Intervention and Implementation Research

Annual Report 2016

Intervention and Implementation Research

IIR Annual Report 2016

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TDR/IIR/17.1

Copyright © World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases 2017

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Table of contents

Acronyms list ............................................................................................................................ 5

Introduction ............................................................................................................................. 7

Objectives................................................................................................................................. 8

Key achievements in 2016 ....................................................................................................... 8

Progress in 2016 and planned future activities ....................................................................... 9

Objective 1: Facilitate Innovation ................................................................................................... 12 Expected result 1.1.5: Facilitate innovation to generate tools to achieve control programme objectives ................................................................................................................................................... 12

Objective 2: Sustain effectiveness of available interventions ........................................................ 14 Expected result 1.1.4: Vulnerability of preventive chemotherapy programmes for helminths to emergence of resistance ............................................................................................................................ 14 Expected result 1.1.9: Strategies for early detection of resistance where Seasonal Malaria Chemoprevention (SMC) is deployed ......................................................................................................... 18

Objective 3: Strengthen evidence base .......................................................................................... 19 Expected result 1.1.7: maximize the utility of available data for policy decisions and programme implementation.......................................................................................................................................... 19 Expected result 1.1.8: Optimize acquisition and analysis of new safety data for policy decisions and programme implementation ...................................................................................................................... 22

Objective 4: Optimize implementation of public health programmes ........................................... 26 Expected result 1.1.1: Support adequate country response to epidemic challenges: evidence-based guidance for ARBOVIRUS outbreak detection and response ..................................................................... 26 Expected result 1.2.1: Intervention and implementation research to inform policies for the elimination of visceral leishmaniasis (VL) in the Indian subcontinent (Bangladesh, India and Nepal) ...... 29 Expected result 1.2.2: Community-based scheduled screening and treatment of malaria in pregnancy for improved maternal and infant health (COSMIC) ................................................................ 31 Expected result 1.2.3: Research in support of control programmes: Improved management of febrile illnesses ........................................................................................................................................... 32 Expected result 1.2.4: Structured Operational Research and training initiative (SORT IT) ........................ 33 Expected result 1.2.6: Research in support of control programmes: improved TB control in line with GTB strategy .............................................................................................................................................. 35 Expected result 1.2.7: Research in support of elimination programmes: onchocerciasis elimination ....... 37 Expected result 1.2.5: translating new and traditional knowledge into healthy environmentally sustainable housing for poor communities ................................................................................................ 39


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OTHER PROJECTS: Piloting new research capacity strengthening schemes ................................... 40 1. Modelling research fellowships to build capacity for modelling in LMICs ............................................. 40 2. Accelerating research-to-policy and research-to-Implementation transition ........................................ 40 3. Clinical REsearch During Outbreaks (CREDO) training curriculum: generating clinical evidence during outbreaks in LMICs ......................................................................................................................... 42 4. Title: Development of a good data management practices (GCDMP) training course .......................... 43

IIR budget and financial implementation .............................................................................. 44

Funding by project ................................................................................................................. 46

2018-19 outlook within the proposed 2018-2023 TDR strategy ........................................... 57

TDR funding in 2016 ............................................................................................................... 60


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Acronyms list ADP Access and Delivery Partnership aDSM Active tuberculosis drug-safety monitoring and management AFRO WHO Regional Office for African Region AMRO/PAHO WHO Regional Office for the Americas APOC African Programme for Onchocerciasis Control AQ-SP Amodiaquine and sulphadoxine/pyrimethamine BMGF Bill and Melinda Gates Foundation CDTI Community-Directed Treatment with Ivermectin CL Cutaneous Leishmaniasis C-Path Critical Path Institute CREDO Clinical REsearch During Outbreaks DENFREE Dengue research Framework for Resisting Epidemics in Europe DNDi Drugs for Neglected Diseases initiative DWL Durable wall lining EC Ethics Committee EMRO WHO Regional Office for Eastern Mediterranean Region ER Expected Result ERC Ethics Review Committee EURO WHO Regional Office for European Region EVIPNet WHO-led Evidence Informed Policy Network EWARS Early Warning and Response System GCP Good Clinical Research Practices GF Global Fund GRADE Grading Recommendations Assessment, Development and Evaluation GTB WHO Global Tuberculosis Programme HERG Health Experiences Research Group (Oxford University) IDAMS International Research Consortium on Dengue Risk Assessment,

Management and Surveillance IIR TDR unit on Vectors, Environment and Society IR Implementation Research IRD Institut pour la Recherche et le Développment (France) IRS Indoor residual spraying ISC Indian subcontinent countries ITC Insecticide-treated curtains ITN Insecticide-treated bednets IWP Insecticidal wall painting JCB Joint Coordinating Board of TDR LF Lymphatic Filariasis LIH Luxembourg Institute of Health LLIN Long-lasting insecticidal nets LMIC Low- and Middle-Income Country


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LSTMH London School of Hygiene and Tropical Medicine KPI Key performance indicators MDA Mass Drug Administration MDGH Medicines Development for Global Health MDR-TB Multidrug-resistant tuberculosis M&E Monitoring and Evaluation NMP National Malaria Programmes MPMP Malaria Parasite Metabolic Pathways MoH Ministry of Health MoU Memorandum of Understanding NGO Non-Governmental Organization NTD Neglected Tropical Diseases NWCL New-world Cutaneous Leishmaniasis OR Operational Research OWCL Old-world Cutaneous Leishmaniasis PHE Public Health, Environmental and Social Determinants of Health PI Principal Investigator PV Pharmacovigilance R&D Research and Development RCS-KM TDR unit on Research Capacity Strengthening – Knowledge Management SDF TDR Strategic Development Funds SDG Sustainable Development Goals SMC Seasonal Malaria Chemoprevention SORT IT Structured Operational Research and Training Initiative STH Soil Transmitted Helminth SWG Scientific Working Group TB Tuberculosis TB-PACTS TB-Platform for Aggregation of Clinical TB Studies TDR Special Programme for Research and Training on Tropical Diseases UN United Nations UNDP United Nations Development Programme VES TDR unit on Vectors, Environment and Society VL Visceral Leishmaniasis WAHO West African Health Organization WARN TB West-African Regional Network for TB control WHO World Health Organization


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Introduction The Intervention and Implementation Research (IIR) unit endeavours to cover areas of research addressing some of the critical obstacles to achieving the Sustainable Development Goals (SDG) for health. This report summarises the IIR workplan, achievements and future plans with respect to four main questions:

1. What new tools are critically needed to improve disease control and possibly achieve elimination? This covers how to provide a directional perspective to new developments so that they generate the health solutions that disease-endemic countries need; and how TDR, through its convening power and its special positioning and close links with both research and disease control, helps promote innovation to generate more adapted health solutions. These requirements have been exposed by the recent succession of outbreaks.

2. How can the current medicines be protected? Available effective interventions are few, and some diseases rely on a single drug for control, prevention and treatment. Antimicrobial resistance is now a general concern worldwide, at all levels of country development. IIR’s current focus is on drugs used for mass drug administration, in particular for preventive chemotherapy for helminthiases, but the approach can be expanded to other diseases and drug classes.

3. How best can informed recommendations and policy decisions be made on the use of available health interventions? The evidence base for a number of recommendations is weak due to a combination of insufficient research, insufficient standardisation of research methodologies and insufficient level of analysis of research results. Correcting these shortcomings is of paramount importance, and is expected to translate into a more efficient use of resources and more informed directions for both research and disease control. TDR’s recognised convening power is applied to broker agreements across a range of stakeholders towards optimising the use of available data for sharing and analysis.

4. How can proven interventions be effectively deployed and adapted to achieve disease control and elimination objectives, while building sustainable in-country capacity? A number of approaches are used, such as supporting defined programme objectives (e.g. the elimination of visceral leishmaniasis in the Indian subcontinent; sub-regional initiatives to achieve the objectives of the endTB strategy; outbreak preparedness for dengue and other arboviruses); and creating in-country capacity for operational and implementation research.


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Objectives The workplan of the intervention and implementation research (IIR) unit covers the following four objectives:

1. Facilitate innovation 2. Sustain effectiveness of available interventions 3. Strengthen the evidence base for policy decisions 4. Optimize implementation of available interventions

Research capacity strengthening is an integral part of the workplan, and new capacity building schemes are being piloted. The above-mentioned objectives are being implemented through 13 expected results developed in coordination with the Scientific Working Group.

Key achievements in 2016

• Preparedness for early identification and response to dengue outbreaks: A ‘Model Contingency Plan’ was developed and published, which will be further supported by a ‘How-to Guide’ for an Early Warning System for Dengue Outbreaks to help countries survey dengue and get ready for impending outbreaks. These achievements have allowed devising a plan towards a wider approach that encompasses response to Aedes-borne arboviral diseases, including Zika and chikungunya.

• Visceral leishmaniasis elimination in the Indian Subcontinent: TDR-supported research has been instrumental in helping Nepal and Bangladesh reach the elimination target. A systematic review of current knowledge of transmission dynamics and how they affect


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disease elimination was published, which should inform new lines of attack and modelling studies for maintaining the achievements and sustaining elimination.

• Enhanced country research capacity to support the EndTB strategy: The newly-established West-African Regional Network for TB control (WARN TB) comprising 16 countries has identified TB control gaps and research priorities at the country and sub-regional level, which are currently being addressed through implementation research projects.

• Safety first: TDR brings safety to the fore as an essential element of evidence-based decision-making. Two initiatives were launched ̶ one for countries to share safety data on drug exposures during pregnancy (in collaboration with WHO HIV/AIDS Programme) and another on novel treatments for multidrug resistant TB (in collaboration with the WHO Global TB Programme). These will generate evidence of drug safety in routine use that is needed to support treatment guidelines.

• Expanded data sharing: TDR has put into practice the WHO recommendation on more open forms of data sharing. Scientists now have access to TB clinical trial data from three studies through a multiple partner agreement. This should open up new possibilities for expanded research into this growing disease threat. Two databases of schistosomiasis and soil-transmitted helminths trials were also established and analysed.

• Increased capacity for operational research (OR) in public health programmes and expanded access for women: The well-established TDR-led Structured Operational Research and Training Initiative (SORT IT) programmes are for the first time being led and implemented by those in the countries where the research is being conducted. SORT IT has a strong network of trainers in low- and middle-income countries who are helping each other out. The programme has also been included as a component of the new WHO Action Plan to Strengthen the Use of Evidence, Information and Research for Policymaking in the European Region. Women make up 45% of the participants.

Progress in 2016 and planned future activities IIR workplan overall progress

Expected results and deliverables by outcome Indicators and targets

Facilitated innovation: Knowledge of specific gaps, needs, opportunities, potential approaches applied by partners

By 2019, at least 75% of tools, solutions or new knowledge generated are adopted by countries On track

1.1.5. Facilitate innovation to generate tools to achieve control programme objectives: i) open-source and open-access approaches in research promoted and facilitated; ii) optimised methodologies to assess the effects of interventions for NTDs; iii) R&D projects conducted by other organizations facilitated; iv) updated target product profiles for interventions

By 2017, at least one open-access approach and one improved and optimised methodology developed On track


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Sustained intervention effectiveness: Informed disease control decisions based on new knowledge on risk of resistance and options for response applied in countries

By 2019, at least 75% of tools, solutions or new knowledge generated are adopted by countries On track

1.1.4. Vulnerability of preventive chemotherapy programmes for helminths to emergence of resistance: i) genetic markers of response of O. volvulus to ivermectin identified; ii) models of transmission of parasites with low level of response to drugs; iii) quantitated variability of response of parasites to the drugs

By 2017, report on models of transmission of parasites with low level of response to drugs submitted to the scientific working group and disease control stakeholders On track

1.1.9. Strategies for surveillance/early detection of malaria drug resistance in seasonal malaria chemoprevention areas: i) evidence on the cost-effectiveness of various approaches for surveillance/ early detection of drug resistance; ii) estimation of the prevalence of drug resistance; iii) estimation of the impact of seasonal malaria control on parasite susceptibility

By 2017, surveys are completed in three countries and data are available to estimate the impact of seasonal malaria control on parasite susceptibility On track

Strengthened evidence base for policy: WHO and country normative guidance based on improved evidence on drug safety

By 2019, at least 75% of concerned countries adopting the new knowledge On track

1.1.7. Maximize utility of available data for policy decision and programme implementation: i) systematic review and meta-analyses; ii) databases across existing clinical trials generated analysed; iii) disseminate IIR results and scoping needs; iv) response to control programme needs

By 2017, at least two databases across existing clinical trials generated analysed On track

1.1.8. Optimize acquisition and analysis of new safety data for policy decision and programme implementation: i) capacity for safety monitoring of new drugs built in target countries ii) Improved evidence of drug toxicity in specific patient groups; iii) Innovative approaches for safety monitoring piloted

By 2016, at least one database related to drug exposure obtained and analysed, in collaboration with control programmes and other WHO departments Two databases in place.

Optimized interventions in support of control programmes: countries have enhanced capacity for operational research in their disease control programmes and are translating optimized tools into policy and practice

By 2019, at least 75% of tools, solutions and new knowledge generated are adopted by countries On track

1.1.1. Research in support of control programmes: arbovirus outbreak response : i) evidence-based guideline for dengue outbreak response; ii) consensus agreement of major stakeholders on guidelines; iii) validated early outbreak alert tools and strategy for dengue and Chikungunya outbreak detection and response

By 2017, new computer assisted alert tool developed, tested and discussed with stakeholders On track


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1.2.1. Research in support of elimination programmes: visceral leishmaniasis elimination in the Indian subcontinent: i) cost-effective strategies for case detection, management and vector control adapted to changing epidemiological patterns; ii) simplified monitoring and evaluation (M&E) toolkit for vector control developed and tested in selected districts

By 2018, studies comparing the effectiveness of different strategies in reduction of VL cases completed On track

1.2.3. Research in support of control programmes: improved management of febrile illnesses: evidence for antibiotics management of severe infection and febrile illnesses in young infants

By 2017, evidence provided on pathogens involved in severe infection in young African infants On track

1.2.5. Translating new and traditional knowledge into healthy, environmentally-sustainable housing: i) lessons learnt from first pilot area disseminated; ii) strategic framework and methodology for translating traditional and new international and local knowledge into healthy environmentally sustainable housing options

By 2017, project initiated Project put on hold

1.2.6. Research in support of control programmes: TB control in line with GTB control strategy: i) strengthened regional network of West African national tuberculosis programmes; ii) five-year capacity building plan; iii) results of implementation research that address TB research priorities; iv) cost-effective TB screening algorithms for subjects with co-infection

By 2017, a five-year capacity building plan is defined and capacity building activities of the first two years of this plan (2016-2017) have been implemented On track

1.2.7. Research in support of elimination programmes: onchocerciasis elimination onchocerciasis: i) genetic markers suitable for inclusion in a 'Rapid Diagnostic Test' format identified; ii) prototype 'Rapid Diagnostic Test' available for piloting by onchocerciasis control programmes

By 2017, report provided on the identification of genetic markers suitable for inclusion in a ‘Rapid Diagnostic Test’ format On track

1.2.4. Structured Operational Research and Training Initiative (SORT IT): i) more evidence into policy and practice; ii) expanded range of public health issues and diseases addressed by SORT IT programmes; iii) increased complexity of operational research undertaken with appropriate integrated training; iv) expanded partnership base

In 2016-2017, conducting at least twice as many SORT IT programmes as in 2014-2015 On track

1.2.2. Strategies to accelerate research to policy translation (COSMIC): i) plans for policy and practice change developed for each country; ii) scientific and policy information on project disseminated internationally; iii) report on impact of policy panels

By 2017, impact report produced On track


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Objective 1: Facilitate Innovation

EXPECTED RESULT 1.1.5: FACILITATE INNOVATION TO GENERATE TOOLS TO ACHIEVE CONTROL PROGRAMME OBJECTIVES

TDR, through its convening power and expertise, provides a directional perspective and adapted methodologies for the development and assessment of new interventions and tools to achieve program objectives for poverty related diseases.

Progress in 2016

Moxidectin for onchocerciasis control. Following transition of moxidectin to Medicines Development for Global Health (MDGH), IIR provided clarification of project implementation required for preparation of the registration dossier by MDGH. Standardised trials for cutaneous leishmaniasis (CL): researcher and patient perspectives. TDR, jointly with DNDi and WHO/NTD, are working towards standardising methodologies of clinical trials for CL. Today we have few treatment options for the different forms of CL and little confidence that they work. Deficiencies and inconsistencies in the design of clinical trials for treating CL have made it difficult to construct evidence-based treatment guidelines which address the needs of the affected populations. To correct this, we need not only to step up investments in R&D but also to promote improved standardized methodologies to assess treatment effects. • Stakeholder meetings were organized at the TDR training centre in Tunis gathering clinical

researchers in old-world CL (OWCL; 7 countries, 10 trial sites from the AFR, EMR and EUR regions), and in Brazil with members of the RedLeish group on new-world CL (NWCL; 7 countries, 11 trial sites from the AMR/PAHO region). Standardised clinical trial methods were discussed and agreed upon via a collaborative agreement-seeking process based on a guidance paper (Olliaro et al, PLoS NTD, 2013) with special focus on core eligibility criteria and outcome measures. The agreement reached allows standardisation of future clinical research across OWCL and NWCL sites. Adopting common standards is expected to optimize research outcomes and use of resources. The expertise present between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL.

• In addition, patient interviews at 8 sites representative of OWCL (Burkina-Faso, Iran, Morocco, Tunisia) and NWCL (Brazil, Colombia 2 sites, Peru) have taken place (67 completed, 9 awaited). Analyses are underway. This is an innovative approach, for several reasons: (i) mid-career investigators in LMICs trained in qualitative and mix-method research; (ii) patients perspective investigated in order for it to be taken into consideration when designing trials (desired outcomes) and products (desired product characteristics).

Technical advice for R&D projects was provided for a Loa loa diagnostic (Drugs and Diagnostics for Tropical Diseases), a new drug for onchocerciasis (Drugs for Neglected Diseases Initiative), the paediatric praziquantel consortium, as well as in consultations on research facilitation and strategies for different products organized by different WHO departments.


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Malaria genome data sharing. TDR has provided support to a functional genomics database, Malaria Parasite Metabolic Pathways (MPMP: http://mpmp.huji.ac.il/) which aims at assisting knowledge-guided discovery and development of new drug candidates in malaria. TDR has supported the continuous update of the MPMP data, development of new features as well as automation of many tasks to improve its functioning. Plasmodium vivax biology. As part of the WHO plan for the control and elimination of Plasmodium vivax malaria (http://apps.who.int/iris/bitstream/10665/181162/1/9789241509244_eng.pdf), TDR has coordinated, on behalf of WHO/GMP, the work of an international panel of experts to summarise the specificities of the biology of P. vivax with respect to P. falciparum (explaining why P. vivax-tailored interventions are required), as well as the knowledge gaps where investments in research are needed to help identify and develop such specific interventions (Olliaro et al, AJTMH, 2016).

Plans for 2017

• Moxidectin for onchocerciasis control. Technical/scientific input into the registration dossier and community studies upon request by MDGH.

• CL standardised methods. Results will be presented at the WorldLeish 6 congress in May 2017 (5 abstracts submitted; one plenary presentation invited). Various papers in preparation or planned. Pooled analyses of patient interviews will be completed by 1Q17, individual site analyses by 3Q17.

• Continued involvement in optimising research methods and facilitating research during outbreaks in low- and middle-income countries.

• Continue provision of directional perspective and adapted methodologies for the development and assessment of new interventions and tools to achieve program objectives for poverty related diseases to stakeholders within and outside WHO.

Leverage created from this project: DNDi provides in-kind and financial support (country projects, networks, meetings)

Gender balance: CL patient interview project: 4 women, 4 men investigators.

Publications: Moxidectin phase 3 trial final results: Opoku et al, submitted

Olliaro PL, Barnwell JW, Barry A, Mendis K, Mueller I, Reeder JC, Shanks GD, Snounou G, Wongsrichanalai C. Implications of Plasmodium vivax Biology for Control, Elimination, and Research. Am J Trop Med Hyg. 2016 Dec 28;95(6Suppl):4-14.

Training: CL patient interview project: 8 investigators trained at HERG, Oxford University, on mixed-method and qualitative research (two one-week workshops)

Related news: Malaria Parasite Metabolic Pathways: http://mpmp.huji.ac.il/

http://apps.who.int/iris/bitstream/10665/181162/1/9789241509244_eng.pdf


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Objective 2: Sustain effectiveness of available interventions

Tropical disease control and elimination programmes are vulnerable to the emergence of parasite resistance to the drugs used to control or eliminate them, especially when only a single drug or drug combination is available. For the programmes to have the data they need to plan for and implement appropriate strategies in response to emerging resistance, research is needed on:

i. The probability and expected time frame of resistance emerging and spreading within and across geographical areas;

ii. The impact of emerging resistance on control programme objectives; iii. Options for reducing the probability of emergence of resistance; iv. Strategies to detect emerging resistance; v. Strategies for mitigating the impact of emerging resistance including both currently

available and potential new tools and strategies.

TDR is addressing these needs in two different ERs:

1. ER 1.1.4: Vulnerability of preventive chemotherapy programmes for helminths to emergence of resistance

2. ER 1.1.9: Strategies for early detection of resistance where Seasonal Malaria Chemoprevention (SMC) is deployed

EXPECTED RESULT 1.1.4: VULNERABILITY OF PREVENTIVE CHEMOTHERAPY PROGRAMMES FOR HELMINTHS TO EMERGENCE OF RESISTANCE

This South-South-North synergistic research programme will provide a reference point for detecting changes in helminth susceptibility to preventive chemotherapy during mass drug administration. It will generate models to estimate how fast resistant parasites would spread under current and alternate control strategies for onchocerciasis, lymphatic filariasis, soil-transmitted helminths and schistosomiasis. It will also assess whether genetic markers of O. volvulus response to ivermectin can replace current invasive methods used to measure treatment effects. Helminths infecting humans cannot be cultured and subjected to drug pressure to identify mutations reducing drug susceptibility, unlike, for instance, bacteria. Knowledge from the veterinary field is transferrable only to a limited extent. Consequently, helminth control and elimination programmes have no methods or strategies for large-scale monitoring of potential changes in drug susceptibility; we do not know if and when resistance could emerge under current control and potential alternative strategies are unknown. Research supported by TDR has shown that the currently used methods for characterising drug response on a population basis are unsuitable for measuring changes in drug susceptibility and may be either generate unjustified concerns or fail to identify diminishing drug efficacy. One reason is that they do not take into account inter-individual variability of response. Knowledge of this variability before or early on during mass drug administration (MDA) is, however, needed as a reference point for assessing any changes in drug susceptibility patterns during long term MDA.


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Should drug susceptibility diminish over time, programmes need transmission models which take into account such variability in drug susceptibility and allow modelling of the spread of low-susceptibility/resistant parasites, their impact on control or elimination objectives and the potential of alternative control strategies to reduce the spread and impact of these parasite populations. Current models do not take into account genetically determined differences in drug susceptibility. Concern about diminishing susceptibility of O. volvulus to ivermectin was first raised in Ghana and subsequently in Cameroon. The fact that drug susceptibility quantitation is currently based on multiple skin snips (before and after ivermectin administration) or nodulectomies limits the extent to which the prevalence of low response to ivermectin and changes with duration of ivermectin MDA can be assessed. Researchers in Australia, Burkina Faso, Cameroon, Canada, France and Ghana are collaborating to identify potential genetic markers of response to ivermectin. The work builds on that initiated in collaboration with the African Programme for Onchocerciasis Control in previous years. The field work as well as the genotyping conducted contribute to ER 1.2.7 (Research in support of elimination programmes: Onchocerciasis elimination).

1. Variability of response of parasites to the drugs used to control their transmission and morbidity before or early on during mass drug administration

Progress in 2016

Systematic literature searches to identify studies providing response data before or early on during mass drug administration were completed for STH and schistosomiasis. Individual participant data bases have been established for these helminths. A modelling framework incorporating the effects of demographic and geographic covariates and imprecise diagnostics on estimated anthelmintic drug responses was generated. Remaining challenges: None anticipated

Plans for 2017

Databases will be established for onchocerciasis and lymphatic filariasis. The analyses of these data bases as well as of those for STH and schistosomiasis to quantify the variability of drug response including by demographic strata and geographic origin will be completed. Dissemination of results will continue. Leverage created from this project: NA

Gender balance: PI is a man, Co-PI is a woman

Publications: • Crellen T, Walker M, Lamberton PHL, Kabatereine NB, Tukahebwa EM, Cotten JA, Webster JP.

Reduced efficacy of praziquantel against Schistosoma mansoni is associated with multiple rounds of mass drug administration. Clin Infect Dis 63: 1151-1159.

• Frempong KK, Walker M, Cheke RA, Tetevi EJ, Gyan ET, Owusu EO, Wilson MD, Boakye DA, Taylor MJ, Biritwum NK, Osei-Atweneboana M, Basáñez, MG. Does increasing


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treatment frequency address sub-optimal responses to ivermectin for the control and elimination of river blindness? Clin Infect Dis 2016; 62: 1338-1347.

• Julé AM, Vaillant M, Lang TA, Guérin PJ, Olliaro PL. The Schistosomiasis Clinical Trials Landscape: A Systematic Review of Antischistosomal Treatment Efficacy Studies and a Case for Sharing Individual Participant-Level Data (IPD). PLoS Negl Trop Dis. 2016 Jun 27;10(6):e0004784.

• Walker M, Mabud TS, Olliaro PL, Coulibaly JT, King CH, Raso G, Scherrer AU, Stothard JR, Sousa-Figueiredo JC, Stete K, Utzinger J, Basáñez MG. New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel. Parasites & Vectors 2016; 9:41.

• Zwang J and Olliaro P. Efficacy and safety of praziquantel 40 mg/kg in preschool-aged and school-aged children, a meta-analysis. Parasites & Vectors, in press

Training: N/A

2. Development of parasite transmission models which take into account genetically determined differences in parasite drug susceptibility.

Current parasite transmission models do not take into account genetically determined differences in parasite drug susceptibility. The models being developed would allow modelling the long-term effects of the presence of such parasites on the ability of control and elimination programmes to achieve their objectives and the effects of alternative control strategies.

Progress in 2016

A WHO/TDR facilitated meeting brought together modelling expertise of both groups which had received grants for this work with the population genetic expertise of one of the groups funded under 3. below. On this basis a novel conceptual model for helminth drug resistance as a quantitative trait was developed that can be adapted to different helminths. It has been applied to date to ascariasis, hookworm infection and onchocerciasis to cover different types of drug effects and life spans. The model for STH (ascariasis and hookworm) was presented at the annual meeting of the American Society for Tropical Medicine and Hygiene (ASTMH) in Atlanta, Georgia, USA (October 2016). The approach, methods, and results were received with great interest, leading to several citations on Twitter, and also interest from the veterinary field. Remaining challenges: Validation of the models

Plans for 2017

Expansion of model to schistosomiasis and LF. Dissemination of results. Leverage created from this project: 0

Gender balance: 2 men PIs

Publications: 0

Training: N/A


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3. Genetic markers of response of O. volvulus to ivermectin suitable for monitoring O. volvulus susceptibility in parasites present in the blackfly vector.

Progress in 2016

Results to date suggest that ivermectin susceptibility is a polygenically-determined quantitative trait. The extent of response of O. volvulus to ivermectin is likely determined by identical or related molecular pathways, not individual genes. In both Ghana and Cameroon, field studies have been conducted in areas under long-term Community Directed Treatment with Ivermectin (CDTI) to obtain parasite samples for validating the potential genetic markers of response to ivermectin identified previously. These studies are also providing additional data on the prevalence of infection in these areas. The Cameroonian study has been completed while the study in Ghana is still ongoing - delayed because of the relative timing of CDTI and Ethics Committee approval. Remaining challenges: Validation of the models

Plans for 2017

• Validation of potential markers using samples obtained previously and during the ongoing field studies for validation of the potential markers identified to date.

• TDR will collaborate with current investigators on applications for funding that can complement the funding TDR can provide in the next biennium to continue this work.

Leverage created from this project: Estimated US$ 300 000 plus additional in-kind contributions from the implementing countries (across this project and ER 1.2.7)

Gender balance: All PIs are male. Both PhD students being trained within this project are male.

Publications:

• Doyle, S. R., Armoo, S., Renz, A., Taylor, M. J., Osei-Atweneboana, M. Y. and Grant, W. N. (2016). Discrimination between Onchocerca volvulus and O. ochengi filarial larvae in Simulium damnosum (s.l.) and their distribution throughout central Ghana using a versatile high-resolution speciation assay. Parasites & Vectors, 9: 536

• Submitted: One manuscript with the results of the first part of this project.

Training: One of the two Ghanaian PhD students whose studies were co-funded by this project obtained their doctorate in Australia and has returned to Ghana to lead the laboratory work for this as well as the synergistic project (ER 1.2.7, Research in support of elimination programmes: Onchocerciasis elimination). The second Ghanaian PhD student supported by this project has submitted his thesis.


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EXPECTED RESULT 1.1.9: STRATEGIES FOR EARLY DETECTION OF RESISTANCE WHERE SEASONAL MALARIA CHEMOPREVENTION (SMC) IS DEPLOYED

In 2016, some 18 million children received preventive treatment for malaria during the rainy season in West and Central Africa. This means there is a vast pool of parasites at risk of drug resistance to amodiaquine and sulphadoxine/pyrimethamine (AQ-SP) now and in the future. The research project aims at informing the national malaria programmes of those countries on how best to detect the emergence of this drug resistance in the context of mass drug administration. Following a 2012 WHO recommendation, 13 sub-Saharan Africa countries with highly-seasonal malaria transmission have adopted and integrated seasonal malaria chemoprevention (SMC) in their policy documents and strategic plans. Little is known concerning the risk of drug-resistant parasites being selected and spreading while implementing SMC at a large scale, and which options for cost-effective strategies can be made available to national malaria programmes (NMP) to monitor drug sensitivity. This project, conducted in partnership with NMPs and the LSHTM, compares two surveillance strategies: (i) Drug resistance survey in the general population before and after SMC campaigns; (ii) Monitoring of drug resistance at 32 outpatient sentinel sites. The rationale is that, while the latter might suffer from a selection bias (only malaria cases coming to a clinic are investigated), the proportional change in parasite susceptibility and genetic profiles might generate signals to pinpoint drug resistance early and more cheaply than cross sectional survey sampling across the general population, which, though providing a more unbiased estimation of the prevalence of drug resistance indicators in the general population, is burdened with complex and costly logistics.

Progress in 2016

The study protocol was developed by the National Malaria Programme of Senegal with TDR and LSHTM support. Ethical approval was obtained from the Senegalese National Ethical Committee and the WHO ERC. Pre- and post-SMC surveys were conducted and data from the sentinel sites were collected. Samples were sent to LSHTM for molecular tests to identify resistance markers to SP & AQ. Leverage created from this project: around US$ 100 000

Gender balance: the PI of this project is a man

Publications that have come out of this work: None so far

Number of advanced degrees underway due to this project: None

Remaining challenges: It took more time than expected to perform the molecular tests on the samples shipped to London.

Plans for 2017

Finalise data analysis and communicate the results (written communication but also feedback discussions with the national malaria programme managers of SMC countries).


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Objective 3: Strengthen evidence base

EXPECTED RESULT 1.1.7: MAXIMIZE THE UTILITY OF AVAILABLE DATA FOR POLICY DECISIONS AND PROGRAMME IMPLEMENTATION

TDR promotes, supports and contributes to databases from both research and control programmes to strengthen the evidence base for better informed treatment policy decisions, and identify research gaps. Through its convening power and networks, TDR plays a role as honest broker and guarantor of process integrity, at the crossroad between research, control and policy.

1. TB-PACTS data-sharing platform

The TB-Platform for Aggregation of Clinical TB Studies (TB-PACTS) is a partnership among the institutions providing the data – TDR, the TB Alliance, and St. George’s, University of London, with the platform developed by the Critical Path Institute (C-Path). The platform contains fully anonymised, patient-level data from the REMoxTB, RIFAQUIN, and OFLOTUB clinical trials can be accessed and analyzed in aggregate, or filtered and viewed as individual records. Types of data available include demographic information, concomitant medications information, dose/concentration information, outcomes data, and relevant covariates of interest. The platform is equipped to host data from additional studies in the future. Researchers applying for access must agree to the Terms and Conditions for Use of the TB-PACTS data platform and submit an online application form to request access to the data platform. Web link http://c-path.org/programs/tb-pacts/ for more information.

Progress in 2016

The platform became accessible in April 2016. By December 2016, 28 total requests were received, 21 of which were approved by the steering committee within an average nine days; two were cancelled; four rejected; and one is to-date pending. Explanation for rejection: Two applications canceled by the requester once they learned that the data would not suit their research needs. Four applications were rejected due to insufficient information in the application. The requesters did not respond to attempts to update their application. Explanation for pending: the application was approved by a simple steering committee majority but access is on hold until steering committee member’s concerns are discussed at the next TB-PACTS meeting.

Plans for 2017

Continue and monitor effects.

http://www.tballiance.org/

http://www.sgul.ac.uk/

http://www.c-path.org/

http://c-path.org/programs/tb-pacts/


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2. Helminths data-sharing platform

Progress in 2016

Researchers have contributed approximately 12 000 individual patient records of schistosomiasis and soil-transmitted helminth infections treated with standard medications. These data are currently hosted at the Luxembourg Institute of Health (LIH) and have been shared with the specific purpose of agreed analyses that are taking place at LIH and Imperial College, London. An additional database of praziquantel treatments in preschool-aged children is currently under construction at the LIH upon request by WHO/NTD in order to gather evidence about the efficacy and safety in younger children of the standard praziquantel 40mg/kg dose.

Plans for 2017

Continue and expand. A process has also been started with stakeholders to expand the currently ‘fenced’ database so that it can be accessed by a wider range of researchers.

3. Relationship between microfilaremia, clinical symptoms of filariasis and treatment regimens: analysis of historical data of Loa loa in Gabon

Loiasis (aka African eye worm) is a filariasis caused by the worm Loa loa. Clinically, it can manifest as eye and skin disease (Calabar swelling) which requires treatment, though most infections remain asymptomatic. Adult worms, however, can live in humans for several years and keep generating thousands of microfilariae every day. Loiasis is a concern because subjects dually-infected with Loa loa and Onchocerca could experience serious and even life-threatening adverse events when treated with ivermectin – which is why preventive chemotherapy (PC) cannot be implemented in areas of co-endemicity. However, patients with symptomatic loiasis also need treatment, but no comprehensive data exist on treatment long-term efficacy and safety. For this reason, TDR, in collaboration with the French IRD (Institut pour la Recherche et le Développment) and LIH (Luxembourg Institut of Health), is supporting the Dept of Parasitology & Mycology at the University of Health Sciences in Gabon to strengthen country capacity to collect and analyse loa loa data in order to understand the relationship between microfilaraemia, symptoms and treatment outcome. The initial target is to double-enter 3000 of the 45 000 patient files in their possession – the largest known database on loiasis.

Progress in 2016

All permissions have been obtained and ~1800 files have been entered. Difficulties have been encountered with internet connectivity and civil unrest.

Plans for 2017

• Complete 3000 records and analyse data by 2Q17. • Assess feasibility and desirability of expanding the database.


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4. Systematic review of vector control methods that can be implemented on the household level

In the context of the Housing and Health Guidelines being prepared by WHO/PHE and ER 1.2.5, IIR commissioned a systematic literature review to assess the effectiveness of vector control methods focused on protecting dwellings and its inhabitants against vectors and the diseases potentially transmitted by these vectors, including a gap analysis that can inform future research.

Progress in 2016

The review addressing Chagas disease, dengue, visceral and cutaneous leishmaniasis and lymphatic filariasis was completed and the manuscript has been submitted. Intra-domiciliary residual spraying, use of insecticide-treated materials (especially LLIN and ITCs) and larval habitat treatment with biological and chemical methods emerged as the most effective methods across several diseases. Waste management and/or clean-up campaigns did not produce consistent results. The review concluded that studies examining the effect of a combination of interventions on protecting household members against several diseases are needed to provide further evidence for effective vector control methods, especially in densely populated urban areas. The authors recommend that best practices for the design of randomized and cluster randomized studies (size, timing, outcome parameters, including human disease outcomes) are developed to guide the future studies needed.

Plans for 2017

Dissemination of results.

5. Development of guidance on the use of modelling to support WHO guidelines

Models are used to address different types of questions which are relevant to WHO guidelines when it is impossible or impractical to directly measure outcomes, either under experimental or natural conditions. These include estimate of disease burden; infectious disease dynamics (inter-host and intra-host); non-infectious disease dynamics; impact of interventions on efficacy, effectiveness and harms outcomes; and economic efficiency (cost effectiveness or cost benefit analyses). Modelling is increasingly used to support WHO guidelines. Models played an important role in describing the shape and trajectory of the Ebola outbreak in 2014-15, and in understanding the potential utility and impact of introducing interventions, including novel therapeutics and vaccines. Guideline developers at WHO currently have no guidance on when and how to incorporate modelling into the development of recommendations, including the types of questions which might be addressed with models, when models add value to existing primary studies and data, the limitations of modelling, how to evaluate the quality of a model, how to incorporate a model into the GRADE (Grading Recommendations Assessment, Development and Evaluation) approach for evaluating the quality of a body of evidence, how to integrate the outcomes of models with primary data, and how to present the results of modelling to a guideline development group which is tasked with formulating recommendations based on evidence.


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In 2015, TDR provided funding to the WHO unit in charge of guideline development (HIS/KER/WHP) to prepare guidance for WHO staff and publications that can inform guideline developers in countries.

Progress in 2016

A workshop held in April 2016 brought together modellers and GRADE experts to discuss when it is appropriate to consider modelling studies as part of the evidence that supports a guideline; how to assess the quality and risk of bias in mathematical modelling studies; and how to adapt the GRADE approach for assessing the quality of a body of evidence; and for formulating recommendations to include the results of modelling. Several publications summarizing the results are in preparation.

Plans for 2017

Dissemination of results, including publications and communications. Leverage created from this project: the maintenance and functioning of the TB-PACTS is funded by the BMGF. In-kind contributions are also provided by LIH for data analysis.

Gender balance: the PIs of the TB PACTS and Loa-loa projects are women

Publications that have come out of this work: TB-PACTS: 1 presentation at the Union Conference in October 2016

Number of advanced degrees underway due to this project: 0

Related news: http://www.who.int/tdr/news/2016/global-database-adsm/en/

Remaining challenges: Though data sharing is an accepted principle, agreements and formalisation of this take considerable time.

EXPECTED RESULT 1.1.8: OPTIMIZE ACQUISITION AND ANALYSIS OF NEW SAFETY DATA FOR POLICY DECISIONS AND PROGRAMME IMPLEMENTATION

We actively promote safety evaluation. TDR works with countries to improve systems to monitor and use effectively drug safety data, so as to strengthen evidence informing treatment guidelines and improve patient outcomes. This expected result has been slightly evolving over time, but remains a key, distinctive area of work for TDR. This expected result had four projects in 2016. A major limitation of ongoing efforts to ramp-up access to medicines is the lack of monitoring programmes of similar scale to evaluate potential safety issues. In many disease-endemic countries, safety monitoring systems are still weak, and under-reporting is a persistent problem. New approaches need to be identified in order for countries and programmes to be equipped with more efficient and reliable systems. This is especially true for preventive mass drug administration (MDA) programmes where drugs are administered at the community level and/or through non-medical personnel. At the same time, it is also important to optimize the use of safety data collected by different partners; sharing and pooling data is promoted to improve our understanding of risks related to


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medications, and TDR works with other WHO programmes to that effect. In collaboration with WHO HIV department a pregnancy drug safety database was developed which pools country data issued from national or local pregnancy exposure registries to document risks to mothers and their babies following drug exposures during pregnancy. On a similar project, TDR works with the WHO GMP to develop a global database to pool and consolidate safety information on medications used to treat multidrug-resistant TB, called aDSM (active drug safety monitoring) in different countries.

1. Central databases for safety data (central database for pregnancy exposure registries and global aDSM database for TB drugs)

Progress in 2016

• Central database for pregnancy exposure registries: The central registry and the data entry programme have been finalized. A stakeholder meeting was organized to bring together country collecting information from pregnancy exposure registries and birth defect surveillance; there was a general consensus that data sharing is needed and we are currently working now on the data transfer agreement. Data from the first countries has been transferred.

• Global aDSM database for TB drugs: Global database and data entry programme finalized. Contact with countries has been initiated and is led by GTB. First data transfer agreement obtained from Belarus, and we hope to have few more by the end of the year.

Leverage created from this project: US$ 20 000. Time from experts involved in the project and collection work.

Gender balance: NA

Publications that have come out of this work: 1 presentation at the Union Conference in October 2016


Related news: http://www.who.int/tdr/news/2016/global-database-adsm/en/

Remaining challenges: Though data sharing is an accepted principle, agreements and formalisation of this take considerable time.

Plans for 2017

• Advocacy for the registries and facilitation of the data transfer, collation and analysis of data from contributing countries.

• First analysis to be done in 2017. • Dissemination of results, including publications.


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2. Innovative approaches for safety monitoring at community level

Progress in 2016

Innovative approaches for safety monitoring are being tested in the context of mass drug administration.

• A follow-up “lessons learned” meeting was organized in February 2016 to share experiences in safety monitoring during the 2015 SMC campaign. The workshop brought together the different SMC implementing countries to review the performance of the PV system, identify areas that may need strengthening, identify further steps to improve the functioning of the system and disseminate and communicate results and lessons learnt.

• In response to a call for applications for studies on PV in the context of MDA published in 2015, two studies were initiated in Ghana and Tanzania to evaluate the use of m-health tools to improve efficiency of safety monitoring in the context of MDA for NTD. Analysis is expected for 2017.

Leverage created from this project: US$ 30 000 worth of country infrastructure and support

Gender balance: Of the two PIs on the study of PV in MDA: 1 is a woman and 1 is a man

Publications that have come out of this work: 0


Related news: 0

Remaining challenges: There was some delay due to a lengthy ethics review process. Implementation at larger scale of piloted approaches and sustainability of interventions remains to be assessed.

Plans for 2017

• Analysis of the data obtained from the studies on safety monitoring in MDA expected to be available in 2017.

• Planning and preparing for future activities to be conducted in the 2018-19 biennium according to the new TDR strategy

• Dissemination of results, including publications.

3. Optimize acquisition and analysis of safety data

Progress in 2016

• Loa-loa: See above 1.1.7/1

• Safety of antimonials in CL patients. Antimonials remain the key treatment for patients with Cutaneous leishmaniasis (CL) but there are concerns about their tolerability, in particular cardiac toxicity, which remain largely undocumented. Discussions are ongoing with the medical department of the Colombia Army to digitalize medical records from the last years for patients treated with antimonial for cutaneous leishmaniasis (about 7500 records). This will allow us to generate more evidence on the safety profile of antimonials.


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Leverage created from this project: Data collection in country

Gender balance: PI for Loa Loa is a woman and PI for CL Colombia will be a woman



Remaining challenges: Delay of signature of agreements; stop/go decision by Q2/2017. How to integrate information collected into decision-making for both research and control.

Plans for 2017

• Loa-loa in Gabon: Upgrade data management system, analyse data and report results. Communicate results and promote policy uptake.

• Safety of antimonials in CL patients. Finalize MoU, analyses and publish results.

4. Capacity building for safety monitoring (UNDP Access and Delivery partnership project)

Progress in 2016

Different capacity building activities were organized or funded under the scope of the Access and Delivery Partnership (ADP) project in Ghana, Indonesia and Tanzania responding to a workplan prepared by the countries and related to strengthening safety monitoring capacity in the focus countries.

• Indonesia: Indonesia has been identified as one of the few pilot countries where bedaquiline will be introduced in the near future as part of a combination therapy of pulmonary tuberculosis due to multi-drug resistant strains of Mycobacterium tuberculosis (MDR-TB) in adults. In that context, the Indonesian Food and Drug Authority and Indonesia National TB Programme identified active safety monitoring as one of the key priority areas requiring capacity strengthening and support. A workshop on pharmacovigilance and introduction to cohort event monitoring was organized. The efforts toward building capacity for active safety surveillance will serve not only the introduction of bedaquiline but will give the country tools to ensure better safety monitoring of future drugs.

• Tanzania: The country prepared a 4-year workplan aimed at building further capacity on safety monitoring. Training sessions and support to the customer-based reporting of adverse events was provided.

• Ghana: Following reorientation of the priorities of the PV centre, we are supporting the Ghana Food and Drugs Authority with the development of an electronic system for Individual Case Safety Reports. This will help the countries to deal more efficiently in the future with safety reports issued in particular for new health technologies. This will find a direct application with the programmatic introduction in pilot area of the new malaria vaccine that still need a close safety monitoring in place.

Leverage created from this project: US$ 50 000 (in kind of countries and other collaborators participating to projects)

Gender balance: NA



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Remaining challenges: Though needs are evident in all countries, it has taken some time to get the right people engaged in the countries and for them to dedicate time to the project.

Plans for 2017

Funding continues until March 2018. Capacity building activities will continue based on the annual renewed workplan for the project and the needs from each country. The workplan for the remaining period has been discussed with the countries. We are preparing a proposal for request for renewal of funding.

Objective 4: Optimize implementation of public health programmes

EXPECTED RESULT 1.1.1: SUPPORT ADEQUATE COUNTRY RESPONSE TO EPIDEMIC CHALLENGES: EVIDENCE-BASED GUIDANCE FOR ARBOVIRUS OUTBREAK DETECTION AND RESPONSE

TDR is working with country control programmes and researchers to identify signals that can alert country control programmes to an impending dengue outbreak so that they can react quickly and efficiently curb the epidemic. This has led to a model contingency plan that countries can test and potentially customize to apply also to other arboviral diseases like Zika and chikungunya. Dengue and other Aedes-borne ‘arboviruses’ like Zika and chikungunya cause outbreaks which generate enormous health, social and economic burden across all continents, not restricted to tropical areas. Country response usually starts late and is of limited efficacy, as documented in an earlier part of this project. Early detection will allow control programmes to ‘nip the outbreak in the bud’. This is what this project aims at. TDR coordinates research across a number of dengue-endemic countries in Latin America and Asia on how to improve dengue surveillance, outbreak preparedness, detection and response. This has already led to an evidence-based model contingency plan adaptable to country needs, providing countries with practical solutions to respond to dengue outbreaks. TDR has worked closely with the WHO/NTD Department and other major stakeholders, such as national control programmes of dengue-endemic countries in Asia and Latin America, WHO regional offices, research institutions and international organizations (Red Cross Red Crescent, and others) in order to translate research findings into policy and practice. The project, originally centred on dengue, has evolved to cover more broadly arboviruses like Zika and chikungunya that are transmitted by the same mosquito species, Aedes.

Progress in 2016

TDR-supported research has produced research outputs that can contribute to policy and practice. The analysis of the retrospective study on alarm signals for dengue outbreaks in five countries (Brazil, Dominican Republic, Malaysia, Mexico and Viet Nam) and the first months of experience with the ongoing prospective study led to the following conclusions: (1) The sensitivity and predictive value (PPV) of alarm indicators of an impending dengue outbreaks is between 70-90%.


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However, the signals vary among and even within countries; therefore, country teams need further training to identify their specific signals (Bowman et al. 2016); (2) Preliminary prospective country reports show that ongoing active data capture and improved in-country capacity for predictive dengue outbreak assessments; (3) The handbook for dengue surveillance, outbreak prediction and response (the model contingency plan) is now published in its entirety and can be downloaded from the TDR website; a shorter version for dissemination is also published in an open access Journal (Runge-Ranzinger et al. 2016). (4) A ‘How-to’ guide was developed and published on the TDR website) to help country teams operationalise the model contingency plan, determine locally-relevant alarm indicators, and use the Early Warning and Response System (EWARS) prospectively; (5) Preliminary cost-effectiveness modelling shows the potential break-point when early warning and response are or are not cost-effective. These topics were discussed with national control programmes, WHO/NTD and regional offices, academics and international experts in two meetings: (1) an international research-to-policy forum organized jointly by IIR and VES in August 2016; and (2) the dissemination meeting jointly co-organized by TDR and Institut Pasteur Paris on the research outputs produced by two complementary research programmes (IDAMS and DENFREE). Both meetings aimed to collate and analyse research results and distill their implications for policy and remaining future research. Remaining challenges:

• Further refining the predictive value of alarm signals. The growing datasets are being reanalysed in order to stabilise correlations between alarm and outbreak indicators; and new analyses are done on additional indicators, such as the NS1 positivity rate (testifying an acute infection) and notified cases. We will also test an arbovirus alert tool which includes both qualitative and quantitative risk indicators for dengue/Zika/chikungunya outbreaks.

• Ensuring dissemination and uptake. These tools need to be disseminated through scientific publications, communication, information included in WHO dengue guidelines, and policy briefs to increase uptake at WHO, regional and country level.

• Verifying applicability of approaches identified in a broader range of countries.

• Developing and testing a framework for countries to cope with the rapid increase of cases during outbreaks (improved surge capacity); strengthen country capacity to conducting clinical and operational research during outbreaks.

Plans for 2017

Completion of current activities:

• The prospective study will be completed in 4Q2017 and subsequently analysed – delays were caused by the Zika and chikungunya outbreaks in study countries, rendering the comparison of intervention vs. control districts impossible in 2016.

• The above mentioned ‘How-to’ workbook will be applied and validated in a number of dengue-endemic countries.

http://www.who.int/tdr/publications/year/2016/tech_handbook_dengue/en/


http://www.who.int/tdr/news/2016/handbook-dengue-outbreak/en/


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New activities:

• The outline for designing and testing a more comprehensive alert and response tool (EWARS plus) which includes the range of Aedes-borne arboviral infections (dengue, Zika, chikungunya) will be developed and discussed with partner countries. This tool will focus on urban settings, where these outbreaks tend to occur.

• The findings on outbreak detection and response will be adopted by the Caribbean Network established by the TDR VES unit, and the findings from novel dengue vector control methods in urban settings developed in the VES programme will be made available to the counties and teams working on dengue outbreak management for use during the inter-epidemic period and as an early outbreak response.

Leverage created from this project: This project is funded through a combination of TDR core funds and the European Union-funded IDAMS consortium estimated US$ 1.3 million plus considerable co-financing of workshops and visits to study districts by ministries of health in the participating countries.

Publications that have come out of this work:

1. Bowman LR, Tejeda GS, Coelho GE, Sulaiman LH, Gill BS, McCall PJ, Olliaro PL, Ranzinger SR, Quang LC, Ramm RS, Kroeger A, Petzold MG. Alarm Variables for Dengue Outbreaks: A Multi-Centre Study in Asia and Latin America. PLoS One. 2016 Jun 27;11(6):e0157971.

2. Runge-Ranzinger S, Kroeger A, Olliaro P, McCall PJ, Sánchez Tejeda G, Lloyd LS, Hakim L, Bowman LR, Horstick O, Coelho G. Dengue Contingency Planning: From Research to Policy and Practice. PLoS Negl Trop Dis. 2016 Sep 21;10(9):e0004916

3. WHO/TDR. Technical handbook for dengue surveillance, dengue outbreak prediction/detection and outbreak response (Model contingency plan). Sep 2016 ISBN 978 92 1 154973 8. http://www.who.int/tdr/publications/year/2016/tech_handbook_dengue/en/

Number of advanced degrees underway due to this project: D. Benitez (PhD), JK Harrington (MSc)

Related news: New handbook for dengue outbreak contingency planning Critical research findings for managing dengue New approaches to address the dengue, chikungunya and Zika crises http://www.who.int/tdr/news/2016/dengue_diag_test_progress/en/


http://www.who.int/entity/tdr/news/2016/handbook-dengue-outbreak/en/index.html

http://www.who.int/tdr/news/2016/critical-research-findings-dengue-management/en/

http://www.who.int/tdr/news/2016/dengue-chikungunya-Zika-crises/en/

http://www.who.int/tdr/news/2016/dengue_diag_test_progress/en/


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EXPECTED RESULT 1.2.1: INTERVENTION AND IMPLEMENTATION RESEARCH TO INFORM POLICIES FOR THE ELIMINATION OF VISCERAL LEISHMANIASIS (VL) IN THE INDIAN SUBCONTINENT (BANGLADESH, INDIA AND NEPAL)

An endemic country-led, long-term project that generates the evidence base for approaches and interventions to be deployed throughout the different phases of the VL elimination programme, and ensures policy uptake and rollout. Since 2005, TDR has been working with both research and control in the Indian subcontinent countries (ISC) to conduct research that informs policy and practice in the region to achieve the elimination target of one case of visceral leishmaniasis (VL) per 10 000 inhabitants. One of the longest and most successful implementation research programmes at TDR, these efforts have contributed to a sharp reduction of cases. One of the reasons for this success is that the research has been planned and executed by country control programme managers and researchers, ensuring the pertinence of research and facilitating result uptake into policy and practice. In the past few years, support has been concentrated in Bangladesh and Nepal for increased efficiency. Now Nepal is filing for certification of elimination, and Bangladesh is but a couple of sub-districts away from reaching the target. However, further investments and new approaches are required to ensure elimination is sustained, and to prevent resurgence of disease and waste of the current efforts to control the spread of the disease. To address this, work is underway with the countries at the level of (1) active case detection; (2) vector control and reduction of transmission; and (3) research policy interface.

Progress in 2016

• Two parallel studies have been conducted in Nepal and Bangladesh comparing different strategies for active case detection and vector control. In Bangladesh, when a case is notified (index case), a team is dispatched to their household and surrounding houses looking for cases and applying insecticide residual spraying (IRS). The study shows that impregnated durable wall lining (DWL) and insecticide-treated bednets (ITN) are very effective in reducing sand fly densities. In Nepal the effects of insecticidal wall painting (IWP) on sand fly density lasted longer than IRS and ITN. Both studies found that sand flies are still susceptible to available insecticides. Importantly, both studies point to promising alternatives to traditional IRS, which is not sustainable in the long term. However, both studies also show persistent, significant delays of 2-3 months before a case is correctly identified and treated, during which the person continues to be a source of transmission.

• A systematic review of the literature was conducted that summarises all current knowledge and knowledge gaps in terms of transmission dynamics, and the role of clinically manifested visceral leishmaniasis, asymptomatic infections and post-kala azar dermal leishmaniasis cases in transmitting the infection. This information is extremely valuable in helping direct research and interventions, as well as feeding modelling studies.

• Participants at the Kathmandu meeting of national VL control programme managers, academics from the target countries and international experts came to the conclusion that in the post-elimination phase, speedy detection of new cases in low endemicity areas (“non-programme areas”) should be a focus, and that the search for secondary cases and vector control can be done by the community. A research programme towards this end was proposed.


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Leverage created from this project: In-kind contribution to research in countries

Gender balance: Sub-project on information system in Nepal and feasibility study in Bangladesh were carried out by women researchers. Likewise, the Nepal field staff includes 3 women. In Bangladesh, due to the remote areas where the project takes place, no women could be included; previously a woman was the economist but she left for Australia.

Publications that have come out of this work:

1. Hirve S, Boelaert M, Matlashewski G, Mondal D, Arana B, Kroeger A, Olliaro P. Transmission dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review. PLoS Negl Trop Dis. 2016 Aug 4;10(8):e0004896.

2. M. Mamun Huda, Vijay Kumar, Murari Lal Das, Debashis Ghosh, Jyoti Priyanka, Pradeep Das, Abdul Alim, Greg Matlashewski, Axel Kroeger, Eduardo Alfonso-Sierra, and Dinesh Mondal. 2016 Entomological efficacy of durable wall lining with reduced wall surface coverage for strengthening visceral leishmaniasis vector control in Bangladesh, India and Nepal BMC Infectious Diseases (2016) 16:539 DOI 10.1186/s12879-016-1881-8

3. Rajib Chowdhury, Vijay Kumar, Dinesh Mondal, Murari Lal Das, Pradeep Das,

Aditya Prasad Dash & Axel Kroeger 2016. Implication of vector characteristics of Phlebotomus argentipes in the kala-azar elimination programme in the Indian subcontinent. Path. Glob. Hlth. 110(3): 87-96 DOI 10.1080/20477724.2016.1180775

4. Dinesh Mondal, Murari Lal Das, Vijay Kumar, M. Mamun Huda, Pradeep Das, Debashis Ghosh, Jyoti Priyanka, Greg Matlashewski, Axel Kroeger, Alexander Upfill-Brown, Rajib Chowdhury. 2016 Efficacy, Safety and Cost of Insecticide Treated Wall Lining, Insecticide Treated Bed Nets and Indoor Wall Wash with Lime for Visceral Leishmaniasis Vector Control in the Indian Sub-continent: A Multi-country Cluster Randomized Controlled Trial. PLoS Negl Trop Dis 10(8): e0004932. doi:10.1371/journal.pntd.0004932

Number of advanced degrees underway due to this project: Dajull Lim (PhD), Eva Maintz (PhD), P. Boettvher (MSc)

Related news: Sustainable visceral leishmaniasis elimination requires research on infection reservoirs Remaining challenges:

• Knowledge gaps. Clarifying the significance of the elimination target vis-à-vis risk of resurgence of the disease.

• Programmatic issues. Identifying the best, sustainable, multi-disease and inter-sectorial approaches that will eventually lead to zero VL transmission.

• Beyond science and programmes. Elimination is as much a political as a scientific question, requiring the mobilisation of human resources and financial capital to ensure success, as well as identification on sustainable approaches to prevent broken transmission from starting again.

http://www.who.int/entity/tdr/news/2016/visceral-leishmaniasis-research/en/index.html

http://www.who.int/entity/tdr/news/2016/visceral-leishmaniasis-research/en/index.html


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Plans for 2017

• Publication of the two trials that were completed in 2016. • Start of major research initiative in Bangladesh and Nepal to test for the post-

elimination phase the most suitable interventions in low VL/PKDL endemicity areas regarding detection of secondary cases after an index case has been diagnosed in a local hospital, vector control with community managed tools and social mobilization.

• Ten year review of TDR support for the VL elimination initiative. • Video documentation of the TDR efforts supporting the initiative. • Annual meeting with national programme managers and academics for reviewing

achievements and defining research needs. • Presentation of findings at the WorldLeish 6 Congress in May 2017 (several abstracts

submitted).

EXPECTED RESULT 1.2.2: COMMUNITY-BASED SCHEDULED SCREENING AND TREATMENT OF MALARIA IN PREGNANCY FOR IMPROVED MATERNAL AND INFANT HEALTH (COSMIC)

A pilot exploring effective methods for supporting the transfer of research results to policy and practice improvements. This project fits within not only research, but also knowledge management. The overall objective of TDR’s role in this multi-country study is to create “policy panels” that bring together policy-makers, healthcare providers, researchers and the press to learn and contribute to this study. The goal is securing commitment so that policy and practice changes can be considered in light of the findings – negative or positive. The study has been conducted in Benin, Burkina Faso and the Gambia since 2012, investigating the impact of community heathcare workers conducting scheduled screening and treatment of malaria among pregnant women to reduce the incidence of the disease.

Progress in 2016

The study completed data collection and analysis and plans were made for the final policy panels to be held during the month of March, 2017 in each of the three countries where the research was being conducted. Remaining challenges: Early analysis suggests the intervention did not provide the effect intended. However, the study highlights issues that could help countries improve adherence to the national guidelines on attendance at the antenatal clinics. Coordination among the WHO regional and country offices and the ministries of health is critical to the success of the research review and commitment to undertaking any follow-up on the evidence.

Leverage created from this project: pending

Gender balance: 22 women, 21 men

Publications that have come out of this work: pending


Related news: planned for 2017


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Plans for 2017

Produce the three videos and conduct the final policy panels in March, and final reports for each country by June.

EXPECTED RESULT 1.2.3: RESEARCH IN SUPPORT OF CONTROL PROGRAMMES: IMPROVED MANAGEMENT OF FEBRILE ILLNESSES

TDR is leading research on the microbiological causes of severe infection in young infants in rural Africa, to inform guidelines for first line antibiotics treatment. Data on the pathogens causing infection in babies born at home are scarce, particularly for infections in the first weeks and months of life. These data are necessary to provide insights on the antibiotic regimens that can be used in case management for serious infection in young infants in out-patient or home settings in developing countries. The data are particularly valuable in areas of high neonatal mortality to analyse explicitly defined criteria for community acquired infections. Though there is a growing interest for this field of research, most groups usually target children between 2 months and 5 years, but exclude very young infants, particularly in African settings. TDR is one of the few groups working on severe infections in very young infants (0-2 months). This project focuses on the microbiological causes of invasive infections in young infants (0-2 months) in rural African settings and includes one prospective study with two sites (Burkina Faso and Tanzania) and one retrospective study in Kenya.

Progress in 2016

• Prospective study initiated at the two sites and enrolment ongoing. • Retrospective study ethical approvals obtained and preparatory phase of the study

started.

Leverage created from this project: Estimated US$ 200 000 for contribution to diagnostic tests and in-kind.

Gender balance: PIs: 2 men, 1 woman



Remaining challenges: Activities have been slow to start due to delays in approvals by the relevant ethics committees. Due to the low yield and sensitivity of the haemoculture, it may be difficult to draw representative conclusions from the study.

Plans for 2017:

• Study to be completed by end of 2017 and analysis conducted in 2017 (retrospective) and early 2018 (prospective study). Dissemination of results.


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EXPECTED RESULT 1.2.4: STRUCTURED OPERATIONAL RESEARCH AND TRAINING INITIATIVE (SORT IT)

TDR is helping public health communities in low and middle-income countries to collect and analyse data, to inform health policy and practice, and to bring about improvements in public health. Public health programmes routinely collect considerable amounts of data. The full potential of these data to inform improvements in the programme performance is rarely achieved. One reason for this is that public health programmes do not have the capacity for basic operational research and knowledge management. Through an approach which emphasises capacity building, the Structured Operational Research and Training Initiative (SORT IT) supports countries to formulate and prioritise research questions, conduct operational research around these priorities, and transition new knowledge into evidence-informed decision-making. SORT IT objectives are to support countries to: 1) Conduct operational research (OR) around their own public health priorities; 2) Build adequate and sustainable OR capacity in their public health programmes, and 3) Improve public health programme performance through evidence informed policies The efforts in 2016 were concentrated on:

• Increased number of projects and people trained • Broader range of public health issues addressed • Increased complexity of research conducted • Expanded partnership base, with a particular focus on increased national capacity for OR • Developing national leadership of SORT IT programmes • Linking SORT IT activities to knowledge transaltion platforms such as EVIPNet

Partners include ministries of health, WHO regional and country offices, International Union Against Tuberculosis, Médecins Sans Frontiers (MSF), Royal National Tuberculosis Foundation (KNCV), Global Fund, United States CDC, China CDC, USAID, DFID, Institute of Tropical Medicine (Belgium), University of Nairobi (Kenya), University of Antioquia (Colombia), Makarere University (Uganda), University of Toronto, Dignitas International, Partners in Health, and EVIPNet. Synergies include linking of the operational research and related capacity-building of SORT IT with the evidence-informed policy-making and related capacity building of the WHO-led Evidence Informed Policy Network (EVIPNet).

Progress in 2016

1. More research, more capacity-building and more evidence into policy

More than 6 SORT IT operational research supplements were published or in publication during 2016 – all open access. One hundred and twenty-two trainees completed training in 2016. A new training workshop on the development of Issue Briefs for Policy was developed and piloted in the WHO EURO Region. Two-thirds (66%) of trainees completing SORT IT courses during 2014 and 2015 reported that their research had an impact on policy and/or practice (publication submitted).


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2. Expanded range of public health issues addressed by SORT IT programmes

SORT IT programmes are now addressing a wide range of public health issues. Two SORT IT programmes, one in Liberia and one in Sierra Leone, that were completed during 2016 focused on research needed to inform the health systems recovery plans following the 2014-16 Ebola outbreak in West Africa. 3. Increased complexity of operational research undertaken with appropriate integrated

training SORT IT training in India is now including mixed methods research and qualitative research. WARN-TB, with funding from SORT IT, has adopted SORT IT methods and aspects of the TDR IR Toolkit for training in implementation research. 4. Expanded partnership base contributes facilitators/support to SORT IT programmes and

other OR/IR capacity-building activities, with a particular focus on national capacity-building for SORT IT training.

5. In Rwanda and Nigeria, the SORT IT model has been taken up and used as the basis for new

approaches to operational research and capacity building. Two publications describing these experiences are in preparation.

A number of new partners joined SORT IT during 2016 including the University of Nairobi, the Pakistan Ministry of Health, the Global Fund (Pakistan) and China CDC. Six national SORT IT programmes were conducted during 2016, all with the ministry of health playing a leading role. One SORT IT Programme in Kenya was entirely led by the MoH and implemented solely through South-South collaboration. The 2016 Pakistan national SORT IT programme was funded in country by the Global Fund; this may be a model for expansion to other countries. Leverage created from this project: Approximately US$ 1.8 million, including time of trainees and cost of research in countries.

Gender balance: 45% of trainees were women

Publications that have come out of this work: Total to date: 385 submitted of which 288 published or accepted. 2016 only: 122 submitted; 32 of these published or accepted.

Number of advanced degrees underway due to this project: 12 SORT IT Operational Research Fellows pursuing PhD.

Related news: The Global Fund in an Information note for applicants (Building Resilient Systems for health through Global Fund Investments. 15th December 2016) specifically states that it will fund operational research and related capacity building in countries to support GF grant implementation.

Remaining challenges: SORT IT is making great progress in transferring technical and leadership capacity to low- and middle-income countries so that they can run their own independent national SORT IT programmes. Three major challenges remain to:

- Create a sustainable funding environment so that operational research and capacity building may become embedded in public health programmes.


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- Develop objective verifiable indicators and more robust methods to assess the impact of SORT IT research on public health policy and practice.

- Integrate SORT IT and other operational/implementation research and training models into a broader effort to improve research, knowledge management and capacity-building for better implementation of public health programmes.

Plans for 2017

1. Continue to support core SORT IT partners for wider activities. 2. Support sub-regions and countries to become independent of SORT IT facilitation and leadership from Northern partners. 3. Drive SORT IT from a programme/initiative to a routine embedded practice in MoHs. 4. Build SORT IT activities into a broader, more comprehensive effort to use research for improving public health programme implementation.

EXPECTED RESULT 1.2.6: RESEARCH IN SUPPORT OF CONTROL PROGRAMMES: IMPROVED TB CONTROL IN LINE WITH GTB STRATEGY

An innovative approach is piloted in West Africa to assess if a collaborative regional model with countries facing similar issues and constraints could create a regional dynamic and enhance the conduct of operational and implementation TB research addressing national and regional TB research priorities. Within a year, sixteen pilot projects on TB research priorities have been developed. As recommended by the WHO Global TB (GTB) programme as part of the End TB Strategy endorsed by the World Health Assembly in May 2014, the use of existing diagnostic tests and treatments in a more cost-effective way could help decrease the burden of tuberculosis. More operational and implementation (OR/IR) TB research is needed in countries to identify better ways of controlling their TB epidemic. A regional, collaborative, multi-pronged, step-wise approach to support the West African countries was adopted in this endeavour. The following steps were defined:

1. Establish a network of the National TB programmes of the West-African subregion

2. Support this network towards identifying OR/IR priorities and developing country and regional TB research agendas and plans

3. Support the countries of this network towards:

a. Building their research capacities according to the above-mentioned plan;

b. Implementing relevant country-specific and region-wide OR/IR projects.

This project also aims at combining the efforts of all major partners and funders involved in TB control and TB research in West Africa by bringing them together in this regional initiative. A total of US$ 1.7 million was so far leveraged and the following partners were associated to this initiative: the WHO Global TB programme, the WHO inter country support department, the WHO health information system, the Global Fund, the Union, Damien foundation, the West African Health Organisation (WAHO) and Expertise France, as well as northern and southern universities such as: the London School of Hygiene and Tropical Medicine (UK), the Liverpool School of Tropical Medicine (UK), the Institut de Recherche et Development (IRD, France) the


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Medical University of Reims (France), the University Cheick Anta Diop (UCAD, Senegal), the Centre Muraz (Burkina Faso), the Medical University of Conakry (Guinea), the Medical University of Cotonou (Benin), and the University of Accra (Ghana).

Progress in 2016

In June 2015, the West African Regional Network for TB control (WARN-TB) composed of the National TB programmes of the 16 West African countries was established with TDR support. In 2016, the following activities were conducted: • Seed funding for the establishment of multidisciplinary national TB committees in the 16

countries (TB taskforces), to develop the national TB research agenda as per Global TB framework guidance and monitor its implementation.

• Strengthening country TB surveillance systems with standard and benchmark analysis in the 16 countries, safeguarding historical TB data in a DHIS2-TB module piloted by the WARN-TB countries, developing implementation plans for moving from paper to electronic TB case notification, strengthening capacity for the analysis of the key TB indicators at national and sub-national level (activity conducted in collaboration with the WHO/GTB and funded in part by the Global Fund for AIDS, TB and Malaria).

• Definition of the key country-specific and region-wide TB research priorities: (1) enhance TB case finding for children and adults; (2) reduce TB treatment defaulters; (3) reduce TB mortality.

• Conduct of modules 1 and 2 of a training programme on OR/IR dedicated to 2 NTP staff (or 1 NTP staff and 1 local researcher) for the development of a pilot IR or OR project. Sixteen projects were developed. To date, six have ethical approval and two are completed.

• Advocacy activities for raising funds for the long-term sustainability of the WARN-TB network.

Concerning WARN-TB regional activities, the RAFAscreen project was launched in Benin, Senegal and Guinea (TDR co-funded project with “France expertise”). This project aims at defining the most appropriate TB screening strategies for diabetic and HIV patients (who are at higher risk of having TB as well) and piloting their implementation at all levels of the healthcare system. So far, 80% of the target sample size has been recruited (i.e. 6 000 patients). Leverage created from this project: Total leverage of US$ 1.7 million

a) US$ 1 300 000 from the French government (FEI) for conducting a US$ 1.7 million project (RafaScreen project), for which TDR contributes 18% of the total amount

b) US$ 300 000 from the GF for strengthening the capacity of the national TB surveillance systems of the WARN-TB for defining OR/IR priority

c) US$ 50 000 from WAHO for organizing the annual meeting of the WARN-TB in 2016

d) US$ 50 000 from Damien Fundation to participate in the training and financial support for projects conducted in Guinea as part of the WARN-TB activities

Gender balance: N/A


Number of advanced degrees underway due to this project: None


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Related news: http://www.who.int/tdr/news/2015/west-african-regional-network/en/ http://www.who.int/tdr/research/tb_hiv/warn-tb/en/ http://www.who.int/tdr/news/2016/childhood-tb-senegal-ghana/en/ http://www.who.int/tdr/news/2016/cultivating-tuberculosis-research/en/ http://www.who.int/tdr/news/2015/screening-stras-tb-diabetic-patients/en/ Remaining challenges: No specific unexpected challenge to report

Plans for 2017

• Research strengthening capacities: module 3 and 4 in May and September, • Support for the finalisation of the OR/IR projects conducted by the countries and

communication of the results (oral, written, policy briefs). • Resource mobilisation for:

WARN-TB network meeting Developing of new research projects in line with the TB regional research

priorities Scale-up of some IR projects piloted in 2016

• Communication around the WARN-TB activities • Exploratory activities for replicating the WARN-TB initiative in the central African region • Conduct of the scale-up phase of the RAFAscreen project and potentially its piloting in

countries other than Benin, Senegal and GuineaDissemination of results, including publications (four papers are at a draft stage to document WARN-TB activities and lessons learned).

EXPECTED RESULT 1.2.7: RESEARCH IN SUPPORT OF ELIMINATION PROGRAMMES: ONCHOCERCIASIS ELIMINATION

(Note: Activities under this ER are funded from ER 1.1.4 due to the extensive synergy in data acquisition and analysis)

1. O. volvulus population genetic marker based tool to aid in delineation of O. volvulus transmission zones

New WHO guidelines provide epidemiological and entomological methodology and criteria for stopping onchocerciasis control in a transmission zone but do not address how to determine transmission zones. Taking advantage of results obtained for ER 1.1.4, TDR is working on providing the basis for tools African countries, faced with vast onchocerciasis endemic areas, including cross-border areas, can use to delineate transmission zones. The onchocerciasis control programmes in Africa are expected to achieve elimination in a number of areas by 2020, in others by 2025. For onchocerciasis control activities to be stopped, all areas within a transmission zone (defined in the new WHO guidelines as a geographical area where transmission of Onchocerca volvulus occurs by locally breeding vectors and which can be regarded as a natural ecological and epidemiological unit for interventions, i.e. a geographic area with a common vector and parasite population) have to meet stopping criteria.

http://www.who.int/tdr/news/2015/west-african-regional-network/en/

http://www.who.int/tdr/research/tb_hiv/warn-tb/en/

http://www.who.int/tdr/news/2016/childhood-tb-senegal-ghana/en/

http://www.who.int/tdr/news/2016/cultivating-tuberculosis-research/en/

http://www.who.int/tdr/news/2015/screening-stras-tb-diabetic-patients/en/


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Given that onchocerciasis is endemic over large sections in Africa covering areas in different countries, with different levels of endemicity, different onchocerciasis control start dates and different programme performance, the time at which stopping criteria are met in neighbouring areas will differ. Information on whether these neighbouring areas belong to the same transmission zone is needed to ensure that control activities are stopped neither too early, nor too late. Currently, determination of different vector species/strains via morphological and chromosomal characteristics is the basis for determining transmission zones, which is a time consuming method requiring special entomological expertise which is not readily available. A tool that could aid transmission zone definition based on genetic markers in the parasite could significantly simplify the process resulting in significant cost savings for countries and donors. This project evolved from the results of ER 1.1.4. Its objective is to develop an O. volvulus population genetic marker-based tool to aid in delineation of O. volvulus transmission zones. The project was designed and is implemented by a group of researchers in Australia, Burkina Faso andGhana. The field work, as well as the genotyping conducted for ER 1.1.4 (Vulnerability of preventive chemotherapy programmes for helminths to emergence of resistance), contribute to this ER and consequently, the researchers in Cameroon, Canada and France funded under ER 1.1.4 also contribute to this ER.

Progress in 2016

Markers have been identified which allow differentiating parasite populations from Cameroon, the Democratic Republic of Congo and Ghana. Markers also show that a large geographic area in Ghana shares a parasite population supporting the hypothesis underlying this ER that transmission zone markers, rather than geographic distance or river basins, need to be considered for the decision to stop onchocerciasis control in one endemic area when other areas do not yet meet stopping criteria. Remaining challenges: (1) Sufficient funding. TDR will work with the investigators to raise funds from other organizations. (2) Access to parasites from different onchocerciasis endemic areas. Building on collaboration on this project with APOC until its closure, TDR and TDR-funded investigators will work with the WHO/AFRO/Expanded Special Project for Elimination of Neglected Diseases monitoring and evaluation laboratory. (3) Identification of funding and partners to implement in onchocerciasis endemic areas undergoing evaluation for stopping CDTI.

Plans for 2017

Continue evaluation of parasites from different geographical areas to confirm results to date, and if applicable, establish a potential cross-African panel of transmission zone markers. Dissemination of results. Identification of funding sources and partners. Leverage created from this project: Estimated US$ 300 000 plus additional in-kind contributions from the implementing countries (across this project and response marker project in ER 1.1.4)

Gender balance: All PIs are men as are the two PhD students supported under the project

Publications

• Doyle, S. R., Armoo, S., Renz, A., Taylor, M. J., Osei-Atweneboana, M. Y. and Grant, W. N. (2016). Discrimination between Onchocerca volvulus and O. ochengi filarial larvae in


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Simulium damnosum (s.l.) and their distribution throughout central Ghana using a versatile high-resolution speciation assay. Parasites & Vectors, 9: 536.

• Armoo, S., Doyle, S. R., Osei-Atweneboana, M. Y. & Grant, W. N. (2016). Significant heterogeneity in Wolbachia copy number within and between populations of Onchocerca volvulus. Parasites & Vectors, (in press).

Training: One of the two Ghanaian PhD students whose studies were co-funded by this project obtained their doctorate in Australia and has returned to Ghana to lead the laboratory work for this as well as the synergistic project (See response marker project under ER 1.1.4). The second Ghanaian PhD student supported by this project has submitted his thesis.

EXPECTED RESULT 1.2.5: TRANSLATING NEW AND TRADITIONAL KNOWLEDGE INTO HEALTHY ENVIRONMENTALLY SUSTAINABLE HOUSING FOR POOR COMMUNITIES

In the 'UN Decade of Sustainable Energy for All (SE4All) and the SDG era, TDR is planning on developing a model for poor urban and rural LMIC communities and local, national and international experts and organizations to collaborate on improving their housing to reduce exposure to infectious diseases and other health risks (SDG 3, Good Health and Well Being) and to contribute to meeting SDGs 4 (quality education), 6 (clean water and sanitation), 7 (affordable and clean energy), 11 (sustainable cities and communities), 15 (life on land) and 13 (climate action). 'Housing' covers not only the structure, but also water supply, sanitation, ventilation, heating/cooling, lighting, energy provision, humidity, privacy, security, safety, protection against disease vectors … . Inappropriate housing exposes inhabitants to a large number of avoidable health risks ranging from communicable diseases to injuries. The negative impact of inappropriate housing is not limited to health but affects other socio-economic determinants of quality of life. In LMICs, inappropriate housing is frequently associated with lack of access to energy. SDG7 recognizes that 'Energy is crucial for achieving almost all of the Sustainable Development Goals, from its role in the eradication of poverty through advancements in health, education, water supply and industrialization, to combating climate change' which translates into SDG 7.1: '… universal access to affordable, reliable and modern energy services' by 2030. A number of UN organizations and NGOs work on elements of housing related to their mandate (e.g. WHO on Housing and Health Guidelines - to be issued in 2017, UN – World Bank partnership on sustainable energy for all, UN habitat on participatory slum upgrading). This project, conducted in collaboration between IIR and VES, aims at developing a model for cross-disciplinary collaboration to optimize housing for the poor.

Progress in 2016

Search for funding sources has been initiated.

Plans for 2017

In collaboration with VES, a call for proposals on how to approach and implement this project in urban areas will be issued by 2Q17.


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OTHER PROJECTS: Piloting new research capacity strengthening schemes

New research capacity strengthening schemes are being piloted with funding from both IIR and the TDR Strategic Development Funds. These schemes target specific capacity needs identified during previous/ongoing research projects and discussion with stakeholders. If successful and approved by the relevant external advisory groups, they will be included in the TDR portfolio of activities.

1. MODELLING RESEARCH FELLOWSHIPS TO BUILD CAPACITY FOR MODELLING IN LMICS

As modelling becomes more important in informing policy, disease-endemic countries need to have their own capacity. Modelling is becoming more and more important for areas such as economic/cost-effectiveness analyses of interventions, assessment of the potential effect of interventions on transmission, morbidity or mortality and for aiding decisions on interventions required to achieve specific objectives. Recent examples are a BMGF funded economic analysis of onchocerciasis control vs. elimination vs. eradication (Swiss TPH) and the award by BMGF, Novartis and Children's Investment Fund Foundation (CIFF) of a grant to the 'NTD modelling consortium'. There is, however, little experience for modelling in LMICs. Building on the experience of the TDR Clinical Research Fellowship, TDR piloted a Modelling Fellowship which placed two fellows (one from Ghana, one from Tanzania) in modelling groups currently receiving grants from TDR within ER 1.1.4 and 1.2.7 (in Australia and the Netherlands).

Progress in 2016

Implementation of the pilot, administered by RCS/KM and managed by IIR, was completed. This experience supports and can inform large-scale rollout. TDR initiated discussion with potential funders to expand the pilot into calls for applications for modelling fellowships.

Plans for 2017

Provided approval by TDR advisory groups is obtained and funds can be raised, TDR RCS/KM will issue calls for applications for modelling fellowships. Leverage created from this project: 0

Gender balance: Both fellows were men

Publications: 0

Training: 2 fellows

2. ACCELERATING RESEARCH-TO-POLICY AND RESEARCH-TO-IMPLEMENTATION TRANSITION

This project utilises in-country research capacity to overcome barriers to achieving control objectives. Aimed at accelerating the research-to-policy and research-to-implementation transition and strengthening research capacity in MoHs, grants are provided for implementation


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research collaboratively designed and conducted by staff from MoH and research institutions in the same country. In many countries, in particular in Africa, progress towards meeting health related MDGs or disease control/elimination targets is lagging because implementation of national policies is suboptimal. Areas where implementation needs optimization differ between programmes and countries, are numerous and very diverse (e.g. supply chain, health care worker training/motivation/supervision, community/patient information, education and communication). Furthermore, the guidelines that inform a particular national policy may be based on assumptions that are not exactly applicable within the country, and effective implementation would require significant modification based on in-country data and data analysis. MoH programme managers need to identify the problems which impede optimal implementation, identify potential solutions and motivate decision-makers to invest in these solutions. They also may have to prioritize the implementation of solutions based on investment/impact ratio when all solutions cannot be implemented due to resource limitations. Implementation research is required to provide the necessary database. MoH staff at all levels of the healthcare system rarely have research training. TDR is addressing this gap through both disease-specific (e.g. WARN-TB) and disease-independent (e.g. SORT IT) projects. A complementary path to effective implementation research and research capacity building is collaboration between MoH staff and academic institution researchers. In 2015, IIR initiated piloting a grant for collaboration between MoH and country academic institutions to build research capacity in the MoH to plan, design and implement research identified by the MoH as a priority and to translate the research results into recommendations (policy-briefs) for MoH decision-makers.

Progress in 2016

Staff in the NTD Programme of the MoH Ghana and at the Ghana Noguchi Memorial Institute for Biomedical Research completed development of a research protocol to address challenges for meeting LF elimination goals. They also used the TDR funding to leverage funds for the planned study to include field validation of four new diagnostic tests for onchocerciasis and LF programmes. This will require not only Ethics Committee, but also regulatory agency approval, delaying study start. The outputs of the planned field validation will not only benefit Ghana but also other LF- and onchocerciasis-endemic countries.

Plans for 2017

Preparation of submission to the Ghana Food and Drugs Authority, submission of revised protocol to Ghana Food and Drugs Authority and all ECs, study initiation (provided approval is obtained). Leverage created from this project: US$ 42 000

Gender balance: PI, Co-PI from Ghana Health service and project lead at Noguchi are all men.

Publications: 0

Training: 0


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3. CLINICAL RESEARCH DURING OUTBREAKS (CREDO) TRAINING CURRICULUM: GENERATING CLINICAL EVIDENCE DURING OUTBREAKS IN LMICS

A training curriculum to help clinicians and researchers in low- and middle-income countries generate clinical evidence during outbreaks of infectious diseases.

The conduct of clinical research during epidemics poses special challenges and historically has been inadequate. The Clinical REsearch During Outbreaks (CREDO) training curriculum will support researchers in low- and middle-income countries to generate clinical evidence during outbreaks of infectious diseases. The CREDO training curriculum will encompass the full spectrum of activities that generate clinical evidence, from gathering good quality descriptive clinical data right through to clinical trials of experimental therapeutic interventions.

The aim of CREDO is to strengthen the national capacities of LMICs to generate clinical evidence during outbreaks. The CREDO training curriculum will be targeted specifically towards individuals living and working in LMICs in order facilitate networking and the sharing of resources and thus improve national response to disease outbreaks.

This developmental project will define, develop and pilot a curriculum and training programme to specifically strengthen in-country capacities to conduct clinical research in epidemics. The programme will be tested in Uganda initially with the potential of being expanded to cover both a wider range of countries and situations. The training programme can be integrated into the TDR training activities (RCS/KM) and contribute to the TDR commitment to strengthen country responses in emergencies (IIR).

The project aims to bridge the gap that exists in the availability and resources for training on how to conduct research in emergencies. CREDO training will consist of ten course modules: 1) Good Clinical Practice; 2) ‘Evidence-based’ medicine for epidemic infections; 3) Rapid ‘evidence-needs’ appraisal; 4) Research study planning and governance; 5) Study design; 6) Logistics and operational planning; 7) Ethics; 8) Special groups: children, pregnant women, mother/child; 9) Communications & engagement; 10) Data sharing and harmonisation.

The training will be delivered in a blended format comprising face-to-face workshops and self-directed web-based learning.

Key deliverables: 1) Completion of the pilot training in-country; 2) Course assessment completed; 3) Providing online access to all CREDO course materials.

Progress in 2016

• The Core Development Team established (including representatives from WHO, Oxford University, Wellcome Trust and countries: Uganda, Brazil and China).

• Four multi-disciplinary teams comprising 17 participants have been selected for the CREDO pilot. The teams are based at University of Gondar, Ethiopia; PACCI Research Programme, Ivory Coast; Kumasi Centre for Collaborative Research, Ghana and MRC Uganda. The first workshop will take place 9-10 March, 2017 at the Uganda Virus Research Institute in Entebbe.

• Outlines and intended learning outcomes for eight out of ten of the modules received, with contributions from other WHO departments.


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Plans for 2017

• January-February: finalise module content and build eLearning modules • March: hold first face-to-face workshop at UVRI, Entebbe • March-May: participants work through eLearning, complete formative and summative

assessments • June: hold second face-to-face workshop at UVRI, Entebbe • June-July: grade assessments and feedback to participants • August-November: make changes to curriculum based on feedback from pilot participants

and update eLearning • December: update study design module with final WHO materials (design, decision tree, trial

simulator and protocol) • December: all CREDO pilot deliverables completed

4. TITLE: DEVELOPMENT OF A GOOD DATA MANAGEMENT PRACTICES (GCDMP) TRAINING COURSE

A short course on data management to improve management practices and use of routine programmatic data by the national control programmes in LMICs

In-country capacity for data management covers not only clinical research (where it is a critical element to generate high-quality research data according to Good Clinical Research Practices and regulatory requirements), but also routine and surveillance data generated by national control programmes. Indeed, accumulated routine control programme data are of great value in measuring the effects of national programme strategies and for guiding researchers to define operational research priorities. This requires adequate databases. Unfortunately, few control programmes – particularly in low- and middle-income countries are actually prepared and equipped to effectively manage these data. The proposed project builds upon previous TDR-supported experiences and goes one step further. Data managers already trained by TDR (fellowships or training as part of research projects) will develop a short course on good data management practices, addressing the training needs of control programme data managers for managing routine and research data with high quality standards.

Progress in 2016

The development of the course is coordinated by the Luxembourg Institute of Health (LIH). Five data managers who had gone through previous training from either research institutes or national control programmes (tuberculosis, malaria, neglected diseases) of Benin, Burkina Faso, Conakry, Guinea and Senegal were selected. Data managers (or monitoring evaluation staff) of the national control programmes of French-speaking LMIC countries were targeted. A meeting was organized in June 2016 to define the curricula of the training course and another one in December 2016 to discuss a draft version of the training modules developed by the data managers.

Plans for 2017

Course development is expected to be finalised by the end of Q2 2017 and the course piloted Q3/Q4 2017 in Burkina Faso and/or Senegal. Funds are being sought for organizing these pilots.


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IIR budget and financial implementation

Table 5: IIR Budget for 2016-2017

Implement. rate

Expected result UD DF Total UD DF Total Total

Intervention and Implementation Research (IIR) 4,605,600 2,400,000 7,005,600 2,218,354 1,154,255 3,372,609 48%

Facilitate Innovation

1.1.5 Facilitate product innovation to support control programmes 271,900 271,900 153,010 153,010 56%

Sustain intervention effectiveness

1.1.4 Vulnerability of chemotherapy for helminths to resistance 775,700 775,700 218,901 218,901 28%

1.1.9 Enhance surveillance for malaria drug resistance -

Strengthen evidence base for WHO recommendations and Country policies

1.1.7 Maximize use of available data for policy decisions 527,600 527,600 311,792 311,792 59%

1.1.8 Optimize acquisition and analysis of new safety data for policy decisions

624,200 977,200 1,601,400 455,028 533,633 988,661 62%

Optimize interventions in support of control programmes

1.2.4 Structured Operational Research and Training Initiative (SORT-IT) 673,000 1,037,800 1,710,800 224,753 339,003 563,756 33%

1.2.2 Strategies to accelerate research to policy translation (COSMIC) 85,000 85,000 - 0%

1.1.1 Research on Dengue outbreak response 205,000 300,000 505,000 51,062 281,619 332,682 66%

1.2.1 Research on elimination of VL in the Indian Sub-Continent 571,700 571,700 241,217 241,217 42%

1.2.3 Research on management on febrile illnesses 434,500 434,500 394,618 394,618 91%

1.2.5 Translating knowledge for healthy housing - -

1.2.6 Research on improved TB control 522,000 522,000 167,971 167,971 32%

Revised planned costs Implementation as at31 December 2016


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Table 6: IIR Budget for 2018-2019

UD DF Total UD DF Total

Proposed 2,000,000 2,460,000 4,460,000 3,800,000 3,240,000 7,040,000

Research for Policies

1.1.4 Country resiliance to the threat of drug-resistant infections 350,000 80,000 430,000 850,000 100,000 950,000

1.1.1 Country preparedness for disease outbreaks 140,000 200,000 340,000 600,000 300,000 900,000

Research for Implementation

1.1.7 Maximized utilisation of data for public health decision making 400,000 650,000 1,050,000 650,000 1,000,000 1,650,000

1.1.8 Maximized utilisation of safety information for public health decision making 200,000 800,000 1,000,000 200,000 1,100,000 1,300,000

1.2.1 Strategies to achieve and sustain disease elimination 360,000 200,000 560,000 550,000 200,000 750,000

1.2.6 Optimised approaches for effective delivery and impact assessment of public health interventions

450,000 430,000 880,000 700,000 440,000 1,140,000

Research for Innovation

1.1.5 Directions for development and accelerated access to new tools and strategies 100,000 100,000 200,000 250,000 100,000 350,000

Expected result Research for Implementation (IIR)

Lower scenario Higher scenario


46|

Funding by project

Unit Ref. ID

Principal Investigator (PI)

PI gender

Supplier Name (institution) Service Short Description (title) PO Total Amt

USD Disease or

research topic Country

B40448 Gomes, Melba Filimina *S064543 F Gomes, Melba Filimina

*S064543

Management and implementation of activities in support of Safety in Pregnancy and microbiological causes of severe infections in young infants

19,442 Fever management Safety

France

B40484 Vaillant, Michel M Lih - Luxembourg Institute of Health

Data Analysis of Response to Anthelmintic Treatment 9,868 Helminths Luxembourg

B40199 Guillerm, Martine Marguerite Jeanne *S200892

F Guillerm, Martine Marguerite Jeanne *S200892

Technical support to research on the etiological causes of serious infections in young African infants

22,950 Fever management France

NULL Mondal, Dinesh M ICDDR, B (International Centre for Diarrhoeal Disease Research)

Assessment of longevity of rK39 positive test among kala-azar patients and individuals with asymptomatic leishmania infection in Bangladesh.

24,963 VL Bangladesh

B40452 Obiero, Christina F

Kenya Medical Research Institute/ Wellcome Trust Research Programme

Preparation and conduct of the study on the microbiological causes of severe invasive infections in young infants in Africa

128,471 Fever management Kenya

B40009 Kroeger, Axel M Kroeger, Axel Lothar *TRl795

Research Programme on “Effective, affordable and evidence-based dengue early warning and response systems”

24,300 Dengue Germany

B40306 (2015/544940)

Mondal, Dinesh M ICDDR, B (International Centre for Diarrhoeal Disease Research)

Improved Visceral Leishmaniasis (VL) Case Detection and Vector Control to Support the VL Elimination Initiative in Bangladesh


B60000 Yodi Mahendradhata M Universitas Gadjah

Mada

Preparation for stakeholders consultation on development of the national operational /implementation research capacity building strategy for effective control of tuberculosis (TB), malaria and neglected tropical diseases (NTDs) in Indonesia

21,030 Access and Delivery Indonesia


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Unit Ref. ID


PI gender


USD Disease or


EDIT/ENG/20 000 Howes, Penny F Howes, Penny

Technical editing services for Public Health Panorama, Journal of the WHO regional Office for Europe

2,597 SORT IT United Kingdom

B40284 Walker, Dr. Martin M Imperial College London

Evaluating Variation Among Anthelmintic Drug Response to Support the Control and Elimination of Human Helmith

14,041 Oncho, LF, schisto, STH

United Kingdom

B40308 (2015/538540)

Raj Banjara, Megha M

Public Health and Infectious Disease Research Centre (PHIDREC)

Improved Visceral Leishmaniasis (VL) Case Detection and Vector Control to Support the VL Elimination Initiative in Nepal

13,000 VL Nepal

TRA/ENG/25000 Izotov, Volodymyr M Izotov, Volodymyr

English-Russian translation services for Public Health PAnorama, Journal of the WHO Regional Office for Europe

6,500 SORT IT Ukraine

B60002 Kroeger, Axel M Universitätsklinikum Freiburg

Improved VL surveillance, case detection and vector control for the support of the VL elimination initiative in Bangladesh and Nepal with emphasis on the consolidation and maintenance phase

24,500 VL Germany

B60001 Yodi Mahendradhata M Universitas Gadjah

Mada

Stakeholders consultation on development of the national operational/implementation research capacity building strategy for effective control of tuberculosis (TB), malaria and neglected tropical diseases (NTDs) in Indonesia


B40010 Petzold, Max M Petzold, Max Research Programme on “Effective, affordable and evidence-based dengue early warning and response systems”.

22,676 Dengue Sweden

B40014 Benitez Valladares, David M Benitez Valladares,

David

Research Programme on “Effective, affordable and evidence-based dengue early warning and response systems”.

11,338 Dengue Mexico

B40335 Bowman, Leigh Robert *TRl112964

M Bowman, Leigh Robert *TRl112964


34,014 Dengue United Kingdom


48|

Unit Ref. ID


PI gender


USD Disease or


TRA/E/20053

Tolkachov, Dmytro Vadymovych

M Tolkachov, Dmytro Vadymovych

Written translation from UKR/RUS to ENG of protocols for SORT IT II workshop in April 2016, Kyiv, Ukraine

1,003 SORT IT Ukraine

B60005 Hussain, Laith Naser M Hussain, Laith Naser


7,000 Dengue Sweden

B60004 Schwarb, Lisa *S083518 F Schwarb, Lisa *S083518

Production of general TDR identity projects and high level, cross-cutting scientific documents, and ESSENCE documents

12,950 N/A Switzerland

TDR-CMM Hopkins, Diana F Hopkins, Diana

Provide technical editing and final formatting in Word and PowerPoint of EVIPNet Africa Meeting, Key enabling factors in effective and sustainable research networks and Technical handbook for surveillance, dengue outbreak prediction/detecti

5,379 Dengue Switzerland

HQTDR N/A N/A Tais Designer services for layout of PH Panorama, Volume 2, Issue 1 14,093 SORT IT Denmark

HSS N/A N/A Government of Sierra Leone

Fund for the Structured Operational Research and Training Initiative (SORT IT) Workshop in Sierra Leone.

82,645 SORT IT Sierra Leone

EDIT/ENG/30000 N/A N/A Alchemy Editorial

Services Ltd Proof reading for Panorama Journal, Volume 2, Issue 1, TB in Central Asia 690 SORT IT - TB United

Kingdom

B20340 Runge-Ranzinger, Silvia *TRl50092 F Runge-Ranzinger, Silvia

*TRl50092

Research Programme on "Effective, Affordable, and Evidence-Based Dengue Early Warning and Response Systems".


B60011 N/A N/A Universitätsklinikum Freiburg

Protocol writing workshop related to “Improved VL surveillance, case detection and vector control for the support of the VL elimination initiative in Bangladesh and Nepal”

8,380 VL Germany


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Unit Ref. ID


PI gender


USD Disease or


TME Anderson, Laura F. F Anderson, Laura F.

To provide epidemiological support to strengthening TB surveillance, and improving the analysis and use of TB surveillance data - continuation of contract of 1 Jan - 15 May 2015, registration no. 2015/580318, PO201389881.

24,300 TB United Kingdom

B60015 Armstrong, Jana Marie F Armstrong, Jana Marie IIR’s potential for funding diversification 8,083 N/A Switzerland

B60016 France, Tim M Inis Communication Ltd

Strategic communications advice and support / development and delivery of communications products – access and delivery partnership project

59,930 Access and Delivery Thailand

B60022 Vaillant, Michel M Lih - Luxembourg Institute of Health

Development and hosting of central database platform for collection of safety data in the scope of active TB drug-safety monitoring.

61,500 TB Luxembourg

B60023 Gowelle, Otilia Flavian *TRl64343 F Gowelle, Otilia Flavian

*TRl64343 Training on integrated management of childhood illness for Haydom study site. 23,000 Fever

management

Tanzania, United Republic of

B60031 Affolabi, Dissou M Programme National Contre la Tuberculose

West African National Tuberculosis Network training module 1. 52,000 Tuberculosis Benin

B60036 N/A N/A Instituut Voor Tropische Geneeskunde

External Quality Assessment (bacteriology) for study sites in Burkina Faso and Tanzania 1,956 Fever

management Belgium

B60037 Abu-Agla, Ayat Siddig Yousif *TRl86826

F Abu-Agla, Ayat Siddig Yousif *TRl86826

Technical revision of the IR Tool Kit to support capacity to identify and address country-specific health research priorities for effective control of tuberculosis (TB), malaria and neglected tropical diseases (NTDs) in LMIC

1,750 Access and Delivery Ireland

B60044 Krentel, Alison F Krentel, Alison


5,400 Access and Delivery Canada


50|

Unit Ref. ID


PI gender


USD Disease or


B60042 Najjemba, Robinah F Najjemba, Robinah


7,500 Access and Delivery Switzerland

B60041 Okorosobo, Temituoyo K. *S069779

M Okorosobo, Temituoyo K. *S069779


5,000 Access and Delivery Nigeria

B60039 Dako-Gyeke, Phyllis *TRl135480

F Dako-Gyeke, Phyllis *TRl135480

Technical revision of the IR Tool Kit to support capacity to identify and address country-specific health research priorities for effective control of tuberculosis (TB), malaria and neglected tropical diseases (NTDs) in LMIC.

2,400 Access and Delivery Ghana

B60038 Andono Ahmad, Riris *TRl49024 M Andono Ahmad, Riris

*TRl49024

Technical revision of the IR Tool Kit to support capacity to identify and address country-specific health research priorities for effective control of tuberculosis (TB), malaria and neglected tropical diseases (NTDs) in LMIC.


B60040 Gyapong, Margaret *TRl1365

F Gyapong, Margaret *TRl1365



B60043 France, Timothy David *S066656 M France, Timothy David

*S066656




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Unit Ref. ID


PI gender


USD Disease or


B60046 N/A N/A Bruyere Research Institute

Local organization of the 2nd meeting of the Review of the TDR Implementation Research Toolkit” Ottawa, Canada, 13-15 June 2016.

3,059 Access and Delivery Canada

B60034 N/A N/A Food and Drugs Authority, Ghana

Development of Individual Case Safety Reports (ICSR) Management System for Pre- and Post- Approval Safety Data in Ghana


B60051 Murtagh, Maurine M *TRl3535

M Murtagh, Maurine M *TRl3535

Landscape analysis of diagnostic technologies to detect Zika virus (ZIKV) and chikungunya virus (CHIKV) for clinical management, including differentiation among dengue virus (DENV), ZIKV and chikungunya, surveillance and research

18,900 Arbovirosis United States

B60020 Thant, Kwaw Zin M Department of Medical Research

SORT IT Operational Research Fellows (Tuberculosis and Malaria) Programme 60,000 SORT IT - TB /

Malaria Myanmar

B60057 Zachariah, Rony *TRl41264 M Zachariah, Rony

*TRl41264

Archiving of SORT IT courses, participants, facilitators, milestones, outcomes, publications and other relevant materials

13,000 SORT IT Luxembourg

B60055 Affolabi, Dissou M Programme National Contre la Tuberculose

West African National Tuberculosis Network training module 2. 75,743 Tuberculosis Benin

B60060 Oduro, Abraham M Navrongo Health Research Centre

Mobile technology (MOTEC-PV) for safety monitoring of community-based integrated administration of ivermectin, praziquantel and albendazole for the control of schistosomiasis and lymphatic filariasis and intestinal helminthes in northern Gh

99,862 Safety Ghana

B40238 Warwick, Grant M La Trobe University Literature Review on the determinants of parasite drug response and transmission 2,000 Oncho, LF,

schisto, STH Australia

B40237 Warwick, Grant M La Trobe University

Coordination and facilitation of the collaboration between two TDR-funded research groups on models of transmission of parasites

2,000 Oncho, LF, schisto, STH Australia


52|

Unit Ref. ID


PI gender


USD Disease or


B40480 Bonsu, Franck M National Tuberculosis Control Programme National TB Task Force in Ghana 3,570 Tuberculosis Ghana

B40009 Kroeger, Axel Lothar *TRl795 M Kroeger, Axel Lothar

*TRl795

Research Programme on “Effective, affordable and evidence-based dengue early warning and response systems”


B40261 Warwick, Grant M La Trobe University Risk Management Plan for Projects B40131 and B40133 3,685 Onchocerciasis Australia


Study design and genetic analyses: Developing molecular tools to define Onchocerca volvulus transmission zones and estimate transmission risks between zones.

10,377 Onchocerciasis Australia

B40122 Osei-Atweneboana M

Council for Scientific and Industrial Research (CSIR)

Development of diagnostic genetic markers to detect sub optimal response to ivermectin. 6,490 Onchocerciasis Ghana

B40123 Wanji, Samuel M Research Foundation In Tropical Diseases and Environment

Research for genetic markers of O. volvulus response to ivermectin and development of an onchocerciasis control programme surveillance tool.

17,966 Onchocerciasis Cameroon

B40127 Warwick, Grant M La Trobe University A population genetic model for the selection and transmission of ivermectin sub-optimal response genotypes




Development of diagnostic genetic markers to detect sub optimal response to ivermectin treatment

5,175 Onchocerciasis Ghana


Study design and genetic analyses: Development of diagnostic genetic markers to detect sub optimal response to ivermectin treatment.


B40517 Bolay, Fatoma M Liberian Institute for Biomedical Research

Informing participants in the moxidectin phase 3 study and their communities about the results of the study.

1,629 Onchocerciasis Liberia


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Unit Ref. ID


PI gender


USD Disease or




Developing molecular tools to define Onchocerca volvulus transmission zones and estimate transmission risks between zones.

2,057 Onchocerciasis Ghana

B40358 Martinez, Dalila F Universidad Peruana Cayetano Heredia

Disease experiences of Cutaneous Leishmaniasis (CL) patients 2,875 Cutaneous

Leishmaniasis Peru

B40360 Fernandes Cota, Glaucia F Centro de Pesquisas

Rene Rachou - Fiocruz Disease experience of Cutaneous Leishmaniasis (CL) patients 550 Cutaneous

Leishmaniasis Brazil

B40357 Handjani, Farhad M Shiraz University of Medical Sciences

Disease experiences of Cutaneous Leishmaniasis (CL) patients 2,419 Cutaneous

Leishmaniasis Iran, Islamic Republic of

B40134 Wanji, Samuel M Research Foundation In Tropical Diseases and Environment

Research for genetic markers of O.volvulus response to ivermectin and development of an onchocerciasis control programme surveillance tool.

63,107 Onchocerciasis Cameroon

B60070 France, Tim M Inis Communication Ltd

Local organization of the final meeting of the review of the TDR implementation research toolkit” Chiang Mai, Thailand. 12-17 September 2016.


B40356 Ben Salah, Afif M Institut Pasteur De Tunis Disease experiences of Cutaneous Leishmaniasis (CL) patients 2,688 Cutaneous

Leishmaniasis Tunisia

B40501 Plugge, Emma Harriet F Plugge, Emma Harriet

Cutaneous Leishmaniasis (CL) Clinical Trial Methodology project Training and practical exercises in conduct and analysis of qualitative patient interviews.

331 Cutaneous Leishmaniasis

United Kingdom

B40355 Castro Noriega, M F Fundacion Cideim Conducting interviews with CL patients (CL) patients 2,868 Cutaneous

Leishmaniasis Colombia

B40221 Gurung, Chitra Kumar M

Public Health and Infectious Disease Research Centre (Phidrec)

Improved VL case detection and vector control for the support of the VL elimination initiative in Bangladesh and Nepal

12,000 VL Nepal


54|

Unit Ref. ID


PI gender


USD Disease or


B40177 Alfonso Sierra, Eduardo Andres M Alfonso Sierra, Eduardo

Andres

Improved Visceral Leishmaniasis case detection and vector control for the support of the Visceral Leishmaniasis elimination initiative in Bangladesh and Nepal.

15,000 VL Colombia

B40479 Chia M Programme Nationale de Lutte Contre la Tuberculose Et la Lepre

National TB Task Force in Mauritania 3,450 Tuberculosis Mauritania

B40513 N/A N/A Oxford University

Cutaneous Leishmaniasis (CL) Clinical Trial Methodology project Training and practical exercises in conduct and analysis of qualitative patient interviews - Workshop.

21,857 Cutaneous Leishmaniasis

United Kingdom

B40464 Densem, James M Biomedical Computing Limited

Evaluation of potential to link national database and a central registry for the epidemiological surveillance of drug safety in pregnancy

3,900 Safety United Kingdom


Development of a birth defect database for developing countries 35,263 Safety United

Kingdom

B60075 Bonsu, Franck M National Tuberculosis Control Programme West African National Tuberculosis Network 10,000 Tuberculosis Ghana

B60074 Sarr, Marie F Programme National de Lutte Contre la Tuberculose (Plnt)

West African National Tuberculosis Network 10,000 Tuberculosis Senegal

B40352 Bouyou, Marielle F Departement de Parasitologie Mycologie

Relationship between microfilaremia, clinical symptoms of filariasis and treatment regimens: analysis of historical data of Loa Loa in Gabon

8,645 Loa-loa Gabon

B40348 Singlovic, Jan M Singlovic, Jan

Development of database and data management services for study on microbiological causes of invasive infections in young African infants

27,000 Fever management

Czech Republic

B40446 Sarr, Marie F Programme National De Lutte Contre la Tuberculose (Plnt)

National TB Task Force in Senegal 3,750 Tuberculosis Senegal


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Unit Ref. ID


PI gender


USD Disease or


B40220 Raj Banjara, Megha M

Public Health and Infectious Disease Research Centre (PHIDREC)


12,015 VL Nepal

B40227 Mondal, Dinesh M ICDDR, B (International Centre for Diarrhoeal Disease Research)

Improved VL case detection and vector control for the support of the VL elimination initiative in Bangladesh and Nepal: Complementary analysis of vector control interventions for the control of VL vectors on the Indian sub-continent


B40432 Salomon, Hainga M Pnlt-Togo National TB Task Force in Togo 3,750 Tuberculosis Togo

B40222 Mondal, Dinesh M ICDDR, B (International Centre for Diarrhoeal Disease Research)


6,000 VL Bangladesh

B40434 Kessely, Dede F National Leprosy and Tuberculosis Control Program

National TB Task Force in Liberia 3,750 Tuberculosis Liberia

B40240 Chowdhury, Rajib *S204513 M Chowdhury, Rajib

*S204513

Determining insecticide resistance for supporting improved visceral leishmaniasis vector control in Bangladesh


B60094 France, Tim M Inis Communication Ltd Revised TDR Implementation Research Tool Kit Design, development, beta testing and launch of self-learning website


B60093 France, Tim M Inis Communication Ltd Revision of TDR Implementation Research Tool Kit Technical editing and presentation at the 4th Global Symposium on Health Systems


B60002 Kroeger, Axel M Universitätsklinikum Freiburg

Improved VL surveillance, case detection and vector control for the support of the VL elimination initiative in Bangladesh and Nepal with emphasis on the consolidation and maintenance phase.

24,500 VL Germany


56|

Unit Ref. ID


PI gender


USD Disease or


B60015 Armstrong, Jana Marie F Armstrong, Jana Marie

Development and Initial Implementation of Project Proposal prepared for the IIR, RCS/KM and VES Teams

36,000 N/A Switzerland

B60096 Oriyo, Ndeki F National Institute for Medical Research

Electronic data capture for safety monitoring of preventive chemotherapy interventions for the control of neglected tropical diseases in rural areas of Tanzania

99,978 Safety Tanzania, United Republic of

B60101 Sanon Epouse Gouem, Clarisse *TRl35470

F Sanon Epouse Gouem, Clarisse *TRl35470

Clinical Monitoring of the study on microbiological causes of invasive infections in young African infants in Burkina Faso

4,575 Fever management Burkina Faso

B40009 Kroeger, Axel Lothar *TRl795 M Kroeger, Axel Lothar

*TRl795

Research Programme on “Effective, affordable and evidence-based dengue early warning and response systems"


B60104 Hirve, Siddhivinayak *TRl869

M Hirve, Siddhivinayak *TRl869

TDR supported research on “Improved VL case detection, case management and vector control for the VL elimination initiative in Bangladesh, India and Nepal”

15,000 VL India


Hosting of the central registry for the epidemiological surveillance of drug safety in pregnancy and support for database management

6,536 Safety United Kingdom

B60106 Najjemba, Robinah F Najjemba, Robinah Collation and consolidation of 21 case studies

for the revised IR TK 8,250 Access and Delivery Switzerland

B60112 Raguenaud, Marie-Eve *TRl18693

F Raguenaud, Marie-Eve *TRl18693

Tuberculosis epidemiological Review in Burkina Faso and Mali 14,000 Tuberculosis France


|57

2018-19 outlook within the proposed 2018-2023 TDR strategy Within the frame of the proposed 2018-23 strategy, IIR will focus on research for guidelines, policies and their effective implementation in public health programmes, in order to respond to needs for improved disease control, elimination and response to emerging threats. The workplan provides for supporting research to evaluate WHAT ‘tools’ (medicinal products, diagnostics, interventions, approaches/strategies) that have been developed are suitable for introduction into guidelines and policies, HOW guidelines and policies can be implemented (scaled up) in public health programmes to maximize their impact, and how to assess the IMPACT of their implementation. In line with TDR's overall strategy, IIR will not sponsor R&D, but may inform R&D by providing a directional perspective on INNOVATION required to address insufficiently as well as yet unattended health needs.

Objectives and Expected Results have thus been reorganized into three areas of activity:

1. RESEARCH FOR POLICIES: to understand and produce evidence on large-scale performance, acceptability, feasibility, implementation needs and potential impact of available tools as a basis for determining WHAT tools are suitable for guidelines and policies.

2. RESEARCH FOR IMPLEMENTATION: to understand and address barriers to effective, quality and equitable implementation of health interventions, strategies and guidelines/policies to provide the evidence as to HOW guidelines /policies can best be implemented for maximum IMPACT.


58|

3. RESEARCH FOR INNOVATION: to provide directions for the development of improved/adapted/new tools and strategies needed, and to promote their development.

Expected outputs and targeted output users and outcomes are summarized below:

The budget assigned to the three areas of activity for the 2018-2019 biennium (within the US$ 40 million budget scenario), as well as to the individual ERs within each area, are presented below:

Inputs Outputs Output Users Outcomes RESEARCH FOR GUIDELINES/POLICIES (Research for Policies):

Understanding large scale performance, implementation needs and potential impact of available tools and strategies • Global, regional, national health

needs/priorities • Products, tools, interventions,

R&D results • Country experience with

introduction of new tools and scale-up

• Effectiveness and safety of available tools with current and new strategies

• Requirements for large-scale use of current and new approaches with available tools within health systems

• Implementers: Global, regional, national MoH, NGOs

• Researchers: global, regional, national

• Funders: Health service provision funders, research funders

FOR POLICY • New/modified

guidelines, policies FOR RESEARCH • Needs and plans for

Research for Implementation

• Innovation needs

RESEARCH FOR OPTIMAL IMPLEMENTATION INTO HEALTH SYSTEM ROUTINE (Research for Implementation): Understanding and addressing barriers to effective, quality and equitable implementation of health interventions,

strategies and guidelines/policies and assessing their impact • Products, tools, interventions,

R&D results • OUTPUT of Research for Policies • Guidelines/policies • Health system characteristics • Health system experience with

new/comparable tools/strategies • Global, regional, national health

needs/priorities

• Data informing new/improved strategies for implementation of specific products/services/policies

• Data informing new/improved estimate of potential impact (cost-effectiveness)

• Data informing new/improved monitoring and evaluation strategies

• Implementers: Global, regional, national MoH, NGOs

• Researchers: global, regional, national

• Funders: Health service provision funders, research funders

FOR IMPLEMENTATION • New/improved policy

implementation strategies

• New/improved M&E and impact assessment strategies

• Improved programme performance

• Improved health impact FOR RESEARCH • Innovation needs

INFORM RESEARCH FOR INNOVATION (Research for Innovation) Defining improved/new tools and strategies needed and promoting their development

• OUTPUT of Research for Policies • OUTPUT of Research for

Implementation • Country scale up experience • Health Impact Assessments

• Public-health need directional perspective for research of new products, tools and interventions

• Specifications for innovations defined

• Innovation needs disseminated

• Global, regional, national researchers, R&D Organizations,

• Research funders

FOR RESEARCH FOR POLICY • New, adapted tools

developed


|59


60|

TDR funding in 2016

Core Contributors Amount ($)

Belgium 1,114,827

China 55,000

Cuba 5,000

Germany 665,927

India 110,000

Japan 280,000

Luxembourg 1,133,787

Malaysia 25,000

Mexico 30,000

Nigeria 302,602

Norway 952,268

Spain 42,463

Sweden 4,031,277

Switzerland 1,685,393

Thailand 41,911

Turkey 5,000

United Kingdom of Great Britain and Northern Ireland 3,053,435

World Health Organization 901,195

Contributors providing specific project funding

Bill & Melinda Gates Foundation 2,080,582

Switzerland 128,205

The Union 340,000

United Nations Development Programme (UNDP) 1,194,604

United States of America 628,103

Intervention and Implementation Research

Documents

Transcript of Intervention and Implementation Research