Jubilee Trust / DFID? 75K HKI’s USAID MMDP grant 75K (proposal submitted to COR-NTD to evaluate use of microfinance groups in Tanzania) 75K (HKI’s USAID MMDP grant).
KCCO (Courtright)
Wake Forest (Gower) / LSHTM (Burton) / Emory (Haddad)
1. Rajak et al, PLoS Med 2011 2. Habtamu et al, PLoS NTD 2015
KCCO (Courtright) LSHTM (Burton) / Emory (Haddad) / KCCO (Courtright) / Wake Forest (Gower)
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Activities for objective A5: To develop, and make accessible, quality-assured systems for measuring the prevalence of ocular CT infection, and of circulating anti-CT antibodies, for the purposes of research at programmatic scale Relevant previous and ongoing work There is an extensive literature on assessing ocular CT infection in trachoma, and multiple commercially-available assays. Suggested approach (potential locations) Train laboratory personnel in CT PCR in at least one laboratory in each WHO region for research and programme purposes. Produce manuals on the use of het Cepheid GeneXpert Tentative cost (USD), possible funders Dana Center has existing funds for and extensive experience in certifying laboratories for CT detection Cepheid has agreed to donate 12 GeneXpert II units (commercial value 500K) 101K in FY15; 150K in FY16 (Primarily funded through an interagency agreement between USAID and CDC). Nominated lead(s) to develop proposal Dana Center (Gaydos/West) and Emory (Emerson)
Activity 1. Assure the reliability and validity of regional systems for measuring the prevalence of ocular CT infection
2. Develop, and make accessible, quality-assured systems for measuring the prevalence of circulating antiCT antibodies
1. Goodhew et al, PLoS NTDs 2012 2. Liu et al, PLoS NTDs 2013 3. Goodhew et al, BMC Infect Diseases 2014 4. Martin et al, PLoS NTDs 2015
Develop kits, with appropriate instructions, to enable laboratories to undertake ELISA or beadbased immunoassays for anti-CT antibodies, as well as a system of international quality assurance.
CDC (Martin)
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Activities for objective B: To plan and undertake capacity building and training initiatives to support trachoma elimination programmes Relevant previous and ongoing work Ad-hoc Suggested approach (potential locations) Electronic survey Tentative cost (USD), possible funders 10K (ITI) Nominated lead(s) to develop proposal KCCO (Courtright) / WHO (Solomon)
Activity 1. Undertake a capacity assessment in all trachoma endemic countries to determine capacity building needs 2. Make mannequin-based TT surgery training available to national programmes
HEAD-START
Training
150-1000K depending on scope; 500K used for the purposes of providing summary calculations on this report HKI’s USAID MMDP grant? 75K (HKI’s USAID MMDP grant) 157K Proposal being discussed with Queen Elizabeth Diamond Jubilee Trust
Wake Forest (Gower) / Dana Center (Merbs)
3. Build the capacity of national programmes to undertake routine audit of TT surgery outcomes 4. Build knowledge, understanding and practical skills relevant to trachoma elimination amongst districtlevel trachoma, prevention of blindness, and neglected tropical disease programme
Limited. The Mali programme presented results of a pilot audit to the 2016 meeting of the Alliance for GET2020. WHO Neglected Tropical Diseases Programme Managers’ Training Course
Develop and introduce a training manual for audit, with oversight included as part of supervision activities Massive Open Online Course offered on the FutureLearn or Moodle platforms
Emory (Haddad)
LSHTM (Burton/Patel)
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managers 5. Build understanding of and skills in leadership amongst national trachoma programme managers 6. Provide members of the Alliance for the Global Elimination of Trachoma by 2020 with periodic updates on research findings of immediate relevance to programmes
KCCO leadership training course, Cape Town, April 2015 Trachoma Information Service, currently in abeyance
3 x small group, face-to-face courses Revive the Trachoma Information Service
75K (ITI)
KCCO (Courtright)
3K (ITI)
KCCO (Courtright)
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Activities for objective C: To collaborate in the collection, collation and dissemination of information about trachoma elimination and reference substances relevant to trachoma elimination programmes Relevant previous and ongoing work First edition Suggested approach (potential locations) Coordinate a group to undertake the revision Tentative cost (USD), possible funders 7K required for printing and distribution can be met by WHO 90K (Sightsavers + HKI’s USAID MMDP grant) 20K Nominated lead(s) to develop proposal WHO (Solomon)
Activity 1. Draft, circulate and coordinate revisions to “Trachoma control: a guide for programme managers” to produce a second, updated edition 2. Convene the second global scientific meeting on trichiasis 3. Refine the standard operating procedures on where to map and where not to map for trachoma 4. Bank conjunctival swabs for CT whole genome sequencing by the Wellcome Trust Sanger Centre
First global scientific meeting on trichiasis, Moshi, January 2012 Current standard operating procedures developed by WHO/GTMP Harris et al, Nat Genetics 2012
Plan for Cape Town, November 2015 Test the current standard operating procedures in Latin America Opportunistic collection of conjunctival swabs from individuals with signs of active trachoma seen in surveys or research projects. Joint database
KCCO (Courtright) / Wake Forest (Gower) Dana Center (West) / WHO (Solomon) LSHTM (Thomson) / Dana Center (Quinn)
Incremental cost to collect swabs is small Cost of sequencing supported by the Wellcome Trust Cost for vector and antigen storage is minimal
5. Maintain a library of validated antigens for use in anti-CT antibody studies
1. Lu et al, Invest Ophthalmol Vis Sci 2012 2. Goodhew et al, PLoS NTDs 2012 3. Martin et al, PLoS NTDs 2015
Joint database of antigens and constructs available
CDC (Martin) / LSHTM (Holland)
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Activities for objective D: To help standardize the use of terminology and data about trachoma Relevant previous and ongoing work None Suggested approach (potential locations) Once agreed, the list will be maintained on the WHO trachoma website, and periodically updated as needed Use and encourage the use of preferred terms and abbreviations relating to trachoma, and the latest data on trachoma prevalence and implementation activities, in all WHOCC outputs (and in the course of peer review). Tentative cost (USD), possible funders Negligible Nominated lead(s) to develop proposal LSHTM (Harding-Esch)
Activity 1. Draft, circulate and coordinate revisions to a standard list of preferred terms and abbreviations relating to trachoma 2. Use and encourage the use of preferred terms and abbreviations relating to trachoma, and the latest data on trachoma prevalence and implementation activities, in all outputs.
None
Negligible
All
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Activities for objective E: To coordinate efforts towards research and development; capacity building and training; collection, collation and dissemination of information and reference substances; and standardized use of terminology and data. Relevant previous and ongoing work Ad-hoc Suggested approach (potential locations) Appoint an academic with experience in trachoma, at lecturer or senior lecturer level, to coordinate activities of the network, and take the lead on some activities. Email, phone calls and teleconferences as required, plus face-to-face meetings on an annual basis in conjunction with the meeting of the Alliance for GET2020. Tentative cost (USD), possible funders 630K over four years Nominated lead(s) to develop proposal LSHTM (Mabey)
Activity 1. Coordinate efforts towards research and development; capacity building and training; collection, collation and dissemination of information and reference substances; and standardized use of terminology and data.
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Annex 1: Inception meeting participants Name Steve Ault Robin Bailey Kelly Callahan Paul Courtright Paul Emerson Matt Freeman Huub Gelderblom Danny Haddad Martin Holland PJ Hooper Jeremy Keenan Diana Martin Beatriz Muñoz Martha Saboya Anthony Solomon Affiliation WHO/PAHO LSHTM Emory KCCO Emory Emory Emory Emory LSHTM Emory UCSF CDC Dana Center WHO/PAHO WHO/HQ Contact email aultstev@who.int robin.bailey@lshtm.ac.uk ecallah@emory.edu pcourtright@kcco.net pemerson@taskforce.org mcfreem@emory.edu hgelderblom@taskforce.org dhaddad@emory.edu martin.holland@lshtm.ac.uk phooper@taskforce.org jeremy.keenan@ucsf.edu hzx3@cdc.gov bmunoz@jhmi.edu saboyama@who.int solomona@who.int
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Annex 2: Inception meeting agenda Thursday, 19 February 2015 Time 08:30 – 09:00 09:00 – 09:30 Topic Breakfast Welcome and introductions Purpose, outcome and outputs of meeting Adoption of agenda How we will work Administrative matters Introduction to WHO Collaborating Centres Vision, aim and objectives of the Network of WHOCCs for Trachoma Group photograph, coffee Discussion of potential functions of the Network 1. collection, collation and dissemination of information; 2. standardization of terminology and nomenclature, of technology, of diagnostic, therapeutic and prophylactic substances, and of methods and procedures; 3. development and application of appropriate technology; 4. provision of reference substances and other services; 5. participation in collaborative research developed under the Organization's leadership, including the planning, conduct, monitoring and evaluation of research, as well as promotion of the application of the results of research; 6. training, including research training; 7. the coordination of activities carried out by several institutions; 8. capacity-building work at country level; 9. provision of monitoring, preparedness and response services to deal with disease outbreaks and public health emergencies. Revisit aim and objectives Lunch What other institutions should we be looking to involve? Research priorities Coffee Development of proposals for specific activities Speakers Anthony Solomon
09:30 – 10:30 10:30 – 11:00 11:00 – 12:00
Kim Jensen Beatriz Muñoz Anthony Solomon All All
12:00 – 12:30 12:30 – 13:30 13:30 – 15:00 15:00 – 15:30 15:30 – 17:00
All All All All
Friday, 20 February 2015 Time 08:30 – 09:00 09:00 – 10:30 10:30 – 11:00 11:00 – 12:30 12:30 – 13:30 13:30 – 15:00 15:00 – 15:30 15:30 – 16:30 16:30 – 17:00 Topic Breakfast Discussion of proposals Coffee Further development of proposals for specific activities Lunch Further development of proposals for specific activities Coffee Terms of reference and work plan for each WHOCC Next steps, meeting feedback and close Speakers All All All All All
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