research for implementation...er 1.3.6: evaluation and improvement of malaria control policies...

Annual Report 2019

Research for Implementation

Research for Implementation Annual Report 2019

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Table of contents

List of abbreviations ............................................................................................................................. 3

Introduction ......................................................................................................................................... 5

Objectives ............................................................................................................................................. 5

Key achievements in 2019 ................................................................................................................... 6

Summary progress description ............................................................................................................ 9

Progress description in 2019 and plans for 2020-2021 ..................................................................... 14

Workstream: Research for policies ........................................................................................................ 14 ER 1.1.1: Country preparedness for disease outbreaks ................................................................................. 14 ER 1.1.4: Country resilience to the threat of drug-resistant infections ......................................................... 17 ER 1.3.3: Population health vulnerabilities to vector-borne diseases (VBDs): Increasing resilience under

climate change conditions in Africa ............................................................................................. 26 ER 1.3.7: Environmental prevention and control of VBDs and infectious diseases in South-East Asia ......... 28

Workstream: Research for Implementation .......................................................................................... 46 ER 1.1.7: Maximized utilization of data for public health decision-making .................................................. 46 ER 1.1.8: Maximized utilization of safety information for public health decision-making ........................... 52 ER 1.2.1: Strategies to achieve and sustain disease elimination .................................................................. 56 ER 1.2.6: Optimized approaches for effective delivery and impact assessment of public health

interventions ................................................................................................................................ 60 ER 1.3.8: Develop, pilot test and replicate an innovative training course for capacity building on

gender-based analysis in VBD research and other infectious diseases of poverty ...................... 71 ER 1.3.12: Strategies to promote gender-responsive health interventions on prevention and control of

infectious diseases ....................................................................................................................... 73

Workstream: Research for innovation ................................................................................................... 77 ER 1.1.5: Directions for development and accelerated access to new tools and strategies ......................... 77 ER 1.3.10: Urban health interventions for the prevention and control of vector-borne and other

infectious diseases of poverty ...................................................................................................... 78

Workstream: Research for Integrated approaches................................................................................ 81 ER 1.3.6: Evaluation and improvement of malaria control policies through study of the impact of

insecticide resistance on LLINs and IRS efficacy, and preliminary analysis of the burden and causes of residual malaria .................................................................................................... 81

ER 1.3.11: Multisectoral approach for prevention and control of malaria and emerging arboviral diseases ........................................................................................................................................ 90

Outcomes of past projects ............................................................................................................... 100

Budget and financial implementation ............................................................................................. 101

Projects and activities funded .......................................................................................................... 104

TDR funding in 2019 ......................................................................................................................... 119

Scientific Working Group recommendations ................................................................................... 120


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List of abbreviations ADP Access and Delivery Partnership

aDSM Anti-TB drugs active drug safety monitoring

AFRO WHO Regional Office for Africa

AMR Antimicrobials resistance

ASEAN Association of Southeast Asian Nations

ASEAN NDI Association of Southeast Asian Nations – Network for Drugs, Diagnostics, Vaccines and Traditional Medicine Innovation

CARN-TB Central African Regional Network for TB Control

ClimDevAfrica Climate for Development in Africa Initiative

DEC Disease endemic, low- and middle-income countries

EDCTP European and Developing Countries Clinical Trials Partnership

ESPEN Expanded Special Project for Elimination of NTDs

EWARS Early Warning and Response System

EURO WHO Regional Office for Europe

GBA Gender-Based Analysis

GFCS Global Framework for Climate Services

GFTAM Global Fund to Fight AIDS, Tuberculosis and Malaria

GTB WHO Global TB Programme

H-NAP Health National Adaptation Plans

IAEA International Atomic Energy Agency

IDDO Infectious Diseases Data Observatory

IDP Infectious Diseases of Poverty

IDRC International Development Research Centre (Canada)

IIR Intervention and Implementation Research team

IR Implementation research

IRI International Research Institute for Climate and Society at Columbia University, New York, USA

IRS Indoor Residual Spraying

ISC Indian Sub-Continent

JCB TDR Joint Coordinating Board

LLINs Long-lasting insecticidal nets

LMIC Low- and middle-income country

LSHTM London School of Hygiene and Tropical Medicine

M&E Monitoring and evaluation

MDA Mass drug administration

MDGH Medicines Development for Global health

MDR-TB Multidrug resistant tuberculosis

MoH Ministry of Health

MPH Master of Public Health

MSA Multi-sectoral approach

NDCs National Determined Contributions

NDRS National TB drug resistance surveys


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NMAIST Nelson Mandela African Institute of Science and Technology, Arusha, the United Republic of Tanzania

NMP National malaria programme

NPCS National surveys of cost faced by TB patients and their household

WHO/UCN/NTD WHO Control of Neglected Tropical Diseases Department

NTDs Neglected Tropical Diseases

NTP National Tuberculosis Programme

NTPS National TB prevalence surveys

OR/IR Operational and implementation research

PAHO Pan-American Health Organization

PHE Public Health England

PHE (WHO) Public Health, Environmental and Social Determinants of Health

PHE (AFRO) Protection of Human Environment

PI Project investigator

RCS TDR unit on Research Capacity Strengthening

RTC Regional Training Centre

RVF Rift Valley fever

SDF Strategic Development Funds

SDG Sustainable Development Goals

SEARO WHO Regional Office for South-East Asia

SIT Sterile Insect Technology

SMC Seasonal malaria chemoprevention

SORT IT Structured Operational Research and Training Initiative

SPH School of Public Health, University of Ghana

SPT Special Project Team

STAC TDR Scientific and Advisory Committee

STH Soil-transmitted helminth

SWG Scientific Working Group

TDR Special Programme for Research on Tropical Diseases

The Union International Union Against Tuberculosis and Lung Disease

UHC Universal health coverage

USAID United States Agency for International Development

US-FDA United States of America Food and Drug Administration

VBD Vector-borne disease/s

VES TDR team on Vectors, Environment and Society

VL Visceral Leishmaniasis

WAHO West African Health Organization

WARN-TB West African Regional Network for TB control

WASH WHO’s provision of safe water, sanitation and hygiene intervention

WHO HQ World Health Organization Headquarters in Geneva, Switzerland

WMO World Meteorological Organization

WPRO WHO Regional Office for the Western Pacific


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Introduction Research for Implementation is one of the two arms of the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) within its 2018–2023 strategy. The supported research activities are contributing to achievement of the Sustainable Development Goals (SDGs) by 2030, specifically SDG3 “Ensure healthy lives and promote wellbeing for all at all ages” and SDG 10 “Reduce inequalities within and among countries,” as well as supporting universal health coverage (UHC). The Research for Implementation activities are focusing mainly (but not exclusively) on research leading to the development of policies and guidelines and their effective implementation in public health programmes. The activities are also producing the evidence needed to reduce the burden of infectious diseases of poverty in low- and middle-income countries (LMICs).

Objectives The Research for Implementation activities focus on finding new solutions to reduce the burden of infectious diseases of poverty and ensure access to health technologies for those in need.

Four main areas of activity are included within TDR’s current strategy: 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, guidelines and policies to provide the evidence as to how these can best be implemented for maximum impact.


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

4. RESEARCH FOR INTEGRATED APPROACHES: to understand the complex interactions between people and their environment that affect disease transmission.

The above-mentioned objectives are being implemented through 14 expected results that have been developed in coordination with TDR’s Scientific Working Groups (SWGs).

Key achievements in 2019 Research on the burden and causes of residual and persistent malaria

Research projects on residual malaria and the impact of insecticide resistance on the efficacy of long-lasting insecticidal nets (LLINs), demonstrated that vectors and human behaviours as well as resistance to insecticides and inadequate control tools, were the main cause of residual malaria, although persistent malaria transmission in many settings was not residual but due to inadequate coverage and use of available tools (LLINs and IRS). The results were made available to decision-makers and the general public through the production of information briefs and video vignettes developed for the 13 countries from the four WHO regions involved in the six projects. The briefs and video vignettes can be found at the following link: http://vbd-environment.org/.

New plans for fighting malaria through implementation of multisectoral approaches and control tools more adequate to the local context have been developed for two projects, one in Africa including Benin, Burkina Faso, Mali and Nigeria and the other in the Greater Mekong Subregion including Cambodia and Viet Nam. Environmental prevention and control of vector-borne diseases (VBDs) in South-East Asia

• Implementation of projects on sustainable community-centred adaptation strategies within a framework of complex socioecological systems.

Urban health

• Scoping reviews were published in a special issue of the Journal of Infectious Diseases of Poverty on urban health, VBDs and other infectious diseases of poverty.

• A Memorandum of Understanding has been signed between TDR and IAEA to support joint activities to test the Sterile Insect Technology (SIT) against mosquitoes as vectors of diseases.

• A joint IAEA/TDR Guidance document on how to test SIT against mosquito vectors of arboviruses has been developed and was presented at an international press event, co-organized by TDR and the WHO communications office in November 2019. The event was attended by journalists from more than 30 countries and was followed worldwide in several languages.

• A call for applications to support research projects for testing SIT was launched in June 2019 and closed in October 2019. Ten applications were received among which six were deemed eligible. The review process of the eligible applications started in November 2019 and will close in early 2020.

Research initiative on VBDs and climate change

• New strategic development funds implemented to inform the framing of a proposed new expected result for operationalizing a One Health approach for the control of vector-borne diseases in the context of climate change in Africa.

http://vbd-environment.org/


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Multisectoral approaches

• Activities on multisectoral approaches for prevention and control of VBDs supporting six commissioned reviews, one workshop and one special session at the 2018 Geneva Health Forum attracted the interest of the Swedish International Development Cooperation Agency (Sida), to support the development of a cooperation between TDR and the WHO WASH1 group to implement a multisectoral collaboration on prevention and control of VBDs.

• A guidance framework on multisectoral approaches for prevention and control of VBDs is being developed.

Country preparedness for disease outbreaks: Early warning system for arboviruses

• Demonstration of the use of EWARS in outbreak preparedness and detection for other arboviruses, e.g. chikungunya and Zika. Update of the operational guidance to make provision for this extension.

Gender • The University of Ghana has institutionalized the gender training course being offered to students in their

Master of Public Health (MPH) programme. • The University of the Witwatersrand in South Africa ran the training at the end of 2019 and is exploring

avenues to institutionalize it within their MPH and PhD programmes. • The final draft of the TDR Toolkit on intersectional gender analysis in research on infectious diseases was

completed and the pilot began in December 2019. Expected results and research outcomes from the pilot are expected to be published in 2020.

• Outcomes of a 2018 TDR Expert Group meeting on gender and intersectionality consolidated the strategic direction to embrace intersectional gender analysis and promote an inclusive gender research agenda within TDR’s core research and research capacity strengthening efforts. Drawing from these outcomes, a TDR Strategy on gender and intersectionality was developed in 2019 and will be launched in 2020.

Africa sub-regional networks for TB control (WARN-TB / CARN-TB)

• Strategic approach in West and Central Africa to enhance TB research embedded in national TB programmes to support WHO’s End TB strategy.

• Improved case finding and access to TB care for vulnerable populations.

Research in support of TB control

• Convened 45 African countries for a regional meeting that resulted in identification of research barriers for the implementation of new treatment guidelines for multidrug-resistant TB and how to move forward.

• Development of a generic research package for facilitating the use of all-oral MDR-TB treatment regimens under operational research conditions.

Structured Operational Research & Training Initiative (SORT IT)

• Fourteen SORT IT courses held in 2019, 107 trainees and 96 publications. Expansion to 92 countries, 37 implementing partners and embracing SDGs and UHC. Fifty-one percent (51%) of trainees continue research independently and 69% of projects influence policy and practice.

1 WHO’s provision of safe water, sanitation and hygiene intervention (WASH)


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Antimicrobial resistance (AMR)

• Initiation of an AMR SORT IT programme. Using a “One Health” approach, engagement and alignment with national AMR action plans was achieved in all target countries. Thirty-six (36) operational research projects already under way with strong country collaboration and endorsement.

Research to support visceral leishmaniasis elimination in Indian sub-continent

• Two studies initiated to evaluate new approaches for active case detection, vector control and entomological surveillance adapted to the maintenance phase of VL elimination in Bangladesh, India and Nepal.

Strategic Development Fund (SDF) projects on networks and plague

• A network on preventing emerging VBDs in the Caribbean established in 2017 is still active and self-sustainable in 2019.

• A Worldwide Network on Insecticide resistance (WIN) distribution and mechanisms for Aedes mosquitos established in 2015 is still active and self-sustainable in 2019, and has produced a cost analysis for testing insecticide resistance in more than 70 countries.

• A network on preventing emerging VBDs in West Africa was formalized during a special event in July 2019 in Dakar and the needs assessment of 16 countries was finalized in 2019.

• High level resistance of fleas, the vectors of the Plague disease, to insecticides, in Madagascar has been demonstrated, with strong negative consequences on the control of this disease.


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Summary progress description TABLE 1: Research for implementation workplan – Overall progress

Ongoing expected results by outcome Indicators and progress against targets Research for policy 1.1.1 Country preparedness for disease outbreaks: i) Training curriculum and 'train the trainers' curricula; ii) consensus agreement of major stakeholders on critical elements of policies/guidelines for arbovirus surveillance; iii) consensus agreement of major stakeholders on critical elements of policy/guidelines for arbovirus outbreak response

By 2018, training curriculum made available on TDR website and shared with TDR regional training centres and other interested stakeholders. • Completed in 2018, curriculum available online and has

been shared with interested stakeholders as well as TDR regional training centres.

By 2019 critical elements for policy/ guidelines for arbovirus surveillance (ii) and response (iii) identified for further development. • Completed: Stakeholder meeting took place in November

2018 to discuss national surveillance system. Another stakeholder meeting took place in 2019 to discuss surveillance systems and how to strengthen collaboration in the field.

1.1.4 Country resilience to the threat of drug-resistant infections: i) OR/IR strategies for countries to build effective systems for monitoring and responding to emerging drug resistance of all relevant infectious agents; ii) Evaluation of practical approaches to improve targeted treatment and reduce drug misuse and risk of resistance; iii) Strategies for monitoring and responding to potential emergence of drug resistance in helminths; iv) Strategies for monitoring potential emergence of resistance during Seasonal Malaria Chemoprevention

By 2019, i) initial set of approaches to support countries selected for piloting, (iii) strategy related to helminths proposed to WHO/UCN/NTD department/ESPEN for discussion with stakeholders; (iv) potential strategy for monitoring potential malaria resistance during SMC evaluated. • (i) & (ii) Completed and in full implementation mode:

AMR SORT IT programme initiated in six target countries with 36 projects under way by December 2019.

• (iii) Delayed (and moved to ER 1.2.1, output 2). • (iv) Completed: analysis of study being completed.

1.3.3. Population health vulnerabilities to vector-borne diseases (VBDs): Increasing resilience under climate change conditions in Africa: i) vertical scale-up from the community level to use lessons learned to inform decision-making at higher levels; ii) replication of community participatory initiatives based on the initial intervention; iii) capacity building for the development of new models to better address social issues around adaptation

By 2019, five interdisciplinary communities of practice in five African countries established and functioning. By 2019, five countries utilize the new knowledge from research and the adaptation practices that make VBD-affected communities more resilient to climate change. • A new SDF implemented in 2019 is expected to inform

the framing of a proposed new expected result for operationalizing a One Health approach for the control of vector-borne diseases in the context of climate change in Africa. This will also form the basis for a new portfolio of projects to facilitate increased integrated coverage of health, agricultural and environmental interventions for the prevention/ control of VBDs while preserving ecosystem integrity in Africa.

1.3.7. Environmental prevention and control of vector-borne diseases and infectious diseases in South-East Asia: i) Environmental public health concerns and risks identified, characterized and assessed; ii) a sustainable, community-centred adaptation strategy developed and implemented; iii) benefits resulting from the use of the strategy assessed and monitored.

By 2018, two new vector control approaches available for the communities and added to existing tools for the implementation of vector control programmes. • Innovative solutions for VBD control are currently being

tested. Data have been generated for analysis.


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Ongoing expected results by outcome Indicators and progress against targets Research for implementation 1.1.7 Maximized utilization of data for public health decision making: i) capacity built for effective collection and analysis of data; ii) effective policies and outputs in countries to stimulate use of data; iii) support for interoperable data platforms; iv) evidence-informed policy

By 2018 (i) training curriculum for data managers developed; (ii) at least four self-sustained SORT IT programmes established at country and subregional levels. • (i) Completed. 11 planned training modules were

developed. One additional module focusing on the use of new applications for data collection is at the drafting stage.

• (ii) Completed. By 2019, (iii) support provided to at least three platforms. • Completed. Support provided for schistosomiasis, soil-

transmitted helminths and TB clinical trial data. 1.1.8 Maximized utilisation of safety information for public health decision making: i) capacity for safety monitoring of new drugs built in target countries; ii) improved evidence of drug safety in vulnerable patient groups; iii) innovative approaches for safety monitoring piloted that facilitate and improve normative guidance

By 2018, (i) first part of the Access and Delivery partnership completed; (ii) at least two databases related to drug exposure obtained and analysed, in collaboration with WHO control programmes and departments; (iii) utility of one innovative approach for monitoring safety in mass drug administration assessed. • (i) Completed. The first phase of ADP was completed in

March 2018. • (ii) Completed: aDSM database analysed in 2018;

pregnancy exposure central registry analysed in December 2018.

• (iii) Completed: use of mobile phones for safety monitoring evaluated and found to improve reporting rate in Ghana, Senegal and the United Republic of Tanzania.

1.2.1 Strategies to achieve and sustain disease elimination: i) evidence on sustainable strategies for the elimination of visceral leishmaniasis in the Indian subcontinent; ii) improved basis for monitoring progress of preventive chemotherapy-based elimination programmes towards elimination and for decisions to stop interventions; iii) approaches to facilitate malaria elimination in target countries

By 2019, (i) sustainable strategies for maintaining visceral leishmaniasis elimination in the Indian subcontinent proposed to countries; (ii) proposed improved basis discussed with stakeholders. • (i) Completed. Different studies have been completed

and the evidence shared with the relevant national control programmes; suggestions have been made for sustainable strategies for VL elimination.

• (ii) Delayed (in progress but not yet fully completed). 1.2.6 Optimized approaches for effective delivery and impact assessment of public health interventions: i) strengthened regional network of West African National Tuberculosis Programmes (WARN-TB) capable of identifying research priorities, and designing and conducting OR/IR to generate the evidence-base for policy decisions to achieve the goals of the End TB strategy; ii) expanded WARN-TB approach to other geographical areas and/or other diseases; iii) approaches to optimised delivery of preventive chemotherapy based helminth control strategies evaluated

By 2019, (i) report on the strengthened regional network WARN-TB provided to SWG and stakeholders at country, regional and global levels; (ii) feasibility of expanding approach to other areas (e.g. Central Africa) assessed. • Completed. The Central African Network for TB control

(CARN-TB) was established in March 2018 with similar planned activities to those conducted for WARN-TB. The regional model will be replicated in 2020-2022 for strengthening malaria national control programmes of West and Central Africa for optimizing the efficiency of seasonal malaria chemoprevention.


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Ongoing expected results by outcome Indicators and progress against targets 1.3.8. Training course for gender data analysis on vector-borne diseases: Developed, pilot-tested and replicated an innovative training course for capacity building on gender-based analysis in vector-borne disease research and potential other infectious diseases of poverty

By 2019, five research teams completed the training and the course adopted and implemented by the regional training centres. • Completed (course implemented by RTC Ghana and the

University of the Witwatersrand). - To date, the University of Ghana has institutionalized

training courses being offered to Master of Public Health students.

- The University of the Witwatersrand ran the training in 2019 and is currently exploring avenues for it to be institutionalized within its MPH and PhD programmes.

By 2019, at least five case studies completed as a result of the gender-based analysis conducted. • Completed and adjusted.

- Four case studies will be generated under ER 1.3.12 through application of the TDR toolkit on intersectional gender analysis.

- Research teams apply to their own research projects gender-based analysis approaches learned through this training course.

1.3.12. Strategies to promote gender-responsive health interventions on vector prevention and control: Strategies to promote gender-responsive health interventions on vector prevention and control

By 2019, four gender-based analysis guidance tools available for the research and health community, including guidance to gender-sensitive research methodology on infectious diseases of poverty. • Completed and adjusted.

- The final draft of the TDR Toolkit on intersectional gender analysis in research on infectious diseases has been completed and a pilot initiated in December 2019. The Toolkit followed due global consultation and expert peer review feedback before the pilot exercise at country level.

- Four case studies will be generated under ER 1.3.12 through application of the TDR toolkit on intersectional gender analysis.

- TDR Expert Group meeting on gender and intersectionality consolidated strategic direction to embrace intersectional gender analysis and promote an inclusive gender research agenda within TDR’s core research and research capacity strengthening efforts.

- Recognition and analysis of gender intersecting inequalities is being progressively addressed across the whole TDR portfolio: from research for implementation activities, to research capacity strengthening efforts, through global engagement and TDR Global.

- TDR’s gender and intersectionality strategy is being finalized and the launch planned by the first half of 2020.


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Ongoing expected results by outcome Indicators and progress against targets Research for innovation 1.1.5 Directions for development and accelerated access to new tools and strategies: i) evidence and advice to provide directional perspective for R&D for new tools as well as new ways of implementing tools; ii) optimised methodologies to assess response to case-based and population-based interventions; iii) strategy development, implementation and monitoring

By 2019, (i) involvement in at least two initiatives; (ii) optimized methodologies to measure effects of interventions for at least two diseases developed. • (i) Completed. Involved in 3 initiatives. • (ii) Completed. Including evaluation of optimized

methodologies for cutaneous leishmaniasis and schistosomiasis.

1.3.10. Urban health interventions for the prevention and control of vector-borne and other infectious diseases of poverty: i) Vector control response in urban settings enhanced through the following: supported a Working Group on Vectors for Dengue/Zika course in the Caribbean; contributed to the Global Vector Control Response, specifically for the assessment of capacity for testing insecticide resistance; and supported the proposed Network on Arbovirus Infections in Western Africa; ii) scoping reviews on urban health interventions for the prevention and control of vector-borne and other infectious diseases of poverty

By 2018, six scoping reviews and six policy briefs/briefs highlighting implications for policy informed by scoping reviews on VBDs and urban health • Completed. By end 2019, evidence briefs for policy

completed. Ministries of health in Brazil, Burkina Faso and Colombia played an important role during their development and will also take an active role in their dissemination.

Establishment of a collaboration between IAEA and TDR to carry out joint activities on the Sterile Insect Technology (SIT). (This activity will move to ER 1.3.14 in 2020.)

The collaboration was established through an MoU signed in June 2019. • A joint guidance document on how to test SIT against

Aedes-borne diseases has been finalized and will be published early in 2020.

• A joint call to support research projects was launched and applications received are under review.

Research for integrated approaches 1.3.6. Impact of insecticide resistance and residual malaria on malaria control: i) New scientific information on insecticide resistance mechanisms generated to fill critical knowledge gap; ii) link between insecticide resistance mechanisms and malaria control failure established; iii) new knowledge on the causes and burden of residual malaria available; iv) measures to face residual malaria situation proposed to countries in collaboration with WHO/GMP.

By 2018: • Insecticide resistance mechanisms characterized in

three African countries. • Causes and burden of residual malaria established in

ten countries from four WHO regions. • A new worldwide network on residual malaria

established. • Recommendations for mitigating residual malaria

developed in collaboration with WHO/GMP By 2019: The insecticide resistance mechanisms of the malaria vectors have been identified for the following countries: Benin, Mali and Nigeria. The burden and causes of residual malaria have been identified in 13 countries over four WHO regions. A new worldwide network on residual malaria was established and gathered at a second meeting in April 2019. Recommendations on how to mitigate residual malaria are available for stakeholders and published through


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Ongoing expected results by outcome Indicators and progress against targets information briefs and on an open website, allowing improved implementation of malaria control tools. Implementation plans for deployment of new approaches and tools that are adequate to the situation have been developed for each project in collaboration with stakeholders.

1.3.11. Multisectoral approach on malaria control: i) MSA for prevention and control of VBDs implemented in several LMICs for several diseases; ii) knowledge and evidence for MSA generated; iii) improved prevention and control of diseases through MSA and broader stakeholder involvement.

By 2018, commissioned reviews of the different aspects of MSA available for at least ten countries. By 2020, at least two multi-country research projects developed to provide recommendations. By 2019, activities on multisectoral approaches for the prevention and control of VBDs have supported six commissioned reviews and 10 publications in open access and peer review journals. By 2020: • A special issue on the main findings will be published in

a Special Issue of the Journal of Infectious Diseases by mid-2020.

• The Guidance Framework on Multisectoral Approaches is on development and will be released by first quarter of 2020.

• Support to selected case studies will be started by 2020. By 2021, between 4 and 6 countries using and adopting the MSA approach for prevention and control of VBDs in line with the TDR document.


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Progress description in 2019 and plans for 2020-2021

Workstream: Research for policies

ER 1.1.1: Country preparedness for disease outbreaks TDR is working with countries and researchers to identify signals that can alert country control programmes to an impending dengue outbreak. This has led to a model contingency plan and an Early Warning and Response System (EWARS) for arbovirus outbreaks. Countries can test and potentially customize this to apply to other arboviral diseases, such as Zika, chikungunya and yellow fever, and other infectious diseases.

Progress in 2019 Early Warning and Response System

1. The early warning and response system for outbreaks of dengue has been shown to be equally successful

in predicting outbreaks of Zika and chikungunya (study in Colombia and Mexico).

2. Based on EWARS user comments that the calibration of thresholds is time-consuming, this process was automatized so that the software identifies the thresholds which produce the highest sensitivity and positive predictive values for outbreak prediction and alarm signals. Feedback from countries has shown that this is a great step forward in terms of user-friendliness and applicability of the tool in routine surveillance programmes. Additionally, risk mapping will be included in the EWARS tool and potentially human mobility affecting the spread of disease and outbreaks. It is also planned to test EWARS for outbreak prediction of malaria, cholera and other infectious diseases.

3. Dissemination of EWARS has been achieved through in-country training workshops in Colombia, India, Malaysia, Mexico, Sri Lanka and Thailand, as well as through electronic follow-up and TDR expert meetings. A major push was the successful incorporation of EWARS into the national surveillance platform in Mexico. PAHO has translated the EWARS guide into Spanish which will enhance its use in Latin America.


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4. When comparing 11 districts in Mexico with outbreak alarms followed either by outbreaks or non-outbreaks, the frequency and intensity of response activities explains largely the difference; however, further studies are required to confirm this important finding.

5. In collaboration with the WHO Control of Neglected Tropical Diseases (WHO/UCN/NTD) department, an expert meeting with representatives of countries already implementing EWARS, countries who are considering it, representatives of the WHO regional offices was held in September 2019 in Geneva. Its objective was to discuss lessons learned with the use of EWARS and next steps. A collaborative effort is needed to improve surveillance system quality to feed in EWARS. This meeting helped to further strengthen collaboration with the WHO Regional Offices, WHO/UCN/NTD and WHO department of Infectious Hazard Management WHO/IHM (especially the Zika group) but also started to build collaboration with new partners, in particular WHO’s Climate Change and Health Programme, the Department of Public Health, Environment and Social Determinants (WHO/PEH) and the World Meteorological Organization (WMO). A collaborative action plan will be discussed in January 2020 with all partners.

Current status of EWARS use: 1. Country close to full integration of EWARS into the national surveillance platform: Mexico (with 137

endemic municipalities).

2. Countries which have either introduced or started piloting EWARS for later inclusion into their national surveillance system: Brazil, Colombia, Dominican Republic, India, Malaysia, Sri Lanka and Thailand.

3. Countries interested in applying the EWARS tool but are not yet ready due to weak surveillance systems: Bangladesh, Nepal, some African countries.

SITUATION ANALYSIS IN AFRICA The recent emergence of Aedes-borne arboviral infections in Africa raised the question of the adequacy of health systems to identify, prevent and respond to outbreaks in a timely and efficient manner. The answer requires understanding of the existing capacity of countries for arboviral disease surveillance and vector control and of the capacity that requires strengthening. Prevention and control of arboviral diseases includes surveillance and management of cases as well as surveillance and control of vectors in the framework of the Global Vector Control Response. In recognition of the situation, 16 West African countries agreed to conduct a situation analysis of existing resources in the region with the support of TDR and the WHO/UCN/NTD department to identify needs and to target capacity-strengthening interventions. The answers provided show that the region has some capacity in epidemiological and entomological surveillance and vector control but requires support to strengthen their capacity to ensure timely detection of arboviral infections and adequate preparedness for epidemics. EWARS was presented at a regional meeting in September 2019 with the 16 West African countries (one entomologist and one epidemiologist per country) to validate the situation analysis report and discuss next steps. The meeting was organized in collaboration with the West African Health Organization (WAHO) and the WHO Regional Office for Africa (AFRO). Countries expressed interest in EWARS, however to use the system, data (entomological, epidemiological and meteorological data) needs to be available. As this data is not routinely collected by countries, as a first step entomological, epidemiological and meteorological surveillance systems need to be strengthened in order to use EWARS in 2 years’ time. This activity will be conducted in 2020-2021.


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Remaining challenges The further dissemination of EWARS in WHO regions and countries continues to be important as well as incorporation of the tool into national surveillance systems. These systems (entomological and epidemiological) need to be strengthened to build context specific EWARS and implement its use.

Contributions towards TDR key performance indicators Partnerships and collaborations:

Ministries of health and/or national institutes of health in Brazil, Colombia, Dominican Republic, India, Malaysia, Mexico, Sri Lanka, Thailand.

WHO AFRO, ministries of health of the 16 West African countries, the West African Health Organization (WAHO).

Estimated leverage created by this project:

- US$ 50 000 from WAHO to organize a regional meeting to discuss the findings of the situation analysis mentioned above.

- Training workshops in Colombia, India, Malaysia, Sri Lanka and Thailand were financed by partner countries; TDR financed the facilitator only.

Gender aspects and vulnerable populations:

Our target diseases affect more the poor population strata. Activities are conducted with the MOHs of the corresponding countries. Participants in meetings or training are designated by the ministries. TDR cannot interfere in the selection and unfortunately gender balance is rarely respected.

Training:

Training workshops for the use of the Early Warning and Response System on Aedes-borne arboviral diseases in Colombia, India, Sri Lanka with follow-up activities by electronic media.

Strengthened institutions or networks:

- Surveillance and response teams in partner countries.

- Strengthening of the West African network of the reference laboratories for arboviral diseases.

Publications:

- Sistema de alerta y respuesta temprana (EWARS) para los brotes de dengue, Zika and chikungunya. PAHO-WHO web publication 2019.

- Cardenas Sanchez R, Hussain-Alkhateeb L, Benitez D, Tejeda Sanchez G, Kroeger A. 2019. Early warning for chikungunya and Zika outbreaks in Colombia and Mexico. (Submitted)

Results dissemination and uptake:

Uptake of the EWARS tool by a number of countries as described above. Publications completed or in progress.

Plans for 2020-2021 1. To provide support to countries who have just begun to implement the use of EWARS.

2. To strengthen surveillance capacities in African countries willing to implement EWARS.

3. To develop and conduct research demonstrating the impact of the use of EWARS and its cost-effectiveness when triggering vector control activities.


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ER 1.1.4: Country resilience to the threat of drug-resistant infections

SORT IT ANTIMICROBIAL RESISTANCE

Building sustainable operational research capacity to tackle antimicrobial resistance in low- and middle-income countries. The Challenge: Antimicrobial resistance (AMR) is a global public health challenge with the potential to kill as many as 10 million people per year by 2050 and cost the world economy as much as US$ 100 trillion. AMR makes standard treatments ineffective and allows infections to persist and spread to others. The SORT IT Solution: The Structured Operational Research and Training IniTiative (SORT IT) is a global partnership-based initiative coordinated by TDR and implemented with partners. We will use SORT IT to build operational research (OR) capacity that will generate and promote the use of evidence on the emergence, spread and health impact of AMR to tackle this global problem. The aim of SORT IT is to make countries “data rich, information rich and action rich” in tackling AMR. SORT IT objectives for AMR 1. Build sustainable local capacity to conduct operational research using programme data. 2. Improve understanding of AMR along the strategic pillars:

a) Strengthen surveillance, monitoring and reporting; b) Reduce incidence of infection (health facilities, communities, animal health); c) Optimize use of antimicrobials (human, veterinary, agriculture); and d) Sustainable investments in new diagnostics and measuring burden.

3. Build sustainable structures and processes for evidence-informed decision-making and knowledge management to maximize broader research impact.

The SORT IT approach - Training: A training cycle that ranges between 10 to 12 months and comprised of four modules: protocol

writing; quality assured data capture and analysis; manuscript writing for publication; and evidence-informed decision-making.

- Participants (12 per workshop): Implementers and frontline health workers selected using strict eligibility criteria.

- Target countries: Ghana, Myanmar, Nepal, Sierra Leone, Uganda (Fleming Fund early adopter countries), Colombia (with participants from Ecuador).

- Scientific scope: Research priorities addressing country needs and aligned with the Global Action Plan on AMR.

- Strategy: A bottom-up approach through engagement with WHO country offices, AMR country coordinating committees and stakeholders in countries. AMR focal points and OR fellows facilitate this process.

- Mentors: From TDR’s global SORT IT roster of experienced implementing partners. - Monitoring and evaluation: Using SORT IT performance indicators. Expected results: At least 72 priority OR projects and about 90 individuals trained; six country AMR focal points and six OR fellows as future OR leaders; an AMR community of practice; an enlarged SORT IT partnership base; publications; policy/issue briefs; and integration of OR activities within national strategic plans.


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Long-term strategic impact: Improved policy and/or programme practice for preventing the emergence and spread of AMR; sustained capacity and leadership by trained SORT IT participants to publish, teach and use evidence beyond the life of the programme; expanded scope and use of routine programme data; a community of practice at national and international levels through north-south and south-south links.

Progress in 2019 Close collaboration was established with country AMR coordinating committees, WHO country offices and various implementing partners in the six target countries. TDR activities are aligned with national AMR action plans and complement ongoing activities (including those of the Fleming Fund). All countries have endorsed the SORT IT project (2019-2021) and we have moved to a full implementation mode with 36 research studies under way in year 1. The value for money of our project has benefited from using resources and know-how that have been built over the past decade. The use of already trained human resources and expertise brings both economy and operational efficiency. This efficiency is enhanced by focusing on programme generated data (rapidity of results) and leveraging SORT IT partnerships (south-south and north-south). To promote effectiveness and impact, we engaged early with those who are expected to use the results. We are also promoting equity through gender equitable participant selection and LMIC first authorship.

Progress in line with SWG recommendations:

• TDR to focus on niche areas with designated funding such as antimicrobial resistance while promoting global engagement, intersectoral approaches and south-south-partnerships.

• Transition the AMR-SORT IT to improve upstream data collection, downstream use of evidence for decision-making and data sharing.

1. Ensuring coordination and engagement of stakeholders

Planning visits were completed in the six target countries (Colombia, Ghana, Myanmar, Nepal, Sierra Leone and Uganda). Through early face-to-face meetings, presentations and discussions, good collaboration was established with the AMR secretariat at WHO, the “One Health” platform, national AMR coordination committees, WHO country offices, SORT IT alumni and implementing partners, including the Fleming Fund.

This process allowed engagement in the planning process and rapid endorsement of SORT IT implementation plans at all levels. TDR activities are complementary.

2. Embedding SORT IT into country AMR action plans

To ensure a bottom-up approach that is adapted to local needs, practical aspects of project implementation were discussed with the multisectoral AMR coordinating committees in each country. It was agreed that research priorities would focus on the five pillars of the national AMR action plans – to make them “data rich, information rich and action rich”. The mechanics of participant selection (including quotas for “One Health”) were endorsed by the national committees. TDR will provide additional financial and human resource support to catalyse ongoing activities and this was gladly welcomed.

Excellent engagement of countries was achieved, with participants (and their research subjects) being formally endorsed. This enhances country ownership and should facilitate dissemination and evidence uptake.


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Figure 1: AMR SORT IT Research Prioritisation meetings in (from l. to r.) Colombia, Uganda and Myanmar.

3. Implementation is in full swing

Contractual arrangements have been finalized to ensure that SORT IT focal points are employed in each of the six target country WHO offices. The venues and timelines for SORT IT workshops were set, mentors and consultants identified (from the north and south), ethics procedures defined, the curricula finalized, the reporting metrics set and fliers to facilitate communication produced. A call for operational research fellowships to reinforce research leadership in countries was opened.

The first Regional Asian SORT IT started in July 2019, the first Regional African SORT IT in September 2019 and the first national course in Nepal in November 2019. A small grants research programme is running in parallel to promote prospective research studies that will complement SORT IT studies stemming from the use of programme data.

By December 2019, 36 operational research projects are under way in five countries in Asia and Africa

Figure 2: Participants and mentors at the Regional Asian and African SORTIT courses in Kathmandu, Nepal and Entebbe, Uganda


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4. SORT IT topics and data overview (2019)

Research topics include: data quality for AMR surveillance in humans and animals; national antibiotic consumptions; antibiotic resistance patterns in neonates and in various human specimens; resistance patterns of priority pathogens; infection, prevention and control in health facilities; antibiotic resistance in waste-water effluents; water safety in hospitals; antibiotic use in veterinary clinics and animal husbandry; and AMR in ambient air.

TABLE 2: Data overview (2019)

Number (%)

Total operational research projects in 2019 36

Female participants 17 (47%)

Projects under way (January to December 2019) 36

Participant completion rate (milestones 1-2) 100%

Average participant satisfaction score/module (SORT IT target = 80%) 90%

Number of implementing institutions facilitating 21

- Northern institutions (north-south collaboration) 6

- Southern institutions (south-south collaboration) 17

Number of WHO country offices involved 6

Percentage of SORT IT alumni facilitating SORT IT courses 76%

Figure 3: 53% of studies focus on strengthening surveillance and monitoring data. This is vital to “feel the pulse” of the AMR situation in countries. Without good surveillance data, we would be thinking and acting blindly.

53%,

17%19%

11%

19%

02468

101214161820

Strengthensurveillance and

monitoring

Reduce incidence ofinfection

Optimizeantimicrobial use

Sustainableinvestments (AMR

burden, diagnostics..)

One-health

Rese

arch

pro

ject

s

AMR pillars


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Remaining challenges • Inclusion of Ecuador: Columbia and Ecuador have established excellent cross-border activities and

the WHO regional AMR focal points requested the inclusion of four participants from Ecuador in the Colombia SORT IT. This was not planned initially but it was agreed that this provides an excellent opportunity to expand the “community of practice”.

• Budgetary issues: There was an increase in salaries of SORT IT focal points from US$ 20 000 to US$ 50 000 per year due to WHO salary adjustments in Ghana, Sierra Leone and Uganda. This difference will be covered through savings made in other budget lines.

Contributions towards TDR key performance indicators

Partnerships and collaborations: A new era of collaboration has been opened with six WHO country offices and with 23 institutions who have partnered with TDR on the AMR programme.

South-South Collaborations: 17 of the 23 institutions are from the South and include: AmPATH – Kenya, Bahirdar University, Ethiopia, Blantyre Light house Trust, Malawi, Department of Medical Research, Myanmar, International Union Against TB and Lung Disease, South East Asia office, India, Institute of medical research, Bangalore, Koirala Institute of Health Sciences, Nepal, Ministry of Health, Zimbabwe, Ministry of Health of Uganda, Ministry of Health of Sierra Leone, Ministry of Health, Pakistan, National Center for Rural Research and Training, Conakry, Guinea, School of Public Health, Kathmandu, Nepal, Stellenbosch University, South Africa, Sustainable Health Systems, Sierra Leone, TB- Research and Prevention NGO (TB-RPC), Armenia and Zambart, Zambia.

North-South collaboration: Six institutions are from the North and include: The Institute of Tropical Medicine Antwerp, Belgium, The International Union Against TB and Lung Diseases, Paris, France, Médecins Sans Frontières – Luxembourg, The University of Exeter, United Kingdom, The University of Toronto and the University of Washington.

Estimated leverage created by this project: The total budget of this project is about US$ 10 million from the Department of Health and Social Care, United Kingdom. Initiatives are under way to leverage another 1.5 million with UNICEF for an AMR course in Bangladesh.

Gender aspects and vulnerable populations: Of the 36 selected participants for 2019, 47% are women. The aim is to reach 50% or more. The AMR target countries are all LMICs with high AMR burdens. The selection of Sierra Leone was a deliberate choice being a vulnerable and fragile state recovering from decades of civil war.

Training: The core focus of SORT IT is “research implementation coupled with capacity building” so as to empower participants and facilitators.

Number of advanced degrees: It is hoped that six operational research fellows will start work in 2020 and reinforce research activities at country level.

Strengthened institutions or networks: Through AMR, the SORT IT partnership is strengthened with new funding, new institutional partners, new facilitators and new alumni. Implementing partners include WHO country offices, disease control programmes, academia and NGOs.

Publications: No publication as yet as the programme is in starting phase. In 2019, 36 study protocols are under way. These projects will be written up for publication in peer-reviewed journals.

Related news:

Operation research on the frontline to fight AMR: https://www.who.int/tdr/news/2019/or-on-frontline-to-fight-amr/en/

TDR updated website: https://www.who.int/tdr/capacity/strengthening/sort/en/

Results dissemination and uptake: Roughly 70% of SORT IT studies report an impact on policy and/or practice and we estimate that the uptake would be similar for AMR.

https://www.who.int/tdr/news/2019/or-on-frontline-to-fight-amr/en/

https://www.who.int/tdr/news/2019/or-on-frontline-to-fight-amr/en/

https://www.who.int/tdr/capacity/strengthening/sort/en/


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Plans for 2020-2021 • The principal focus is to ensure effective implementation of the SORT IT programme focused on AMR

in Asia, Africa and Latin America (US$ 10 million grant). • Develop a SORT IT curriculum that teaches practical skills to enhance uptake of research findings. • Ghana and Uganda have requested national SORT IT courses: Although included in regional SORT IT

courses, due to the tight timelines, neither country is included in plans for national courses. However, depending on the availability of funds, an additional SORT IT course(s) could be run in 2020-2021.

STRATEGIES FOR MONITORING POTENTIAL EMERGENCE OF RESISTANCE DURING SEASONAL MALARIA CHEMOPREVENTION (SMC)

This project supports countries to define and implement the most cost-effective drug resistance surveillance strategies in the context of mass drug administration (MDA). Malaria remains a major public health problem in sub-Saharan Africa. WHO announced in 2018 that the gains made in malaria control efforts in the 15 years prior to 2015 have not been sustained. The previous steady decline in the global number of malaria deaths has reached a plateau and the number of cases is increasing. The majority of malaria deaths occurred in 10 sub-Saharan African countries, many of these being countries where malaria is highly seasonal. Following a 2012 WHO recommendation, 13 sub-Saharan Africa countries (Burkina Faso, Cameroon, Chad, The Gambia, Ghana, Guinea, Guinea Bissau, Mali, Mauritania, Niger, Nigeria, Senegal and Togo) with high seasonal malaria transmission have adopted and integrated SMC into their policy documents and strategic plans. The total number of children who received SMC (at least one treatment) was estimated to be 15.7 million in 2018. SMC has been shown to substantially reduce cases and deaths due to malaria, however:

- Little is known concerning the risk of drug-resistant parasites being spread while implementing SMC at a large scale, or which cost-effective strategy options can be made available to national malaria programmes (NMPs) to monitor drug sensitivity;

- Although countries have been quick to adopt SMC, fewer than 50% of eligible children had access to SMC in 2018. There is a need to optimize delivery of SMC in order to close these gaps; and

- Safety monitoring remains a challenge.

Progress in 2019 - The results of an implementation research (IR) project conducted in Senegal that compared two drug

resistance surveillance strategies in terms of feasibility, acceptability and effectiveness: i) drug resistance surveys in the general population before and after SMC campaigns; and ii) monitoring of drug resistance at 32 outpatient sentinel sites, was submitted. The findings were that: (i) the level of drug resistance is low despite implementing SMC since 2010 in Senegal; (ii) monitoring drug resistance at outpatient sentinel sites is feasible; and (iii) despite selection bias (only malaria cases coming to a clinic are investigated) compared to cross-sectional survey sampling across the general population, the estimation of the prevalence of drug resistance in both studies does not appear to differ.

- Based on a previous study, sampling from malaria cases at clinics is logistically much easier but could potentially over-represent individuals harbouring parasites resistant to first line treatments. A new IR study was therefore launched to assess if drug resistance could be monitored with integrating surveillance in antenatal care and sampling pregnant women.


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- A review of all evidence on SMC accrued since 2012 (on effectiveness, SMC delivery best practices, safety monitoring, drug resistance surveillance, etc.) was commissioned. This review served as a basis for a technical consultation at the end of 2019, organized in collaboration with the WHO Global Malaria Programme to:

o Discuss SMC evidence for policy review; o Define research gaps for updating policies; and o Update the SMC field manual accordingly.

This last activity was conducted in order to prepare 2020-2021 activities where IR projects for optimizing SMC delivery will be conducted by national malaria programmes implementing SMC. Funding from the European and Developing Countries Clinical Trials Partnership (EDCTP) was leveraged (€2.5 million). The approach that will be taken will be similar to what was done with the national TB programmes in the West African region as part of the WARN-TB activities:

- Strengthening of the West and Central Africa SMC malaria network (WARN-SMC); - Strengthening of the malaria surveillance system to monitor SMC activities (in collaboration with the

WHO Global Malaria Programme (GMP)); - Strengthening capacity of the NMPs to understand their programmatic data and define malaria

control gaps and research priorities for optimizing SMC effectiveness; and - Strengthening capacity of the NMPs to conduct IR/OR projects addressing research priorities to

improve SMC effectiveness.


Through the projects conducted for this ER, TDR is collaborating with all key players involved in the implementation of seasonal malaria chemoprevention in West and Central Africa (i.e. the 13 national malaria programmes of West and Central Africa implementing SMC, GMP, AFRO, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Medicines for Malaria Venture (MMV), PMI (USAID), Malaria Consortium, CRS, WAHO, University Cheick Anta Diop and Thies, Senegal).


US$ 60 000 from the WHO Global Malaria Programme


Strengthening of national control programmes for the delivery of SMC (see above, and funding from EDCTP)

Publications:

Publication of an SMC review in discussion.


Through the large collaboration (see above under partnerships and collaborations), evidence generated has been disseminated to the national control programmes, the WHO Global Malaria Programme and other key partners.

Plans for 2020-2021 1. To finalise the IR project on drug resistance monitoring in ANC that was launched in 2019.

2. To support the 13 countries implementing SMC for optimizing the delivery of SMC (including drug resistance surveillance). This work area will move under ER 1.2.6 for the next biennium.


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EVALUATION OF PRACTICAL APPROACHES TO IMPROVE TARGETED TREATMENT AND REDUCE DRUG MISUSE AND RISK OF RESISTANCE

(1) Evaluation of C-reactive protein (CRP) as a biomarker for bacterial infection or marker of severity in dengue; and (2) Identification of microbiological causes of invasive infection in young infants Febrile illnesses lacking proper diagnosis are leading to suboptimal case management and unnecessary overuse of antimicrobials, raising the risk of antimicrobial resistance (AMR). There is therefore a need to obtain better evidence on causal agents of fever and assess effectiveness and feasibility of point-of-care markers to guide the use of antibiotics and medical management in general at field level.

Progress in 2019 CRP as a biomarker of severity in dengue: In areas of dengue transmission, yearly seasonal epidemics occur and can very quickly overwhelm health facilities. As the vast majority of symptomatic infections result in a benign disease course, the ability to identify patients at high risk of progression is a priority. Analysis of data from patients with dengue shows that high CRP is associated with more severe clinical presentation. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may help to differentiate dengue from other febrile illnesses. Microbiological causes of invasive infection in young infants in rural Africa: 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 infections in young infants in outpatient or home settings in developing countries. The data are particularly valuable in areas of high neonatal mortality in order to analyse explicitly defined criteria for community-acquired infections. TDR carried out a study to generate data that could improve the evidence-based management of cases of severe invasive infections in newborns and young infants in rural communities in sub-Saharan Africa through knowledge of the causative pathogens and their antibiotic resistance profile. The project was designed as a prospective multicentric non-interventional study to identify the pathogens causing severe invasive infections in young infants aged 0-59 days old.

Analysis of the data shows: - A small percentage of samples were either positive for haemoculture or for PCR due at least in part to the low

sensitivity of both methods and the small volume of blood obtained for the analysis;

- Poor correlation between results for haemoculture and PCR, which could also be due to low sensitivity of both methods and limited detection rate due to the volume of blood;

- Correlation of the mortality rate with positive result at haemoculture;

- Resistance profile defined for the pathogen, highlighting resistance of some pathogens to the most commonly used antibiotics (e.g. ampicillin/ gentamycin); and

- Death rate the highest as age is lower.

Remaining challenges Potential use in clinical management for CRP would require much bigger trials. The fact that there is not enough data on final diagnostics for the fevers makes the evaluation for specificity very difficult.


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Haydom Lutheran Hospital, United Republic of Tanzania Nanoro Research Center, Burkina Faso University of Virginia


Provision of Taqman cards and laboratory work for the analysis by PCR (estimated to US$ 100 000).


The work focusses on an extremely vulnerable population, newborns between 0 and 59 days old, which is a population where mortality remains very high and where there is limited research.

Publications:

Althaus T, Lubell Y, Maro VP, Mmbaga BT, Lwezaula B, Halleux C, Biggs HM, Galloway RL, Stoddard RA, Perniciaro JL, Nicholson WL, Doyle K, Olliaro P, Crump JA, Rubach MP. Sensitivity of C-reactive protein for the identification of patients with laboratory-confirmed bacterial infections in northern United Republic of Tanzania. Trop Med Int Health. 2019 Dec 6. doi: 10.1111/tmi.13358.


The results of the research have been shared with the scientific communities.

Plans for 2020-2021 The results of the analysis will be published. Subject to availability of funds (this work is funded under TDR’s US$ 50 million budget scenario):

• Research to evaluate the use of CRP in decision-making in primary health care settings (impact of the use on CRP in decisional algorithm in Africa)

ER 1.3.3: Population health vulnerabilities to vector-borne diseases (VBDs): Increasing resilience under climate change conditions in Africa The overall goal of this ER is to generate evidence to enable development of innovative strategies to reduce VBD-related human vulnerability and to increase resilience of African populations to VBD-related health threats. In addition, it aims to broaden and extend knowledge, research capacity, collaboration and policy advice products that can be used throughout Africa and other regions.

In 2018, the Scientific Working Group gave the following recommendation for this ER: Any future phase of this project should consider including Implementation Research / Participatory Action Research approaches to document the process and extract key new learning. Crystallising knowledge generated to date is needed to identify key new questions that TDR is uniquely well placed to address. This would define research for implementation priorities that will attract substantial TDR funding (in the region of US$ 10 million from a new funding source, e.g. African Development Bank, Africa Climate Change Fund, IDRC). In addition, recommended interventions (from policy briefs and other outputs) need to be implemented and tracked as a form of implementation research. Where implementation success is seen, scale-up should be facilitated. Networks could help facilitate the advancing of this initiative and test the generalisability of findings across different geographic areas. Although the inter-relationship between climate and health will remain highly topical, the team needs to specify priorities for future work programmes before an SWG approval of new plans for research can be made.


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Progress in 2019 In response to the above recommendation, the following steps have been taken:

• A new SDF project, implemented in 2019, is expected to inform the framing of a proposed new expected result to operationalize a One Health approach for the control of vector-borne diseases (VBDs) in the context of climate change in Africa. This will also form the basis for a new TDR call for research proposals that will facilitate increased integrated coverage of health, agricultural and environmental interventions for the prevention/control of VBDs while preserving ecosystem integrity in Africa.

• One of the deliverables from this project is a synthesis report on the outcomes and outputs from the TDR IDRC Research Initiative and an analysis of how the research products can be aligned with the implementation of the Libreville Strategic Plan of Action to Scale Up Health and Environment Interventions in Africa (2019-2029).


Partnerships and collaborations:

Ministries of Health & Ministries of Environment in Africa, WHO-PHE, AFRO, UNEP, FAO, OIE, Wellcome Trust, UNDP, IDRC, Fondation Mérieux, Global Health Institute, Pan-African Mosquito Control Association.

Publications:

1. Barclay HJ, JW Hargrove, P van den Driessche. 2019 Estimating tsetse fertility: daily averaging versus periodic larviposition. Med Vet Entomol. 10.1111/mve.12399.

2. Fouque F, Reeder JC. 2019. Impact of past and on-going changes on climate and weather on vector-borne disease transmission: a look at the evidence. Infect Dis Poverty. 8(1):51. doi: 10.1186/s40249-019-0565-1.

3. Hargrove J, S English, SJ Torr, J Lord, LR Haines, C van Schalkwyk, J Patterson, G Vale. 2019. Wing length and host location in tsetse (Glossina spp): Implications for control using stationary baits. Parasit Vectors. 12(1):24.

4. Hargrove JW, GA Vale. 2019. Models for the rates of pupal development, fat consumption and mortality in tsetse (Glossina spp. Bull Entomol Res. 13:1-13.

5. Kajunguri D, EB Are, JW Hargrove. 2019. Improved estimates for extinction probabilities and times to extinction for populations of tsetse (Glossina spp). PLoS Negl Trop Dis. 13(4).

6. Kalinda C, S Mushayabasa, MJ Chimbari, S Mukaratirwa. 2019. Optimal control applied to a temperature dependent schistosomiasis model. Biosystems. 175:47

7. Kone V, Y Oulhote, A Mustapha, T Olaniyan, K Kuome, T Benmarhnia, N Munyinda, N Basu, JN Fobil, S Etajak, I Annesi-Maesano, J Chevrier, K Ebi. 2019. Environmental health research challenges in Africa. Env Epid. doi:10.1097/EE9..0000000000000074.

8. Scalway T, M Otmani del Barrio, B Ramirez. 2019. Research on vector-borne diseases: implementation of research communication strategies. Infect Dis Poverty. 8(1): 101. doi.org/10.1186/s40249-019-0610-0.

9. Wilcox BA, Echaubard P, de Garine-Wichatitsky M, Ramirez B. 2019. Vector-borne disease and climate change adaptation in African dryland social-ecological systems. Infect Dis Poverty. 8(1):36. doi: 10.1186/s40249-019-0539-3.

Plans for 2020-2021 A draft plan for guidance in operationalizing the One Health approach is currently being developed. The design of this plan will take into consideration the new knowledge and evidence from the TDR IDRC Research Initiative and the Libreville Strategic Plan of Action.


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Part of the plan will be to identify needs in African countries for institutional capacity, organizational set-up and the administrative/financial systems to implement the One Health approach. It will also propose key result areas for research. The plan will be presented to stakeholders for feedback (researchers, ministry officials from the health and environment sectors, WHO-PHE, AFRO, UNEP, FAO, OIE, Wellcome Trust, UNDP, IDRC, Fondation Mérieux, Global Health Institute and Pan-African Mosquito Control Association) during a One Health Consultation Meeting on 17-18 December 2019, in Brazzaville, Republic of the Congo. Fondation Mérieux has pledged additional funds (€10 000) in support of the One Health Consultation Meeting. They have also expressed interest in partnering with TDR for the new call for proposals and implementation of a new project portfolio for 2020-2021.

ER 1.3.7: Environmental prevention and control of VBDs and infectious diseases in South-East Asia The overall goal of this research initiative is to contribute to improving environmental public health through strengthening community-centred environmental health services for the control and prevention of priority VBDs. The specific objectives are:

• Identify and characterize environmental public health concerns and risks and assess their potential impact on priority infectious diseases in a community;

• Develop and implement a sustainable, community-centred adaptation strategy to access environmental health support services, promote improved monitoring of environmental parameters and encourage the use of environmentally friendly health technologies; and

• Assess and monitor the benefits resulting from the use, uptake and adoption of a sustainable, community-centred adaptation strategy for access to environmental health support services for the control and prevention of priority infectious diseases.

The main focus of this initiative, entitled ‘Collaborative research on health and the environment in the South-East Asian region: Innovative socioecological strategies for the prevention and control of VBDs,’ is to generate a positive, transformative impact on health outcomes for populations challenged by VBDs within the context of an ever-changing environment and within a framework of complex socioecological systems. The initiative supports and contributes to the use, uptake and adoption of VBD control and prevention products that are preventive and sustainable.

Progress in 2019 Project 1. Impact of socioecological systems and resilience (SESR) strategies on dengue vector control in schools and neighbouring household communities in Cambodia (Principal investigator: Dr Leo Braack, Malaria Consortium, Thailand)

Children are disproportionately exposed to mosquito bites due to their higher risk of exposure during peak biting times of dengue vectors at home and school, where they are often surrounded by water reservoirs in the form of jars and containers. To mitigate this risk, this project combines a health education and community-participatory and capacity building approach to vector surveillance and control, using guppy fish, autocidal traps and COMBI (Communication for Behavioural Impact) – integrative tools that have been shown to have positive results in reducing dengue-transmitting Aedes mosquito populations, through high community participation and ownership.

While school-based health education is effective to ensure the translation of knowledge into practice, such programmes across Cambodia are accorded low priority, strategies are not developed based on evidence and activities are not routinely evaluated. Given the growing evidence for its positive impact on mosquito control, a school-based education programme provides the opportunity for a low-cost, integrated and locally acceptable strategy for dengue control.


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This randomized control trial will investigate whether a set of disease-specific interventions, including IVM (integrated vector management)-based source reduction tools, COMBI-based health education and socio-ecological systems approach will, significantly reduce mosquito pupae and adults in rural primary schools and households in two rural districts in Cambodia (see Table 1.3.7a. Interventions randomized to each study arm; Table 1.3.7b. Distribution of 16 primary schools selected among 20 Intervention Villages/Clusters). The hypotheses are that vector control interventions will significantly reduce mosquito breeding in key water containers and free flying adult mosquitoes in schools, households and public spaces, compared to areas that do not receive these interventions.

TABLE 1.3.7a. Interventions randomized to each study arm

Intervention type

Intervention Component

Intervention short description

Arm 1 Arm 2 Arm 3

CONTROL

Schools Village Schools Village Schools & villages

Biophysical

Vector control

Autocidal gravid ovitraps (AGO) –and pyriproxyfen (Sumilarv MR)

Biological control Guppy distribution

Solid waste management

Larval source control through improved solid waste management

Empowerment/ Adaptive capacity

Education and training

Place-based educational campaign on dengue disease; vector biology; ecology, and control; role of solid waste, clean water & health relationships

Communication and behaviour change

Communication for Behavioural Impact using multipronged communication channels including interpersonal communication through volunteers, folk or local media and mass media.

Participatory mapping

Map co-creation as a tool for community ownership of dengue decentralized surveillance and management


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TABLE 1.3.7B. Distribution of 16 primary schools selected among 20 Intervention villages/clusters in Kampong Siam and Prey Chhor Districts, Kampong Cham Province, Cambodia*. Note that several villages could share the same school

Village Arm School name Total Students*

Number of Households*

1. Kleng Por 1 S1: Khleng Por 74 85

2. Sya 1 S2: Angkor 421 82

3. Ro Meas 1 S2: Angkor 421 89

4. Ampil Chrom 1 S3: Trapaing Russei 110 165

5. Bantay Reoung and Krolorng 1 S4: Kralorng 131 245

6. Kork Sro Lao 1 S5: Kork Sralao 91 199

7. Krasaing Pul 1 S6: Krasaing Pul 392 172

8. Banteay Thmor 1 S7: Wath Thlear 49 177

9. O Thnung 1 S8: Prey Chakrey 145 109

10. Rorng Kor 1 S10: Rorng Kor 106 208

11. Char Chork 1 S11: Koh Taphem 247 173

12. Sbeng and Oda 2 S12: Prinh Bei Deum 229 176

13. Kloy Ti Mouy 2 S12: Prinh Bei Deum 315 75

14. Ampil Kranhannh 2 S8: Prey Chakrey 145 77

15. Sam Nak Tbong 2 S12: Prinh Bei Deum 229 145

16. Sam Nak Cheung 2 S10: Rorng Kor 106 95

17. Wat Chas 2 S13: Tapaing Beng 120 98

18. Sdach Noun 2 S14: Khel Chey 119 86

19. Teouk Neoum 2 S15: Trapaing Ampil 206 128

20. Cheung Kok 2 S16: Krala 93 127

* Sources: The names of the schools were provided by the district education office; the number of students for academic year 2017-2018 was obtained from the director of each school; the number of households per village was obtained from the village chiefs.

This project is articulated and is dependent on the successful achievement of four complementary phases and associated deliverables: 1) Research evidence documenting the application of the described socio-ecological systems and resilience (SESR)-

based dengue vector control protocol, characterizing its outcomes and evaluating the sustainability of the public health solutions provided in selected settings in the GMS (Greater Mekong Subregion);

2) Detailed and contextualized research protocol (including all necessary steps and participatory tools) for implementing SESR-based dengue vector control (DVC) in Cambodia;

3) Recommendations on further studies on community-based DVC for eventual policy outputs in the GMS; and 4) Standardized international protocols and tools for implementing SESR-based dengue vector control.


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Goals and Objectives

This study aims to investigate whether a set of disease-specific interventions, including IVM-based source reduction procedures and COMBI-based health education, will significantly reduce dengue entomological indicators in rural primary schools and households in two districts in Cambodia. The hypothesis is that the vector control interventions will significantly reduce the dengue vector infestation in key water containers and adult mosquito transmission in schools and households, compared to areas that do not receive the interventions. The original study objectives are to: 1) implement multi-stakeholder-driven, ecosystem-based innovative tools and approaches to address the challenge of dengue, especially in areas with inadequate health infrastructure; 2) undertake training activities for research capacity building; and 3) facilitate the uptake of new knowledge and research results through translation of research for best practice and influence on policies. Table 1 outlines the indicators of achievement for each of the objectives. These objectives remain unchanged. TABLE 1.3.7c. Study objectives

Objectives Expected outcomes Expected outputs

1. Implement multi-stakeholder-driven, ecosystem-based innovative tools and approaches to address the challenge of dengue, especially in areas with inadequate health infrastructure

A clearer understanding of the application of school-based COMBI and biocontrol source reduction tools incorporated within school and home-based settings in a number of different dengue transmission sites. Robust approaches for assessing the contribution of students and teaching staff in IVM

• Papers and reports evaluating the impact of a randomized control trial

• Stakeholder map • Co-created epidemiological

dynamics map and assessment/report of the participatory methodology used to create it

2. Undertake training activities for research capacity building

Training needs assessment and capacity building and strengthening framework consisting of training and awareness activities, including strengthening the role of women in health outreach programmes, technical assistance advice, information exchange and dissemination, quality control, guidelines and Standard Operating Procedures (SOPs), good laboratory practice, monitoring and evaluation

• Paper describing new approaches in place-based participatory health education in schools and engaging children as change agents towards integrated disease control

• Place-based education workshop involving teachers and education professionals

3. Facilitate the uptake of new knowledge and research results through translation of research for best practice and influence on policies

Extensive development of knowledge translation tool and integrated knowledge translation activities resulting in increased knowledge and understanding of dissemination of results and utilization of research findings

• Tools, protocols for ecosystem approaches to community-based dengue control

• Recommendations for further research and interventions


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This project was aimed at social engagement processes to achieve a series of outcomes that capacitate households and communities to understand the dynamics of the disease and deploy this knowledge as inexpensive self-help tools to bring about improved family and community health by way of mosquito reduction in and around households, schools and other community gathering places such as temples and health facilities. The process depended on targeting young school children, parents and key community leaders such as teachers, village chiefs and community health workers. These are key linkage points for bi-directional knowledge exchange, from which the research team could disseminate knowledge and message reinforcement but also monitor research uptake, implementation and sustainability of messages and processes. Aside from public education and gaining sustained community support, the key tools for achieving mosquito reductions were through simple community-made mosquito traps, from recycled containers, clean-up and disposal of discarded bottles and other containers potentially serving as breeding sites, and establishment of central guppy fish banks at schools and community health centres where households, through school children, could access larviparous guppy fish (bio-control agents) to be placed in water storage jars.

Progress Baseline entomology survey completed. This involved a baseline survey of the density of adult female Aedes aegypti mosquitoes (i.e. the number of mosquitoes collected per time unit) in each school, village or wat (pagoda). The collections were done in school toilets, bedrooms/living rooms of households, prayer rooms and sleeping quarters in the wats. Survey results (see Table 1.3.7d. Number of Female Aedes Adult Mosquitoes per house by location) showed that there were 0.75 adult female Aedes per house over all arms of the study, with slightly higher averages in Arm 2, although the difference between arms was not statistically significant. The average was higher in households than in schools or wats, although relatively few mosquitoes were collected from these sites and the study was not able to detect a difference between location. A two-pronged control method is needed as, despite low immature or pupal numbers, free-flying mosquitoes can be controlled by autocidal gravid ovitraps. TABLE 1.3.7d. Number of Female Aedes Adult Mosquitoes per house by location

Number By location Mean (95% CI) 1 All locations 0.75 (0.62-0.87) 2 Arm 1 0.63 (0.42-0.83) 3 Arm 2 0.88 (0.62-1.14) 4 Arm 3 0.74 (0.55-0.92) 5 Households 0.76 (0.63-0.89) 6 Schools 0.57 (0-1.9) 7 Wats 0.25 (0-1.04)

Mosquito indices. The results from the baseline entomology survey (at zero months post-intervention) show that arm one had slightly higher container and house indexes but had a much higher Breteau index (Table 1.3.7e. Immature indicators by arm from baseline entomology survey, August 2018). This suggests that the number of positive houses and containers was slightly higher in arm one, but there were many more containers per house than in arms two and three. The pupal productivity index used (Pupae Per Person) showed a mean of 0.9 pupae per person in all arms, with much higher results in arm one which was statistically different from other arms (Table 1.3.7f. Pupae per person by arm and location from baseline survey, August 2018). All immature measures show consistently higher positivity and mosquito density in arm one. There were much higher averages of pupae per person in schools than households or wats, but similar to adult measures relatively few mosquitoes were collected in schools or wats and the study was not powered to detect a difference between locations.


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TABLE 1.3.7e. Immature indicators by arm from baseline entomology survey, August 2018

No. Houses visited

No. of containers examined per

house

Container Index (CI) – Mean %

House Index (HI) – Mean % Breteau Index (BI)

Arm 1 200 7.6 58% 64% 120 Arm 2 200 4.2 51% 52% 76.5 Arm 3 200 4.1 55% 56% 73

TABLE 1.3.7f. Pupae per person by arm and location from baseline survey, August 2018

Number By location Mean (95% CI) 1 All locations 0.90 (0.67-1.13) 2 Arm 1 1.50 (0.95-2.05) 3 Arm 2 0.64 (0.37-0.91) 4 Arm 3 0.58 (0.38-0.79) 5 At households 0.90 (0.67-1.12) 6 At Schools 2.87 (0-6.57) 7 At wats 0 (0-0)

Quantitative research on knowledge, attitude and practice (KAP).The results of the quantitative KAP survey showed that knowledge of dengue transmission, symptoms and prevention are high. This is similar to earlier studies in this site (https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006268). Ninety percent of people knew fever was a sign of dengue and nearly everyone knew at least three signs or symptoms (Table 1.3.7g. Respondents who knew signs and symptoms of dengue, August 2018). Respondents also felt that dengue was a serious disease and that they were at risk (Table 1.3.7h. Attitudes of respondents around seriousness of dengue, August 2018). The reported prevention practices were also high, although previous studies showed no correlation between reported practices and observed practices. TABLE 1.3.7g. Respondents who knew signs and symptoms of dengue, August 2018

No. Signs/Symptoms reported N = 735 Proportion (Percent)

1 Fever 664 90.3

2 Rash 336 45.7

3 Somnolence 309 42.0

4 Headache 152 20.7

5 Nausea/vomiting 61 8.3

6 Bone pain 25 3.4

7 Blood discharge 24 3.3

8 Shock 4 0.5

9 Muscular pain 7 1.0

10 Other symptoms 59 8.0

https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006268


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TABLE 1.3.7h. Attitudes of respondents around seriousness of dengue, August 2018

Question Response N=735 Proportion (95% CI)

Is dengue disease serious?

No 2 0.20 (0.05-0.78) %

Yes 730 99.35 (98.56-99.71) %

Do not know 3 0.45 (0.17-1.20) %

Are you at risk to contract dengue?

No 3 0.37 (0.12-1.18) %

Yes 729 99.26 (98.40-99.65) %

Do not know 3 0.37 (0.14-1.02)%

Qualitative research. In the first phase of qualitative data collection, a formative research approach was followed. This means that results of this phase will be used to facilitate community dialogues, as well as a source for the COMBI message and material development workshops to be held with key community, volunteers and district stakeholders in schools included in arms 1 and 2.

In-depth interviews (IDI), focus group discussions (FGD), participant observation and informal conversations were conducted during the data collection phase. Informants included several levels of stakeholders and actors at the community level, such as community health workers, health centre chiefs, school directors, monks, priests, teachers, farmers and members of the local education office. IDI and FGD guides were designed to address the following questions: When and where to carry out COMBI activities; Who - institutions and individuals that should be involved throughout COMBI strategies ; Why - understanding the reasons behind project obstacles and enablers for the implementation of the proposed strategies ; What - messages, form and content of the implementation ; and How - recommended tools and strategies to be used.

The information collected at this stage is currently under analysis (organization of data and coding of transcripts through NVivo software). Preliminary results indicate that communities are familiar with and willing to implement prevention measures proposed for arms 1 and 2.

As already mentioned, coding is under way, and the ideas previously mentioned could change substantially at the final stage of aggregated data analysis. Similarly, the specific COMBI strategies to be developed can vary across villages depending on specific dynamics identified through data analysis. The research team will report on those variations as they need to be understood to motivate action and facilitate maximum involvement of affected communities in subsequent phases of implementation.

Social-ecological systems and transdisciplinary approach. Transdisciplinary approaches involve knowledge co-creation and a common vision not only among academic disciplines but also with beneficiary communities, resulting in community empowerment and project ownership. Measuring community empowerment could therefore be seen as a key indicator of transdisciplinary approaches and successful operationalization. The research project used the “community health development framework” which sets community participation as a continuum (narrow participation at one end and wide participation at the other end) and assesses five process indicators which are given a score (1-5 from community mobilization to empowerment) and transformed into spider grams. The process indicators are: 1) Leadership; 2) Planning and management; 3) Women’s involvement; 4) External support for programme development; and, 5) Monitoring and evaluation. Current assessment of community participation is illustrated in Figure 1.3.7a below:


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Figure 1.3.7a: Spider gram showing the five process indicators together assessing baseline community participation. From Draper et al (2010).

Aside from baseline studies, six-month follow data have just been recently available. These are currently being encoded and analysed. From the initial findings, the observation is that the community and governmental officials have been highly engaged and that the project has the ability to produce an effective curriculum and corresponding evaluation. To date, the research team is now firmly in place, the SESR protocol being implemented, development of SOPs and COMBI strategy development are nearly finished, guppy banks have been established, traps have been produced (and are reproducible in community/school contexts) and are being distributed. Local women’s groups have been engaged in the production of ovitraps, thus increasing the likelihood of adoption by the community. Results from future entomology surveys should provide critical information to draw further conclusions. Project 2. Innovative vector birth control and socioecological strategies for the prevention of dengue, chikungunya and Zika diseases in Thailand (Principal investigator: Dr Pattamaporn Kittayapong, Mahidol University, Thailand)

An innovative vector birth control strategy using the super-sterile mosquito technique, combined sterile insect technique (SIT) and the Wolbachia-induced incompatibility approach, was successfully developed and applied in a small-scale pilot operation in Thailand. After a six-month release of super sterile male mosquitoes, the pilot study demonstrated that proof-of-concept for the successful reduction of natural populations of Aedes aegypti, the major vectors of dengue, chikungunya and Zika diseases, in a semi-rural village in the Pleang Yao District, Chachoengsao Province, in eastern Thailand (Kittayapong P et al, 2018. Parasit Vectors: 11(Suppl)2:657. Doi: 10.1186/s13071-018-3214-9).

In the current project, a transdisciplinary, socioecological strategy was used to implement this innovative vector control tool, combined with conventional vector control methods, to suppress Aedes aegypti populations and to reduce disease incidence in selected study sites in Bangkok, Thailand. If successful, this project will provide a powerful demonstration of a new tool for the control of an important mosquito vector of diseases in Thailand, which is highly endemic for arboviral diseases.


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Goals and Objectives 1. To implement a pilot innovative and environmentally-friendly vector birth control intervention using

ecosystem-based and multi-stakeholder driven strategies in selected global outreach tourist settings.

2. To build capacity of participating network countries in the ASEAN region in applying innovative and environmentally-friendly vector birth control interventions using ecosystem-based and multi-stakeholder driven strategies.

3. To disseminate knowledge on the intervention of innovative and environmentally-friendly vector birth control interventions using ecosystem-based and multi-stakeholder driven strategies.

Study design: This study is designed as a cluster randomized trial. The four selected sub-districts, ranking within the top ten of the average morbidity rate of dengue incidence per 100 000 population in Bangkok, will be divided into two groups. Each group will consist of two sub-districts matched by the area size, the number of households and the population density of inhabitants per square kilometre, i.e. 1) Lat Yao Sub-district, Chatuchak District and Bang Khae Sub-district, Bang Khae District (area size = 10.690 - 10.963 sq.km., population density = 3,509 – 4,035 inhabitants per 1 sq.km., average morbidity rate of dengue = 380.54 - 411.89 per 100 000 population), and 2) Wang Thong Lang Sub-district, Wan Thong Lang District and Huai Kwang Sub-district, Huai Kwang District (area size = 5.342 - 5.644 sq.km., population density = 4,465 – 4,779 inhabitant per 1 sq.km., average morbidity rate of dengue = 425.62 - 643.32 per 100 000 population).

Progress in 2019 During the current year, the research team focused on study site selection, preliminary baseline epidemiological and entomological data collection from the potential study sites, as well as experiments to determine vector competence of sterile Aedes aegypti mosquitoes. Mosquitoes from potential sites were collected in order to establish a mosquito colony for future mass-rearing. In addition, the materials for public education to promote the project were developed.

Study site selection. The study site was selected based on the following criteria: 1) at least one vector-borne disease (possibly dengue) is endemic; 2) there is international tourism which makes the location vulnerable for global disease spread; 3) there is good cooperation of the local government and local communities; and 4) the size of the selected study site should be manageable and partly isolated geographically. After careful consideration, Bangkok was selected. In 2018, a total of 8781 dengue cases were reported in Bangkok with a morbidity rate of 154.57 per 100 000 population (Bureau of Epidemiology, Ministry of Public Health), which is higher than the country’s morbidity rate of 129.95 per 100 000 population (85 849 dengue cases), making Bangkok an important hotspot and suitable for selection as the study site.

In this study, site selection was primarily based on morbidity rate of dengue. Reported dengue cases provided by the Department of Health, Bangkok Metropolitan Administration and Population Census provided by the Official Statistics Registration System, Department of Provincial Administration, Ministry of Interior, were used to generate the dengue morbidity rate (per 100 000 population) from 2008 to 2017. The data were obtained on a yearly basis at sub-district level. A two-stage sample method was used to select the study site in Bangkok. Firstly, average morbidity rate of dengue from 2008 to 2017 was used to select the first ten sub-districts with the highest average morbidity rate of dengue. Secondly, the ten sub-districts were divided into groups by using area size, population density and the average morbidity rate of dengue. Following the two-stage sampling method, four out of ten sub-districts were selected; 1) Wang Thong Lang `Sub-district, Wang Thong Lang District; 2) Huai Kwang Sub-district, Huai Kwang District; 3) Lat Yao Sub-district, Chatuchak District; and 4) Bang Khae Sub-district, Bang Khae District (Figure 1.3.7b). The four selected subdistricts were then subdivided into two groups: 1) Lat Yao Sub-district, Chatuchak District and Bang Khae Sub-district, Bang Khae District (area size = 10.690 - 10.963 sq.km, population density = 3,509 – 4,035 inhabitants per 1 sq.km, average morbidity rate of dengue = 380.54 - 411.89 per 100 000 population); and 2) Wang Thong Lang Sub-


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district, Wang Thong Lang District and Huai Kwang Sub-district, Huai Kwang District (area size = 5.342 - 5.644 sq.km, population density = 4,465 – 4,779 inhabitant per 1 sq.km, average morbidity rate of dengue = 425.62 - 643.32 per 100 000 population) (Table 1.3.7i. Demographic information of four selected sub-districts in Bangkok; Figure 1.3.7b. Map of 4 selected sub-districts in Bangkok).

TABLE 1.3.7i. Demographic information of four selected sub-districts in Bangkok

No Sub-district District Area (sq. km)

Number of households

Population density (inhabitants/

sq. km)

Average morbidity rate of dengue (per 100 000)

1 Wang Thong Lang

Wang Thong Lang 5.644 13 191 4465 643.32

2 Huai Kwang Huai Kwang 5.342 27 560 4779 425.62

3 Lat Yao Chatuchak 10.690 26 582 4035 411.89

4 Bang Khae Bang Khae 10.963 23 830 3590 380.54

Figure 1.3.7b. Map of four selected sub-districts in Bangkok

Retrospective epidemiological study. Retrospective data obtained from the Department of Health, Bangkok Metropolitan Administration from 2008 to 2017 showed that there were 117 588 reported cases of dengue in Bangkok, whereas 4291, 4051, 2908 and 2118 cases were reported in Chatuchak, Bangkhae, Wang Thong Lang and Huai Kwang Districts respectively. However, higher morbidity was found in Huai Kwang District (267.37 per 100 000) followed by Chatuchak (267.03 per 100 000), Wang Thong Lang (254.61 per 100 000) and Bangkhae (210.43 per 100 000) when compared to the whole area of Bangkok (205.37 per 100 000) (Figure 1.3.7c. Morbidity rate of dengue cases per 100 000 populations from 2008 to 2017 in Bangkok Metropolis). Therefore, the study was planned to be mainly focused in the Districts of Chatuchak, Huai Kwang, Wang Thong Lang and Bangkhae.


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Figure 1.3.7c. Morbidity rate of dengue cases per 100 000 populations from 2008 to 2017 in Bangkok Metropolis (Source of data: Department of Health, Bangkok Metropolitan Administration and Bureau of Epidemiology, Disease Control Department, Ministry of Public Health, Thailand).

Study Design. The study design is a cluster-randomized trial to be conducted in Chatuchak, Huai Kwang, Wang Thong Lang and Bangkhae Districts. The study will be primarily conducted by pairing four districts into two groups, based on area size and morbidity of dengue; group 1) Chatuchak and Bangkhae, and group 2) Wang Thong Lang and Huai Kwang, with the expectation of having 10 clusters with an area size of 1 km2 (5 control and 5 treatment clusters), with a distance of at least 1 km between clusters in order to limit the spread of the released sterile male mosquitoes from the treatment to the control clusters; therefore, a total of 20 clusters (10 control and 10 treatment clusters) will be required for this study. However, following site visits to the four selected districts, Wang Thong Lang District was excluded from the study due to the impossibility to conduct and manage the study within the area. Therefore, the study will be conducted in three districts only. (TDR funding support will be used in Chatuchak District; additional funds from the Bangkok Metropolitan Administration and Mahidol University will support the study areas in Huai Kwang and Bangkhae Districts). Entomological baseline data collection. A total of 153 ovitraps have been placed inside and outside 51 households in Chatuchak District, Bangkok Metropolis since July 2018. Entomological survey is ongoing on a monthly basis and progress will be included in the next report. After one week, the traps were collected and taken to the Center of Excellence for Vectors and Vector-Borne Diseases at Mahidol University in Salaya, Nakhon Pathom. Egg papers were identified and counted, eggs were then hatched and the egg hatch rate was calculated. Once hatched eggs developed into adults, mosquito species identification was performed. Determination of egg hatch rate (sterility). A total of 1812 eggs (ranged 0 - 189, mean 35.53 36.77) were found in 153 egg papers placed in 51 households, an average of 35.53 eggs per household. Nearly 57% of


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households had a higher egg hatch rate than the average (0.64). Out of 1812 eggs, 1,527 were successfully hatched and became larvae with an average egg hatch rate of 0.64 ± 0.37 (Figure 1.3.7d. Hatch rate of eggs collected by using ovitraps in Chatuchak District, Bangkok Metropolis).

Figure 1.3.7d. Hatch rate of eggs collected by using ovitraps in Chatuchak District, Bangkok Metropolis.

Identification of mosquito species. Out of 1527 hatched eggs, 79% were developed into larvae, pupae and adult stages. All adult mosquitoes (100%) were identified as Aedes aegypti of which 53.22% were male and 46.78% female (Figure 1.3.7e. Distribution of Aedes aegypti male and female mosquitoes developed from eggs collected by using ovitraps in Chatuchak District, Bangkok Metropolis).

A total of 1107 ovitraps have been placed inside and outside 369 households in Chatuchak District, Bangkok Metropolis since July 2018. Entomological survey was done on a monthly basis. After one week, the traps are collected and taken to the Center of Excellence for Vectors and Vector-Borne Diseases. Egg papers were identified and counted, eggs were hatched and the egg hatch rate calculated. Once hatched eggs developed into adults, mosquito species identification was performed. Out of 6713 eggs collected, 67.9% was developed into larvae, pupae and adult stages. Out of 4236 adult mosquitoes, 94% were Ae. aegypti and 5.95% Ae. albopictus (Figure 1.3.7f. Distribution of Aedes aegypti and Aedes albopictus in Chatuchak District). Slightly more males were detected for both Ae. aegypti and Ae. albopictus, i.e. 54.79% and 51.59% respectively.


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Figure 1.3.7e. Distribution of Aedes aegypti male and female mosquitoes developed from eggs collected by using ovitraps in Chatuchak District, Bangkok Metropolis (blue represents the percentage of males and yellow represents the percentage of females).

Figure 1.3.7f. Distribution of Aedes aegypti and Aedes albopictus in Chatuchak District


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Experiments on vector competence of sterile mosquitoes. The aim of this study is to assess and compare blood feeding success and infectivity of irradiated and non-irradiated Ae. aegypti females when they are infected with either DENV-1 or ZIKV. Female Ae. aegypti aged 3-5 days old either non-radiated or radiated with the radiation dose of 70 Gy, were fed with blood mixed with either medium, DENV-1, ZIKV or DENV-1 and ZIKA, by using the hemotek blood feeding system for 3-5 hours. Collection was done at D0, D7, D14 and D21 after feeding time. Mosquito samples were stored at - 80oC. Each sample was dissected in four, i.e. head and thorax, abdomen, legs and wings, and analysis was performed by using RT-PCR (reverse transcriptase-polymerase chain reaction). The results demonstrated that, after radiation, Ae. aegypti females reduced their ability to feed on blood meals, either non-infected blood mixed with only medium (p=0.020) or blood infected with DENV-1 (p=0.025) and ZIKV (p=0.002) (Figure 1.3.7g. Comparison of the average percentage of engorged mosquitoes between non-irradiated and irradiated Aedes aegypti mosquitoes after feeding on blood mixed with medium, DNV-1, ZIKV or combined DENV-1 and ZIKV). However, RT-PCR detection of DENV-1 and ZIKV in irradiated mosquito samples showed that both DENV-1 and ZIKV infections were only found in the abdomen but not in the head and thorax or legs, in contrast to nonirradiated mosquitoes where infection was detected in all parts (Figure 1.3.7h. Percentage of infectivity of engorged Aedes aegypti mosquitoes after feeding on virus-infected blood meals). In addition, the infection rate of both DENV-1 and ZIKV were significantly reduced (p<0.05) when comparing irradiated and non-irradiated samples (Table 1.3.7j. Statistical comparison between non-irradiated and irradiated Aedes aegypti mosquitoes after feeding on virus-infected blood meals). It is speculated that high radiation dosage, i.e. 70 Gy, may have a negative impact on Ae. aegypti females, hence reducing their vector competence. These results should reduce the concerns related to an accidental release of some radiated Ae. aegypti females together with radiated sterile males during implementation of a SIT based vector control programme, since these small numbers of irradiated Ae. aegypti females were found to be less competent as the vector of both dengue and Zika diseases.

Figure 1.3.7g. Comparison of the average percentage of engorged mosquitoes between non-irradiated and irradiated Aedes aegypti mosquitoes after feeding on blood mixed with medium, DENV-1, ZIKV or combined DENV-1 and ZIKV


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Figure 1.3.7h. Percentage of infectivity of engorged Aedes aegypti mosquitoes after feeding on virus-infected blood meals

Table 1.3.7j. Statistical comparison between non-irradiated and irradiated Aedes aegypti mosquitoes after feeding on virus-infected blood meals.

Stakeholder engagement. Three meetings among relevant parties were organized in 2018. The first two were hosted by the Department of Disease Control at the Ministry of Public Health, with 14 and 17 participants, respectively. Eighteen participants attended the third meeting which was hosted by the Department of Health, Bangkok Metropolitan Administration. In each meeting, participants from the Department of Medical Sciences, Department of Disease Control, Ministry of Public Health, the Department of Health, Bangkok Metropolitan and the Center of Excellence for Vectors and Vector-Borne Diseases, Faculty of Science,


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Mahidol University, were gathered. The topics of discussion were related to the study design, criteria for site selection, workflow, the Memorandum of Understanding (MOU) signed between institutions, and progress of the project. For the third meeting, health care staff from the four health services responsible for the areas of Chatuchak, Huai Kwang, Wang Thong Lang and Bangkhae Districts also participated, in order to provide detailed information from each district. Site visits in 18 selected communities were arranged following the meetings.

Community engagement in study sites. Following the meeting in December 2018, the site visits in 18 communities located in four selected districts were arranged during 2019. The visits began in Huai Kwang and Wang Thong Lang Districts; followed by Chatuchak District and Bangkhae District respectively (Figure 1.3.7i. Map of the communities visited). The visits were organized through close collaboration with the Public Health Center (PHC)-25 Huai Kwang, PHC-17 Pracha Niwet, PHC-15 Lad Prao, and PHC-40 Bangkhae, the Department of Health, Bangkok Metropolitan Administration and support from the Chair and health volunteers of each community. For each visit, researchers from the Department of Medical Sciences, the Department of Disease Control, and the Center of Excellence for Vectors and Vector-Borne Diseases, were gathered. The location of each community, the area size, the number of populations and the number of dengue reported cases were collected for further study site selection and cluster design. During the site visits, the heads of communities expressed their positive feedback toward the project. They would all welcome researchers to conduct research in their communities since they gain enormous benefits from vector control. However, following the site visits, Wang Thong Lang District was excluded from the study as the communities were too large, with more than 1000 households located in the area with very heavy traffic, making it impossible to access and monitor the project in the long term.

Figure 1.3.7i. Map of the visited communities in Chatuchak, Huai Kwang, Wang Thong and Bang Khae Districts


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Public education. Two brochures were generated to educate the public on sterile mosquitoes and sterile insect technique (SIT). The brochures include the most frequently asked questions (FAQs) and useful answers about: 1) What are sterile mosquitoes? 2) How are they produced? 3) What are the impacts of sterile mosquitoes on the environment? and 4) What are the benefits of sterile mosquitoes? (in both Thai and English) (Figure 1.3.7j. Brochures for public education about sterile mosquitoes and sterile insect technique). The brochure in English is being developed and will be translated and produced in Thai. In addition, more materials, including brochures, leaflets, infographics and other materials, will be developed to address the key messages to a wider audience.

Figure 1.3.7j. Brochures for public education about sterile mosquitoes and sterile insect technique


• Malaria Consortium partners in Thailand, Cambodia and the United Kingdom

• Go Green

• Health, Environment and Education Ministries


• Special Project Team members were comprised of 57% men (four experts), and 43% women (three experts).

• The project sites are located among vulnerable populations that are economically disadvantaged and have a high risk for VBDs.

• A gender perspective is embedded within the implementation of the research projects, including gender analysis to address gender disparities and differences in the communities. For example, in the Cambodia project, one of the process indicators for community empowerment and project ownership is women’s involvement. To achieve this, the research teams have included training activities to strengthen the role of women in health outreach programmes for the control of dengue in the community. There was strong women representation in developing responsive actions for the community’s protection and preventative approaches for dengue and other mosquito-borne diseases. Women’s groups also lead in the sustainability of dengue control efforts in the community by locally fabricating and producing Autocidal Gravid Ovitraps for catching adult mosquitoes.


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Publications:

Cambodia project

1. Kumaran E. Doum D, Keo V, Sokha L, Sam B, Can V, Alexander N, Bradley J, Liverani M, Prasetyo DB, Pachmat A, Lopes S, Hii J, Rithea L, Shafique M, Hustedt J. 2018. Dengue knowledge, attitude and practices and their impact on community-based vector control in rural Cambodia. PLoS Negl Trop Dis. 12(2):e0006268. doi: 10.1371/journal.pntd.0006268. eCollection 2018 Feb.

2. Duboz R, Echaubard P, Promburom P, Kilvington M, Ross H, Allen W, Ward J, Deffuant G, de Garine-Wichatitsky M, Binot A. 2018. Systems thinking in practice: Participatory modeling as a foundation for integrated approaches to health. Front Vet Sci.5:303. doi: 10.3389/fvets.2018.00303. eCollection 2018.

3. Alonso Aguirre A, Basu N, Kahn LH, Morin XK, Echaubard P, Wilcox BA, Beasley VR. 2019. Transdisciplinary and social-ecological health frameworks: Novel approaches to emerging parasitic and vector-borne diseases. Parasite Epidemiol Control. 4: e00084. doi: 10.1016/j.parepi.2019.e00084. eCollection 2019 Feb.

4. Shafique M, S Lopes, D Doum, V Keo, L Sokha, B Sam, C Vibol, N Alexander, J Bradley, M Liverani, J Hii, L Rithea, S Aryal, J Hustedt. 2019. Implementation of guppy fish (Poecilia reticulata), and a novel larvicide (Pyriproxyfen) product (Sumilarv 2MR) for dengue control in Cambodia: a qualitative study of acceptability, sustainabilityhttps://doi.org/10.1371/journal.pntd.0007907

5. Wilcox BA, Aguirre AA, De Paula N, Siriaroonrat B, Echaubard P. 2019. Operationalizing One Health: Employing Social-Ecological Systems Theory – Lessons from the Greater Mekong Sub-Region. Front Public Health 7:85. doi: 10.3389/fpubh.2019.00085. eCollection 2019.

Thailand project

1. Kittayapong P, Kaeothaisong NO, Ninphanomchai S, Limohpasmanee W. 2018. Combined sterile insect technique and incompatible insect technique: sex separation and quality of sterile Aedes aegypti male mosquitoes released in a pilot suppression trial in Thailand. Parasite Vectors. 11(Suppl 2):657. doi: 10.1186/s13071-018-3214-9.

2. Kittayapong P, S Ninphanomchai, W Limohpasmanee, C Chansang, U Chansang, P Mongkalangoon. 2019. Combined sterile insect technique and incompatible insect technique : the first proof-of concept to suppress Aedes aegypti vector populations in semi-rural settings in Thailand. PLoS Negl Trop Dis. Doi.org/10.1371/journal.pntd.0007771.

3. Wilder-Smith A, Tissera H, AbuBakar S, Kittayapong P, Logan J, Neumayr A, Rocklov J, Byass P, Louis VR, Tozan Y, Massad E, Preet R. 2018. Novel tools for the surveillance and control of dengue: findings by the DengueTools research consortium. Glob Health Action. 11(1):1549930. doi: 10.1080/16549716.2018.1549930.

Plans for 2020-2021 TDR support for these projects covered the 2018-2019 biennium only.

https://doi.org/10.1371/journal.pntd.0007907


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Workstream: Research for Implementation

ER 1.1.7: Maximized utilization of data for public health decision-making

STRUCTURED OPERATIONAL RESEARCH AND TRAINING INITIATIVE (SORT IT)

Many public health programmes in low- and middle-income countries are “data rich but information poor”: too often, data that is relevant for improving public health is left unused on shelves or electronic servers. The Structured Operational Research and Training IniTiative (SORT IT) seeks to change this paradigm by making countries and institutions “data rich, information rich and action rich,” thereby improving health care delivery and outcomes. SORT IT is a global partnership-based initiative coordinated by TDR and implemented with partners. The SORT IT objectives: Support countries and institutions to improve programme performance and outcomes through: 1) using their health data to conduct operational research (OR); 2) building sustainable OR capacity; and 3) building structures and processes for evidence-informed decision-making. The SORT IT approach: SORT IT targets front-line health workers and decision-makers with little or no research experience. It focuses on programme generated data and, through a “learning by doing” approach, simultaneously combines “research training with research implementation”, thereby empowering participants. The model has inbuilt metrics and performance targets for accountability.

Participants are supported through hands-on mentorship provided by experienced mentors. The SORT IT training cycle runs over 10-12 months with four training modules run sequentially: module 1 (protocol writing), module 2 (quality assured data capture and analysis), module 3 (manuscript writing for publication), and module 4 (knowledge management). The SORT IT cycle

Engagement of National Stakeholders

Assessement of research priorities and research capacity building needs

Conduct and publish operational research.

Build sustainable research capacity

Buiild structures and processes for evidence

informed decision making

Enhance mechanisms for knowledge sharing and

uptake


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SORT IT performance targets (80-80-80-80): All SORT IT courses are assessed for performance standards: 80% participant satisfaction score by module; 80% participants complete all milestones; 80% projects published within 18 months and; 80% of research assessed for impact on policy and practice. The latter is a specific survey to systematically assess impact. SORT IT relevance and recognition: The SORT IT model has been proven to be adaptable to various geographic contexts, thematic areas and research methodology. It is thus relevant to achieving the Sustainable Development Goals (SDGs) and Universal Health Coverage (UHC). Any given SORT IT programme offers the unique opportunity of embracing six to eight SDG goals at the same time. For example, a SORT IT on AMR addresses SDG 12 (focused on AMR), SDG 3 (good health), SDG 4 (quality education), SDG 5 (Gender equity), SDG 6 (safe water and sanitation), SDG 9 (research and innovation), SDG 15 (healthier environments) and SDG 17 (Partnerships). The model is well recognized by WHO, donors and partners.

Progress in 2019 The SORT IT global partnership became stronger than ever before. It has now reached 91 countries, re-oriented to embrace the SDGs and UHC, close to US$ 10 million was secured for tackling antimicrobial resistance (AMR), and the model was efficiently franchised to several new partners. A new era of collaboration was opened with WHO offices in seven countries. These achievements have reinforced TDRs coordination role and elevated SORT IT to a new level of strength and international recognition.

The “value for money” has benefited from continued use of resources and the know-how that have been built over the past decade. The use of already trained human resources, north-south and south-south partnerships and expertise brings both economy and operational efficiency. To promote effectiveness and impact, we engaged early with those who are expected to use the results. We are also promoting gender equity and LMIC first authorship.

Progress in line with the main Scientific Working Group recommendations.

• SORT IT to expand but, increasingly franchised while ensuring quality control and impact.

• TDR to focus on niche areas with designated funding such as antimicrobial resistance while promoting global engagement, inter-sectorial approaches and south-south-partnerships.

• Transition the AMR- SORT IT to improve upstream data collection, downstream use of evidence for decision-making and data sharing.

• Set benchmarks for “Quality of Implementation Research” evidence.

1. Development of franchising tools for continued expansion while ensuring TDR quality standards

Franchising for continued SORT IT expansion was achieved by developing Standard Operating Procedures (SOPs) to allow the independent planning and organization of SORT IT courses, making new online tools and resources available (facilitator inventories, online lectures) and developing databases and quarterly monitoring metrics.

Any institution wanting to conduct a SORT IT course needs to formally register with TDR and agree to reporting in line with TDR’s 80-80-80-80 performance standards.


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2. Expanding SORT IT with emphasis on franchising, LMIC and gender equity

By October 2019 the SORT IT partnership was strengthened and franchised to include over 35 implementing institutions, reached 92 countries, trained over 859 participants, published 542 papers in 52 peer-reviewed journals, with 67% of projects reporting an impact on policy and practice.

In 2019, there were 96 publications, LMIC authors constituted 98% of first authors (48% women) and 92% of last authors (up from 61% in 2017).

Of six new SORT IT courses started in 2019 (excluding two on AMR), all were led by alumni in partner institutions and only one (17%) required TDR ground presence and funding. There were 11 completed SORT IT courses (all national), which were all led by alumni in partner institutions and only 3 (25%) required TDR funding. This highlights the success of franchising.

There are many examples of countries that have successfully nationalized the SORT IT model. Examples include: Kenya where the focus was on tuberculosis and neglected tropical diseases; Sierra Leone and Liberia on the health systems recovery following the sustained 2015-2016 Ebola outbreak; Pakistan on embracing various public health problems; Armenia and Ukraine on access to health care for vulnerable populations; India on training innovations; Papua New Guinea focused on service providers of tuberculosis; Rwanda on using a deliverable-driven with a learning-by-doing pedagogy; and the United Kingdom on health protection issues.

The example from Public Health England (PHE) is worthy of mention as it is a unique example of “South-to-North” learning. Last year, TDR encouraged and supported franchising to PHE who led an adapted SORT IT course which led to: 1) new evidence to inform health protection practice in the UK; 2) agreement within PHE to continue with two SORT IT courses per year; and 3) showed how a research capacity building initiative for low- and middle-income countries can be adapted and used in a high-income country.


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3. Sustainable operational research leadership

There is evidence of sustainable capacity built with 51% of SORT IT alumni (n-388) independently completing new research projects and 31% of them joining and strengthening the 260 strong TDR pool of facilitators.

In 2019, three SORT IT research fellows (from Benin, India and Zimbabwe) completed PhDs supervised by TDR, and four others (from Armenia, Egypt, Ethiopia, and Iran) were enrolled through TDR collaboration with universities.

4. Focusing on antimicrobial resistance, SDGs and UHC

SORT IT has redirected its compass to embrace AMR and UHC. Close to US$ 10 million was received for AMR and the current momentum is to build sustainable operational research capacity that can generate and use evidence on the emergence, spread and health impact of AMR. Target countries include Colombia, Ecuador, Ghana, Myanmar, Nepal, Sierra Leone and Uganda. In 2019, collaboration was established with all AMR country coordinating committees and a new era of collaboration with WHO country offices was opened. A total of 36 projects are already under way in five countries. More information on the SORT IT AMR project is given under ER 1.1.4.

TDR also initiated “catalytic initiatives” linked to the SDGs and UHC. These include: a) assessing the longer-term legacy of Ebola on health systems in Sierra Leone; b) conducting a pioneering SORT IT on neglected tropical diseases in Ethiopia (a UHC target country); and c) helping SORT IT alumni in Armenia and Ukraine lead excellent work on key populations (“leaving no one behind”). The findings from the latter are already making an impact. For example, the evidence is being used to optimize current programmes funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria and PEPFAR, as well as informing the implementation of the roadmap for implementation of the Tuberculosis Action Plan for the WHO European Region.

Further, The Alliance for Public Health (APH) in Ukraine, (a lead SORT IT partner) has become the principal Global Fund recipient to improve programmes on key populations in 14 countries in East Europe and Central


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Asia. Their work was awarded the International AIDS Society prize for work on vulnerable populations. This typifies how SORT IT collaboration leads to a “community of practice” that strengthens regional efforts to use operational research to improve public health.

5. Set benchmarks for “Quality of Implementation Research” evidence

To establish benchmarks for quality of operational research, TDR has introduced two new initiatives. The first is the systematic monitoring and reporting of SORT IT performance standards for all SORT IT courses. Table 1.1.7a shows the progress against these targets. Table 1.1.7a: Progress against SORT IT monitoring and evaluation targets (n-36 completed courses)

Performance Indicator Target Progress (as of October 2019)

Participant satisfaction scores per SORT IT module 80% 100%

Participants completing all course milestones 80% 92%

Papers published within 18 months of submission 80% 93%

Papers assessed for impact on policy and practice 80% 91%

The second is an independent assessment of all published SORT IT studies in relation to the STROBE reporting standards and checklist (Strengthening Reporting of Observational Studies in Epidemiology). A total of 392 original publications from 50 completed courses (January 2009 to December 2018) were assessed in 52 journals by two independent reviewers. 89% of papers achieved > 85% compliance to STROBE (graded as excellent reporting), 10% scored between 76-85% (good reporting) and 1% scored 65-75% (fair reporting). None were deemed as being unsatisfactory (less than 65% score).

95% papers had an LMIC first author, 55% an LMIC last author and 44% of first authors were female. 350 publications (89%) were immediate open access.

Remaining challenges • Helping countries to sustain operational research through improved use of Global Fund grants, other

donor applications and embedding within strategic plans and academic institutional curricula.

• Helping countries build and retain a “critical mass” of researchers for UHC.

• Finding new ways to address the exorbitant cost of open access publications.

• Addressing the demand for SORT IT in Francophone Africa.


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16 SORT IT partners were brought on board in 2019, including academic institutions, nongovernmental organizations (NGOs), various WHO departments and ministries of health. EURO and WHO offices in six countries now collaborate with TDR.

Specific examples of collaboration include: The Institute of Tropical Medicine and Gondar University supporting a national SORT IT in Ethiopia; Kirby Institute in New South Wales supporting countries in the Pacific; Public Health England running a SORT IT focused on health protection issues in the United Kingdom; Burnett Institute in Papua New Guinee providing SORT IT for TB workers; Damien Foundation implementing a SORT IT for their own workers; and Partners in Health adapting SORT IT for the Rwandan context. Ministries of health in China, Kenya, Pakistan and Sierra Leone also supported national SORT ITs.


Approximately US$ 10 million was received from the Department of Health and Social Care, National Institute of Health Research (NIHR), United Kingdom for a SORT IT on AMR. In 2019 US$ 660 000 for six new courses was financed by other partners.


In 2019, 47% of trainees and 40% of facilitators were women. The aim is to reach 50% or more. In 2019, TDR supported SORT IT courses focused on Ebola and Health Systems (Sierra Leone), vulnerable and key populations (Armenia) and neglected tropical diseases (Ethiopia).

Training:

The core focus of SORT IT is research implementation coupled with capacity building. In 2019, there were 8 SORT IT courses (including two on AMR) with 87 participants. These courses were run in Sierra Leone (Ebola), Ukraine (key populations), Ethiopia (NTDs), Nepal (AMR) and Uganda (AMR).

Number of advanced degrees:

In 2019, three SORT research fellows (from Benin, India, Zimbabwe) completed PhDs and four others (from Armenia, Egypt, Ethiopia, EURO) were enrolled through TDR collaboration with universities.


The SORT IT partnership now includes over 37 implementing partners and a network of over 859 alumni and 260 mentors. Partners include disease control programmes, academia and NGOs and WHO country offices.

Publications:

• In 2019, there were 120 publications with individuals from LMICs constituting 98% of first author and 92% of last author (up from 61% in 2017).

• Cumulatively since 2009, there have been 542 publications by the SORT IT partnership in 52 journals (impact factor 0.4–19) and in five languages (English, Russian, Spanish, Portuguese and French).

Related news:

• Updated TDR website: https://www.who.int/tdr/capacity/strengthening/sort/en/ • Work by alumni in Ukraine and Armenia on key populations and “leaving none behind”

https://www.who.int/tdr/news/2019/accelerating-uhc-ukraine-armenia/en/ • Longer term legacy of Ebola on health systems in Sierra Leone:

https://f1000research.com/gateways/tdr/ebolaimpact


Roughly 70% of SORT IT studies report an impact on policy and/or practice.

https://www.who.int/tdr/capacity/strengthening/sort/en/

https://www.who.int/tdr/news/2019/accelerating-uhc-ukraine-armenia/en/

https://f1000research.com/gateways/tdr/ebolaimpact


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Plans for 2020-2021 • The principal focus will be to ensure effective implementation of the AMR - SORT IT programme in

target countries in Asia, Africa and Latin America (US$ 10 million grant). (See SORT IT-AMR project under 1.1.4).

• Along with implementing partners, continue franchising for expansion of SORT IT while maintaining quality standards.

• Support “catalytic initiatives” to enhance TDR leadership, visibility and funding linked to the SDGs and UHC.

• Develop a SORT IT curriculum that teaches practical skills to enhance uptake of research findings.

• Pilot a distance learning (online) SORT IT with alumni from Armenia.

ER 1.1.8: Maximized utilization of safety information for public health decision-making TDR actively promotes safety evaluation, working with countries to improve systems to monitor and effectively use drug safety data to strengthen evidence informing treatment guidelines and improve patient outcomes. A major limitation of current 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. At the same time, it is 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 medications. TDR works with WHO programmes to that effect, and in collaboration with WHO HIV Department, a pregnancy drug safety database has been developed which pools country data issued from national or local pregnancy exposure registries to document risks to mothers and their babies following drug exposure during pregnancy. On a similar project, TDR is working with the WHO Global TB Programme to develop a global database (the global aDSM database) to pool and consolidate safety information on medications used to treat MDR-TB in different countries. More recently, TDR collaborated with the HIV Department to set up a new database for antiretroviral (ARV) toxicity monitoring. This expected result has been slowly evolving over time, but remains a key, distinctive area of work for TDR. There were four main areas of work in 2019:

• The central databases for safety data (for pregnancy exposure registries, the global aDSM database for TB drugs and the central ARV database);

• Strategies to improve safety monitoring in public health programmes; and

• Capacity building for safety monitoring in the scope of the ADP project, focusing on building capacity to facilitate access and delivery of new health technologies for tuberculosis, malaria and neglected tropical diseases (NTDs);

This work is funded by both core funding and designated funds from UNDP for the Access and Delivery Partnership project.


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Figure 1.1.8a: Overview of projects under the scope of “ER 1.1.8: Maximized utilization of safety information for public health decision-making”

Progress in 2019

1. Central databases for safety data

Central database for pregnancy exposure registries: Advocacy and work continues to formalize data transfer agreements and proceed to data transfer. Networking with countries has been strengthened, however formal data transfer has not yet been fully completed for some of the projects, despite obtaining a data sharing agreement. There is growing interest in teratovigilance and monitoring of drug safety in pregnancy. The recent epidemic of Zika in pregnant women reminded countries of the importance of having regular monitoring systems in place and constitutes a good opportunity to build further capacity for safety monitoring in pregnant women in regions such as Africa. Global aDSM database for TB drugs (for active TB drugs safety monitoring and management): The WHO Central Database for safety monitoring of anti-TB drugs, was developed in the context of aDSM, to facilitate data sharing and pooling of safety data issued from national or local databases developed in the scope of aDSM, and hence enhance the detection of new signals and inform future updates of global policies on the use of anti-TB drugs. aDSM should also provide information on rare and as-yet unrecognized adverse effects and drug-drug interactions. Additional data was acquired in 2019. A first data analysis took place and the conclusion is that no new signal was identified. The duplication of reporting systems has been flagged as an issue: from the data being collected directly in the TB control programme, there is tendency to have a data flow separate from the normal PV channels (the


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national TB programme centralizing their own aDSM database). Discussion has been engaged with WHO programmes EMP and GTB and the WHO Collaborating Centre in Uppsala, Sweden, to try and facilitate linkage between the aDSM national databases and Vigiflow to streamline the reporting flow in countries. Vigiflow (the reporting system from Uppsala) could be used for data entry in the TB programme. This database is funded by the WHO Global TB programme. Central database for the safety monitoring of dolutegravir and antiretrovirals in the general population: Discussion and guidance has been provided to different groups in order to facilitate data sharing. Several groups have indicated interest to participate in the data sharing efforts initiated by TDR, mainly from groups following up cohorts of HIV patients, but no additional formal agreement has been signed. This database is funded by the WHO HIV Department.

2. Innovative approaches to safety monitoring at community level

Innovative approaches to safety monitoring are being tested in the context of mass drug administration (MDA). Two studies (in Ghana and the United Republic of Tanzania) to evaluate the use of m-Health tools to improve the efficiency of safety monitoring in the context of MDA for neglected tropical diseases were completed and their publications are in preparation. The analysis shows that m-Health tools can greatly improve adverse event reporting.

A meeting brought together the principal investigators of three studies and their counterparts from the national pharmacovigilance (PV) centres. They reviewed challenges and lessons learned across the three different studies, focusing on the tools used and evidence generated to identify best practices for future implementation. While the m-health tools clearly improved the reporting rate, the scale-up of those initiatives and linkage with the national PV centre has proven to be challenging.

Based on the lessons learned from previous studies, a call has been issued for research to evaluate how best to embed PV in public health systems with a long-term view and in a sustainable way.

3. Capacity building for safety monitoring (UNDP Access and Delivery Partnership project)

Different capacity-building activities were organized or funded under the scope of the Access and Delivery Partnership (ADP) project in Ghana and the United Republic of Tanzania, responding to national workplans and related to strengthening safety monitoring capacity. In April 2018, three new countries (India, Malawi and Senegal) were included, and in April 2019 one new country (Burkina Faso) was added and initial activities have started in all four countries.

The activities in each country focus on priorities identified following discussion with the national pharmacovigilance centres and national control programmes (mainly, TB, malaria and NTDs) to ensure that the activities to strengthen capacities will support access to safe drugs.

TDR also works at a regional level, beyond the focus countries, when there is an opportunity to reach a larger audience. For example, as MDR-TB remains a key priority for many LMICs, we have initiated discussions with African countries to see how strengthened pharmacovigilance and IR/OR can help countries in the control of TB infection, in line with the WHO End TB Strategy.

A workshop took place in 2019 following an update by the Global TB Programme of the WHO recommendations for the treatment of patients with multidrug-resistant tuberculosis (MDR-TB), as well as patients with latent tuberculosis. The new recommendations for MDR-TB treatment insist on the shift towards fully oral regimens as the preferred option for most patients. These new regimens will more frequently include newer molecules such as bedaquiline. In general, the new recommendations insist on the important of active TB drug safety monitoring and management (aDSM) for anyone starting an MDR-TB regimen and the possibility for countries to implement new regimens under the scope of implementation research.

Many countries have little knowledge of the steps and procedures required for implementation of aDSM and


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there is generally a huge need for further training and advocacy on this topic, in particular in French speaking African countries. aDSM will be key as countries move to larger deployment of bedaquiline and new MDR-TB regimens and ADP is eager to follow up with interested countries and partners on this aspect to build the required capacity at country level.

(See the report of the workshop under ER 1.2.6)

From the workshop, it showed that countries need further support to develop capacity for implementation research as well as support to strengthen pharmacovigilance systems, in particular for aDSM for new TB drugs. As a first step, ADP supported the translation of an aDSM training package into French.

While ADP will follow up actively with focus countries (in particular Ghana, Malawi and Senegal), a regional approach will also be considered to allow more countries to benefit from the capacity strengthening efforts that are very much needed in the region.

The current funding is to March 2020, with discussions ongoing to extend the project for another four years.

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



• WHO control programmes at HQ: in particular, WHO/HIV and WHO’s Global TB Programme.

• Countries involved in safety data collection who are contributing data to the central databases.

• UNDP, WHO (strengthening regulatory capacity) and PATH are partners of the ADP projects.


• US$ 15 000 representing time from experts involved in the project and collection work; and

• US$ 150 000 (in-kind from countries and other collaborators participating to projects, in particular for data collection).


• The project on pregnancy exposure registry specifically targets needs and gaps in knowledge with reference to women’s health.


Institutions within the MoHs in target countries were supported with capacity for safety monitoring through the ADP project.


Presentation at congresses and conferences, use of evidence generated by the central databases as part of the review of evidence for treatment guidelines.

Plans for 2020-2021 • Databases: Continuation of data sharing efforts, acquisition of additional data and analysis of data.

• Completion of studies on safety in public health, initiation of new studies to strengthen pharmacovigilance in countries.


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• ADP: Support for capacity strengthening in ADP target countries will continue, including expansion to new countries (workplan to be developed in Q1-2020).

ER 1.2.1: Strategies to achieve and sustain disease elimination The SWG identified research for such strategies as ‘big-ticket items’ for TDR to focus on. Currently, there are two projects within this ER:

• Visceral leishmaniasis (VL) elimination in the Indian Subcontinent – aka KEP (kala-azar elimination programme)

• Onchocerciasis elimination in Africa For both diseases, TDR managed research was critical for availability of the tools and strategies that have allowed VL in the Indian Subcontinent and onchocerciasis in Africa now being considered for elimination.

VISCERAL LEISHMANIASIS ELIMINATION IN THE INDIAN SUBCONTINENT

This is a country-led, long-term project that aims to generate an evidence base for approaches and interventions to be deployed throughout the different phases of VL elimination programmes, and ensures policy uptake and rollout. Since 2005, TDR has been working with research institutions and control programmes in the Indian Subcontinent to conduct research that informs policy and practice for the elimination target of one case of VL per 10 000 inhabitants. As one of TDR’s longest running and most successful implementation research programmes, these efforts have contributed to a sharp reduction in cases. However, further investment and new approaches are required to ensure elimination is sustained, and to prevent resurgence of the disease and the consequent waste of the current efforts to control the spread of the disease. To address this, work is under way at the level of: i) active case detection; ii) vector control and reduction of transmission; and iii) research policy interface.

Progress in 2019 • Follow-up to the study comparing vector control alternatives has been completed in Bangladesh.

Insecticide wall painting has shown longer efficacy at the 2 years follow-up and could be considered as an alternative for control programmes in the future. A publication is being prepared.

• A study to evaluate the use of the rK39 diagnostic test in febrile populations presenting in secondary-level health centres in Bangladesh and India is ongoing and should provide insight into the best diagnostic tool for the elimination phase.

• New studies were initiated in Bangladesh and Nepal to evaluate community-based surveillance of infected VL vectors, active case search by village health workers and community-based vector control.

• TDR commissioned the review of literature on safety of ambisome in clinical trials. The study revealed no increased mortality under treatment by ambisome (vs other VL treatment). However, it should be noted that the conditions of administration on routine treatment may be less strict than under clinical trial and it is recognized that a strengthened follow-up on the safety of VL treatment is required at field level. In some countries the death rate of VL patients is as high as 3%.

• The annual TDR expert meeting on VL took place end of September to discuss priority research in the context of VL elimination in the Indian Subcontinent. Key priorities identified include:

Integration of surveillance and case finding into other programmes (e.g. leprosy or TB programme, polio campaign, etc.)

Improvement of follow-up compliance and patient retention (e.g. role of inventive, e-tools to strengthen follow-up, etc.)

Case investigation and identification of (new) areas of infection


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Role of HIV co-infection as a risk factor Understanding hotspots (Why do certain areas remain hotspots despite extensive vector control and

surveillance?)

Remaining challenges • Beyond implementation research: some priority areas were identified during the expert meeting but are

outside the scope of implementation research. TDR should, however, advocate as much as possible to other partners to see how they can be addressed. They include: trans-border coordination, need for a more specific test useful at point-of-care for diagnosis of new patients when the prevalence is very low and a leishmanin test to diagnose relapse and post-kala-azar dermal leishmaniasis (PKDL).


Partnerships and collaborations: VL control programmes in countries. WHO VL programmes (WHO/UCN/NTD department). Academics and other stakeholders: LSHTM, SPEAK India, DNDi. Estimated leverage created by this project: In-kind contributions and direct investments into research in countries. Direct financial support for meeting participants (about 30% of the meeting budgets). Gender aspects and vulnerable populations: VL is one of the neglected tropical diseases, affecting the most vulnerable populations in endemic countries. Strengthened institutions or networks: The research generates evidence that helps countries to decide on the best interventions for VL control and elimination. Publications: Mondal D, Ghosh P, Chowdhury R, Halleux C, Ruiz-Postigo JA, Alim A, Hossain F, Khan MAA, Nath R, Duthie MS, Kroeger A, Matlashewski G, Argaw D, Olliaro P. Relationship of Serum Antileishmanial Antibody With Development of Visceral Leishmaniasis, Post-kala-azar Dermal Leishmaniasis and Visceral Leishmaniasis Relapse. Front Microbiol. 2019 Oct 9;10:2268. doi: 10.3389/fmicb. Rajib Chowdhury ID, Vashkar Chowdhury, Shyla Faria, Sakila Akter, Aditya Prasad Dash, Sujit Kumar Bhattacharya, Narayan Prosad Maheswary, Caryn Bern, Shireen Akhter, Jorge Alvar, Axel Kroeger, Marleen Boelaert, Qamar Ban.2019. Effect of insecticide-treated bed nets on visceral leishmaniasis incidence in Bangladesh. A retrospective cohort analysis. PLoS Negl TropDis 13(9): e0007724.https://doi.org/10.1371/journal. Mazin Omer, Axel Kroeger, Anand B. Joshi, MurariLal Das, LinaGhassan Younis, Vivek Kumar Singh, Chitra Kumar Gurung, Megha Raj Banjara. 2019. Role of Female Community Health Volunteers for Visceral Leishmaniasis case detection and vector surveillance in Nepal. Health Promotion International (accepted for publication). Lina Ghassan Younis, Axel Kroeger, Anand B. Joshi, Murari Lal Das, Vivek Kumar Singh, Chitra Kumar Gurung, Megha Raj Banjara. 2019.Housing structure including the surrounding environment as a risk factor for visceral leishmaniasis transmission in Nepal. (Submitted) Lim D, Banjara MR, Singh VK, Joshi AB, Gurung CK, Das ML, Matlashewski G, Olliaro P, Kroeger A. . 2019. Barriers of Visceral Leishmaniasis reporting and surveillance in Nepal: comparison of governmental VL-program districts with non-program districts. Trop Med Int Health. 2019 Feb;24(2):192-204. Doi:10.1111/tmi.13189. Banjara MR, Das ML, Gurung CK, Singh VK, Joshi AB, Matlashewski G, Kroeger A, Olliaro P.2019. Integrating Case Detection of Visceral Leishmaniasis and Other Febrile Illness with Vector Control in the Post-Elimination Phase in Nepal. Am J Trop Med Hyg. 2019 Jan;100(1):108-114.


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Results dissemination and uptake: Evidence from the research has been presented to national control programmes and is used by countries for policy decisions. In 2019 Nepal revised its national guidelines for VL surveillance and control and incorporated some of the research findings. Ministries of health take part in the research priority setting meetings and are informed regularly of the research in order to facilitate research uptake. However, more may be done, in particular it was suggested by the MOH representative from India that when presenting results of implementation research, a full package of training and SOPs be made available in order to facilitate research uptake and translation of evidence into practice.

Plans for 2020-2021 • Current studies will continue, and study reports and related publications will be completed.

• New studies will be initiated. Focus of the research in the Indian Subcontinent will be to test for the post-elimination phase for the most suitable interventions in low VL/PKDL-endemicity areas. This will be aimed at better understanding of the epidemiological situation of new cases, detection of secondary cases after an index case has been diagnosed in a local hospital; vector surveillance (detecting infected vectors in new foci); vector control with community managed tools; and social mobilization. An effort will be made to see how best surveillance can be integrated into other programmes to ensure sustainability of the surveillance in the long term.

• An annual meeting will be held with national programme managers and academics to review achievements and define research needs.

ONCHOCERCIASIS ELIMINATION IN AFRICA

Progress in 2019 The focus was on two major elements:

• Research on tools for elimination programmes to support decisions to stop ivermectin mass drug administration: a) delineate parasite transmission zones and estimate risks of recurrence should the criteria to stop ivermectin mass drug administration be met in only one part of the transmission zone; b) monitor the adult work population by estimating the minimum number of reproductively active females. Research has been funded to apply knowledge and methodologies previously developed for parasites in West Africa (Côte d’Ivoire, Ghana, Mali) and Central Africa (Cameroon, Congo-Brazzaville) to East Africa (Ethiopia, northeast Democratic Republic of the Congo, Sudan). Current data suggest that a small panel of up to 25 genetic markers may suffice to identify the likely origin of a sample with high accuracy.

• Research to support adoption of moxidectin in onchocerciasis elimination guidelines and policies. Legal agreements, financing, study designs, protocol and implementation plans for a study to inform elimination strategies with ivermectin or moxidectin and a study to provide data to support use of moxidectin during mass drug administration have been finalized.

Remaining challenges • Expansion to parasites and vectors from more areas in Africa to confirm the feasibility of a pan-

African panel of genetic markers vs a requirement for regional/subregional panels and establishment of related panels, development and selection of methodologies suitable for increased collaboration of laboratories without specialized equipment, selection of a ‘platform’ for large scale use.


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• Implementation, completion and analysis of studies described above, a study to assess safety of moxidectin in Loa loa co-infected individuals, collaboration with different WHO units towards coordination of progress towards registration in African countries and decisions on inclusion of moxidectin in guidelines and Essential Medicines List.



Noguchi Memorial Institute for Medical Research, Ghana; Onchocerciasis Elimination Programme laboratory Ethiopia; La Trobe University, Australia; University of Antwerp, Belgium; Division Provinciale de la Santé, Democratic Republic of the Congo; Medicines Development for Global Health, UK and Australia; Division Provinciale de la Santé, Democratic Republic of the Congo; Eglise du Christ au Congo, Democratic Republic of the Congo; European and Developing Countries Clinical Trials Partnership; Erasmus University, Netherlands; Imperial College, UK; Luxembourg Institute of Health, Luxembourg; Royal Veterinary College, UK; University of Health and Allied Sciences, Ghana; Centre for Research on Filariasis and other Tropical Diseases (CRFilMT), Yaoundé, Cameroon; Institut de Recherche pour le Développement, France.


The studies planned include a paediatric pharmacokinetic and safety study in children which will also provide the final set of data required as a basis for recommendations regarding treatment of breast feeding women. Pregnant women will be excluded from the moxidectin studies. Women becoming pregnant during the studies, despite commitment to contraceptives, will be followed to delivery and their infants followed up to 1 or 2 years of age (pending feedback from Ethics Committees and Regulatory Authorities in Ghana and the Democratic Republic of the Congo and other countries, if applicable).

Training:

1 PhD student from Ghana in Australia

Publications:

Accepted for publication and made available on journal website in 2019: Hedtke SM, Kuesel AC, Crawford KE, Graves PM, Boussinesq M, Lau CL, Boakye DA and Grant WN (2020) Genomic Epidemiology in Filarial Nematodes: Transforming the Basis for Elimination Program Decisions. Front. Genet. 10:1282. doi: 10.3389/fgene.2019.01282

Related news:

https://www.who.int/tdr/news/2019/newsletter-May2019/en/

https://www.medicinesdevelopment.com/debossed-code.htm

https://www.medicinesdevelopment.com/news-190220.htm





Plans for 2020-2021 • Expansion to parasites and vectors from more areas in Africa to assess the feasibility of a pan-African

marker panel vs the requirement for regional/subregional panels and establishment of related panels.

• Implementation of studies of moxidectin, initiation of WHO cross-functional team to reduce barriers between initial registration by a stringent regulatory authority to LMIC policies on their use.

https://www.who.int/tdr/news/2019/newsletter-May2019/en/

https://www.medicinesdevelopment.com/debossed-code.htm







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ER 1.2.6: Optimized approaches for effective delivery and impact assessment of public health interventions Collaborative models to create a regional dynamic, synergize all partner efforts and enhance the conduct of operational and implementation research addressing national and regional research priorities.

In WHO’s End TB Strategy, endorsed by the World Health Assembly in May 2014, the role of research is distinctly recognized as a key driver for improving TB control and is the third pillar of the strategy. Tuberculosis is the first worldwide single infectious agent killer, despite the availability of effective treatments. Embedded operational/implementation TB research within national TB programme activities is needed in countries to identify more efficient ways of using existing tools to control TB and facilitate implementation at scale of new tools.

While TB is the initial focus, it is also seen as the entry point for the long-term plan of bridging OR/IR and health systems. In parallel with the activities described below, foundations for working with other control programmes – such as malaria (seasonal malaria chemoprevention, SMC delivery)2, arboviral disease control (arboviral disease surveillance and vector control interventions3), HIV/AIDS and noncommunicable diseases (diabetes) – have been established.

TDR activities are conducted at national, regional and global levels.

At regional level: The West and Central African regional networks for TB control (WARN-TB & CARN-TB)

A collaborative model was adopted in West and Central Africa (WCA) to create a regional dynamic, synergize all partner efforts and enhance the conduct of operational and implementation research addressing national and regional research priorities. The WCA region is composed of a series of small countries (except Nigeria and the Democratic Republic of the Congo) facing similar challenges and thus eligible for similar solutions. These regions were selected when taking into consideration the TB burden, the country needs, and international support already received that is far less compared to the support provided to countries of the Eastern and Southern African sub-regions.

It was decided initially to focus support on West Africa and, if successful, to extend the initiative to Central Africa. The following phases were defined for enhancing TB research:

Phase 1: Creating an enabling environment at regional and national levels with: (i) the establishment of a regional network; (ii) the establishment of a national TB task force for research in each county; and (iii) strengthening the national TB surveillance systems.

Phase 2: Helping countries develop their TB research plan using standard procedures and integration into the TB National Strategic Plan.

Phase 3: Facilitating implementation of countries’ TB research plan through the development and delivery of a “learning by doing” training programme to strengthen OR/IR research, NTP capacities and conducting at least one research project considered as a priority by the NTP of each country.

Phase 4: Sharing the lessons learned through WCA regional workshops, the development of a sharing platform (website) and the use of social media (Facebook, WhatsApp, WA group).

2 This is one of the key interventions supported by the Global Malaria Programme for reducing childhood malaria mortality

rate. 3 Arboviral disease outbreaks of dengue, chikungunya and Zika are a major threat in West and Central Africa.


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The West African Regional Network for TB control (WARN-TB), composed of the national TB programmes of the 16 West African countries4, was established with TDR support in June 2015 and regional funding was secured for its functioning in 2018-2019 (WAHO and Global Fund). The Central African Regional Network for TB control (CARN-TB) was established in March 2018. It is composed of 11 countries5. The activities of both networks are coordinated by a unique secretariat hosted by the national TB programme in Benin (see activities conducted with the WARN-TB and CARN-TB in the section progress in 2019).

Figure 1.2.6a: WARN-TB and CARN-TB countries

At global level, new activities began to facilitate the conduct of operational/implementation research projects using generic research tools. Experience of collaborating with national TB programmes has shown that even if countries are able to develop research protocols (either themselves or in partnership with local research institutions), they do not necessarily have the time and personnel to focus on this and to develop all study documents quickly. This is a real barrier for the NTPs to conduct more OR/IR projects.

We therefore propose to develop research material (a generic protocol, data collection tool, key study procedures) that can be used by the NTPs and adapted easily to their country context for conducting OR projects. In addition, for a similar problem investigated by several countries, this initiative, if adopted and used by countries, will allow application of a more standardized methodology. Similar data should be collected (at least for the key variables) that would ease data sharing if countries are willing to do so. This can be particularly useful for informing TB guidelines update. More details are given in the following section.

4 Benin Republic, Burkina Faso, Cape Verde, Cote d’Ivoire, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania,

Niger, Nigeria, Sierra Leone, Senegal and Togo. This network has two co-chairs (Guinea and Ghana) and an executive secretariat hosted by the NTP of Benin.

5 Angola, Burundi, Cameroon, Chad, Congo, Democratic Republic of the Congo, Guinea-Bissau, Rwanda, Sao Tome & Principe.


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Progress in 2019 The following activities were conducted in 2019. 1. Strengthening the capacities of WCA countries for conducting OR/IR projects addressing TB control

priorities

• Regional activities to strengthen countries’ TB surveillance systems to better understand TB control gaps at national and subnational level and defining TB research priorities (one-week regional workshop in collaboration with GTB to support CARN-TB countries, facilitation of piloting use of the TB case-based tracker module of the DHIS2-TB in WARN-TB countries, intercountry technical assistance for the conduct of epidemiological reviews).

• Establishment of national TB task forces in CARN-TB countries for the development of a national TB research agenda and strengthening of the already established TB task forces of WARN-TB countries.

• Regional training programme for strengthening NTPs’ capacities in CARN-TB countries to conduct operational/implementation research projects (delivery of modules 1, 2 and 3 of the training programme through one-week regional workshops and mentoring by a team of multidisciplinary facilitators). All countries defined their research priorities. Nine countries (out of 11) developed a OR/IR project.

• More focused training on social science and health economics (WARN-TB): two one-week regional training workshops for WARN-TB countries.

• Development of a TB costing tool in collaboration with McGill University and GTB to facilitate the integration of a health economic component within implementation research projects.

• Development of a one-week workshop on good data management practices. This project goes beyond the support of national TB programmes and targets all national disease control programmes in the WCA region. The project is funded through Luxembourg cooperation and conducted in collaboration with the Luxembourg Institute of Health (LIH). The objective of the course is to strengthen the capacity of national disease control programmes to generate good quality data for programmatic (i.e. surveillance) and research activities. The course is a mix of lecture, practical and group work. It is composed of eleven modules delivered face-to-face. The course was developed by data managers working in research institutes and national TB, malaria and neglected diseases programmes in five West African countries (Benin, Burkina Faso, Guinea, Mali and Senegal) with the support of LIH and TDR.

The course was piloted in Senegal (Q3 2019) and delivered by the data managers who developed it. This was a training-of-trainers. On top of the data managers of each country who developed the course, two people from each country participated to get a team of at least 3 persons per country able to deliver the course in their own countries in Q4 2019.

This short course will be proposed in the five West African universities involved in the development of this course, but there are also plans to integrate the course in the curricula of medical and para-medical students. In addition, the creation of a virtual platform developed by data managers of this group who are able to provide advice and technical assistance to national disease programme professionals for the data management aspects of their research project is under discussion.


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2. Evaluation of the impact of the WARN-TB activities after 3 years

A before and after evaluation of the WARN-TB activities for strengthening OR/IR capacities of the NTPs of the West African region was conducted beginning of 2019 (as recommended by the SWG).

A questionnaire administered before the start of the WARN-TB activities and after 3 years (end of the first cycle of the training programme) aimed at assessing West African NTP staff knowledge and practices concerning OR/IR aspects.

We were particularly interested to see if all regional activities conducted as part of the WARN-TB activities programme enhanced country-led TB research and if the establishment of the network and of the national TB task force was strengthening the leadership of the NTP for the conduct of research projects addressing TB control priorities of NTPs.

The questionnaire was administered at the beginning of the WARN-TB activities and in January 2019 to up to two persons per country (the NTP team in charge of conducting TB research). The analysis was performed by the WARN-TB secretariat.

For all methodological aspects of the design and conduct of OR/IR projects there is a drastic improvement in participants’ knowledge.

When looking at the change in NTP practices, the diagram below illustrates the progress made.

Figure 1.2.6b: Percentage of NTPs answering “yes” to the questions listed below, a comparison before (in blue) and 3 years after the conduct of WARN-TB activities (in orange).

19.2

34.6

11.5

0

38.5

76.9

19.2

46.2

38.5

30.8 30.8

88.5 88.5

65.4

38.5

80.884.6

73.1

65.4 65.4

73.176.9

0

10

20

30

40

50

60

70

80

90

100

Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11


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Question: Which activities listed below correspond to your current situation? 1: Active involvement in research to improve TB control 2: Written or contributed to writing a research protocol 3: Networking for research: Have approached collaborators outside the programme (e.g. other

national researchers) for initiating a research project for your programme 4: Networking for research: Have assisted, or have been assisted by, another TB programme in the

sub region to plan research 5: Collected and interpreted research data 6: Performed a literature search 7: Used literature management software (such a Mendeley, Zotero, etc.) 8: Written or contributed to writing a research abstract 9: Take into account research findings when preparing the strategic plan for TB control or Global Fund

concept note 10: Have used research to solve a problem in your National TB programme 11: If necessary, you have a network of partners to “use” /”collaborate with” for developing your

research project, conducting and analysing the study results It is interesting to note that NTPs are not only more actively involved in research that addresses TB control issues (88.5% vs 19.2% previously) but also more inclined to develop partnerships/ collaborations outside the NTP for conducting OR projects that address their TB control gaps. This may show that NTP staff gained confidence and increased their leadership for conducting this type of research. In addition, it is important to note that 65% and 73% of NTPs have respectively taken into account research findings when preparing their NSP or Global Fund concept note and/or used their research finding to solve a problem of their national TB programme (versus 1/3rd before the conduct of WARN-TB activities). There is a qualitative component of this evaluation that is currently being analysed. The training programme for CARN-TB started in 2019. An evaluation “before the start of the CARN-TB activities” like the one done for WARN-TB has been completed. A full evaluation taking into consideration all aspects of WARN-TB and CARN-TB activities and their impact (i.e. including the impact of the regional approach on programmatic activities) will be conducted for the next annual WARN-TB/CARN-TB meeting. The results will be used for advocacy and fundraising purposes for the two networks.

3. Strengthening of the WARN-TB and CARN-TB secretariat and sharing platforms

The secretariat of the two networks is unique and hosted by the national TB programme in Benin. It was strengthened with the hiring of a full-time person in charge of the secretariat. Among other activities (e.g. organization of all regional workshops), this person:

- Developed a database of all NTP contact persons (WARN-TB/CARN-TB focal person, NTP coordinators, national reference laboratory head, M&E focal point, research focal point, WHO country office NPOs).

- A WhatsApp group was created to share TB news at least once a month. All WARN-TB/CARN-TB members are also encouraged to share events of their NTPs through WhatsApp. This creates an emulation among the NTPs, particularly for World TB day. Next year a contest of the most innovative activity conducted by the NTPs will be run for World TB day.


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- The WARN-TB/CARN-TB website (French and English versions) was finalized. There are still some adjustments to be made but it gives a good idea of all network activities being conducted. It also serves for sharing new guidelines and recommendations. (http://warn-carn-tb.org/en/home/)

Figure 1.2.6c. The WARN-TB/CARN-TB website

4. Improving the effectiveness of TB case finding activities of the NTPs of WARN-TB through the conduct of

implementation research projects

This is a theme that was considered by WARN-TB countries as priority one for 2019-2020. The following IR projects were designed and are currently being conducted:

http://warn-carn-tb.org/en/home/


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For the development and conduct of all of these implementation research projects, technical support was provided by TDR and WARN-TB partners. Funding was provided through TDR grants, the use of countries’ Global Fund grants and financial support provided by international partners (Damien Foundation). Results are expected in 2020. 5. Improving access to TB care for vulnerable populations and favouring a patient-centred care approach

Conduct of a one-week WCA regional workshop in collaboration with GTB and the WHO Regional Office for Africa for the development of TB patient cost survey protocols. Countries have started to raise funding to conduct surveys in 2020.

Development of a tool to assess the health quality of life of TB patients (tool to be piloted in the WCA region in 2020 - project conducted in collaboration with GTB, the Karolinska Institute and KNCV).

A mixed method research study was designed and conducted in Benin to evaluate the vulnerability level of TB patients and the reason and potential solutions to minimize this vulnerability (ETAP project conducted by the NTP of Benin). A multi-ministries, NGOs and TB professionals meeting was organized in November 2019 to discuss the results of this study and the development of IR projects minimizing this vulnerability through social engagement and innovation.

A WCA regional meeting was organized in collaboration with the Global Fund and the Stop TB Partnership (STP) in June 2019 to discuss strategies for improving community engagement in TB care. Following this meeting, the mapping of all NGOs involved in TB care in the WCA region was done in collaboration with STP. The purpose is to try to better understand who is doing what in the region and discuss the establishment of a network of the TB NGOs in the region (subgroup of the WARN-TB meeting). This was recognized by NTP coordinators of WARN-TB and CARN-TB as a good start for enhancing community involvement in TB care, sharing experiences and best practices, facilitating collaborations (in particular for TB care at country borders) and involving communities in OR/IR projects. The result of this mapping and the next steps will be discussed at the annual meeting in February 2020.

6. Improving TB diagnostics

The Diagnosis of multidrug-resistant tuberculosis in Africa (DIAMA) project was launched in June 2017, led by the Benin NTP. Collaborators are: TDR; the Institute of Tropical Medicine (ITM), Belgium; and the NTPs of eight African countries (Cameroon, the Democratic Republic of the Congo, Ethiopia, Guinea, Mali, Nigeria, Rwanda and Senegal). The project explores the feasibility and accuracy of diagnosing TB resistance to first- and second-line drugs through novel molecular multiplex assays developed by GenoScreen. The project is also developing and setting up alternative culture-free approaches for the monitoring of patient response to rifampicin-resistant treatment. Collaboration with FIND was established to contribute to the validation of a 2nd line drug sensitivity molecular test (Xpert 2nd line). As part of this project, the Molbio resistance molecular platform is also being tested in Benin and Rwanda. The project is ongoing, with funding from EDCTP for five years.

7. e-health technology for improving TB management and care

This is a new project conducted in collaboration with and funded by GTB, aiming at supporting NTPs in the development of implementation research projects to strengthen evidence and implementation of digital innovations at critical stages of the TB patient pathway. The method adopted is :

1. Adaptation of the IR toolkit (developed by TDR) to specifically develop IR projects to assess the feasibility, acceptability, coverage and implementation costs of strategies using digital


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innovation for improving TB control. For example, digital technology has been used for improving TB treatment adherence. Case studies from BRICS countries will be used to illustrate the toolkit.

2. The use of these adapted versions of the toolkit will be piloted during a workshop organized by the China National TB programme in May 2020 with representatives from BRICS countries and the WHO Western Pacific region.

3. The validated tool will be made available free to all countries willing to use it to develop this type of research project. A translated version in French will be made available.


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8. Facilitating the implementation of all oral shorter regimen for MDR-TB patients

The ShORRT research package is also a new project, conducted in collaboration with and funded by the Global TB Programme (GTB) and USAID to support countries in the conduct of operational research on the use of all-oral shorter MDR/RR-TB regimens.

This project was developed following discussions with the NTP coordinators and NTP MDR-TB focal persons from 45 countries in the WHO African region who attended a 3-day workshop organized by TDR in collaboration with AFRO and GTB on the new WHO recommendations for the treatment of MDR-TB patients and the research gaps/barriers for implementing these recommendations. Among these, the development of appropriate OR protocols was identified as a barrier to the implementation of all-oral shorter treatment regimens.

The objective of this initiative is therefore: (i) to develop a generic research package (comprising a template protocol, data collection tools, and study procedures) for the conduct of OR on the use of all-oral shorter drug regimens led by NTPs; and (ii) to provide technical assistance to NTPs/country teams in Africa, Asia and Latin America for the implementation of these OR projects.

This project is a collaborative effort led by TDR in collaboration with GTB and key technical partners involved in MDR-TB treatment, care, and research: GDI, Damien Foundation, the Union, MSF, KNCV, McGill University, LSTM, LSHTM, the Sentinel Project, Harvard University, the Global Fund to Fight AIDS, Tuberculosis and Malaria, USAID, and all WHO regional offices.

ShORRT was officially launched and presented during a satellite symposium at the 50th Union World conference on Lung Health (Hyderabad, Nov 2019). In addition, this project was discussed at regional meetings organized by the WHO Regional Office for the Western Pacific (WPRO), by the WHO Regional Office for Europe (EURO), and by PAHO. Tt was also presented at a meeting of the regional Green Light Committee (rGLC) of the WHO South-East Asia region, and it will be discussed at an upcoming rGLC meeting organized by AFRO. Countries who have already expressed interest in implementing ShORRT are: Argentina, Benin, Cambodia, Colombia, Democratic Republic of the Congo, Ecuador, Haiti, Mexico, Nigeria, Peru, Philippines, Viet Nam and Zimbabwe. Planning with these countries is ongoing regarding technical support for the adaptation of the research package, and setting up of the studies.


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9. Ensuring the compliance of TB surveys with the Good Clinical Practices principles.

National population-based surveys of the prevalence of pulmonary TB disease (NTPS) in adults are the best way to directly measure the burden of TB disease in countries that do not yet have routine surveillance data that meet quality and coverage standards. In a meeting of the Task Force in April 2016, progress to date and the future direction of NTPS were discussed. In several surveys, the quality of laboratory work (culture testing) and data management (for tens of thousands of participants interviewed and screened in the community) were the two major challenges faced. To address and mitigate such challenges in future surveys, one of the major recommendations was to develop guidance on how to apply Good Clinical Practices (GCP) and Good Data Management Practices (GDMP) in the context of NTPS.

GTB requested TDR to help them develop a one-year project to guide the implementation of TB surveys (population and facility-based TB surveys) and to ensure survey data credibility, i.e. that surveys are conducted in an ethical manner and that the outcomes reported are comprehensive and accurate.

This project is funded by GTB and has three objectives that correspond to three steps over a one-year period:

(1) To provide training on GCP and GDMP to a core group of consultants who are providing technical assistance for the design, implementation, analysis and reporting of national TB prevalence surveys (NTPS), national TB drug resistance surveys (NDRS) and national surveys of cost faced by TB patients and their households (NPCS).

(2) To develop a guide on how to apply GCP/GDMP principles in the context of NTPS, NDRS and NPCS, including: (i) standard procedures; (ii) checklists to assess compliance with relevant GCP/GDMP principles; and (iii) specific training materials that can be used (and integrated into a broader training package if appropriate) at the beginning of each type of survey.

(3) To train a pool of consultants on the content of the guide.

The training (1) was conducted in September 2019.

Remaining challenges Compared to WARN-TB countries, the NTPs of the CARN-TB countries are weaker and most of them are understaffed and have poor collaboration with local universities/research institutions. This is slowing down the conduct of the CARN-TB strengthening programme put in place by TDR. There are success stories with some countries such as with the NTP of Chad which established good collaboration with the University in Ndjamena and developed/conducted several OR projects that will inform the NTP for addressing TB control gaps.

The volume of activities for this ER has grown compared to previous years. Around US$ 3 million was leveraged in 2019. A total of US$ 1.7 million was raised over a period of 2 years but these funding will end in 2020. Two consultants full time were hired to provide support for the two new projects mentioned previously (MDR-TB Short all oral treatment OR project and IR-toolkit for TB digital health solutions). Additional funding will need to be sought to maintain TDR contribution/support for these two projects (global level activities).


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WHO Global TB programme; WHO regional offices; WHO Department for West and Central Africa; WHO Health Information Systems; GFTAM; The Union; Damien foundation; West African Health Organization (WAHO); Expertise France; Agency for International Development (USAID); London School of Hygiene and Tropical Medicine; MacGill University; Action contre la Faim, France; Institut de Recherche pour le Développement, France; Université de Reims, Faculté de Médecine, France; Université Abomey Calavi, Benin; Université Cheikh Anta Diop and Université of Thies, Senegal; Institut de Santé publique et Centre Muraz, Burkina Faso; Université Gamal Abdel Nasse, Faculté de Médecine, Guinea Conakry; National TB programmes of the WARN and CARN-TB countries; NTP Brazil, India, South Africa; FIND (DIAMA); MOLBIO; Institut of Tropical Medicine of Antwerp, NRL Rwanda, Ethiopia, University FAN


Leveraged: US$ 70 000 (AFRO); US$ 70 000 (GFTAM), US$ 30 000 (GTB), co-financing from GFATM through country grant, Xpert free from Cepheid, Molbio, DIAMA (EDCTP year 3 budget)

Raised: MDR-TB (GTB – US$ 400 000); USAID (US$ 700 000), e-health (US$ 100 000)


All TB patients are vulnerable.

Training:

One key component of WARN/CARN-TB activities is to strengthen research capacities of the National TB programmes of these two networks through the conduct of the OR/IR project: a “learning by doing” activities with guidance of mentors / experts in research methods, statistics, social science and health economics and short courses on key aspects of operational/implementation research (protocol development, conduct, analysis and translation of the research findings into policy).


Strengthening of the national TB programmes of the West and Central African regions and south-south collaborations beyond research activities.

Publications and related news: https://www.who.int/tdr/news/2019/social-innovation-to-research-for-tb-care/en/

https://www.who.int/tdr/news/2019/shorrt-ir-or-package/en/

https://www.who.int/tdr/news/2019/shorrt-launched/en/

https://www.who.int/tdr/news/2019/smarter-solution-missing-tb-casess-in-children/en/

https://www.who.int/tdr/news/2019/44-African-countries-plan-for-implementation-of-WHO-TB-guide/en/


- Benin and Senegal changed their national policy for TB screening in HIV patients and Senegal for their diabetic patients. Mali improved practices to reduce the percentage of patients lost to follow-up . All countries are using research findings for the development of their national strategic plan and concept note for the Global Fund grants.

- RAFAscreen results used for updating the WHO TB Screening Guidelines

- Eight oral communications at the World TB Congress

- SHOORT research protocol (English, French, Spanish and Portuguese versions)

https://www.who.int/tdr/news/2019/social-innovation-to-research-for-tb-care/en/

https://www.who.int/tdr/news/2019/shorrt-ir-or-package/en/

https://www.who.int/tdr/news/2019/shorrt-launched/en/

https://www.who.int/tdr/news/2019/smarter-solution-missing-tb-casess-in-children/en/

https://www.who.int/tdr/news/2019/44-African-countries-plan-for-implementation-of-WHO-TB-guide/en/


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Plans for 2020-2021 At regional level: - Publication of all TB screening study results (special issue and use of videos - in discussion). - Piloting of the TB costing tool (workshop in collaboration with McGill – WHO collaborating centre).

- Finalization of CARN-TB OR training (module 4) and the OR/IR project conducted. - Discussion with PAHO for the establishment of a Latin American regional research network for the

conduct of OR/IR projects in the region. - Definition of regional TB research priorities (in collaboration with the WARN-TB/CARN-TB) and regional

call for proposals. - Replication of the WARN-TB activities with the malaria programme of 13 countries in WCA (those

implementing the seasonal malaria chemoprevention campaign) for strengthening their malaria surveillance system, understanding malaria data, defining malaria control gaps and research priorities, conducting one OR/IR project addressing a research priority.

At global level - Support countries to implement ShORRT (WHO AFR, SEAR, WPR and AMR regions).

- Piloting of the IR toolkit for the implementation of digital innovation to address TB care gaps. - Finalization of the TB surveys and GCP compliance project. - If funding is available, further develop generic research protocols: implementation of LTBi new

recommendations.

ER 1.3.8: Develop, pilot test and replicate an innovative training course for capacity building on gender-based analysis in VBD research and other infectious diseases of poverty Incorporating gender analysis in vector-borne disease research requires technical capacity among researchers. This capacity is limited, particularly in disease endemic countries. Thus, capacity building in this area is a gap that needs to be filled. The target audience for this training is researchers and policy-makers from disease endemic countries.

TDR supported a delivery method of learning that will deviate from the traditional concept, that is, an innovative global classroom approach (use of online learning, web conferencing, video conferencing, discussion forum, blog moderation and use of social media for assignments). The course modules were developed in collaboration with the University of Ghana School of Public Health (UGSPH), and it has followed two rounds of peer review, and was piloted and replicated in 2019 at the University of Ghana and at the University of Witwatersrand in South Africa (last trimester of 2019).

During the 2019 phase of the Gender-Based Analysis (GBA) Project, the course aimed at institutionalizing the GBA course to ensure sustainability across the African region. In order to reduce inequities in health and health outcomes, there is a need for capacity strengthening in GBA among researchers, programmers, governments and agencies across the continent. The scale-up of the GBA course within and outside the University of Ghana has therefore become imperative.

The University of Ghana worked through existing networks of academic institutions to facilitate the process of increasing uptake of the course content and developing skills among facilitators. This will also expedite the creation of a critical mass of experts in GBA across the African region. One such network is the Association of Schools of Public Health in Africa (ASPHA).


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Institutions were proposed different options for how they institutionalize the course. These included:

• Strengthening postgraduate training through integrating the course module into existing courses.

• Submitting the GBA course as a new course to an academic development office within an institution to ensure that it can be offered as either a required or selective course in postgraduate programmes. In this way the course will contribute towards a Degree.

• Registering the course in the academic institution as a short-course which can be offered to researchers and programme implementers. Participants should receive a certificate either of attendance/participation or for competency.

• Or through any other innovative approach for integrating the GBA course within existing institutional structures.

Progress in 2019 The UGSPH ran the GBA online in 2019. Wits University run the course in the last trimester of 2019.

Within the UGSPH, the GBA online course has been integrated within existing gender and health courses offered at both undergraduate and postgraduate levels. This is expected to continue into 2020. In 2019, The University of Ghana collaborated with Wits University and ASPHA to identify other eligible African academic institutions (e.g. schools of public health) which may plan to integrate the GBA short course in one of the modalities listed above. In 2019 Wits University also initiated a process for the institutionalization of the GBA course within their curricula, including building the course on the Wits platform, facilitation of an online course, preparation of application forms for a new short-course and revising current course content.

Wits University worked to integrate modules from the GBA into a Master of Public Health (MPH) course on the social determinants of health: Health and Society (COMH7221). The course is scheduled to run in February 2020. Integration of academic plans and curricula was finalized in 2019.

Wits will also apply to the Academic Development Office for approval to run the course as one of the short-courses offered by the SPH and explore the possibility of integrating it as an optional course within the transdisciplinary PhD programme in 2020.

Remaining Challenges Institutionalization of the GBA course requires time and adequate planning to efficiently integrate it into the universities’ existing curricula. Study plans are difficult to adapt to introduce new content and this process takes time. Additional challenges include TDR needing to offer the course (TDR copyright) free of charge, but if in parallel the course needs to be offered online apart from the one integrated within existing curricula, universities may require a fee, which is not in line with TDR’s practice of no charges/fees to course participants.


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Contributions toward TDR key performance indicators


University of Ghana, Wits University (South Africa); Association of Schools of Public Health in Africa (ASPHA)


Once the course is integrated into the universities’ curricula, there will be no cost to TDR as it will be self-sustained by contributions and funding leveraged by the institution itself. Estimated US$ 100 000 for two institutions in the Africa region.


• Lead facilitators of the projects at both universities are women.

• More than 50% of GBA course students are women (final figures to be confirmed once students complete the course).

Training:

Course participants who complete the course will obtain a diploma. Students of schools of public health that pursue studies in public health (Masters level) will be required to complete the GBA course in participating institutions.


Facilitators working at schools of public health have seen their capacities in gender-based analysis in public health research strengthened.

Plans for 2020-2021 Wits University is working to integrate modules from the GBA into an MPH course on the social determinants of health: Health and Society (COMH7221). The course is scheduled to run in February 2020.

Plans are under way to explore how to institutionalize the GBA course in additional universities.

ER 1.3.12: Strategies to promote gender-responsive health interventions on prevention and control of infectious diseases

Main goals and expected results include:

- To strengthen research capacities and provide innovative tools to generate evidence that informs the design and implementation of gender responsive health interventions to control and prevent VBDs. In addition, it will result in knowledge, strengthened research capacity, policy advice and research products that can be used within and beyond the broad research community. This portfolio is also expected to contribute to WHO’s Thirteenth general programme of work 2019−2023, WHO’s Global Vector Control Response (2017-2030) and the UN Sustainable Development Goals (2015-2030).

- To strengthen the capacity of researchers working on infectious diseases of poverty on how to incorporate an intersectional gender approach, TDR has developed a Toolkit to incorporate intersectional gender analysis into research on infectious diseases of poverty. The objectives of this document are to: 1) strengthen the research capacity of disease-affected countries in intersectional gender approaches; 2) understand and address barriers to effective and quality implementation of health interventions oriented to prevent and control infectious diseases; and 3) explore solutions for equal access to quality health care.


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Great progress has been made towards combatting infectious diseases of poverty (IDPs). However, considerable public health challenges remain, including gender and intersecting inequalities that affect health conditions associated with infectious diseases. This expected result focuses on gender intersecting inequalities that influence differentials in vulnerability to, and the impact of, health conditions associated with infectious diseases in low- and middle-income countries.

It defines, promotes and recognizes the importance of intersectional gender analysis as the process of analysing how gender power relations intersect with other social stratifiers to affect people’s lives, to create differences in needs and experiences and to understand how policies, services and programmes can help to address these differences. Through this expected result, research teams in low- and middle-income countries use an intersectional gender lens; this approach enables to better understand and consequently more effectively intervene in the prevention and control of infectious diseases, as it enhances insights into vulnerability to disease(s), exposures to disease(s), experiences of disease, health-related decision-making, responses to treatment and discrimination and unequal access to healthcare. It also allows to see how these factors are experienced differently by different groups of men/boys, women/ girls and people with non-binary identities, and where these differences might be the result of inequities.

Scientists, including those focusing on implementation research, would benefit from adequately considering sex and gender intersecting social dimensions within their research programmes, by strengthening both the practice and science of implementation, and by contributing to improved health outcomes and reduction of gender and health inequalities. For this purpose, the TDR Toolkit on Intersectional Gender Analysis in Research of Infectious Diseases of Poverty has been developed and its pilot started in December 2019 at country level in Nepal and Uganda, in collaboration with institutions of the Rings Network (Makerere University School of Women and Gender Studies and HERD International). Following a research call for applications and the identified research strands at the 2018 gender meeting, the toolkit started its pilot in 2019 to ensure its effectiveness and applicability. The following resulting case studies with an intersectional lens are expected to be submitted to a peer review journal in 2020:

• Two research teams (from Nepal and Uganda) developed research protocols in 2019 and will apply an intersectional gender lens and follow guidance from the TDR toolkit to generate research case studies focusing on schistosomiasis and tuberculosis (TB) in Uganda and lymphatic filariasis (LF) and tuberculosis in Nepal. This work will serve to pilot the above-mentioned toolkit and assess feasibility of its implementation in the real world. The toolkit, which followed a global consultation and peer review process in 2019, can be improved by incorporating the findings generated after piloting so that it can be used practically in various settings.

• Four research case studies will be generated. Three infectious diseases have been identified for inclusion in the case studies, schistosomiasis, LF and TB. Within each case study, the toolkit will be used to develop specific research questions and identify key social stratifiers to explore how they intersect with gender dimensions to influence vulnerability to illness, exposure to pathogens, response to illness, treatment received and discrimination and/or unequal access to healthcare. The research generated from the case studies in Nepal and Uganda will allow a path to be set for strengthened evidence on how gender intersects with other social stratifiers in patient treatment, access and care and how these influence infectious disease perception, understanding and awareness, among others.


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Figure: How gender intersects with other social and economic characteristics that influence access to health services and health outcomes. From TDR Toolkit: Incorporating intersectional gender analysis into research on infectious diseases of poverty, forthcoming, adapted from Intersectionality Wheel (Simpson, 2009).

Progress in 2019 The 1st TDR Expert Group Meeting on Gender and Intersectionality in Research on Infectious Diseases of Poverty (November 2018) initiated the process of strengthening the strategic path for the gender portfolio. A strategy developed in 2019 will be launched in 2020, coinciding with the World Health Assembly. The strategy will go through editing and layout in 2020, prior to being published and launched.

• Two strategic shifts will be incorporated and drive the strategy: 1) the focus on intersectional gender analysis given the increasingly recognized importance of an intersectional lens in research; and 2) an inclusive research agenda that recognizes men, boys, women, girls and non-binary identities within infectious disease research efforts.

• Also, following this external and internal consultation, key activities and research strands have been identified for the 2020-2021 biennium and beyond, including: - Strengthening research capacities through institutionalization of (intersectional) gender analysis

training (already initiated). - Developing an intersectional gender analysis module within TDR MOOC on implementation research. - Ensuring TDR research calls include as a requirement conduct of an intersectional gender analysis as

defined in the Toolkit reference source6

6 Intersectional gender analysis: The process of analysing how gender power relations intersect with other social

stratifiers to affect people’s lives, create differences in needs and experiences, and how policies, services, and programmes can help to address these differences.


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- Key research strands identified for subsequent research calls include: o Intersection of sex and gender with other social stratifiers to understand marginalization and disadvantage

in access to health services and interventions. o Research on the intersection of gender and other axes of inequality: delivery and access to prevention and

control approaches and products to prevent and control infectious diseases. o Considering ways in which underlying gender power relations can be challenged and progressively changed

during research process. o How to optimize health interventions in structural violence conditions where the most vulnerable people

live with a high burden of infectious diseases.

Key principles and values identified during the 2018 meeting, as well as requirements to conduct an intersectional gender analysis, will be incorporated in future research calls within other TDR Research for Implementation activities. Teams and individual staff will be requested to add this requirement to their calls and assign a specific budget for it to ensure this is not done on a piecemeal basis and with the appropriate funds and human resources within the local research teams.

Although this is not a gender analysis activity per se, some staff have already started to recognize the importance of understanding gender dynamics at local level and projects try to engage communities in vector control in an inclusive way so that not only men take an active role. Some good examples – adapted and depending on the local context – can already be found for example in VES research projects in Cambodia, where one of the process indicators for community empowerment and project ownership is recognition of the importance of women’s involvement. To achieve this, the research teams have included training activities to strengthen the role of women in health outreach programmes for the control of dengue in the community. There was strong representation of women in developing responsive actions for the community’s protection and preventative approaches for dengue and other mosquito-borne diseases. Women’s groups also lead in the sustainability of dengue control efforts in the community by locally fabricating and producing Autocidal Gravid Ovitraps for catching adult mosquitoes. In addition, teams are requested to start by (at least as a minimum) ensuring sex and age disaggregated data is included within their own research projects, as well as other social stratifiers when possible and as adequate.

Specifically, expansion has started within the gender research portfolio and progress has been made following recommendations of the Scientific Working Group in 2018 and 2019, by developing a toolkit to build and strengthen research capacities to conduct an intersectional gender analysis within infectious disease research. In addition, and following a research call and the identified research strands at the 2018 gender and intersectionality meeting, the toolkit is currently being piloted to ensure its effectiveness and applicability. Research case studies will be generated in two LMICs (Nepal and Uganda) through application of the toolkit by generating four intersectional gender analysis case studies of infectious diseases. The three diseases identified for inclusion are schistosomiasis, LF and TB.

A subsequent research call in 2020 will expand this area of work to generate further evidence on how gender intersects with other axes of inequality that shape health conditions and access to treatment and care.

Remaining Challenges To obtain local ethics approvals for research studies at country level and WHO headquarters takes time and may delay the research process. Adequate planning has been ensured to minimize this risk as much as possible.

Apart from this, and in relation to other TDR projects beyond the gender research portfolio, conducting a deep retroactive gender analysis within existing projects that did not budget for it, and which do not have the adequate human resources, and did not consider gender at the initial stages of their research design, may not be possible and would need to happen progressively.


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Contributions toward TDR key performance indicators


Makerere University, HERD International


The project description above highlights the specific focus on gender and other intersecting axes of inequality. PI’s of both Institutions are women.


The toolkit will be disseminated widely across countries and research institutions in LMICs.

Plans for 2020-2021 A subsequent research call in 2020 would expand this area of work to generate further evidence on how gender intersects with other axes of inequality that shape health conditions and access to treatment and care.

Workstream: Research for innovation

ER 1.1.5: Directions for development and accelerated access to new tools and strategies 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 programme objectives for poverty related diseases, including technical advice to external organizations as well as to WHO programmes and departments.

Progress in 2019 Drug development for onchocerciasis (Drugs for Neglected Diseases initiative, DNDi): TDR staff continue to provide expertise and network in support of DNDi activities as and when requested.

A database for case reporting and clinical trial data and a discussion forum on off-label use of drugs for indications with either no or insufficient approved treatments (CURE ID). CURE ID was initiated by the US Food and Drug Administration (US FDA) and the US National Institute of Health (NIH). TDR is working with WHO/UCN/NTD, GTB, PQT and other WHO departments to obtain global expert input into the deployment of this tool. TDR also worked to developed generic protocol to support research in key priority areas (see generic protocol under 1.2.6).



DNDi, US FDA, NIH

Plans for 2020-2021 • Continue collaborations and development of generic protocol where needed.


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ER 1.3.10: Urban health interventions for the prevention and control of vector-borne and other infectious diseases of poverty Scoping reviews and research gap analyses on urban health interventions for the prevention and control of vector-borne and other diseases of poverty were conducted in collaboration with the consortium coordinated by the University of Montréal on six key topics, with research teams from Brazil, Burkina Faso, Colombia and Spain. An overarching commentary, a study protocol, a research article and six scoping reviews were completed and submitted to a peer reviewed journal in January 2018 and published in September 2018. Six different research teams of three to eight people each undertook scoping reviews in four different institutions covering the following topics:

• Field validation and implementation of rapid diagnostic tests for vector-borne and other infectious diseases of poverty in urban areas;

• Surveillance systems for VBDs in urban settings; • Impact, economic evaluation and sustainability of integrated vector management in urban settings; • Transmission dynamics, vector capacity and co-infection; • Containment measures of emerging and re-emerging vector-borne and other infectious diseases of

poverty in urban settings; and • Interventions for vector-borne diseases focused on housing and hygiene in urban areas. In 2019, evidence briefs for policy were prepared in collaboration with policy-makers (ministries of health) from three LMICs: Brazil, Burkina Faso and Colombia. This specific project finished in 2019.

Progress in 2019 In 2019, researchers worked hand-in-hand with policy-makers (ministries of health) to analyse, criticise and finalize the development of evidence briefs for policy based on recommendations from published scoping reviews in a journal special issue (Infectious Diseases of Poverty Journal, September 2018) on urban health, VBDs and other infectious diseases of poverty.


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DEVELOPMENT OF A GUIDANCE FRAMEWORK ON TESTING AND DEPLOYING THE STERILE INSECT TECHNIQUE AGAINST MOSQUITO-BORNE DISEASES

A joint IAEA, TDR-WHO initiative Background For public health vector control, the Sterile Insect Technique (SIT) applied to Aedes mosquitoes is designed to control Aedes mosquitoes and Aedes-borne diseases including dengue, chikungunya and Zika. Several member countries expressed the need for guidance on how to develop, assess and plan for SIT-Aedes experimental and operational programmes. To that end, a joint collaboration was established between the Department of Nuclear Sciences and Application (NA) and the Department of Technical Cooperation (TC) of the International Atomic Energy Agency (IAEA) and the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) of the World Health Organization (WHO), with partnership from the WHO Department for the Control of Neglected Tropical Diseases (WHO/UCN/NTD). The ultimate goal is to provide guidance to WHO Member States on the use of SIT as a component of integrated vector control programmes for disease prevention.

Activity An expert working group appointed by the three collaborating agencies has contributed to the development of the guidance framework supporting assessment and planning for experimental and operational use of the SIT technology for Aedes control. This work was facilitated by two face-to-face meetings of the working group in February and July 2019. The guidance document was finalized and edited before the end of 2019.


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Deliverable A joint IAEA/TDR/NTD/WHO publication entitled “Guidance Framework for Testing the Sterile Insect Technique as a Vector Control Tool against Aedes-Borne Diseases” details consideration for the assessment and planning of SIT programmes in Member States, covering the areas of: modalities of implementation, efficacy testing and indicators, cost effectiveness and risk, phases of programmatic implementation, surveillance, community engagement strategies and registration and regulation of the technology. The document has received WHO executive clearance and release online is pending IAEA clearance. The abstract of the document is inserted below: Abstract: This document is intended to be a comprehensive guide for programme managers tasked with recommending a “go/no-go” decision on testing, full deployment and scale-up of the sterile insect technique (SIT ) in regions of the world affected by diseases transmitted by Aedes mosquitoes. However, we hope that the material presented herein will be used more widely—by scientists, decision makers, ad-hoc review groups and others.

The SIT has a long history of successfully combatting many pest species without negatively impacting the environment or health. This guidance document will inform stakeholders and all persons involved with SIT testing on vectors of human diseases about how to plan, develop, test and evaluate the impacts of the technology against Aedes mosquitoes, the main vectors of dengue, yellow fever, chikungunya and Zika. The nine chapters of this document cover the processes for decision support—including risk assessment and regulatory aspects, technical aspects (e.g., insect mass rearing), entomological and epidemiological indicators, as well as community involvement, cost-effectiveness and programme monitoring and evaluation.

The scope of this document covers programme initiation through pilot evaluation, while touching on aspects of scale-up and full implementation. The technical and operational details of SIT implementation are beyond the scope of this guidance, but readers are referred to other sources for this information.

An overview of SIT test planning is provided in Chapter 1. Chapter 2 describes the requirements for assessment of environmental and health risks related to the technology. Chapter 3 informs about regulatory frameworks, which are determined by individual countries and, in some cases, regional or local authorities within countries. Project plans, performance expectations and protection goals should be discussed with key stakeholders in individual countries, including with regulatory authorities, to determine the scope of any risk assessment and risk management activities. Protection-goal-related risk assessment and risk management for mosquito SIT are likely to include technical risks, such as radiation; entomological and epidemiological risks, such as niche replacement by other vector species, new or different disease transmission by alternative vectors, loss of immunity in the human population; and social risks, such as a complacent attitude towards vector control by communities. SIT facilities and operations also pose conventional environmental and health risks related to buildings, processing activities, waste, transport and worker safety.

The SIT requires mass production of sterile insects of high quality (Chapter 4). The technological package for mass rearing, sterilization, release and quality control of sterile Aedes mosquitoes has been developed. Standard operating procedures or guidelines are available for colonization, colony management, mass rearing and irradiation for sterilization. Guidelines for transportation and release, as well as for quality control, are under development. Evaluation of entomological efficacy and epidemiological impacts is key to understanding the impact of SIT (Chapters 5 and 6). A phased conditional approach is proposed to guide the SIT testing programme through a series of evaluation steps of increasing complexity, with “go/no-go” decisions based on robust, established evaluation methods made at each phase. Illustrative “go/no-go” criteria are presented for the key performance indicators.

Chapter 7 highlights issues of ethics and community and/or stakeholder participation in the process of testing SIT interventions to control Aedes-borne diseases. The two issues are mutually interlinked, but with different purpose and objectives. When doing any research that involves human subjects, researchers are obligated to follow the highest possible ethical principles and standards stipulated in international research ethics guidelines, of which informing communities and stakeholders and involving them at the early stages of any research or intervention that will affect their health, life and wellbeing is an essential component. Meanwhile, the understanding, support and collaboration of communities and stakeholders for the research and the intervention are absolutely crucial for the success of any research activity, including SIT testing activities, and for the sustained effect of those interventions. Therefore, the SIT


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testing team must take both issues into account at the very beginning of any SIT testing project and plan and act accordingly. SIT testing teams also need to be aware that the diverse communities where SIT testing will be conducted are embedded within different socioeconomic, political, cultural and environmental contexts and ecosystems; hence, they need to fulfil their ethical responsibilities and plan and adapt their community participation strategies and actions based on locally prevailing conditions.

The decision to implement SIT is also linked to the cost-effectiveness of the technology, which is explicated in Chapter 8. And in Chapter 9, the general concept of monitoring and evaluation (M&E) is discussed in light of the general framework for testing SIT. The relationship between monitoring and evaluation and the requirements for a functioning M&E system are highlighted. Results should be assessed using an input-process-output-outcome-impact framework. Well-designed outputs achieve short-term effects (outcomes), which in turn will lead to the long-term effects (impact). Examples of M&E indicators useful for assessing long-term impact are given for inclusion during the planning and implementation stages. Entomological and epidemiological evaluation components also are provided.

The objectives of the guidance document on testing the sterile insect technique are to provide the necessary and sufficient information for decision-making in testing and for evaluating the outcomes and epidemiological and entomological impacts of this new vector control approach against Aedes mosquitoes, vectors of major arboviruses and Aedes-borne diseases.

Workstream: Research for Integrated approaches

ER 1.3.6: Evaluation and improvement of malaria control policies through study of the impact of insecticide resistance on LLINs and IRS efficacy, and preliminary analysis of the burden and causes of residual malaria This activity was developed in collaboration with the WHO Global Malaria Programme (GMP). Current GMP guidelines recommend long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS) and larval source management interventions to control malaria vectors. However, resistance of the malaria vectors to insecticides threatens the success of malaria elimination. Nevertheless, malaria transmission can also persist even when LLINs and/or IRS are effectively implemented and malaria vectors are susceptible to the insecticides used. This may be due to a combination of vector and human behaviours/bionomics which compromise the effect of the control measures. The rationale of the project is, therefore, to provide information on: i) the impact of insecticide resistance on LLINs’ efficacy; ii) the magnitude of residual malaria transmission (RMT) in different epidemiological settings; and iii) utilizing standardized protocols to identify the main factors driving transmission, including social behaviours or activities, environmental changes, feeding preferences, or changes in mosquito species composition.

The 2017 World Malaria Report shows that the number of malaria cases has decreased in the last 16 years. However, the number of cases in 2016 was higher than the number of cases in 2015. Mortality due to malaria has decreased since 2010 and was about the same between 2015 and 2016, with about 445 000 deaths annually, mostly in the African region (90%), followed by South-East Asia (6%). The reasons for the 2015–2016 slow-down in the decrease of global malaria incidence are multiple and include a lack of effectiveness in vector control. Resistance to insecticide of the malaria vectors, in particular, is of great concern. In Africa, for example, among the 61 countries performing insecticide resistance tests, 50 countries reported resistant mosquito strains to one or more products. Moreover, some malaria transmission is still in progress, even when control measures are well in place and efficient, which is referred to as “residual transmission”.

Six research projects are included in this expected result, and all are focusing on better understanding how to support malaria control and elimination.


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Progress in 2019 All projects have been satisfactorily completed and reviewed by external experts.

Project A outputs:

In Mali, An. coluzzii was the main Anopheles species constituting 95.5% of the Anopheles population in different villages. Resistance to commonly used insecticides (pyrethroid) was very high in all sites, but the mosquito population was fully susceptible to pyrimiphos-methyl (organophosphate) used for IRS. Entomological transmission and parasitological parameters were all low in LLINs+IRS sites compared to LLINs-only sites. Consequently, malaria control with LLINs+IRS was found to be much more efficient then LLINs alone, despite some insecticide resistance.

In Nigeria, with LLINs as the main vector control intervention, multivariate analysis found insecticide resistance was the main factor associated with non-usage or halt in LLIN usage. The data suggest that only the metabolic P450 mechanism of resistance appears to impair LLIN efficacy and performance in terms of Anopheles monthly biting rates, parasite inoculation rates and malaria prevalence.

In Benin, mosquitoes (An. gambiae and An. funestus) from most surveyed sites were found to be resistant to pyrethroid insecticides, with higher resistance recorded in the south. In the selected study sites, multidrug-resistance mechanisms (target sites and metabolic resistance) were recorded and it was observed that more severe malaria cases were recorded in the locality with a higher resistance level.

The main conclusion was that insecticide resistance developed by malaria vectors is one of the main factors affecting the efficacy of LLINs in communities.

Project B outputs:

In Peru, there is a very low entomological Inoculation Rate (EIR) (0–0.25) and a relatively high number of malaria cases (107 in 2016). This suggests either little local transmission or a highly mobile human population. Entomological indices suggest greater risk of malaria transmission in the Mazán district. Indoor Anopheles darlingi EIR 0.25–3, together with indoor Plasmodium falciparum (Pf) incidence rates suggest that IRS could be effective as part of an integrated intervention/eradication programme; little insecticide resistance in An. darlingi has been noted to date.

In Brazil, the overall malaria incidence density high was 17.26 episodes per 1000 person-years at risk; with the highest incidence among males aged 25–39 years. The distribution of malaria episodes was over-dispersed and there was no association between malaria incidence and rainfall. Characteristics from individuals show higher association with risk of infection vs household characteristics. For example, going to bed after 22:00 increased the risk of malaria infection (RR = 1.25, 95% CI 1.14–1.37) whereas the waking time had no association. The use of bednets was not associated with malaria infection. In addition, a high proportion of people (70.5%) reported using nets the night before interviews. Limited access to vector control tools (LLINs, IRS) was detected in Mâncio Lima. An. darlingi is the main malaria vector and it is likely that most transmission is outdoors.

Project C outputs:

In Thailand, LLIN universal coverage has not been achieved in the study area. It has, nevertheless, been ascertained that primary biting vectors are active in the early evening or late morning, with between 20% and 38% of bites occurring when people are not under the nets. Other contributing factors to RMT in the study site include: i) some members of the population have different sleeping times, going to bed later or rising earlier, thereby increasing their risk of exposure to anopheline bites; ii) a large proportion of the


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population stay overnight in farm huts or the forest where sleeping times are different and where net use is low; iii) there were 25% to 50% of households with damaged nets, decreasing protective efficacy; and iv) some people do not use nets even if they are available, thereby exposing themselves to biting during the night. This is particularly important where the housing structure is very open and in farm huts. The key gaps that need to be addressed to reduce the current transmission in this region include: i) achieving universal coverage and usage of LLINs to remove risk from vectors biting during sleeping times; ii) achieving better maintenance of nets either through behavioural change or more frequent replacement of damaged nets; and iii) novel personal protection tools are required to protect people in the forest and from early evening and late morning biting.

In Viet Nam, LLIN coverage in the study site is optimal, however 100% of biting from secondary vectors occurred before 22:00 and around 26% of households had nets that were observed to have holes or tears, decreasing their protective effect. Further, a large proportion of the population stay in the farm field plots for long periods where their sleeping times are different, usually around 19:30 to 05:00. This means they would be exposed to 28.7% of bites if they used LLINs during this time. However, net use in the farm huts was not observed to be universal and farm hut structures are open and offer little or no availability to hang nets . Nets are not used in the forest when people are working or sleeping outside and these people are thus exposed to about 4.73 bites per person per night. The following issues need to be addressed to reduce the current transmission in this region: i) achieve generalized coverage and usage of LLINs in the farm huts to reduce the risk from vectors biting during sleeping times (distribution of more nets per household to ensure coverage at both household and farm hut locations); ii) improve farm hut structures to offer more protection from mosquitoes; and iii) novel personal protection tools are required to protect people in the forest and from early evening and late morning biting.

Project D outputs:

In Burkina Faso, the EIR is very high with 255.45 infectious bites per person per year. A higher density of malaria vectors was observed indoors compared to outdoors. However, a change in the mosquito collection methodology (from CDC traps to miniature double nets), demonstrated higher biting rates outdoors than indoors. High resistance of all malaria vectors to the pyrethroids commonly used in LLINs was reported, with very low mortality rates when mosquitoes were exposed to bednets collected from the households. Community members tended to spend most of the early evening hours outdoors, only moving inside at around midnight. Further, a significant proportion of people in the communities studied were observed to sleep outdoors at night during the dry season due to the hot climate, with no protection against mosquitoes. Finally, surprising observations included the misconception that people could get malaria from eating certain fruit and food or eating food contaminated by mosquitoes; mosquitoes being just one of the ways to contract malaria.

In the United Republic of Tanzania, the EIR was much less, with 8.34 infectious bites per person per year, but surprisingly higher parity was observed in Anopheles funestus compared to Anopheles arabiensis. High resistance of all malaria vectors to the pyrethroids commonly used in LLINs was also reported again, with very low mortality rates when mosquitoes were exposed to bednets collected from the households. As in the other countries studied, community members are usually outdoors in the early evening hours. There was also a misconception that mosquitoes carrying malaria parasites were not active except between midnight and 02:00.

Project E outputs:

In Cameroon, Ethiopia and Kenya it was concluded that use of LLINs by the population in the equatorial forest, highlands and coastal regions was associated with a reduction in malaria transmission intensity. However, several factors related to mosquito species composition, biting and feeding behaviour, insecticide resistance and human behaviour affect the protective efficacy of LLINs. Malaria transmission in scaled-up


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interventions (LLINs and IRS) seems to be driven by more relaxed feeders which are less anthropohillic and more exophilic vectors, such as An. funestus, An. arabiensis and Anopheles moucheti in the three sites. Some secondary vectors, such as Anopheles pretoriensis, Anopheles coustani, and Anopheles Squamosus, also seem to be playing a role in outdoor malaria parasite transmission. These findings highlight the need to identify additional means to control malaria transmission and other related diseases in these foci where the population is particularly exposed to the risk of outbreaks due to the transmission of pathogens from primates to humans. The use of an integrated control approach to improve the performance of LLINs and limit the expansion of insecticide resistance could be indicated. In addition, more sensitization of the population is needed to emphasize the importance of using control measures regularly and avoiding risk activities which could increase their exposure and the transmission of malaria.

Project F outputs:

Background: Papua New Guinea (PNG) has historically had the highest malaria endemicity in the South- West Pacific region and exhibits a particularly complex malaria epidemiology with four Plasmodium species, 13 overlapping Anopheles vector species, and diverse geographical, ecological and climatic zones, giving rise to vast heterogeneities in transmission and disease burden at various scales across the country. Due to this complexity and high endemicity, malaria elimination has long been considered extremely difficult to achieve in PNG. The scale-up of malaria control interventions has resulted in a significant overall reduction in the nationwide prevalence and incidence of malaria. However, this effect has not been uniform across the country and considerable heterogeneity in transmission exists in different areas, despite a standardized approach to implementation of control measures.

Minimal data currently exists on the determinants of heterogeneity and residual malaria transmission in PNG and the human, vector and/or parasite behaviour or characteristics that might be the most important obstacles to elimination. With support from the TDR Residual Malaria Transmission project, this study aimed to address the knowledge gap by conducting detailed investigations of: (i) prevalence and distribution of malaria infection to confirm/identify/update the magnitude of residual malaria at the time of study; (ii) vector studies to characterize the local vector population abundance, composition and behaviour, as well as their determinants; (iii) mosquito-human contact patterns and tracing routes of transmission; (iv) human behaviour, in order to understand what behaviour renders which population groups susceptible to residual transmission; and (v) establishment of a clinical surveillance system linked to geo-referenced village locations in order to validate a routine system for identifying focal areas of transmission. The primary objective of this study was to better understand the characteristics and determinants of residual (or persisting) malaria transmission in PNG.

Methods: Two sites were selected to conduct integrated prevalence, vector and human behavioural studies, one in Madang Province (Mugil Health Center catchment area) and the other in New Ireland Province (Lemakot Health Center catchment area). The health facility surveillance at Mugil was conducted continuously from August 2016 to February 2018 (n =1,635 patients) and data from ongoing surveillance at Lemakot was aggregated from 2015 to 2018 (n = 1427 patients). Census and surveys were conducted in four villages in each catchment area covering a total of 709 households and 3129 individuals. A total of 3124 blood samples were collected for diagnosis of malaria by light microscopy (LM) and quantitative polymerase chain reaction (PCR). A total of 16 focus group discussions were conducted (two in each village) and 16 in-depth interviews (two in each village). In each village, collections of female Anopheles were undertaken by indoor and outdoor human landing catches (HLC) and barrier screen (BS) methods, with both blood-fed and unfed host-seeking Anopheles sampled and analysed by PCR to determine mosquito species and presence of Plasmodium infection.

Results: This study revealed a higher prevalence of Plasmodium spp. infections and incidence of clinical malaria cases in villages on the north coast of Madang compared to villages in Lemakot catchment of New Ireland Province, as well as differential vector bionomics and patterns of human behaviour in the two areas.


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In the catchment area of Mugil health facility, the incidence of clinical malaria cases is 279/month/1000 population and the prevalence of RDT positive symptomatic malaria cases in community cross-sectional surveys was 3.4%. The prevalence of LM-detectable Plasmodium spp. infections was 13.7% (6.9% Pf, 6.0% Pv) and of qPCR-detectable infections was 33.2% (14.8% Pf, 13.8% Pv), with 57% of these subclinical and sub-microscopic. The dominant vectors were Anopheles farauti s.s. (AF) and Anopheles koliensis (AK), with indoor EIR of 24.6 bites/person/year and outdoor EIR of 35.8 bites/person/year. Preliminary analysis suggests that AF, Anopheles punctulatus and Anopheles longirostris in these villages are opportunistic in their host selection and utilize non-human hosts when access to humans is reduced, whereas AK is highly anthropophilic. Reported LLIN use in each village ranged from 81-94%, however correlating data on human and vector behaviour indicated that up to 70% of individuals are exposed (i.e. not under an LLIN) during the peak vector biting period in their village.

In villages of Lemakot catchment, New Ireland Province, the incidence of clinical malaria cases was substantially lower, 49/month/1000 population and the prevalence of RDT positive symptomatic cases in community cross-sectional surveys was 1.9%, although this varied substantially from 0-6% across the four villages surveyed. The prevalence of LM-detectable Plasmodium spp. infections was 3.7% (1.5% Pf, 1.7% Pv). The only Anopheline vector found in surveyed villages was AF, with 63.2% collected outdoors and an estimated human biting rate of 0.00-1.57 bites per person per night (b/p/n) indoors and 0.00 –3.26 b/p/n outdoors in Lossuk and Lavolai villages. In Lossuk village, the AF EIR was 5.37 infective bites/person/year and the peak biting time was 18:00 to 21:00. Reported LLIN use was substantially lower in these villages compared to Madang, ranging from 29-39% and between 45-95% of people reported being exposed during the peak biting period.

Conclusions: Understanding the extent of local heterogeneity in malaria transmission, the driving factors and the interplay between vector and human hosts, is critical to be able to identify and implement targeted control strategies to ensure the ongoing success of malaria control in PNG is sustained in order to make progress towards elimination.

Figure 1.3.6a: Selected study sites are marked with a red cross. Selected sites include Mugil Health Center in Madang Province and Lemakot Health Center in New Ireland Province


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Expected contribution to impact: For the impact of insecticide resistance on malaria incidence, the project has already delivered evidence showing an impact, due not only to mosquito survival, but also to human behaviour associated with a lack of LLIN protective efficacy. Furthermore, the data show that LLIN efficacy is higher when there is no resistance in place and the duration of protection is much longer. In contrast, the efficacy is much less and of shorter duration when there is resistance and even when this resistance to products is due to more than one mechanism. For the residual malaria projects, it is clear from some projects that vector control tools are not implemented well, and consequently ongoing malaria transmission is not residual, but more an implementation problem. In other situations, such as in Brazil, Peru and Thailand, the current tools are not efficient because of human or mosquito behaviour, and thus malaria transmission is not residual according to the current definition. In situations where malaria can be considered residual, such as in Viet Nam, because of the very good coverage of LLINs, the persistence of malaria transmission has moved from villages to farm plots and forests, with secondary vectors. In such places, the deployment of LLINs needs new approaches, but other vector control tools are also needed. In African countries the persistence of malaria transmission is due to a combination of factors with local specificity. In Burkina Faso, the insecticide resistance of the vectors, as well as certain human behaviour, can be favourable to malaria transmission, but this transmission cannot be considered residual since there is an evident lack of efficacy of the recommended vector control tools. In the United Republic of Tanzania, insecticide resistance and human behaviour are also part of the problem, but another mosquito vector is emerging (An. funestus). Consequently, this transmission is partly not residual due to lack of efficacy of the tools, and partly residual due to a new vector species. In Cameroon, malaria transmission persists despite good implementation of the recommended tools through a high diversity of vector species exhibiting different biting behaviours. In Kenya, insecticide resistance was found to be one of the most important factors driving persistent malaria transmission. For all projects, a very strong research component was the study of human behaviour, including sleeping times, net use, activities and also age and gender differences. These specificities should help in developing integrated malaria control approaches adapted to the local context.

The Second Workshop on Residual Malaria Transmission workshop held in Iquitos in 2019 (Figure 1.3.6b) The workshop received and discussed key findings of six supported multi-country research projects on the impact of insecticide resistance and residual malaria transmission undertaken in thirteen countries, within four WHO regions. The workshop combined plenary lectures, PowerPoint presentations, team work and dynamic discussions. A total of twenty speakers and five moderators participated, which consisted of two main plenary lectures on the malaria situation in the Americas, Vectorbase.org Data Base and strengthening research communications, and twelve presentations on the results from WHO-supported research projects and implementation plans. News media from the region were also present at the event, which was attended by scientists, policy-makers and local authorities.

Figure 1.3.6b. at to the second residual malaria workshop held in Iquitos, 30 April to 3 May 2019.


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Outputs of the Workshop: - Presentation of updated description of the main scientific results for the malaria transmission patterns in the local

context. - Presentation and discussion on plans to implement and deploy new approaches for preventing and controlling

malaria transmission. - Discussion on recommendations and guidance options for development of targeted malaria control tools. - Provide baseline information to inform potential future research and training proposals, as well as standardized

protocols for use in future research.

The workshop brought together over forty experts on malaria, specifically residual malaria, from sub-Saharan Africa, South-East Asia, Latin America and Papua New Guinea. While focusing primarily on residual transmission, the workshop also included projects on insecticide resistance and climate change.

During the workshop, twenty-five speakers shared findings from various research projects around the globe. News media from the region were also present. Three plenary lectures were delivered : the first was a general overview of the malaria situation in the Americas based on the WHO World Malaria Report 2018; the second was about VectorBase, a Bioinformatics Resource for invertebrate vectors of human pathogens; and the third was on communications strategy and materials for research projects. Six presentations featured key findings and insights from TDR supported research projects in thirteen countries on four continents.

All participants had the opportunity to visit San Jose de Lupuna, a community located 45 minutes from Iquitos across Nanay River. The goal of the visit was to show visitors the activities carried out by the Peruvian MOH within the malaria programme and the “Plan Malaria Cero” (PMC or Zero malaria plan). In addition, the Peruvian team of the TDR project showed the activities performed during the execution of the project (entomological metrics used, barrier screens set up, use of drones to identify and characterize breeding sites). https://www.who.int/news-room/feature-stories/tackling-malaria-hotspots-in-the-amazon

Research uptake: Uptake of research outputs has already started, with publications and information briefs for stakeholders. This was undertaken through a contract with a communications partner, Lushomo, who will also develop a website platform for publishing findings and exchanging experience and knowledge within research teams.


Partnerships and collaborations: The project was developed and managed in collaboration with WHO/GMP and the technical partners of WHO regions involved. The subject of residual malaria is still very actual and many options of partnering are possible, in the WHO and outside. Estimated leverage created by this project: Project D (Burkina Faso and the United Republic of Tanzania) received supplementary funding from the Agency for International Development, the United States (USAID) to extend research activities to Zanzibar. Leverage has not yet been determined for the other projects. Gender aspects and vulnerable populations: Overall, 62% of project team members were men (22) and 38% were women (13) Project A: four men (100%) Project B: two women (100%) Project C: three men (100%) Project D: six men and four women (60% and 40%) Project E: three men (100%) Project F: seven men and six women (53% and 47%)

Plans for 2020–2021: This project will be closed as it is, following the recommendations of the Scientific Working Group for Implementation Research adopted in September 2018.

https://www.who.int/news-room/feature-stories/tackling-malaria-hotspots-in-the-amazon


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ER 1.3.11: Multisectoral approach for prevention and control of malaria and emerging arboviral diseases General objective: Set the current landscape on the factors and use of multisectoral approaches to prevent and control vector-borne diseases, design a guidance framework for a more extended implementation based on the findings and support case studies of MSA implementations on different diseases such as malaria and emerging arboviruses.

Vector-borne diseases, including malaria and emerging arboviral diseases, account for about one-quarter of all infectious diseases. There has been significant progress for malaria, with a recent decrease in malaria morbidity and mortality rates. Other diseases, however, such as those caused by arboviruses like dengue, chikungunya, yellow fever and Zika, are expanding with increasing numbers of cases and fatalities. It is evident that the prevention and control of these diseases must be driven by more than a single orientation, and that a multisectoral approach is required to effectively address the dynamically interacting transmission patterns, vector, host and pathogen relationships, environmental conditions, and the complexities of human behaviour (Figure 1.3.11a).

Figure 1.3.11a. Determinants of VBDs, extracted from the Guidance Framework document currently being developed.

The emergence, transmission and distribution of VBDs are linked to a wide range of intertwined and partially overlapping factors of varying scales that encompass multiple sectors, from the biological elements of the system such as pathogen mutation and vector behaviour, to social and global elements such as poverty, human behaviour and climate change. Four categories of risk factors were linked to West Nile virus transmission in the United States in a study in 2011: (i) environmental (temperature, precipitation, wetlands); (ii) socioeconomic (housing condition); (iii) built-environment (catch basins, ditches); and (iv) existing mosquito abatement policies. Most cases of malaria in the Amazon River Basin were associated with recent colonization, new agricultural settlements and open-cast mining sites. Emerging chikungunya outbreaks in non-endemic countries initiated from autochthonous cases and re-emerging epidemics after long periods of


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hiatus were suggested to be linked to factors including climate change and the variety of human mobility and displacement. Recent spread and outbreaks of dengue in Asia and sub-Saharan Africa have been attributed to rapid urbanization and globalization. It is thus vital to recognize and understand to the best extent disease determinants and factors and how they belong to different sectors in order to design comprehensive strategies involving multiple sectors for the prevention and control of these diseases.

In this context, IDRC, Canada, STPH and SDC, Switzerland, and the TDR VES team started a collaboration in 2016 on building a multisectoral approach. This collaboration included different steps:

1. Support commissioned review on specific related topics.

2. Organize joint meetings, workshops and events to discuss next steps and put together all relevant sectors.

3. Support the development of a Guidance Framework for the Implementation of the MSA approaches.

4. Support case studies for implementing MSA approaches on different diseases in LMICs.

Progress in 2019 Step 1- The commissioned reviews

A call was launched in January 2017 to support six commissioned reviews on specific topics related to multisectoral approaches for the prevention and control of VBDs. The overall objective of the call was to support a landscape analysis on examples of multi-sectoral approaches to prevent and control VBD transmission that would also identify knowledge gaps. The commissioned reviews were mandated to investigate current knowledge and experiences on the different topics. Abstracts from review reports are included below and the results will be published in a Supplement of the Journal of Infectious Diseases (Journal has accepted the publications) during the first half of 2020.

Review 1: This review had a special focus on gold mining activities that are disrupting the malaria ecosystems in Africa and the Americas (PI: Robert T. Jones)

Abstract: The objective of this report is to review available data and information on the impact of industrial activities on vector-borne disease transmission, with a special focus on mining activities that can greatly disturb existing malaria ecosystems in Africa, Asia and Latin America. Evidence for the impact of mining activities is cited herein, and an evaluation of how this problem can be approached and improved through evidenced-based health programmes is discussed. The report also identifies key knowledge gaps, and outlines and stratifies future research priorities.

The Amazon has gained specific attention in this report for two reasons. First, the region accounts for an overwhelming majority of malaria cases in the Americas, and is threatened by dengue, chikungunya and, most recently, the Zika virus. Second, the Amazon has extensive deposits of extractable resources including copper, gold, aluminium, tin, nickel and coal, and the mining industry in Brazil in particular has shown vigorous growth due to profound socioeconomic and infrastructure changes, bringing large numbers of people into new settlement areas (Figure 1.3.11b). The published literatures provide evidence that these people are exposed to infection and may lack the knowledge and means to protect themselves and be protected.


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Figure 1.3.11b. Forest settlement near Regina, French Guiana (Picture credit from RT Jones, 2009).

However, there are examples of great successes of interventions to protect workers and their communities through programmes funded and managed by large mining companies in partnership with local governments and international bodies (Figure 1.3.11c). These programmes can go on to form the basis of national vector control programmes and can support local health systems.

Gaining a better understanding of the influence of human activities on vector-borne disease dynamics and vector ecology will help guide future efforts to minimize industrial impacts. Where impacts have already been felt, it is crucial that connections are made between industry actors and the health sector to ensure that vulnerable groups are reached with adequate technologies for protection and treatment. The information presented in this report will help to guide policies, practices and research priorities going forward. Key recommendations include:

• Establishing a national inter-ministerial task force for vector control. • Promoting formation of suitable, location-specific multisectoral partnerships. • Mandating the use of health impact assessments or expand the requirements of health aspects in environmental impact assessments. • Reaching the informal sector through local health posts and roaming health-care workers. • Conducting risk mapping to determine transmission risks. • Ensuring community engagement and social outreach when implementing vector control programmes. • Making health messaging and education a component of disease control efforts. • Monitoring and evaluating vector-borne disease programmes.

Review 2: Using dengue virus as a proxy, this review described and assessed the individual and combined impact of vector control strategies including within the eco-bio-social approach (PI: Alfonso J Rodriguez-Morales)

Abstract: Derived from evidence, weighted and prioritized integrated strategies for the prevention and control of VBDs within the context of eco-bio-social approaches, will provide information for progressive implementation more comprehensive ways to control of VBDs. High-level commitment of multiple ministries is central to the intersectoral interactions required to plan, fund, and implement priority activities outlined in this response. Sustained political engagement will be required to maintain momentum for systems reforms required to adjust to an integrated approach. More prospective primary studies addressing in the field the impact of integrated strategies for the prevention and control of VBDs within the context of eco-bio-social approaches and the multisectoral participation, should be more strongly supported and funded to generate evidence about its importance in reducing the burden of VBDs.

Usefulness go beyond current public health VBD threats, but also for emerging and re-emerging ones, especially arboviral diseases.


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Figure 1.3.11c. Trend in average monthly lost days for AngloGold Ashanti employees, due to a 75% reduction of malaria cases.

Review 3: This review focused on gathering knowledge of the impact of migration (for economic, civil unrest or war reasons), displacement of temporary workers, and other population movements. (PI: Rashad Abdulghani)

Abstract: Population displacement and other forced movement patterns following natural disasters, armed conflicts or due to socioeconomic reasons contribute to the global emergence of Aedes-borne viral disease epidemics. In particular, dengue epidemiology is critically affected by situations of displacement and forced movement patterns, particularly within and across borders. In this respect, waves of human movements have been a major driver for the changing epidemiology and outbreaks of the disease on local, regional and global scales. Both emerging dengue autochthonous transmission and outbreaks in countries known to be non-endemic and co-circulation and hyperendemicity with multiple dengue virus serotypes have led to the emergence of severe disease forms such as dengue haemorrhagic fever and dengue shock syndrome. This paper reviews the emergence of dengue outbreaks driven by population displacement and forced movements following natural disasters and conflicts within the context of regional and sub-regional groupings.

Review 4: This review assessed the role of the different stakeholders into a multisectoral intervention on ITNs distribution on mobile populations. (PI: Cho Naing)

Abstract: Myanmar is a pre-malaria elimination country, and malaria becomes increasingly focal to the vulnerable groups such as mobile and migrant population (MMP). Artemisinin resistant to falciparum malaria has been documented in some parts of Myanmar including boarder areas. To control malaria transmission and subsequent malaria elimination, one of the interventions focused upon was increasing utilization of personal protective measures such as insecticides treated bed nets (ITNs) for the MMPS in Myanmar Artemisinin Resistance Containment (MARC) Zones. The objectives of this study were to (i) identify which stakeholders were involved in intersectoral approaches to support the intervention of increasing access to and utilization of ITNs targeted at the MMPs in the MARC Zones, (ii) characterize the ITN interventions targeted to these special groups of population and (iii) how did intersectoral collaboration occur and what supporting this approach to the study population.


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Methods: This is a part of larger study. This systematic review was commissioned by the TDR (2017/721367-0), and was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. MMP in this review included internal migrants such as seasonal workers, forest workers as well as cross-border migrants and internally displaced persons. Defence service personnel were not included as MMP

Results: A total of 10 studies (n = 222130) included in this review. A variety of stakeholders such as Government sector (e.g. Ministry of Health), the UN agencies (e.g. WHO/Global Fund, UNICEF, UNHCR) and non-governmental organizations were identified as engaging in the intersectoral actions to prevent malaria amongst MMPs in the Myanmar MARC zones. There is a lack of information on how these stakeholders shared the roles and responsibilities for implementation, and about the channels of communication between and-within the partners and with the Government sector in Myanmar. Overall, the ITN ownership (60%, 95%CI:41-79%) and utilization rates among these MMPs (48%, 95%CI: 34-62%) are below the WHO recommended targets.

Conclusions: Findings suggest that interventions to distribute ITNs for the prevention of malaria were supported by the multiple stakeholders. However, how intersectoral collaboration was done and the success or otherwise of various approaches were not described. The net ownership and utilization rates did not meet the WHO targets for Myanmar. In order to understand the contribution of intersectoral collaboration in malaria prevention activities and success factors more well-designed studies are required to specifically assess the role of stakeholders involved in interventions targeted to MMPs under the Regional Artemisinin Resistance Initiative in Myanmar and their impact on and contribution towards the reduction of transmission.

Review 5: This review examined how stakeholders are working together to achieve the implementation of a global multisectoral strategy. (PI: H. Herdiana)

Abstract: Background: Vector-Borne Diseases (VBDs) are estimated to be 17% of the total global communicable disease burden annually. They have a major impact on public health and socio-economic development especially in tropical and sub-tropical countries. WHO has recommended inter-sectoral collaboration as one of the key elements of Integrated Vector Management (IVM) and assumed this would make an important contribution to VBDs control and elimination. However, there is limited evidence that measures the effect and contribution of intersectoral approaches compared to health sector only approaches. This paper reports the findings of a systematic review from more than 40 years of scientific literature, undertaken to develop an evidence-based framework of inter-sectoral collaboration and assess its effectiveness in sustaining prevention and control of VBDs.

Method: Articles were identified through a search of PUBMED, Science of Direct, Web of Knowledge, Google Scholar and WHO archives using key words and excluded duplications (n=2,034). The exclusion of non-VBDs control and prevention interventions resulted in 194 eligible titles/abstract/keywords for full text assessment. Further exclusion of non-peer reviewed articles, non-declaration of ethical clearance, reviews and expert opinion articles resulted in 50 articles finally be included for analysis with the extraction of data on outcome (Figure 1.3.11d), factor/s influencing the effectiveness, indicators of collaboration and sustainability.

Result: Of the 50 articles included in the analysis, 19 articles were categorized as of moderate-strong quality. All articles compared pre-intervention (the intervention being inter-sectoral collaboration) and post-intervention outcomes against disease or vector variables. Three papers included outcome variables on intersectoral collaboration and participation indicator. However, no paper undertook component analysis by different sectors or different activities. Only one paper compared cost data for community-intersectoral intervention for IRS and traditional “vertical” IRS. There were six factors identified as influencing the effectiveness of inter-sectoral collaboration. The main ones were using approach factor (37/47), resources (34/47), relationship (33/47) and management (29/47).

Conclusion: The recent global strategy of vector-borne disease control and prevention encourages inter-sectoral collaboration as an approach to achieving cost effective and efficient results from an intervention. This review shows inter-sectoral collaboration has played an important role in achieving impact on reduction of VBDs or vector densities. However, very few studies measured how much inter-sectoral collaboration contributed to the impact. It is recommended that further high-quality studies are undertaken using indicators for inter-sectoral collaboration to address this critical gap.


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Figure 1.3.11d. Distribution of evidence included in the analysis with colour-coding of diseases.

Step 2 – Workshops and events

TDR-SDC-IDRC-Swiss TPH Workshop on Multisectoral Approaches for Prevention and Control of Vector-Borne Diseases: Current knowledge and Research Gaps and Priorities, Starling Hotel, Geneva, Switzerland, 26-28 June 2017

The workshop was attended by about 40 participants and had a specific session with WHO Member States reported below, as well as the conclusions and recommendations of the workshop.

Conclusive Remarks:

Some activities were recognized by the participants as priority activities to be undertaken once the commissioned reviews have produced their results, through final technical reports and publications. These activities include specific work to support the MSA for prevention and control of VBDs and recommendations at different levels, including global, cross-border, national and local.

Recommendations:

Establishment of a guiding and advocacy framework.

Case studies to collect evidence on MSA potential and functioning, including reinforcement of collection and sharing of data, analysis, cost estimates and overall health impacts, risks for potential outbreaks.

Recommendations for international agencies and national/local levels:

Vector control needs assessments

Coordinate health impact assessment

Operationalization of the MSA at country level, creating a coordinated system that is ready to respond to different VBD situations, including when displaced people are affected or spread VBDs.


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Geneva Health Forum 2018: Parallel Session on “Global health security – Towards multisectoral collaborations to confront the increasing threat of vector-borne diseases”

Step 3 -Support the development of a Guidance Framework for implementation of the MSA approaches.

In response to the need identified during Steps 1 and 2, a consultant was engaged to develop a guidance document on MSA, building on past guidance and experiences, aiming to provide practical aid for governments and other stakeholders, supporting them to gain greater understanding on how to perform MSA for VBDs prevention and control. This document will present a systematic and conceptual view on multisectoral structure and processes, as well as sectoral strategies. The development process of this guidance document was strongly based on the six commissioned reviews and discussions on general framework, case studies and recommendations during the workshop held among many different partners and stakeholders and supported by TDR, SDC, IDRC and Swiss TPH in 2017. Other relevant groups were consulted for input, including the Preventive Chemotherapy and Transmission Control (PCT) team and Vector and Ecology Management (VEM) team in the WHO Department of Control of Neglected Tropical Diseases, as well as the WHO Department of Public Health, Environment and Social Determinants (PHE). The guidance document was reviewed by a dedicated review committee consisting of leading VBD and environmental health experts and other scientists and stakeholders.

The guidance document: A Multisectoral Approach for the Prevention and Control of Vector-Borne Diseases: A Conceptual Framework

While the guidance is primarily directed to decision-makers, with specific relevance for governmental sectors, the framework can be tailored to suit the needs of sub-national and decentralized stakeholders. The purpose of this framework is not only to support supra-ministerial leaders and health sector, but also to enhance the capacity of decision-makers in other sectors to achieve in a collective effort efficient prevention and control of VBDs. In the first chapters the document focuses on the collaboration and coordination of government


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sectors who are then responsible to engage nongovernment partners, with the role of key nongovernment sectors also described in the document.

The document starts with two introductory chapters on vector-borne disease basics and multisectoral approaches. The determinants of vector-borne diseases are described which are grouped in four categories: pathogen- and vector-related, environmental and agro-ecological, economic and social and health system-related determinants. Together these determinants go beyond the ministries of health and the health sector, concerning many other sectors and stakeholders. Existing prevention and control methods were laid out with challenges highlighted, among which was the weakness of the health sector alone. Opportunities exist for better coordinated actions such as potential synergy with the global momentum of the Sustainable Development Goals, multiple entry points for intervention across sectors and diseases and empowerment through more research. The historical background of MSA was traced to reveal this inevitable growing consensus. Examples of existing MSA case studies were extracted from the commissioned reviews and briefly discussed.

Chapters 3 to 6 embody the main elements of the document: the conceptual framework, coordination process and sector-specific guidance.

Chapters 3 and 4 present the conceptual framework and its components. The conceptual framework is named “BET” - “Base”, “Energy” and “Technical elements”, and includes seven components: pillars, dimensions, levels, resources, sectors, domains and enablers (Figure 1.3.11e). These components envelope the ingredients to include in a customized and tailored MSA.

Figure 1.3.11e. The “BET” conceptual framework of a multisectoral approach for the prevention and control of VBDs, extracted from the guidance document.


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As the guidance document aims to delineate how to, apart from describing the essential components, recommendations are provided, for instance on how to mobilize political will, how to enhance commitment and coordination among sectors, and how to strengthen community engagement.

Chapter 5 outlines the coordination pathway: Step 1. Mandate the committee; Step 2. Needs and capacities assessment; Step 3. Partnership building; Step 4. Sensitization and capacity building; Step 5. Management of collaboration; Step 6. Assessment of impact. Roles of non-government sectors and bodies are discussed with a focus on NGOs and international organizations, private sectors and community. Financing and legislation are an indispensable part of the entire coordination pathway, thus funding mechanisms and types of norms and policies needed during a multisectoral collaboration are included in this chapter. The guidance also emphasizes integration and synergy with existing institutional structure for MSA within the country as well as with global multinational and multisectoral efforts such as those under the Health and Environment Linkages Initiative, SDG-related programmes and the One Health initiative.

In Chapter 6 Sectoral Guidance, a sectoral pathway is intended to assist government ministries to plan and initiate their work according to an MSA from defining the vision to sectoral monitoring and evaluation, including important steps such as aligning MSA activities with the sector’s existing activities. A non-exhaustive list of key sectors are included, along with health: environment, water and sanitation, agriculture and aquaculture, energy, housing, education and research, finance and legislature. As the first of its kind, sectoral guidance is provided for each of these sectors, including the rationale for including each of the sectors, what’s in it for each key sector, partners within the sector, and examples of specific actions and delivery partners outside each key sector. Importantly, case studies on how each key sector could be engaged in VBD programmes are included. Finally, for each sector there is a “where to start” hint note with actions to consider foremost.

The last chapter of the guidance document is Monitoring and Evaluation (M&E) where focus is given to the joint planning and execution of M&E activities and the development and application of specific, measurable, relevant, realistic and time-bound indicators and milestones. The indicators should reflect both sectoral and multisectoral performances by measuring input, process, output, outcome and impact. Examples of indicators are listed, for instance, the number of non-health sectors included and the number of joint training programmes planned/conducted from the collaboration.

The guidance document is in its final revision process and is expected to be published in early 2020. It has received positive feedback from reviewers. The work on this document was presented at a side event during the 16th International Course on Dengue, Zika and other Emergent Arboviruses in Havana in August 2019 and received recognition.


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The initial partnership was with the Swiss Agency for Development and Cooperation (SDC), the Canadian International Development Research Centre (IDRC) and the Swiss Tropical and Public Health Institute (STPH).

A new partnership was established in 2019 with the WHO WASH group and SIDA to fund joint activities.

Discussions are ongoing for joint activities with the Multisectoral Action Framework for Malaria (MAFM) developed by the Roll Back Malaria Partnership and UNDP.


New funding from SIDA.


For the 6 commissioned reviews, the principal investigators were 2 women and 4 men, for a gender balance of 33 % women and 66 % men.

The consultant hired for the Guidance document is a woman.

Publications:

Herdiana H, Sari JFK, Whittaker M. 2018. Intersectoral collaboration for the prevention and control of vector-borne diseases to support the implementation of a global strategy: A systematic review. PLoS One, 2018, Oct 10;13(10): e0204659. doi: 10.1371/journal.pone.0204659. eCollection.

Jones RT, Tusting LS, Smith HMP, Segbaya S, Macdonald MB, Bangs MJ, Logan JG. The impact of industrial activities on vector-borne disease transmission. Acta Trop, Dec;188:142-151. doi: 10.1016/j.actatropica.2018.08.033. Epub, 2018, Aug 27.

Naing C, Whittaker MA, Tanner M. Inter-sectoral approaches for the prevention and control of malaria among the mobile and migrant populations: a scoping review. Malar J. 2018 Nov 16;17(1):430. doi: 10.1186/s12936-018-2562-4.

Abdul-Ghani R, Mahdy MAK, Al-Eryani SMA, Fouque F, Lenhart AE, Alkwri A, Al-Mikhlafi AM, Wilke ABB, Thabet AAQ, Beier JC. Acta Trop. Impact of population displacement and forced movements on the transmission and outbreaks of Aedes-borne viral diseases: Dengue as a model. 2019 Sep;197:105066. doi: 10.1016/j.actatropica.2019.105066. Epub 2019 Jun 18.


Uptake of commissioned reviews output has already started with publications and new research projects supported in 2020-2021.

Plans for 2020–2021 This project will be expanded, as recommended by the Scientific Working Group for Implementation Research at their 2019 meeting. The project will move forward with the support of research case studies in collaboration with WHO/WASH.


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Outcomes of past projects

Past expected results Progress on outcomes

Expected Results and SDF projects from past biennia

SDF: Implementation of a regional network on surveillance, diagnostic and vector control of vector-borne emerging diseases in the Caribbean region

Deliverables by outcome:

• Organization of two workshops

• Publication of proceedings

• Official network launched

• Workshop held in Trinidad, December 2015 and in Saint Kitts and Nevis, May 2016

• Caribbean Network officially launched in August 2017 in Cuba (carivecnet.carpha.org).

• Four working groups established in 2017 on surveillance, clinical management, diagnostics and vectors.

• By 2019, assessment of facilities and capacities for surveillance and diagnostic of emerging arboviruses available for Caribbean countries

SDFV: Selection of a consortium of institutions for the organization of a workshop and commissioned reviews to develop an international network on surveillance of insecticide resistance and alternative methods of control for vectors of emerging arboviruses (Worldwide Insecticide Resistance Network, WIN)

Deliverables by outcomes:

• Commissioned reviews and organization of a workshop

• Publication of proceedings

• Publication of reviews

• WIN launched and sustainable

• WIN website launched, May 2016

• Workshop held in Brazil, December 2016, with more than 73 000 Internet connections

• Proceedings of the workshops published, February 2017

• By 2018, four commissioned reviews published in peer-reviewed journals

• By 2019, insecticide resistance recommendations used in policies


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Budget and financial implementation TABLE 3: Approved Programme Budget 2018-2019 and funds utilized


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TABLE 4: Approved Programme Budget 2020-2021


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Projects and activities funded

Project ID Principal investigator PI gender Supplier Name

(Institution) Project title Funding in US$

Disease or research topic

Supplier country

2019/933072 Dulce Maria Torres Arencibia

F Pedro Kouri Tropical Medicine Institute (IPK)

TDR-CARPHA-IPK Workshop on Multi-Sectoral Approaches for Prevention and Control of Vector-Borne Diseases in the Caribbean Current Practices and Future Development.

16 644 Multisectoral approaches

Cuba

2019/886743 Dr Rogelio Danis M Instituto Nacional de Salud Publica

Technical and logistics support for the planning/organization/implementation of A joint IAEA, TDR/WHO, NTD/WHO initiative Workshop on the Sterile Insect Technique (SIT) applied to Aedes mosquitoes is designed to control both Aedes mosquito

2 269 Sterile Insect Technique

Mexico

2019/890884 N/A N/A Holiday Inn Express Tapachulas

Logistics support for the planning/organization/implementation of a joint IAEA, TDR/WHO, NTD/WHO initiative Workshop Tapachula, Chiapas 27 February to 1 March 2019.


Mexico

2019/897944 Dr Dionicia Gamboa Vilela

F Universidad Peruana Cayetano Heredia

Technical and logistics support for the planning/organization/implementation of TDR/WHO Workshop on Residual Malaria Research Projects investigating the magnitude and causes of residual parasite transmission in selected settings:

89 837 Residual Malaria Peru

2019/931249 Dr Laura-Lee Boodram

F Caribbean Public Health Agency (CARPHA)

TDR-CARPHA-IPK Workshop on Multi-Sectoral Approaches for Prevention and Control of Vector-Borne Diseases in the Caribbean Current Practices and Future Development.


Trinidad and Tobago

2019/975232 N/A N/A Lushomo Support for communications activities with the management and updating of a website, the continuation of the development of policy information briefs and the management of the publication of a Special Issue on Residual Malaria in a

7 650 Residual Malaria South Africa


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Supplier country

peer-review journal in relation to a TDR funded project

2019/976563 N/A N/A Elkanodata, SL Layout design and editing for: Multisectoral Approaches for Prevention and Control of Vector-Borne Diseases: A Conceptual Framework and Layout design of WHO TDR technical report (SIT)


Spain

2019/890557 Dr Estomih Mduma

M Haydom Lutheran Hospital

Data entry data newborns surveillance in communities for study on microbiological causes of invasive infections in young African infants

2 000 Fever management Tanzania, United Republic of

2019/891290 Dr Halidou Tinto M Institut de Recherche en Sciences de la Sante (Project IRSS)

Data entry data newborns surveillance in communities for study on microbiological causes of invasive infections in young African infants

5 169 Fever management Burkina Faso

2019/893231 Valerie Louis F Louis, Dr Valerie Renee Translation to French of pharmacovigilance documents

10 000 Access and Delivery Partnership project

Germany

2019/893021 N/A N/A Pharmacy Medicines and Poisons Board

Strengthening capacity in monitoring and response to safety issues associated with new health technologies in Malawi


Malawi

2019/894900 Rachida Soulaymani

F Rabat Who Collaborating Centre For Strengthening

Participation to the “Cours Francophone Inter Pays de Pharmacovigilance” in Rabat


Morocco

2019/896468 Rachida Soulaymani

F Rabat Who Collaborating Centre For Strengthening

Evaluation of national pharmacovigilance systems 20 383 Access and Delivery Partnership project

Morocco

2019/898748 N/A N/A Food and Drugs Authority, Ghana

Pharmacovigilance training in the scope of MDA for yaws


Ghana

2019/904594 Ms Martine Guillerm

F Guillerm, Ms Martine Marguerite Jeanne

Verification of translation of methods manual for microscopy in malaria research settings

1 800 Malaria France

2019/946563 Ms Martine Guillerm

F Guillerm, Ms Martine Marguerite Jeanne

Support to laboratory data review and data analysis for the study on neonate infections

11 975 Fever management France


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Supplier country

2019/946610 Mr Jan Singlovic M Singlovic, Mr Jan Data management for analysis of data from study on microbiological causes of invasive infections in young African infants.

19 500 Fever management Czech Republic

2019/959401 Prof Max Petzold M Petzold, Professor Max Gustav

Statistical analysis to support research on the microbiological causes of invasive infections in young African infants

12 500 Fever management Sweden

2019/971554 N/A N/A Pharmacy Medicines and Poisons Board

Strengthening capacity in monitoring and response to safety issues associated with new health technologies in Malawi


Malawi

2019/973888 Dr Michel Vaillant M LIH - Luxembourg Institute of Health

Quality control of mapping and curation of datasets for the global aDSM database

6 720 Safety data Luxembourg

2019/976522 Dr Samantha Akakpo

F Akakpo, Dr Samantha Technical support for projects related to drug safety monitoring


Switzerland

2019/880197 Mr Abdoulaye Samba

M Samba, Dr Abdoulaye Interpretation Services for Access and Delivery Partnership Meeting in Saly, Senegal


Senegal

2019/880720 N/A N/A University of Freiburg Research Programme on “Effective, affordable and evidence-based dengue early warning and response systems”.

15 012 Arboviruses Germany

2019/880357 Mr David Benitez Valladares

M Benitez Valladares, Mr David

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

6 935 Arboviruses Mexico

2019/880379 Mr Laith Naser Hussain

M Hussain, Mr Laith Naser Research Programme on “Effective, affordable and evidence-based dengue early warning and response systems”.

8 004 Arboviruses Sweden

2019/881367 Dr Maquines Odhiambo Sewe

M Sewe, Dr Maquines Odhiambo

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

6 000 Arboviruses Sweden


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Supplier country

2019/892658 N/A N/A University of 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

15 012 Visceral Leishmaniasis Germany

2019/897982 Professor Rachida Soulaymani

F Rabat Collaborating Centre For Strengthening Pharmacovigilance Practices (Rabat Cc)

Pharmacovigilance Training in the Scope of Strengthening of Safety Monitoring Systems


Morocco

2019/907288 Prof Rocio Cardenas

F Cardenas Sanchez, Professor Rocio

Early Warning and Response System (EWARS) for outbreaks of Zika and other Aedes transmitted arbovirus diseases


2019/915691 N/A N/A University of Freiburg Organization of a TDR expert meeting on “Research support for the post- Visceral Leishmaniasis (VL) elimination phase in the Indian Sub-continent”

21 508 Visceral Leishmaniasis Germany

2019/973313 Faria Hossain F Icddr,B (International Centre For Diarrhoeal Disease Research)

Review of HIV seroprevalence in VL patients in Bangladesh

24 995 Visceral Leishmaniasis Bangladesh

2019/965910 Dr Maria Zolfo F Institute of Tropical Medicine Antwerp

Implementing a second cycle of the Structured Operational Research and Training Initiative (SORT IT) on Neglected Tropical Diseases in Ethiopia

70 000 SORT IT Belgium

2019/883414 N/A N/A Programme National Contre La Tuberculose

West African National Tuberculosis Network. 58 597 Tuberculosis Benin


Secretariat WARN and CARN-TB. 24 587 Tuberculosis Benin


TB-cost survey- protocol writing workshop. 98 639 Tuberculosis Benin

2019/892861 Dr Valerie Renee Louis

F Louis, Dr Valerie Renee Arboviral disease in West Africa- situation analysis report.



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Supplier country

2019/899124 Dr C. Hugues Traore

M Traore, Dr Check Asken Hugues

Support to National TB programmes of the WARN-TB and CARN-TB countries for OR/IR activities.

48 000 Tuberculosis Burkina Faso

2019/913045 Ms Debora Pedrazzoli

F Pedrazzoli, Ms Debora MDR/RR-TB implementation Research Package. 14 000 Tuberculosis United Kingdom

2019/912235 N/A N/A Programme National de Lutte Contre La Tuberculose (PNLT) du Mali

West African National Tuberculosis Network- research capacity strengthening.

20 000 Tuberculosis Mali

2019/915074 N/A N/A Programa Nacional de Luta Contra A Lepra E Tuberculose

Guinea Bissau – Research capacity strengthening (WARN-TB activities).

20 000 Tuberculosis Guinea-Bissau

2019/919206 N/A N/A PNLT-Togo Research capacity strengthening (WARN-TB activities) - Togo.

19 981 Tuberculosis Togo

2019/919549 N/A N/A Programme National de Lutte Contre La Tuberculose (PNLT)

Research capacity strengthening (WARN-TB activities) - Burkina Faso.


2019/919574 Dr Marie Sarr F Programme National de Lutte Contre La Tuberculose (PNLT)

Research capacity strengthening (WARN-TB activities) - Senegal.

20 036 Tuberculosis Senegal

2019/923262 Dr Marie Sarr F Programme National de Lutte Contre La Tuberculose (PNLT)

West African National Tuberculosis Network. 1 000 Tuberculosis Senegal

2019/925686 N/A N/A National Tuberculosis, Leprosy and Buruli Ulcer Control Programme

Research capacity strengthening (WARN-TB activities) – Nigeria.

19 026 Tuberculosis Nigeria

2019/926525 Dr Abdourahmane Sow

M West African Health Organization

Arboviral diseases – West African regional meeting- 42 654 Arboviruses Burkina Faso


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Supplier country

2019/918527 N/A N/A Programme National d’appui aux Communes de Convergence (PNACC)

Research capacity strengthening (WARN-TB activities) - Guinea.

19 873 Tuberculosis Guinea

2019/929640 Jacquemin Kouakou

M Programme National de Lutte Contre La Tuberculose (PNLT)

Research capacity strengthening (WARN-TB activities) - Cote d’Ivoire.

18 899 Tuberculosis Côte d'Ivoire

2019/931967 Dr Oumar Abdelhadi

M Programme National de Lutte Contre La Tuberculose

Research capacity strengthening (CARN-TB activities) - Chad.

10 000 Tuberculosis Chad

2019/932639 N/A N/A National Health Development Project

Research capacity strengthening (WARN-TB activities) - Gambia.

19 918 Tuberculosis Gambia

2019/932638 N/A N/A National Tuberculosis Programme

Research capacity strengthening (WARN-TB activities) - Ghana.

20 000 Tuberculosis Ghana

2019/934464 Dr Giuseppina Ortu

F Ortu, Dr Giuseppina Arboviral disease surveillance and control in West Africa.

6 000 Arboviruses United Kingdom

2019/934970 N/A N/A Programme National integre Lepre et Tuberculose (PNLT)

Research capacity strengthening (CARN-TB activities) - Burundi.

10 000 Tuberculosis Burundi

2019/943630 Dr Dissou Affolabi M Programme National Contre La Tuberculose

Research capacity strengthening (WARN-TB activities) - Benin.

19 981 Tuberculosis Benin

2019/944410 Dr Jean Louis Ndiaye

M UFR Santé / Université de Thies

Good Data management practices. 35 103 Data management Senegal

2019/945966 N/A N/A Programme Nationale de Lutte Contre la Tuberculose et la Lèpre

Research capacity strengthening (WARN-TB activities) - Mauritania.

20 000 Tuberculosis Mauritania


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Supplier country

2019/944419 Dr Désiré Lucien Dahourou

M Dahourou, Dr Desire Lucien

Support to National TB programmes of Guinea-Bissau and Togo for conducting OR project on TB screening in HIV patients.


2019/947498 Ms Jennifer Ann Kealy

F Kealy, Ms Jennifer Ann GCP and GDMP compliance of TB surveys. 12 000 Tuberculosis France


West African National Tuberculosis Network. 64 693 Tuberculosis Benin


Tuberculosis in diabetic patients project. 14 342 Tuberculosis Benin

2019/964646 Dr Susana Scott F Scott, Dr Susana Technical Consultation to review the evidence from research, monitoring and evaluation of seasonal malaria chemoprevention, since WHO policy recommendation in 2012.

3 200 Malaria United Kingdom

2019/964415 Alexandre Delamo M Centre de Formation et de Recherche en Sante Rurale de Maferinyah

In-house Good Data management practices courses. 20 000 Data management Guinea

2019/965143 Dr Moussa Djimde M Malaria Research & Training Center (MRTC)

In-house Good Data Management practices courses. 20 000 Data management Mali



In-house Good Data Management practices courses. 20 000 Data management Senegal

2019/967969 N/A N/A Centro Nacional de Endemias (CNE)

Research capacity strengthening (CARN-TB activities) - Sao Tome & Principe.

10 180 Tuberculosis Sao Tome and Principe

2019/968183 N/A N/A Programa Nacional de Lucha Contra la Tuberculosis

Research capacity strengthening (CARN-TB activities) - Equatorial Guinea.

10 350 Tuberculosis Equatorial Guinea


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Supplier country

2019/968141 N/A N/A Programme National de Lutte Contre La Tuberculose (PNLT)

Research capacity strengthening (CARN-TB activities) - Gabon.

10 102 Tuberculosis Gabon


In-house Good Data Management practices courses. 19 872 Data management Benin



Drug resistance emergence & SMC. 20 653 Malaria Senegal

2019/972473 Dr Mourtala Mohamed

M Programme National de Lutte Contre La Tuberculose (PNLT)

Research capacity strengthening (WARN-TB activities) - Niger.

19 991 Tuberculosis Niger

2019/973257 Dr Valerie Renee Louis

F Louis, Dr Valerie Renee French translation- ShORRT protocol. 5 500 Tuberculosis Germany

2019/974129 Dr Bollahi Mohamed Abdalla

M Institut National de Recherche en Santé Publique (INRSP)

Entomologic surveillance for Arboviral disease -Mauritania.

24 991 Arboviruses Mauritania

2019/973640 Dr Maria da Luz de Lima Mendonc

F Instituto Nacional de Saude Publica - Cabo Verde

Entomologic surveillance for Arboviral disease - Cap-Verde.

24 989 Arboviruses Cape Verde

2019/973661 Dr Mawlouth Diallo

M Institut Pasteur de Dakar Entomologic surveillance for Arboviral disease - Senegal.

24 991 Arboviruses Senegal


Support to the secretariat of the WARN and CARN-TB.


2019/974201 N/A N/A Ocean Translations S.R.L. Spanish and Portuguese translation- ShORRT protocol.

6 904 Tuberculosis Argentina


Annual meeting of the West and Central Africa for TB control Networks (WARN-TB & CARN-TB).



112|




Supplier country

2019/975984 Dr Mamadou Brahima Coulibaly

M Coulibaly, Dr Mamadou Brahima

Support to Mauritania for the implementation of a surveillance system for Arboviral Diseases.

2 000 Arboviruses Mali

2019/975966 Dr Samuel Kweku Dadzie

M Dadzie, Dr Samuel Kweku Support to Cape Verde for the implementation of a surveillance system for Arboviral Diseases.

2 000 Arboviruses Ghana

2019/975995 Dr Mawlouth Diallo

M Diallo, Dr Mawlouth Support to Cap Verde and Mauritania for the implementation of a surveillance system for Arboviral Diseases.

4 000 Arboviruses Senegal

2019/976526 Dr Benjamin Seydou Sombie

M Groupe de Recherche Action en Sante (Gras)

In-house Good Data management practices courses. 20 092 Data management Burkina Faso

2019/975952 N/A N/A Lushomo Situation analysis concerning surveillance and arboviral diseases control in West Africa.

8 494 Arboviruses South Africa

2019/977622 Dr Brice Bicaba M Institut National de Santé Publique (INSP)

Support to Burkina Faso for improving their quality assurance system for the integration of Measles and Arboviral Diseases surveillance.

4 000 Arboviruses Burkina Faso

2019/941743 Maria Margarita Ronderos Torres

F Ronderos, Dr Maria Margarita**S085704

To prepare reports of the Expert Meeting on Dengue-Zika-Chikungunya Early Outbreak Warning and Response, WHO-HQ, Geneva, Switzerland, 19-20 September 2019

1 200 Arboviruses Colombia

2019/953370 Dr Lester Chitsulo M Lester Chitsulo To facilitate capacity strengthening activities for the Access and Delivery Partnership Project in Malawi.


Malawi

2019/923563 Prof. Nicola Christofides

F University of the Witwatersrand Faculty of Health Sciences

Coordination, Administration and institutionalization of the gender-based analysis course in vector-borne diseases and climate change research.

60 718 Gender and VBDs South Africa

2019/924964 Sarah Ssali F Makerere University School of Women and Gender Studies

Protocol development to pilot of TDR Toolkit on Intersectional Gender Analysis for research on Infectious Diseases of Poverty through generation of case studies on TB and Schistosomiasis in Uganda.

20 000 Schistosomiasis, TB and Gender

Uganda


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Supplier country

2019/973349 Mrs Elisabeth Heseltine

F Heseltine, Mrs Elisabeth Provide editing services 4 745 Gender France

2019/973322 Vicente Pau Cuervo

M Elkanodata, SL Provide layout services 10 500 Gender Spain

2019/977333 Mr Jaime Munoz Martin

M Munoz Martin, Mr Jaime Provide graphic design support 4 400 Gender Spain

2019/915300 Alexandra Levy F Solthis Organization and coordination of a workshop and conference on vector-borne diseases and urban health

40 004 Urban health France

2019/920492 Dr Chandani Kharel

F Herd International Private Limited

Protocol development to Pilot TDR Toolkit on Intersectional Gender Analysis for research on Infectious Diseases of Poverty through generation of case studies on TB and Lymphatic Filariasis in Nepal

12 000 TB, Lymphatic Filariasis and Gender

Nepal

2019/912867 Dr Phyllis Dako-Gyeke

F University of Ghana Coordination, Administration and institutionalization of the gender-based analysis course in vector-borne diseases and climate change research.

36 300 Gender and VBDs Ghana

2019/946616 N/A N/A Print Point Limited Printing of the AMR strategic plan 3 504 Antimicrobial resistance (AMR)

Sierra Leone

2019/952354 Dr Pattamaporn Kittayapong

F Mahidol University - Centre of Excellence For Vectors and Vector-Borne Diseases

To cover the costs of co-organizing the meeting 50 000 Dengue, Chikungunya and zika

Thailand

2019/956601 Mr Thomas Scalway

M Lushomo Communication support for two research projects on Vector Control in South-East Asia.

10 000 Dengue, Chikungunya and zika

South Africa

2019/958103 Ms Valentina Picot F Fondation Mérieux Support for One Health Consultation meeting 6 667 Vector borne diseases France


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Supplier country

2019/962793 N/A N/A Hotel Mystic Mountain P. Ltd.

Full board accommodation for the Structured Operational Research and Training Initiative (SORT IT) Training in Nepal for tackling Antimicrobial Resistance. Duration (17 to 30 November 2019)

45 402 Antimicrobial resistance (AMR)

Nepal

2019/877096 Dr Joshua Chadwick Jayaraj

M Jayaraj, Dr Joshua Chadwick

Technical support for the review of all SORT IT publications between 2009 and 2018 on reporting quality, relevance, equity and utility

7 040 SORT IT India

2019/887891 Selma Dar Berger F The Union Antimicrobial resistance: Independent review of ethics considerations for analysis of routine programme data


France

2019/892562 Selma Dar Berger F The Union Databases, metrics and archives on SORT IT quality and standards: courses, participants, facilitators, milestones, outcomes, publications, impact and other relevant materials

29 400 SORT IT France

2019/900349 Dr Robinah Najjemba

F Najjemba, Dr Robinah Literature search and archiving of peer-reviewed publications related to five strategic pillars of the Global Action Plan on Anti-microbial resistance.


Switzerland

2019/904968 Dr Karapet Datvyan

M Tuberkulozi Hetazotutyunneri Yev Kankhargelman Kentron

Organization of a SORT IT satellite symposium during the International Medical Congress of Armenia to enhance dissemination, research uptake and networking

9 700 SORT IT Armenia

2019/907368 Ali Engy M Ali, Dr Engy Review of applications and preparation of databases for the selections committee of SORT IT courses on antimicrobial resistance in Asia and Africa


Luxembourg

2019/926178 Alexandre Delamo M Centre de Formation Et de Recherche en Sante Rurale de Maferinyah

Providing senior technical expertise for implementing the Structured Operational Research and Training Initiative (SORT IT) on antimicrobial resistance in Low- and Middle-Income Countries.


Guinea


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Supplier country

2019/926120 Dr Maria Zolfo F Institute of Tropical Medicine Antwerp

Providing senior technical expertise for implementing the Structured Operational Research and Training Initiative (SORT IT) on antimicrobial resistance in Low- and Middle-Income Countries.


Belgium

2019/926140 Debra Donckel F Médecins Sans Frontières Providing senior technical expertise for implementing the Structured Operational Research and Training Initiative (SORT IT) on antimicrobial resistance in Low- and Middle-Income Countries.


Luxembourg

2019/926065 Selma Dar Berger F The Union Providing senior technical expertise for implementing the Structured Operational Research and Training Initiative (SORT IT) on antimicrobial resistance in Low- and Middle-Income Countries.


France



Providing senior technical expertise for implementing the Structured Operational Research and Training Initiative (SORT IT) on antimicrobial resistance in Low- and Middle-Income Countries


Armenia

2019/950659 Katrina Hann F Sustainable Health Systems

Providing operational research data and software support for participants from Sierra Leone selected for the Structured Operational Research and Training Initiative (SORT IT) courses on antimicrobial resistance


Sierra Leone

2019/952863 Nicholas Kirui M Moi Teaching and Referral Hospital

Implementing the Structured Operational Research and Training Initiative (SORT IT) on Neglected Tropical Diseases in Kenya

88 136 SORT IT Kenya

2019/972514 Dr Olga Denisiuk F Denisiuk, Dr Olga Technical and managerial support for conducting a SORT IT programme

20 000 SORT IT Ukraine

2019/972523 Mr Hayk Davtyan M Davtyan, Mr Hayk Technical and managerial support for conducting a SORT IT programme



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Supplier country



Implementing module 3 of the SORT IT programme entitled “Ending TB/ MDR-TB in “vulnerable populations” through operational research capacity building and evidence-informed decision in Eastern Europe and Central Asia (EECA)


2019/942614 N/A N/A Institute of Tropical Medicine Antwerp

Organization and travel of six presenters attending a SORT IT symposium on Neglected Tropical Diseases at the 11th European Congress of Tropical Medicine and International Health, Liverpool, United Kingdom

18 632 SORT IT Belgium

2019/942207 Selma Dar Berger F International Union Against Tuberculosis and Lung Diseases (The Union)

Organization of a TDR sponsored skills building workshop on operational research at the 50th World Conference on Lung Health, Hyderabad, India

21 467 SORT IT France

2019/880791 Dr Qingxia Zhong F Zhong, Ms Qingxia Development of a conceptual framework document on background, definitions and practical tools for implementing multi-sectorial approaches on prevention and control of vector-borne diseases.


Switzerland

2019/919952 Ms Mariska van der Zee

F Van Der Zee, Ms Mariska Hendrika Lena

Study of the feasibility to test the Sterile Insect Technique against the mosquitoes of the species Aedes aegypti.


Netherlands

2019/925793 Ms Debora Pedrazzoli

F Pedrazzoli, Ms Debora Technical assistance and development of generic tools for the conduct of country led TB implementation research.

96 000 Tuberculosis United Kingdom

2019/942406 Dr Varalakshmi Elango

F Elango, Dr Varalakshmi Development of guidance to apply GCP/GDMP principles in the context of National TB surveys and training on its content.

39 000 Tuberculosis India

2019/947664 Ms Vanessa Clare Veronese

F Veronese, Ms Vanessa Clare

Strengthening evidence and implementation of digital innovations at critical stages of the TB patient pathway.

42 000 Tuberculosis France


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Supplier country

2019/942036 Professor Helen Louise Ackers

F Ackers, Professor Helen Louise

Senior Knowledge Management trainer: provide technical support and provide training to participants on the SORT IT Anti-microbial resistance regional course.


United Kingdom

2019/942049 Dr Nasreen Saleem Jessani

F Jessani, Dr Nasreen Saleem

Senior Knowledge Management trainer: provide technical support and provide training to participants on the SORT IT Anti-microbial resistance regional course.


United States

2019/879769 Dr Andrew Robert Ramsay

M Andrew Robert Ramsay Senior Research Specialist: Antimicrobial Resistance 9 000 Antimicrobial resistance (AMR)

United Kingdom

2019/897051 Dr Andrew Robert Ramsay

M Andrew Robert Ramsay Senior Microbiologist: Technical support and needs assessment focused on consumables and reagents for clinical microbiology laboratories at national antimicrobial resistance (AMR) sentinel sites, Myanmar


United Kingdom

2019/926513 Sophi Goyet F Goyet, Ms Sophie Senior Knowledge Management trainer: provide technical support and training to participants on the Asia regional SORT IT Course (Myanmar and Nepal) and country-level SORT IT courses on antimicrobial resistance (AMR)


Nepal

2019/926523 Nilam McGrath F McGrath, Ms Nilam Senior Knowledge Management trainer: provide technical support and training to participants on the Asia regional SORT IT Course (Myanmar and Nepal) and country-level SORT IT courses on antimicrobial resistance (AMR)


United Kingdom

2019/964019 Javier Burgos M Burgos, Mr Javier Senior Knowledge Management trainer: provide technical support and training to participants on the Asia Regional SORT IT Course (Myanmar and Nepal) on antimicrobial resistance (AMR)


Spain


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Supplier country

2019/963859 Sophie Goyet F Goyet, Ms Sophie Senior Knowledge Management trainer: provide technical support and training to participants on the Asia Regional SORT IT Course (Myanmar and Nepal) on antimicrobial resistance (AMR)


Nepal

2019/964035 Samuel Sieber M Sieber, Dr Samuel Senior Knowledge Management trainer: provide technical support and training to participants on the Asia Regional SORT IT Course (Myanmar and Nepal) on antimicrobial resistance (AMR)


Luxembourg

2019/972919 George Hedidor M Hedidor, Mr George Kwesi

Special Services Agreement (SSA) Recruitment - Technical Assistance AMR SORT IT Project, 11 November - 10 March 2020


Ghana

2019/893697 N/A N/A Country Lodge Complex Conference Hall facilities and accommodation for 25 participants for SORT IT 2.0

5 599 SORT IT Sierra Leone

2019/972701 Ms Lisa Schwarb F Schwarb, Ms Lisa Guide méthodologique env. 44 pages - French version

1 008 Malaria Switzerland

2019/973223 Ms Lisa Schwarb F Schwarb, Ms Lisa TDR - adaptation of the EWARS Guide in English 302 Arboviruses Switzerland


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TDR funding in 2019


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Scientific Working Group recommendations The Scientific Working Group for Research for Implementation met on 17 and 18 October 2019. Specific recommendations were made for the different projects and summarised in brief here:

• Arboviruses - surveillance and preparedness: o To conduct further clinical and operational research to evaluate application of the EWARS

system under different settings and its effectiveness in triggering control activities.

• Urban Health and VBD: o To complete this work by seeking synergies with other TDR RFI projects (such as Gender)

to maximize the use of limited resources.

• SORT IT: o To engage proactively to work on the inclusion of gender training as part of SORT IT and

in the identification of topics that enable gender analysis. o Integrate work with the planned Knowledge Management activities in TDR, including for

advancing data sharing, policy-impact and gender-responsive research. To proceed next year to a detailed review to include the longer-term sustainability of SORT IT as an area of work for TDR.

• Climate change and VBDs: o The SWG emphasized the need for prioritization in the next phase.

• Residual malaria: o To conclude this project and transition it into the multi-sectoral approaches project (see

below)

• Innovative vector control tools: o To proceed with caution in testing the sterile insect technique, and to focus on research

to address the substantial unresolved concerns about this intervention.

• Research for TB control: o Continue engagement in West and Central Africa as planned. o Develop a plan to track trends on TB case-finding, incidence and mortality data in order

to explore potential effects of research strengthening activities in countries. o Consider bringing an intersectional gender analysis into the TB patient cost survey data

analysis o Develop an explicit and detailed SMART plan for sustainability and ultimate TDR exit. o If resources permit, expand.

• Research for malaria control: o Support the work with countries to optimize delivery of Seasonal Malaria

Chemoprevention. o If resources permit, expand.

• Onchocerciasis elimination: o Search TDR Global for external reviewers of research proposals. o Share information related to risk of moxidectin in pregnancy.


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• Visceral Leishmaniasis elimination: o Continue research to identify the most suitable interventions in low endemicity areas and

consider tools that can facilitate research uptake and translation of evidence into practice. o If resources permit, expand.

• Use of safety data: o Continue engagement with countries to evaluate how best to embed safety monitoring in

primary health care systems. Consider if artesunate-pyronaridine could provide an opportunity for strengthening and evaluating pharmacovigilance systems.

o If resources permit, expand.

• Multisectoral approaches: o Focus the project on case studies on malaria and emerging arboviruses to enlighten both

process and outcome measures and build in and/or develop a business model within the case studies. Plan the project with careful attention to endemic country engagement / participation and to monitoring and evaluation.

• Networking: o The SWG recommends completing the definition of criteria for TDR engagement,

participation and exit from networks.

• Gender: o Strengthen TDR / RFI’s intersectional lens in research to foster values of diversity,

inclusivity, equity and equality. o Build a shared understanding on what intersectional gender analysis is and is not so that

everybody in RFI can consider what steps they can make towards greater equity in research topics and activities.

o Think strategically about training in that area (e.g. consider the Intersectional Gender Analysis module within TDR’s Implementation Research MOOC and include other relevant tools and resources on the TDR Gateway and other widely accessed platforms).

• Data sharing: o Continue and deepen TDR’s role in facilitating data sharing to advance public health in the

global south, and ensuring that data sharing does not widen inequality.

• For projects ending: o Ensure objectives and deliverables of the projects are achieved.

research for implementation...er 1.3.6: evaluation and improvement of malaria control policies...

Documents