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Innovation for healthResearch that makes a differenceNineteenth programme report | TDR 2007-2008For research ondiseases of povertyUNICEF • UNDP • World Bank • WHO

Innovation for healthResearch that makes a differenceNineteenth programme report | TDR 2007-2008For research ondiseases of povertyUNICEF • UNDP • World Bank • WHO

TDR/GEN/09.1Copyright © World Health Organization on behalf of the Special Programmefor Research and Training in Tropical Diseases 2009All rights reserved.The use of content from this health information product for all non-commercialeducation, training and information purposes is encouraged, including translation,quotation and reproduction, in any medium, but the content must not bechanged and full acknowledgement of the source must be clearly stated. A copyof any resulting product with such content should be sent to TDR, World HealthOrganization, Avenue Appia, 1211 Geneva 27, Switzerland. TDR is a World HealthOrganization (WHO) executed UNICEF/UNDP/World Bank/World Health OrganizationSpecial Programme for Research and Training in Tropical Diseases.The use of any information or content whatsoever from it for publicity or advertising,or for any commercial or income-generating purpose, is strictly prohibited. Noelements of this information product, in part or in whole, may be used to promoteany specific individual, entity or product, in any manner whatsoever.The designations employed and the presentation of material in this health informationproduct, including maps and other illustrative materials, do not imply the expressionof any opinion whatsoever on the part of WHO, including TDR, the authorsor any parties cooperating in the production, concerning the legal status of anycountry, territory, city or area, or of its authorities, or concerning the delineation offrontiers and borders.Mention or depiction of any specific product or commercial enterprise does notimply endorsement or recommendation by WHO, including TDR, the authors or anyparties cooperating in the production, in preference to others of a similar naturenot mentioned or depicted.The views expressed in this health information product are those of the authors anddo not necessarily reflect those of WHO, including TDR. WHO, including TDR, andthe authors of this health information product make no warranties or representationsregarding the content, presentation, appearance, completeness or accuracyin any medium and shall not be held liable for any damages whatsoever as a resultof its use or application. WHO, including TDR, reserves the right to make updatesand changes without notice and accepts no liability for any errors or omissions inthis regard. Any alteration to the original content brought about by display or accessthrough different media is not the responsibility of WHO, including TDR, or theauthors. WHO, including TDR, and the authors accept no responsibility whatsoeverfor any inaccurate advice or information that is provided by sources reached vialinkages or references to this health information product.Compiled and edited by Julie N RezaDesign and layout by Lisa SchwarbCover Photo: WHO/TDR/CraggsThis report represents the combined efforts of many TDR staff, all of whom arethanked for their invaluable input, comments and support.

ContentsPART IForeword by Dr Margaret Chan, Director-General, World Health Organization .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Message from Professor Rolf Korte, Chair of the TDR Joint Coordinating Board (JCB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7About TDR .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9Key achievements during 2007-2008 .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10TDR in a changing global health landscape, Introduction by TDR Director Dr Robert Ridley . . . . . . . . . . . 13PART IIResearch for delivery and access .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Discovery and development of tools and products for neglected diseases .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Empowerment – fostering research leadership .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28Stewardship – harmonizing support and aligning research to country needs .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34PART IIIKey publications and resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41TDR governance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43TDR partnerships 2007-2008 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47TDR financial information 2007-2008 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48Nineteenth programme report | TDR 2007-20083

4“TDR has decades of experience in building national research capacityand promoting local ownership and community engagement. ”

PART I PART IForeword by Dr Margaret ChanDirector-General, World Health OrganizationExecuting agency for TDRWe are at a critical time in our efforts to meet internationalhealth commitments made by United Nationsmember states. Health is the explicit focus of 3 of the8 Millennium Development Goals, and is implicitlypresent in the remaining 5. On current trends, goals setfor reducing maternal and childhood mortality are theleast likely to be met in virtually all regions of the world.In welcome contrast, we see positive signs that malariaand tuberculosis could be controlled by 2015. For bothdiseases, however, problems of drug resistance need tobe monitored as an urgent priority. Globally, numbers ofnew HIV infections have been gradually declining andnumbers of people receiving AIDS treatment have risen,although the unmet need for treatment remains unacceptablylarge. Clearly, attainment of the health-relatedgoals requires more effort on multiple fronts.TDR is a source of innovation for new products andapproaches. Since its inception, this special programmehas given highest priority to the neglected tropicaldiseases, which currently affect around 1.2 billion of theworld’s poorest people. TDR has consistently broughtthe power of rigorous scientific investigation to bear onthese largely ancient diseases, which continue to anchorso many people in poverty.We know from our experiences with primary health carethat demand-led initiatives have the greatest chance ofsustainable success. This is firmly acknowledged in thenew TDR strategy – health leaders in endemic countriesknow best what works and what they need most in theircountries.As the Commission on Social Determinants of Healthconcluded in its 2008 report, efforts to reduce inequitiesin health outcomes depend on improvements in theconditions of daily life and fundamental changes in theinequitable distribution of power, money and resources.TDR looks at the impact of gender and cultural issues aspart of the overall investigation of what works and whatdoes not, and is identifying new strategies that can, forexample, increase women’s status and role within thehealth system.TDR has also made vital contributions to the developmentof WHO’s health research strategy and the GlobalStrategy and Plan of Action on Public Health, Innovationand Intellectual Property, which promotes innovation asa way to improve the range and affordability of medicalinterventions for diseases that disproportionately affectdeveloping countries (approved as WHA resolution61.21).The new strategy that TDR has begun to implementwill increase our ability to attack, on multiple fronts,some very long-standing and seemingly intractableproblems. I mean here our ability to scale up show-casepilot projects to reach large populations, to improveaccess to existing interventions, and to reach the pooron an adequate scale. I also mean our ability to addressmultiple health needs in a cost-effective, integrated way.The new ambitions fixed for this programme greatlyexpand the portfolio of strategies being pursued in ourcollective efforts to improve health and alleviate poverty.TDR is performing a more strategic role and providinga more holistic approach. These are very welcomeattributes in the complex landscape of public health.We greatly need coordination, cohesion and coherence.TDR is using its convening power to catalyze concreteand strategic action. It is empowering disease endemiccountries to take leadership roles, building on itsdecades of experience building national researchcapacity.These tasks are not easy, but they are absolutely vital toour goals and our prospects for long-term success. Thesenew functions, if performed well, will greatly increaseour chances of making life better for the world’s hugepopulation of neglected people with neglected healthneeds. I look forward to supporting and utilizing therange of broadened outcomes as TDR moves forward inthis strengthened strategic role.Nineteenth programme report | TDR 2007-20085

6“TDR has never been an organization that rests on its laurels. Itsfuture success will be measured by its ability to act as a catalyst fordisease endemic countries to initiate and lead sustainable researchinitiatives. ”

PART IMessage from Professor Rolf KorteChair of the TDR Joint Coordinating Board (JCB) *The past two years have been both an exciting andchallenging period for TDR’s Joint Coordinating Board(JCB). Health research has risen as a priority on globalhealth agendas, and is seen as critical to reducingpoverty and achieving the UN Millennium DevelopmentGoals (MDGs).New challenges have emerged with the epidemiologyof infectious diseases constantly evolving. Fresh healthinitiatives are providing new momentum. At the sametime the multiplicity of actors contribute to a morecomplex institutional environment in which diseaseendemic countries (DECs) continue to risk being leftbehind in planning, and priority setting in the globalresearch enterprise as a whole.In response to these developments and challenges,TDR embarked on an extensive review of its operationsand series of stakeholder consultations culminatingin the adoption of a new Ten-Year Strategy in 2007,endorsed at the JCB’s 30 th anniversary session inGeneva in June 2007.In line with the strategy, the JCB also approved a newsix-year business plan, which started to be implementedat the beginning of 2008. This plan positionsTDR to play a global ‘stewardship’ role as facilitatorand knowledge manager in the global research efforton infectious diseases of poverty. Similarly, TDR isstimulating efforts to empower researchers fromDECs to build and exercise leadership at individual,institutional and national levels. The JCB itself has beenan active contributor to this effort by striving to bringmore DECs into the circle of TDR’s governance and tofacilitate their strengthened contribution.The JCB has also welcomed the reshaping of TDR’sresearch activities in the context of this new strategy.Research has been refocused to fill targeted, neglectedneeds in the research continuum. These include boththe discovery of new drugs and tools at the upstreamend of research and, at the other end of the spectrum,improving better use and access among poor populationsto the tools already available.TDR’s research activities are increasingly underpinnedby a trans-disciplinary view of health as defined notonly by biomedical determinants but also social factors,such as gender and socio-economic status.I commend to the global health community the outputand impact of TDR historically, and particularlyover the last two years. Its achievements continueto outweigh its limited budget. Despite this time offinancial crisis, I believe that TDR deserves increased,not merely maintained, financial support from themany stakeholders that benefit from its activities.TDR has never been an organization that rests on itslaurels. Its future success will be measured by its abilityto act as a catalyst for disease endemic countries toinitiate and lead sustainable research initiatives thatproduce the innovative solutions of the future, developa stronger presence in international health research,and effectively use research to inform and influencepolicy and practice.* The Joint Coordinating Board, TDR’s top level governing body which meetsannually and counts 34 members (for more details, see chapter on governance).Nineteenth programme report | TDR 2007-20087

“TDR – three simple letters that stand for the SpecialProgramme for Research and Training in Tropical Diseases,the leading UN-based organization dedicated to researchon infectious diseases of poverty. ”8

PART IAbout TDRTDR – three simple letters that stand for the SpecialProgramme for Research and Training in TropicalDiseases, the leading UN-based organization dedicatedto research on infectious diseases of poverty.Since its establishment at the World HealthOrganization (WHO) in 1975, TDR has stimulatedresearch and development of new drugs and diagnosticsand implementation strategies that contributed toglobal elimination campaigns for four major diseases– Chagas disease, leprosy, lymphatic filariasis, andonchocerciasis – and a regional elimination campaignagainst visceral leishmaniasis. TDR field researchhas been critical in generating evidence that led tothe adoption of major new health strategies, such asthe use of bednets, artemisinin-based combinationtherapies (ACTs), pre-packaged antimalarial drugs inmalaria prevention and treatment, community-directedinterventions (CDIs) against onchocerciasis andmalaria, and multidrug therapy for leprosy. TDR hasalso fostered the training of thousands of developingcountry researchers and has strengthened hundreds ofdeveloping country research institutions while playinga critical role in the birth of organizations such asthe Global Forum for Health Research (GFHR), theMedicines for Malaria Venture (MMV) and the Foundationfor Innovative New Diagnostics (FIND).TDR operates within a broad framework of intergovernmentaland interagency cooperationand participation. It has a budget of approximatelyUS$ 50 million and a staff of 100; its unique positionderives not from this budget or its relatively smallsize, but from the breadth of the consensus throughwhich it operates in partnership with hundreds ofscientists, institutions and networks all over the world,and by the manner in which it is governed, with its4 co-sponsoring organizations as well as an independentgoverning board comprising equal representationof developed and developing countries.Building on a successful past, TDR embarked on anew 10 year-strategy in 2007 in response to changesin the global health and research landscape. Thisstrategy aims to foster ‘an effective global research efforton infectious diseases of poverty, in which disease endemiccountries play a pivotal role’ and has three strategic arms:research on neglected priority needs, empowermentand stewardship.In this report we provide an overview of our progressand achievements in the first phase of implementingthis strategy during 2007-2008.Nineteenth programme report | TDR 2007-20089

Key achievements during 2007-2008TDR achievements fall into four broad categories:• Research for delivery and access• Discovery and development of tools and products for neglected diseases• Empowerment to foster capacity and research leadership• Stewardship to harmonize and align research to country needsWithin research for delivery and access, fourstudies led to significant outcomes that particularlydeserve highlighting. These demonstrated that:• Communities can effectively manage the collection,distribution and administration of multiplecomplex interventions, including the diagnosis andtreatment of malaria. This has major implications forcommunity engagement in strengthening primaryhealth care in Africa.• Delivery of a malaria drug rectally (rectal artesunate)in the community close to the home to childrenseriously ill with malaria can ‘buy them time’ to getto health centres far away from their rural villages,preventing death and neurological damage.• Tuberculosis (TB) detection by microscopy canbe simplified in resource-poor settings, relievingpressure on over-stretched laboratories and limitingthe number of long trips, often on foot, that patientsneed to make to clinics.• Several dengue diagnostic tests meet appropriatestandards and can now be offered at reduced cost topublic health programmes through a WHO procurementscheme.Similarly, under research for discovery anddevelopment of new tools and products therewere several advances that could have a major impactin the future:• A new, simplified skin patch test has been developedfor the diagnosis of onchocerciasis. Approval fromthe ministries of health of endemic countries willnow be sought for its use during large surveillance inonchocerciasis endemic areas which have undergonenumerous rounds of ivermectin treatment.• Lymphatic filariasis lesions of young children inIndia can be reversed by appropriate treatment, withimplications for control strategies.• Two new fixed-dose artemisinin combination drugsfor the treatment of malaria have been developed,led by the Drugs for Neglected Diseases initiative(DNDi) with support from TDR. Mefloquine-artesunatewas registered in Brazil by Farmanguinhos.Amodiaquine-artesunate was registered in Moroccoby Sanofi-Aventis.• TDR drug discovery networks have continuedto generate lead compounds that have beentransitioned into drug discovery projects withother partners.10

PART IAt TDR we believe that how we do our work is just as important as what we do. Our newvision puts the focus on researchers and policy makers living in disease endemic countries.They should increasingly be setting the priorities, leading the research and making thedecisions on how to use research evidence that affects the lives of people in their countries.Developing country scientists either led, or were significantly engaged in the researchhighlights mentioned on page 10.Working with partners, TDR has supported the initiatives listed below that we believe will laya sound basis for the empowerment of developing country researchers and the stewardshipof research on infectious diseases of poverty.Empowerment to foster capacity andresearch leadership in developing countries hasbeen facilitated by supporting (in partnership withothers):• The creation of ANDI, the African Network forDrugs and Diagnostics Innovation, to bring togetherresearchers, research organizations, policy makersand manufacturers in a coordinated manner thatpromotes and sustains African-led product R&Dinnovation and capacity building. This network isgenerating a lot of interest and support.• Establishment of a new initiative, Enhancing Supportfor Strengthening the Effectiveness of NationalCapacity Efforts (ESSENCE), to help increase coordinationamong donors in aligning their supportof research in developing countries with the countryneeds.• The building of new clinical trial research centresin Liberia and the Democratic Republic of Congo(DRC), enabling African scientists to lead the phaseIII trial of a new drug for onchocerciasis.• Biosafety courses, and establishment of the firsttraining programme for countries to address thesocial and ethical issues associated with the potentialrelease of genetically modified mosquitoes.Stewardship through broad stakeholder engagementin the provision of platforms for sharing knowledgeand agreeing on priority strategies and agendas hasbeen facilitated by:• Development and launch of a new web-basedportal – TropIKA.net – to allow more equitableaccess to information that can support evidencebaseddecision making and provide collaborativeworkspaces for key discussion groups and meetings.• Support for the development of the Global Strategyand Plan of Action (GSPA) on Public Health, Innovationand Intellectual Property that was adoptedby the World Health Assembly (WHA) in 2008,creating new momentum and more equal opportunitiesfor health-related research and development(R&D) in developing countries.• Support for the Global Ministerial Forum forResearch on Health in Bamako, Mali in 2008.• Laying the groundwork for the TDR Global Report onResearch on Infectious Diseases of Poverty for early2011 through the establishment of several expertdisease and thematic reference groups.• Development of guidelines and research strategiesaround specific issues in tropical disease research.• Publication of over 400 peer reviewed TDRsupportedresearch articles. More than 60% hada lead author with affiliation to a disease endemiccountry.Nineteenth programme report | TDR 2007-200811

12“TDR is in a unique position to ‘steward’ and promote newperspectives, and new research and capacity building initiativesto address global neglected disease priorities. ”

PART ITDR in a changing global health landscapeIntroduction by TDR Director Dr Robert RidleyThe institutions and policies driving internationalhealth have undergone enormous change in recentyears. World attention on diseases of poverty has beendriven by civil society, governments, philanthropicorganizations, health workers and researchers, and hasled to a focus on the UN Millennium DevelopmentGoals (MDGs). Health research is a key componentof this change. It should be better appreciated as awise investment that can reap huge returns for humandevelopment, saving money and lives and enrichingindividuals and communities.An expansion of product development partnerships(PDPs) is among the recent developments, helping tofind novel ways of fighting disease through the developmentof new and improved treatments, diagnosticsand other interventions. Continued investment andadvances in basic science improve our knowledge andunderstanding of the interplay between infectiousdisease agents, the humans they infect and the vectors(often insects such as mosquitoes) that aid theirtransmission. The global armoury against diseases goeson expanding, and steps continue to be made towardsthe further elimination of several diseases, with talkby some of even globally eliminating malaria. If suchelimination is to occur, however, increased attentionwill need to be paid to research that not only producesinnovative tools, but that better informs how interventionsare best administered and made accessible withinresource poor communities.The scope of health research has thus expanded, sothat basic and clinical health research is beginning tobe better complemented by much-needed research insocial science, operations, implementation and healthsystems. This is exemplified by the release of the2008 report of the WHO Commission on the SocialDeterminants of Health. Sectors such as agriculture,education and the environment are now included aspart of a broader ‘research for health’ approach, withthe need to link the organization of health researchwithin the broader structures promoting science andtechnology in countries increasingly well recognised.This holistic approach should lead to better, moresustainable research and interventions that are directedtowards country and community needs. Success willonly come, however, if it is recognized that developingcountries now have enhanced abilities to undertake,manage, initiate and lead research. Sustainableadvances require strengthening these capabilities andenabling developing country ownership, responsibilityand leadership within the many national and globalresearch initiatives being launched to address infectiousdiseases of poverty.TDR has played a major role in many of the advancesreferred to above, and in many cases, laid thefoundation for new models and approaches that weretaken forward by other organizations. As the leadingUN-based organization dedicated to research on infectiousdiseases of poverty, TDR is in a unique positionto ‘steward’ and promote new perspectives, and newresearch and capacity building initiatives to addressglobal neglected disease priorities. A historical reviewof TDR’s contributions to tropical disease research andcapacity building since its inception was published in2007 to celebrate the 30 th anniversary of TDR’s uniqueco-sponsored and intergovernmental governing body,its Joint Coordinating Board (JCB). It is available onlineat www.who.int/tdr.Nineteenth programme report | TDR 2007-200813

Our new visionOur new vision, launched in 2007, focuses on thefundamentals – to ensure that those who live in lowand middle-income countries, where diseases kill andmaim, can pivotally engage within global partnershipsto find solutions to their problems and take control oftheir health-care needs.We are committed to fostering an effective globalresearch effort on infectious diseases of poverty inwhich disease endemic countries (DECs) play a pivotalrole, focusing on three areas of work to achieve this:• Stewardship: to improve coherence of globalresearch efforts to meet country needs and priorities.• Empowerment: to help enhance and improveDEC capacity and leadership in research.• Research on neglected priority needs: toimprove access to new and improved interventions.Using a two-pronged effort, we are fostering:1) discovery research directly relevant to neglecteddiseases and the targeted development of newproducts and treatment regimens that are notadequately addressed by other partners2) implementation and operational researchassessing new health interventions for real-lifesettings and developing and assessing strategies forimproving and scaling up access and delivery.“Our vision: To foster aneffective global research efforton infectious diseases of povertyin which disease endemiccountries play a pivotal role. ”A new way of working andcommunicatingIn accordance with our new vision and strategy, TDR’sprogramme has been reorganized with new functions,staff and committees. To improve our communicationsabout these issues, we have launched a new website,expanded our regular newsletter TDRnews, publishedthree times per year, and are reporting research resultsin a variety of formats designed to meet the needs ofvaried audiences.This biennial report on TDR’s activities is presentedin a different format to that of previous years.It provides a general overview of TDR’s key activities,complementing a full series of 11 more detailed reportson different lines of TDR activity which are availablein print and online at the TDR website (www.who.int/tdr) along with scientific publications and otherdocumentation. Beginning next year, this progressreport will be published annually to provide timelyinformation on our latest activities and developments.We welcome feedback on these new communicationsapproaches and on our work in general.14

“ Infectious diseases continueto place an immense burden onthe overstretched resources ofdisease endemic countries, andadd to the suffering of thosealready battling with poverty. ”“ The landscape in internationalhealth has changed enormouslyin recent years... and ‘researchiscoveryResearchmpowermentStewardshifor health’ is currently high on theinternational health agenda. ”Nineteenth programme report | TDR 2007-200815

Researchfor deliveryand accessTDR research is helping evaluate, assess and scale up health interventions, enhancingtheir access in the countries and regions (often remote and rural) where they are mostneeded. Multi-site and multi-country studies are carried out to common protocolswherever possible so that findings have general applicability. TDR is also activelyengaged at the forefront of research that is embedded in national control programmes– so that evidence-based interventions are integrated into use within health systems.This results in strengthening systems and minimizing the disruption and distortionthat can often arise from scaling up of specific interventions.Researc16

PART IIKey delivery and access highlights• Studies funded and coordinated by TDR,working with the African Programmefor Onchocerciasis Control (APOC), havedemonstrated that a community-ledapproach in Africa can be utilized to delivermultiple interventions, including doublingaccess to malaria treatment within 24 hoursand increasing delivery of bednets. Thisstrategy has the potential to improve primaryhealth care and strengthen health systems attheir periphery.h• A large, randomized-controlled study fundedand coordinated by TDR demonstrated thatthe use of rectal artesunate by trained volunteersin remote areas prior to hospital referralcould substantially reduce the risk of death ordisability among children with severe malaria.• TDR-sponsored studies and systematicreviews led to a significant change in WHO’stuberculosis (TB) diagnostic policy, reducingthe number of smears required for a laboratorydiagnosis of TB in resource-constrainedsettings – thus making diagnosis more costeffectiveand easier for patients by reducingtheir number of visits to clinics.• Three of nine dengue serological (IgM) testsevaluated by a laboratory network, jointlysponsored by TDR and the Paediatric DengueVaccine Initiative (PDVI), were found to beadequately accurate and sensitive for recommendeduse, leading to their placement onthe WHO procurement list at reduced in costto countries.Nineteenth programme report | TDR 2007-200817

Research for delivery and accessAchievement detailsIntegrated community-directedinterventions – improving accessto drugs and preventive measuresMany simple and effective interventions are available toprevent and treat infectious diseases of poverty, but oftenthese do not reach those that need them most – particularlyin Africa. A TDR-coordinated study 1 addressedthis issue by showing how community-directed deliveryof health interventions (CDI) in an integrated mannercould dramatically improve access to vital drugs andpreventive measures, particularly for malaria, in remoteAfrican communities. The strategy was based on thesuccessful model developed by APOC for distribution ofivermectin for onchocerciasis (river blindness) in remotecommunities, only in this case there was a broaderpackage of interventions (vitamin A, insecticide-treatedbednets, antimalarial medications, and tuberculosistreatment). Carried out among 2 million people inCameroon, Nigeria and Uganda, the study conductedby African researchers showed that bednet coverage, forexample, was two times higher in CDI areas comparedto other control districts, and showed how communityvolunteers, when empowered, could implementmultiple interventions at various levels of complexityand across different diseases. These findings could haveimportant implications both for improving health care atthe primary level and for strengthening health systems.A number of African countries are using these results toimplement such a CDI approach.Rectal artesunate for malaria –saving lives in rural areasA huge problem faced by rural communities is lack ofaccess to malaria treatment at the first signs of illness,resulting in treatment delays that often lead to deathor disability. A large randomized-controlled trial of18 000 patients, 12 000 with malaria, coordinatedby TDR and undertaken by lead investigators frommalaria-endemic areas of Bangladesh, Ghana andthe United Republic of Tanzania, found that one rectalartesunate suppository, administered before referralto the hospital, substantially reduced the risk of deathor disability in patients in rural villages with severemalaria (who could not be given oral treatment andwho were unable to get to a facility for injectionsfor several hours). The Lancet published the study 2and in a commentary wrote, “If there are a handfulof important papers every decade that will influencethe way malaria is treated, this study is one of them.”These results provide additional evidence for theMalaria Treatment Guidelines Committee to maketreatment recommendations. The potential to save livesis huge.A new protocol for diagnosis oftuberculosis – making diagnosis easierfor the patientTDR-sponsored systematic reviews 3 led to a WHOpolicy recommendation that the number of patientsputum specimens to be examined for smearmicroscopy diagnosis of TB be reduced from three totwo, and for these samples to be taken within one dayrather than two days, in areas where workload is highand resources limited. Not only does this allow for asubstantial increase in the numbers of patients thatcan be assessed over a given time period, it also makesdiagnosis a much easier process for patients (as they to18

PART IImake fewer trips to the diagnosis facility). This policychange has important implications for women in thedeveloping world who are often only diagnosed inadvanced stages of the disease as they are unable totake 2 days off from their household and childcareduties to go to a clinic.Evaluation of diagnostic tests –improving detection of dengueThree of nine dengue serological (IgM) tests evaluatedby the PDVI-TDR dengue laboratory network wereshown to meet pre-determined levels of specificityand sensitivity. 4 The results led WHO to include themin its Bulk Procurement Scheme at negotiated prices.This allows health-care institutions and programmesto purchase quality-assured diagnostic tests, which inturn will improve case management and also allow moreeffective detection and monitoring of dengue outbreaks.Tuberculosis – many serological testsshown to have poor performanceTDR coordinated and funded researchers to carry outan evaluation of 19 TB serology tests widely used indisease endemic countries (DECs), finding none thatshowed acceptable performance characteristics. 5 Thisevidence highlights the need for stricter regulatorycontrol of diagnostics.“This evidence highlightsthe need for stricter regulatorycontrol of diagnostics. ”Home Management of Malaria –feasible and effectiveTDR-supported research has continued to demonstratethat the delivery of the artemisinin-combinationtreatment (ACT) Coartem ® via community volunteers,as part of home-based management of malaria, isfeasible and effective. 6-8 Another study – an evaluation ofa pilot – showed that Child, Family and Wellness (CFW)shops were also capable of providing ACTs complyingwith national treatment guidelines. These shops are runby trained nurses or shop operators to dispense and sellessential drugs under a franchise arrangement with aKenyan-based nongovernmental organization (NGO)called Sustainable Healthcare Foundation (SHEF).The evidence suggests that extensions to the health-caresystem like these, where there are no nearby doctorsor health-care centres, provide important avenues forincreased access to care close to home.Schistosomiasis – studies onpraziquantel dosageA series of multi-country clinical trials were sponsoredby TDR to compare the efficacy and safety of the mostcommon single dosages of praziquantel (40 and 60 mg/kg) in patients with the different parasite species in Asia,Africa and the Americas. Results of those trials are nowinforming schistosomiasis treatment policies. 9 In thePhilippines, for instance, where the parasite Schistosomajaponicum is predominant, the 40 mg/kg dose wasshown to be as effective as and better tolerated thanthe higher 60 mg/kg dose. In Brazil, however, resultssupport the use of the 60 mg/kg dose for S. mansoni(which is the only species in Brazil). Data from studiesin the United Republic of Tanzania and Mauritania areunder analysis. Such findings underline the fact thatdifferent drug treatments may be required for differentenvironments in light of variations in species, infectionrates and social interactions.Nineteenth programme report | TDR 2007-200819

Research for delivery and accessOngoing workBearing in mind the importance of adapting interventionsto ensure their effectiveness in real-lifesettings, TDR continues to evaluate interventionsto support disease elimination, community-levelstrategies, diagnostic and drug-based interventions,and vector control measures in the field.Some of our ongoing work is outlined below, andwill be updated in future reports.Research to support disease eliminationVisceral leishmaniasis – improvingcase-finding and treatment strategiesOnchocerciasis – studies on breakingdisease transmissionStudies assessing the potential for multi-year highcoverage preventive treatment with ivermectin to breakthe transmission of onchocerciasis (river blindness) incertain epidemiological settings are close to completionand will be reported in 2009.Community level activitiesHome-based management of malaria –evolving the strategy and expandingto improve management of feverThe fact that ACTs can be successfully integrated intothe home-based management of malaria (HMM) isnow influencing malaria control policy, expanding thecare delivery options. TDR is working with UnitedNations Children’s Fund (UNICEF) and other partnersto develop integrated home-based approaches to themanagement of childhood fevers due to differentcauses such as pneumonia, diarrhoea and malaria.Initial results are anticipated the end of 2009. Studiesare also being done to determine how to include rapiddiagnostic tests into HMM and whether HMM can beadapted to urban areas (results are expected in 2010).TDR is the main research arm of the campaign toeliminate visceral leishmaniasis (VL) in Bangladesh,India and Nepal. Two major multi-centre researchstudies have begun in the Indian subcontinent on VLcase-finding and treatment strategies, and on the costeffectivenessof VL vector management. These studiesare due to be completed in 2011. A key preliminaryfinding is that house-to-house screening can effectivelydouble the number of VL cases identified in one year.Such work brings researchers, national programmemanagers and the communities in which they work,together – and this is beginning to have a positive effectoverall on the VL elimination campaign for the Indiansubcontinent.Diagnostic methodsSyphilis – evaluation of rapiddiagnostic tests leads to eliminationcampaignSix effective rapid syphilis tests previously evaluated byTDR are currently listed in WHO’s Bulk ProcurementScheme. TDR is now working with seven countries(Brazil, China, Haiti, Peru, Uganda, United Republicof Tanzania and Zambia) on how to introduce the tests20

PART IIinto control programmes as part of elimination plans.Work is also underway to complete field assessmentof a framework for the introduction of rapid syphilisdiagnostic tests in countries in Asia, Africa and theAmericas. Results are anticipated in late 2009.Dengue – making disease classificationeasierSince the early 1970s, dengue has been classified intothree categories: dengue fever; dengue hemorrhagicfever; and dengue shock syndrome. However, suchclassification is difficult to apply in many settings,particularly in the context of the changing epidemiologyof the disease. A TDR and European Unionsupported 4-year prospective clinical study (DENCO)in seven Asian and Latin American countries has nowbeen completed and has given rise to an alternativeclassification which is being further assessed with aview to revising the classification and updating clinicalguidelines in 2009.Malaria – evaluation of marketedmalaria rapid diagnostic testsThere is a multitude of marketed rapid diagnostic testsfor malaria. However, there has been no comparativeevaluation of them or assessment of whether they trulymeet the standards required for public health use. Incollaboration with multiple partners, TDR coordinatedthe evaluation of over 40 rapid diagnostic tests, withresults made public in April 2009.TDR has supported country-devised and countrydevelopedresearch associated with the scaled up use ofantiretroviral (ARV) drugs. A first phase of operationalresearch projects on ARV treatment scale-up with fiveHIV/AIDS high-burden countries will be reportedin 2009 and a second phase of research is beingdeveloped. Findings so far have varied from countryto country. Such findings are being incorporatedinto national policy while phase II plans are beingdeveloped. Related to this, TDR and the Global Fundto Fight AIDS, Tuberculosis and Malaria have produceda collaborative framework on implementation/operationsresearch, which can be viewed or downloadedfrom the publications area of our website (www.who.int/tdr). Several of the countries involved inTDR studies have leveraged TDR support to obtainadditional funds from the Global Fund for operationsresearch.Determining the safety and efficacyof concomitant and early use of antitbchemotherapy and highly activeantiretroviral therapy (haart) amonghiv-infected tuberculosis patients insub-saharan africaStudies are under way to assess the safety and efficacyof concomitant use of HAART and TB treatment, and todetermine at what stage of HIV progression it becomesappropriate to start HAART. With four countries and1800 patients, this represents one of the largest everclinical studies on how best to treat HIV-infected TBpatients. First results are anticipated in 2010.Vector control measuresDengue – new approaches to controlDrugsOperations research – scaling upantiretroviral treatment in AfricaWork is under way to assess the potential to combinetwo approaches – building upon a multi-centre costeffectivenessstudy on targeted interventions and workon insecticide-treated materials (ITMs) such as bednets.In collaborations with the International DevelopmentResearch Centre (IDRC), Canada, studies are alsounder way that integrate research on environmental,vector-epidemiological (entomological) and socialfactors to make communities less vulnerable to vectorbornediseases such as dengue and Chagas disease inboth Asia and South America.Nineteenth programme report | TDR 2007-200821

Discovery anddevelopment of toolsand products forneglected diseasesOver the last ten years, global efforts to develop new tools and products for neglecteddiseases (such as drugs, diagnostics and vaccines) have dramatically increased. Therecent Global Strategy and Plan of Action (GSPA) on Public Health, Innovation andIntellectual Property, 10 adopted at the 2008 World Health Assembly recognizes thisneed and calls for building and improving innovative capacity for research (particularlyin developing countries) and for improving, promoting and accelerating transfer andtechnology between developed and developing countries as well as among developingcountries. TDR is focusing its activities in this area through innovative networks andcollaborative efforts that complement the role of other initiatives such as public-privatepartnerships (PPPs).Discovery22

PART IIKey tools and products highlights• A transdermal delivery technology basedversion of a skin patch originally devised byAfrican researchers to detect Onchocercavolvulus infection (in a project funded andcoordinated by TDR) has been successfullydeveloped in collaboration with LohmannTherapie-Systeme AG for the diagnosis ofonchocerciasis infection.• A TDR-funded study in India has shownthat albendazole and diethylcarbamazinetreatment can reverse lymphatic filariasislesions in young children at the early stageof the disease.• Several TDR-supported activities in drug developmenthave reached crucial milestones:– A fixed-dose combination of mefloquineand artesunate for the treatment ofuncomplicated malaria, initiated by TDRand primarily supported by Drugs forNeglected Diseases Initiative (DNDi) incollaboration with Farmanguinhos, hasreceived regulatory approval in Brazil.– A collaborative effort between TDR,Medicines for Malaria Venture (MMV)and GlaxoSmithKline (GSK) to develop afixed-dose combination of chlorproguanil—dapsone—artesunate for the treatmentof uncomplicated malaria was stoppedfollowing observation of adverse safetyevents in phase III studies.– Moxidectin, a new drug in developmentfor onchocerciasis control, has progressedfrom phase II to phase III under TDRcoordination.• TDR’s novel drug discovery networks andpartnerships with both the public andprivate sectors in developed and developingcountries have led to a managed portfolioof new drug leads for malaria and otherdiseases. These leads are undergoing furtheroptimization, and in some cases helping tokick-start drug innovation in some diseaseendemic countries.Nineteenth programme report | TDR 2007-200823

Discovery and development of tools and products for neglected diseasesAchievement detailsDiagnosticsHigh-quality diagnostic tests are often unaffordableor inaccessible to patients in developing countries,while a lack of regulatory approval standards meanspoor quality diagnostics are widely sold and used.TDR has focused on research that can (i) lead to thedevelopment of diagnostic tools and methodologies fordiseases such as TB, onchocerciasis and dengue; and(ii) evaluate currently available and marketed diagnosticsto assess if they meet the standards necessary forpublic health use.Onchocerciasis – a new skin patch testresidual infection in people from areas that haveundergone extensive rounds of ivermectin treatment,and potentially for surveillance for re-emergence inareas that have stopped ivermectin treatment.Drug research and development (R&D)Few drugs are currently available for the managementof neglected tropical diseases, mechanisms of action arepoorly understood and dosage and regimens are notalways based on detailed pharmacokinetic and pharmacodynamicinformation. In addition, their extendeduse carries the risk of drug resistance development. Wesupport drug research and development (R&D) at twolevels – improving the use of drugs already availableand supporting the discovery and development of newdrugs.Lymphatic filariasis – early treatmentreverses lesionsA diethylcarbamazine (DEC)-containing skin patchtest has been developed as a non-invasive tool todetect onchocerciasis infection. The DEC in thepatch kills Onchocerca microfilaria in the skin givingrise to a rash within 24 hours that allows for easydetection. This method replaces the painful methodof ‘snipping’ of pieces of skin and examining it underthe microscope for the parasites. The concept ofusing DEC on the skin in this way arose from Africanscientists, but there had previously been no technologyto allow its standardization and large-scale use. TDRsupported the clinical (unpublished data) and fieldevaluation of the skin patch test, which was developedusing transdermal delivery technology developed byLTS Lohmann Therapie-Systeme AG. Based on thereview of the data from these evaluations and recommendationof the Technical Consultative Committeeof the African Programme for Onchocerciasis Control(APOC), APOC will seek approval from onchocerciasisendemiccountries to use the patch as a tool to detectA TDR-funded study in India on disease progressionin children infected with Brugia malayi and the effectof treatment (albendazole + diethylcarbamazine)showed that lymphatic vessel lesions could be foundin children as young as 3 years. 11 Prompt treatment ofthese children resulted in a decline in microfilaremiaand improvement of the subclinical pathology. Theresults highlight the reversibility of early lymphaticlesions and the need for early treatment. These observationshave been recognized as extremely importantto the Global Programme for Lymphatic Filariasis.Discovery and developmentof new drugs for malaria andonchocerciasisRegistration of amodiaquine-artesunate andmefloquine-artesunateA TDR-initiated project on fixed-dose artemisinincombination therapies (ACTs) for the treatment ofmalaria was transferred to DNDi leadership six yearsago, but with ongoing technical support from TDR.It reached a major achievement within the last twoyears when the amodiaquine-artesunate fixed-dosecombination was registered in Morocco in 2007by Sanofi-Aventis; it is now WHO pre-qualified.Mefloquine-artesunate fixed-dose combination wasregistered in Brazil by Farmanguinhos in 2008.24

PART IIDevelopment of chlorproguanil-dapsone-artesunateterminatedThis treatment for uncomplicated malaria – undertakenin collaboration with GSK and MMV – was stoppedafter phase III studies demonstrated safety concerns inpatients suffering from deficiency in an enzyme calledG6PD. This last example clearly demonstrates the‘high-risk’ nature of drug development.Onchocerciasis drug moxidectin progresses fromphase II to phase IIIFor the past 20 years, ivermectin has successfullycontrolled most onchocerciasis symptoms (e.g.blindness and skin rashes) with an annual treatmentthat kills young worms, but not adult worms. Today,the drug is distributed to more than 60 millionAfricans through community-directed distributionsystems established by APOC. A new drug, moxidectin,owned by Wyeth Pharmaceuticals, is now being testedby TDR in collaboration with Wyeth and APOC as anew treatment that could kill or sterilize adult parasites(which have an estimated lifespan of around 15 years).If proven effective and safe, moxidectin could potentiallybe used to eradicate onchocerciasis using thecommunity-directed distribution mechanisms establishedby APOC for ivermectin. The completed phase Istudies 12-13 and the ongoing phase II proof-of conceptstudy show moxidectin safety and microfilariacidalactivity to be comparable to ivermectin. The phaseIII study was initiated in Liberia (see page 31), and isexpected to be initiated in the Democratic Republic ofthe Congo (DRC) and Ghana by mid-2009. Submissionfor registration is targeted for 2013 in parallel tolarge-scale community studies.Drug discoveryTDR’s approach to drug discovery has been to harnessthe potential of novel networks and partnershipsbetween the public and private sectors in bothdeveloped and developing countries, to help redressthe desperate lack of drug leads and candidates tofeed the development pipelines. 14 At the same time,TDR is able to use this to build the capacity of DECresearchers in drug discovery research and to promoteinnovation for product R&D in DECs.New drug discovery networks –leading to new leadsThousands of compounds have been screened withinthe TDR screening network and several leads arenow being optimized as potential drugs for malaria,Chagas disease and other neglected parasitic diseases.An orally-active lead compound for malaria has beenidentified based on animal data in a project managedat the University of Cape Town, South Africa, andcollaborative discussions are ongoing with MMV asco-funding partner for this project. In another significantdevelopment, Novo Nordisk, in collaborationwith the Chinese National Drug Screening Centre inShanghai, has provided access to its ‘small-moleculecompound library’ so that compounds can be screenedagainst all diseases relevant to TDR’s activities. Thiscomplements the earlier compound libraries contributedby several other pharmaceutical partners forcompound screening within the TDR drug discoverynetwork. It should be emphasized that an open sourcedatabase of drug targets (www.tdrtargets.org) hasbeen developed through this innovative network. 15 Inaddition to supporting drug discovery, the databaseis also supporting diagnostics target discovery forneglected diseases and has the potential to support thediscovery of new vaccine candidates.Nineteenth programme report | TDR 2007-200825

Discovery and development of tools and products for neglected diseasesOngoing workDiagnosticsChagas disease – standardizedpolymerase chain reaction protocolTDR has sponsored a multi-country process ofstandardizing and validating the use of PCR for Chagasdisease studies that could have impact both on patientsand the conduct of clinical trials. Publication of theresults and outcome of these studies are anticipatedin 2009.Drug R&DTB-HIV/AIDS – shortened regimenfor gatifloxacinA new fixed-dose combination therapy containing thefluoroquinolone gatifloxacin is under development asa TB treatment that could shorten treatment for thisdisease from 6 to 4 months. Recruitment in phase IIIstudies is now completed and a decision on whetheror not to apply for regulatory approval will be madein 2010.Human african trypanosomiasis –improving treatment regimensThere are two ongoing studies on treatments forHuman African trypanosomiasis (HAT), both aimed atimproving existing treatment regimens. One study isinvestigating a 3-day regimen of pentamidine againstthe existing 7-day regimen for early stage HAT, withfinal results still several years away. The other studyis on the use of a combination of nifurtimox andeflornithine for the treatment of late stage HAT; thisregimen has the advantage of shortening both thetreatment period (from 14 days down to 10 days) andthe interval of daily injections (from four to two daily)– both important factors in the delivery of treatment inresource-poor settings. This study has been developedand managed in conjunction with a related DNDistudy. Recruitment was completed in December 2007.The follow up of these patients will continue until June2009, after which the results will be analysed.Catalysing vector control interventionsControl of vectors is a key element in the control ofvector-borne diseases. Over the years, TDR has playeda catalytic role in vector research, supporting theactivities of international networks and initiatives andleading a pragmatic response to address the requirementsfor potential deployment – including ethical,legal and social issues of using genetically modifiedvectors (see page 32 for related empowermentactivities).African trypanosomiasis – genomicsProgress continues on sequencing the tsetse fly genomethrough TDR activities on vector control interventionsconvened consortium.Malaria – insecticide resistanceWork supported through the Multilateral Initiativefor Malaria (MIM) is contributing to continent-widedata on insecticide resistance in malaria vectors andproviding country-specific support on integrated vectormanagement. Work within the network (in BurkinaFaso) led to the establishment of a laboratory colonyof Anopheles funestus. This is a novel achievement thatwill provide a valuable resource for understandinginsecticide resistance. Further studies are also beingconducted to assess insecticide resistance mechanismsand the potential epidemiological impact of this inAfrica through TDR activities on innovative vectorcontrol interventions.26

PART IINineteenth programme report | TDR 2007-200827

Empowerment –fostering researchleadershipTDR’s empowerment function builds on the many years of our support for researchcapacity building in developing countries through focused research projects, coursedevelopment and training and networks. With our new strategy, we underscore theimportance of research quality in disease endemic countries (DECs) and have takensteps forward by building quality into our services and products at each stage toensure cost effectiveness, sustainability and competitiveness of the researchers andinstitutions in DECs. TDR is seeking to promote a pivotal role for DECs, not just throughits research but also through its governance structure (see page 43 Governance). Specific‘empowerment’ support activities in TDR are coordinated by an Empowerment team,but empowerment principles and activities are carried out across the entire spectrumEmpowerof TDR’s programmes.28

PART IIEmpowerment highlightsIn line with our focus on networks andcollaborations, many of the highlights listedbelow were carried out in collaboration withpartners:• Launch of the African Network for Drugand Diagnostic Discovery and Innovation(ANDI), an initiative that aims to supportAfrican-led innovation, capacity and infrastructuraldevelopment. This is believed to bea promising model for the implementationof the Global Strategy and Plan of Action forPublic Health, Innovation and IntellectualProperty.• Launch of Enhancing Support for Strengtheningthe Effectiveness of NationalCapacity Efforts’ (ESSENCE), a new initiativeby several funding agencies who requestedsupport by TDR to act as a neutral party toconvene them and increase their internalcoordination.• TDR-established three clinical trialresearch centres in remote, post-conflictareas in Liberia and the DRC to createresearch capacity in preparation for phase IIItrials of moxidectin (a potential drug for theacceleration of the elimination, and possiblyfor the eradication, of onchocerciasis).• TDR has established the first programme of itskind for addressing social and ethical issuesarising from the release of geneticallymodified mosquitoes, leading to continentwidebiosafety training in Africa, Asia andSouth America.• The percentage of peer-reviewed articleson TDR-supported work with a lead authorfrom a developing country increased to 65%during 2007-2008 (59% and 71% for 2007 and2008 respectively).• Refined grant giving and review processeswere initiated to ensure quality andexcellence of research and stronger linkagesbetween individual training and capacitybuilding with institutional and nationalcapacity strengthening needs.Nineteenth programme report | TDR 2007-200829

Empowerment – fostering research leadershipToday, there is a need not only to support thedevelopment of technical research capacity butalso of research leadership in the countries wherethe diseases of poverty occur. Greater equity andsustainable progress will ensue if researchers indeveloping countries play enhanced leadershiproles at institutional, national and internationallevels. To undertake this effectively it is vital thatthe needs of individuals are matched to the needsof their institutions and countries. Quality and excellencein research is a core value that permeateseverything that we do. In 2008, we introducedchanges into our calls for applications, selection,monitoring and evaluation processes of all ourcapacity building programmes so that we couldassure that individual and institutional needs werebeing met. There is now much closer support andfollow up of all TDR grantees funded through theEmpowerment unit.“Empowerment’s goal: Todevelop and sustain leadershipin health research and decisionmakingso that high-qualityinstitutional and national systemscan identify and manageresearch priorities. ”Achievement detailsNetworksWe believe that helping networks to establish themselvesin an organized way is one of the surest ways ofempowering research communities from developingcountries. We have established diagnostics researchnetworks in over 40 countries. During 2007-2008 wealso helped establish several networks that focus onresearch for health, with three of the most importantdescribed below.African Network for Drugs andDiagnostics Innovation (ANDI) –developing country-led capacityTDR’s successful North-South drug discovery networksand fellowship training programmes provided theimpetus for the African Network for Drugs and DiagnosticsInnovation (ANDI) initiative, 16 which is now seenas a promising model for implementation of the GlobalStrategy and Plan of Action on Public Health, Innovationand Intellectual Property. The goal is to developAfrican-led product R&D innovation to support thediscovery, development and delivery of new tools,including those based on traditional medicines, fordiseases that are predominant in Africa. ANDI held itsinaugural meeting in October 2008 in Abuja with thesupport of the Nigerian government and the EconomicCommunity of West African States (ECOWAS), wheremore than 200 delegates from 21 countries endorsedthe concept.Summary of research and developmentlandscape in Africa. For more information pleasesee: www.who.int/tdr/news-events/news/pdf/ANDI-rd-landscape-abstracts.pdfand Mboya-Okeyo et al., 2009. 1630

PART IIESSENCE – funders working togetherto increase research capacity in AfricaEnhancing Support for Strengthening the Effectiveness ofNational Capacity Efforts (ESSENCE) is a new initiativeof development and research funding agencies thatTDR is supporting at their request. It was establishedin 2008 in the spirit of the Paris Declaration on AidEffectiveness – to harmonize donor efforts and tostrengthen research capacity in low-income Africancountries. 17 Members of the initial ESSENCE steeringcommittee include the United Kingdom’s Departmentfor International Development (DFID), Canada’sInternational Development Research Centre (IDRC),the Ministry of Foreign Affairs of the Netherlands,the Norwegian Agency for Development Cooperation(NORAD), the Swedish International DevelopmentCooperation Agency (Sida), the Bill & Melinda GatesFoundation and the Wellcome Trust. The New Partnershipfor Africa’s Development (NEPAD) is also partof the executive group and the European DevelopingCountries Clinical Trials Partnership (EDCTP) is alsoengaged, while TDR hosts the secretariat in Geneva.Regional network forschistosomiasis in africaBuilding on the success of the Regional Network forAsian Schistosomiasis, in 2007 TDR facilitated theestablishment of the African network with the DanishInstitute for Health Research and Development. Thenetwork’s goal is to help develop strong links betweenresearch and ministries of health in Africa, as it hasin Asia, and provide opportunities for South-Southcollaboration with the well established Asian Network.Supporting clinical researchin post-conflict areasAlthough TDR does not normally engage in bricks andmortar infrastructure development, we have been busybuilding physical infrastructure as part of buildingclinical trial capacity in Liberia 18 and the DemocraticRepublic of Congo – in preparation for the phase IIItrial of moxidectin, a potential drug for eradication ofonchocerciasis (see box 1).BOX 1 – Building a research centrein Liberia based around renewableresourcesWith funds provided by the African Programme forOnchocerciasis Control and Wyeth Pharmaceuticals,TDR financed the construction of a modern clinicaltrial centre in Bolahun in a remote corner of Liberia forresearchers to carry out clinical trials starting with thePhase III study for moxidectin. This area was selectedbecause onchocerciasis is endemic there and the15 years of civil conflict have delayed implementationof annual ivermectin treatments available in most otheronchocerciasis-endemic African regions.During the conflict, much of the area – which is difficultto access by road, particularly in the rainy season – wasravaged, with schools, clinics and houses looted andburned. Generators are the only source of electricity.The first task was to construct a mud brick building tohouse the study subjects, laboratories and examinationrooms, and to obtain and install equipment suitablefor conducting clinical trials according to internationalstandards in this environment (with backups in place incase of malfunctioning of a machine). The building wasdesigned with features that keep room temperaturerelatively low without air-conditioning, which meant areduction in the ecological footprint.One of the biggest challenges is to provide a stableelectricity source to power the equipment essential to astudy. A diesel-based system was implemented for themoment. Keeping in mind the difficulty in deliveringfuel by road and the minimal budgets for clinical trialsof diseases of poverty, solar power based electricityis vital for the research in this centre to be financiallysustainable and to reduce the environmental impactof the centre. At present, a donor is being sought andmethods for using local waste as a source of biofuels fora back-up generator are being investigated.Nineteenth programme report | TDR 2007-200831

Empowerment – fostering research leadershipTraining courses – improvingresearchers’ skillsTDR has continued to promote good research througha variety of short courses – including immunology,functional genomics, good clinical practice (GCP),good clinical laboratory practice (GCLP), Good LaboratoryPractice (GLP) and ethics. Our guidelines for GLP,GCP and ethical review continue to be among the mostfrequently downloaded documents from our website.A new development in TDR training courses deservesparticular mention.Encouragingly, this proportion has been steadilyincreasing since 2000 – which suggests progress in ourefforts to increase the role played by DEC researchers(see the figures below).Period time% DEC first authorship2000-2002 47%2003-2004 50%2005-2006 58%2007-2008 65%Ongoing workIn November 2008, a new course designed to buildcapacity in assessment of Biosafety for Human Healthand the Environment was given by the African RegionalTraining Centre (in Bamako). This was followedby the Laboratory Biosafety and Biosecurity coursegiven in December 2008 by the Biorisk Reduction forDangerous Pathogens unit of WHO’s Department ofEpidemic and Pandemic Alert and Response. A similarcourse will be staged at the soon-to-be opened regionalbiosafety training centres in Asia and Latin Americanin 2009. Such courses are particularly important forcountries where the release of genetically modified(GM) mosquitoes, which could play a role in reducingor interrupting dengue and malaria transmission, maybe imminent.NetworksNetworks – ensuring research ethicsare on the agendaA long-established network that continues to havemajor impact is the Forum for Ethical Review Committeesin the Asian and Western Pacific Region (FERCAP). Thisforum has led to legislative changes in human subjectresearch in the past and has recently establishedrecognition programmes for ethical review committees– helping improve the quality of review for humansubject research. Increased effort in 2009 will beplaced on supporting the Pan-African Bioethics Initiative(PABIN). Both of these regional institutions and otherregional groups form part of a global strategic initiative,The Strategic Initiative for Developing Capacity in EthicalReview (SIDCER), to develop capacity for ethicalreview.Authorship by developing countryscientists – an increasing trendDuring 2007-2008 TDR-supported research led toover 400 papers being published in the peer-reviewedscientific press 19 – a high proportion of which have afirst author with DEC affiliation – 65% overall, withapproximately 59% for 2007 and 71% for 2008.32

PART IIResearch networks – building capacitywhile carrying out researchTDR has helped establish networks (involving Northand South research institutions) to conduct researchon neglected tropical diseases. Several scientists andinstitutions from DECs are now taking part in ourNorth–South networks and contributing to researchefforts while helping to build their research capacity. Incollaboration with others, we are supporting researchfellows from DECs to receive drug discovery trainingat pharmaceutical and academic research laboratories,where they benefit from the experience of mentors whosupport and provide guidance.Shifting research management to diseaseendemic countriesTDR is now working to decentralize managerial activitiesfor coordination of research projects and trainingat the regional and country level. We believe that thiswill both enhance local ownership of research and helpto build sustainable centres that can access resourcesfrom other funders. An initial step in this direction wasmade through a Memorandum of Understanding in2008 with Thammasat University in Thailand, whichwill increasingly take on training and research activitiesrelating to clinical studies in the Asia region. Additionalregional centres will be identified and established inthe future.TrainingOver the 2007-2008 period, 19 people received theirPhDs or Masters degrees with TDR financial support.In the context of leadership, several programmes arebeing scaled up and developed to promote the careerdevelopment of post-doctoral and faculty researchersand scientists.Nineteenth programme report | TDR 2007-200833

Stewardship –harmonizingresearch efforts andaligning prioritiesto country needsTDR’s stewardship function is focused on providing the knowledge necessary to makeresearch policy and priority decisions, and advocating for research needed to reduce thediseases of poverty. Activities are designed to bring together institutions, investigators,donors and decision-makers in international health research – helping those in diseaseendemic countries play a pivotal role in setting and implementing relevant, nationalresearch agendas. In line with its new strategy, TDR has created a Stewardship teamspecifically dedicated to the promotion of neglected diseases knowledge management,sharing and priority setting in the global health arena. However, stewardship activitiesare also carried out throughout TDR, as an element integral to disease-related research,capacity building and other activities. To enhance the coherence of research, TDR isStewardshincreasingly taking into account intersectoral issues that impact on neglected infectiousdiseases such as the environment and climate change.34

PART IIStewardship highlights• TDR, with partners, launched TropIKA-net(www.tropika.net), the web-based globalknowledge management platform, on internationalhealth research.• Supported WHO and the IntergovernmentalWorking Group (IGWG) in thedevelopment of the Global Strategy and Planof Action (GSPA) on Public Health, Innovationand Intellectual Property. 10• Supported the partners responsible forpreparation of the programme for theipGlobal Ministerial Forum for Research onHealth in Bamako, Mali in 2008, and provideda web-based meeting hub that broughtparticipants and others together during andafter this major event. 20• Laid the groundwork for the TDR GlobalReport on Research on Infectious Diseasesof Poverty for early 2011 and for severaldisease and thematic reference groups thatwill review research priorities and identifyresearch gaps.• Developed guidelines and informationsources to inform specific activities in tropicaldisease research.Nineteenth programme report | TDR 2007-200835

Stewardship – harmonizing research efforts…Infectious diseases of poverty are a formidablestumbling block to human development andrealization of the health-related MillenniumDevelopment Goals in most low-income countries.Despite increased funding for health research,the impact on human health has been less thanoptimal – partly because research efforts havebeen uncoordinated, fragmented, and sometimesnot well focused with inequity in input from thedeveloping world. At TDR we are trying to redressthis situation.Stewardship will:• help identify priority needs/majorresearch gaps• provide a strategic overview ofinfectious diseases research• provide a global knowledge platformon health research• provide a neutral discussion platformfor stakeholders• advocate for support of healthresearch and the use of its results• foster research networks andinnovative research initiativesAchievementsTropIKA.net – a new knowledgemanagement platform improvinginformation accessFor research to be effective, it is essential thatresearchers can readily access and share informationrelevant to their work. With this in mind, TropIKA.netwas launched in October 2007 as a web-based, globalknowledge management platform (www.tropika.net).TropIKA’s special features useful to stakeholders havebeen widely recognized. It has achieved this successthrough the efforts of the partners involved in itsmanagement such as BIREME/PAHO/WHO (the LatinAmerican and Caribbean Center on Health SciencesInformation) in Brazil and its collaboration withmajor actors in the field of health information: the USNational Library of Medicine (NLM/NIH), the WHOsponsored Health Internetwork for Access to ResearchInitiative (HINARI) and the Public Library of Science(PLoS) journals. During 2009, TropIKA.net aims tobecome a ‘one-stop shop’ for information on researchfor infectious diseases of poverty.“Infectious diseases of povertyremain a formidable stumblingblock to human developmentand the attainment of the healthrelatedMillennium DevelopmentGoals in most low incomecountries ”Complementing this, TropIKA.net knowledge hubshave invigorated dialogue at meetings and conferencesby enhancing preparation, participation, and followup.They also allow those unable to attend in personto provide input during and after the meetings andconferences. Such facilities were used for the first timeat the Ministerial Conference on Research for Health in theAfrican Region in Algiers, (June 2008) and at the GlobalMinisterial Forum on Research for Health in Bamako,Mali (November 2008). Coverage of the Third HighLevel Forum on Aid Effectiveness held in Accra, Ghana36

PART II(September 2008) was also provided through TropIKA,and a self-service version of the knowledge hub wasdeveloped and used for the founding meeting of theAfrican Network for Drugs and Diagnostics Innovation(ANDI) in Abuja, Nigeria (October 2008). Numerouscollaborative workspaces to support activities carriedout by TDR and by partners such as the Global Fundto Fight AIDS, Tuberculosis and Malaria have alsobeen set up on the platform, and TropIKA.net is alsoproviding the framework to facilitate the consultativeand collaborative process of the scientific workinggroups and stakeholders for the Bill & Melinda GatesFoundation R&D initiative on the malaria eradicationresearch agenda (malERA) and the ESSENCE initiative(see page 31).Support for GSPAWHO’s World Health Assembly approved in 2008 aGlobal Strategy and Plan of Action (GSPA) on PublicHealth, Innovation and Intellectual Property. 10 This isa major plan covering research priorities for diseasesthat disproportionately affect developing countries,and promoting equity among countries. TDR playeda significant role, working with WHO, to support theIntergovernmental Working Group (IGWG) that led tothe GSPA. We are particularly involved in the follow-upof three elements of the GSPA, namely (1) researchpriority setting; (2) promoting R&D for diseases thatdisproportionately affect developing countries; and(3) building research capability for innovation indeveloping countries. With respect to element 1, TDR’sStewardship function is seen as pivotal within thecontext of the GSPA to work with stakeholders to helpdevelop priorities for infectious diseases of poverty.The European Commission is currently collaboratingwith TDR and supporting this work. With respectto element 3, TDR is supporting the development ofANDI with various stakeholders including the AfricanDevelopment Bank (see page 30).Bamako Global Ministerial Forum forHealth Research and TDRIn order to assess health research priorities, we havecontinued dialogue with a range of stakeholders – bothregional and global – through meetings, conferences,workshops and the development of stakeholdernetworks. This includes working with the SteeringCommittee of the 2008 Global Ministerial Forum forHealth Research in Bamako, regional consultationscontributing to the Bamako forum for the EasternMediterranean Region (EMR) in Tehran and the AfricanRegion (AFR) in Algiers.The Global Report on Research onInfectious Diseases, Disease ReferenceGroups (DRGs) and Thematic ReferenceGroups (TRGs)Our major effort is to inform and update stakeholderson global research efforts through the publicationevery two to three years of a Global Report on Researchon Infectious Diseases of Poverty. The first editionof this report will be published in early 2011, andwill be based on input from 10 new internationalreference groups (see box 2). These groups willcomprise internationally-recognized experts withmultidisciplinary backgrounds, including representativesfrom national ministries and research bodies,regional economic organizations, philanthropicfoundations, civil society, the scientific community andother stakeholders. Through a consultation processin 10 DECs over a period of two years (along withregional consultations organized in all WHO regions toensure regional input), they will systematically reviewand evaluate relevance of research evidence; assessNineteenth programme report | TDR 2007-200837

Stewardship – harmonizing research efforts…BOX 2 – The reference groupsDisease Reference Groups (DRGs)• DRG 1 Malaria• DRG 2 Tuberculosis• DRG 3 Chagas disease, human Africantrypanosomiasis and leishmaniasis• DRG 4 Helminth diseases (includingonchocerciasis, filariasis, schistosomiasis andsoil-transmitted helminths)• DRG 5 Dengue and other emerging viraldiseases of public health importance• DRG 6 Other infectious diseases, includingzoonosesFramework for Operations andImplementation Research in Healthand Disease Control ProgramsOperations/implementation research (OR/IR)typically examines how to improve programmes byovercoming bottlenecks, and investigates how to scaleup programmes more effectively. OR/IR is increasinglybeing recognized as key to the improvement of healthsystems by health policy-makers. TDR worked with theGlobal Fund to Fight AIDS, Tuberculosis and Malariato develop a strategic framework that countries can useto develop implementation research components totheir funded projects so that they can identify how bestto implement and improve new practices. Endorsednow by several major international aid organizations,the document acts as a source for the Global Fund forall applications relating to operations research.Thematic Reference Groups (TRGs)• TRG 1 Social science research and gender• TRG 2 Innovation and biotechnologyplatforms for health interventions• TRG 3 Implementation research and healthsystems research• TRG 4 Environment, agriculture and humanhealthGuidance on diagnostics evaluationThere is a huge gap in agreed processes for evaluatingdiagnostics technologies for public health. TDRhas thus utilized one of its expert committees andpartnered with Nature Reviews Microbiology to producea series of supplements on diagnostic evaluation guidesfor specific diseases. In the last two years, supplementshave been published on CD4 diagnostics for HIV 21 andvisceral leishmaniasis. 22challenges in control; highlight scientific advances; andprovide independent recommendations and guidanceon priority areas and critical research gaps. The groupon Environment, Agriculture and Infectious Diseases heldits first meeting in October 2008 in Beijing, China; thefull complement of reference groups is expected to beestablished in 2009.Guidance documentation onresearch prioritiesIn the next section of this report on publications andresources, there will be many references to how TDRhas added value to important issues facing infectiousdiseases of poverty. Many of these have already beenreferenced in earlier sections of the report, but severaldeserve highlighting based on their high impact.Stewarding research activities throughnew databases for drug researchThe open source database of potential drug targets(www.tdrtargets.org) 22 aims to facilitate the identificationand prioritization of candidate drug targets forpathogens.Neglected diseases: A human rightsanalysisThis review by Paul Hunt, the Special Rapporteur tothe UN, on the right of everyone to the enjoyment ofthe highest attainable standard of physical and mentalhealth, introduces and explores the connections betweenhuman rights and neglected diseases. It signals how ahuman rights approach can contribute to the fight againstneglected diseases.38

PART IIReferences1Community-directed interventions for major health problems in Africa. Geneva, WorldHealth Organization, 2008. Available from www.who.int/tdr/publications/tdrresearch-publications/community-directed-interventions-health-problems/pdf/cdi_report_08.pdf2Gomes MF et al. Pre-referral rectal artesunate to prevent death and disability insevere malaria: a placebo-controlled trial. Lancet, 2009, 373:557-566.3Reduction of number of smears for the diagnosis of pulmonary TB. Geneva, WorldHealth Organization, 2007. Available from www.who.int/tb/dots/laboratory/policy/en/index2.html4Evaluation of commercially available anti-dengue virus immunoglobulin M tests. Geneva,World Health Organization, 2009. Available from www.who.int/tdr/publications/tdr-research-publications/diagnostics-evaluation-3/pdf/diagnostics-evaluation-3.pdf5Laboratory-based evaluation of 19 commercially available rapid diagnostic tests fortuberculosis. Geneva, World Health Organization, 2008. Available from www.who.int/tdr/publications/tdr-researchpublications/diagnostics-evaluation-2/pdf/diagnostic-evaluation-2.pdf6Ajayi IO et al. Feasibility and acceptability of artemisinin-based combinationtherapy for the home management of malaria in four African sites. Malaria Journal,2008, 7:6.7Ajayi IO et al. Effectiveness of artemisinin-based combination therapy used in thecontext of home management of malaria: A report from three study sites in sub-Saharan Africa. Malaria Journal, 2008, 7:190.8Tiono A et al. Implementation of home based management of malaria in childrenreduces the work load for peripheral health facilities in a rural district of BurkinaFaso. Malaria Journal, 2008, 7:201.9Belizario Jr VY et al. Efficacy and safety of 40 mg/kg and 60 mg/kg single dosesof praziquantel in the treatment of schistosomiasis. Journal of Pediatric InfectiousDiseases, 2008, 3:27-34.10Resolution WHA61:21. Global strategy and plan of action on public health,innovation and intellectual property. In: Sixty-first World Health Assembly, Geneva,19-24 May 2008. Resolutions and decisions, annexes. Geneva, World HealthOrganization, 2008. (WHA61/2008/REC/1). Resolutions and decisions: 31.Available from www.who.int/gb/or/e/e_wha61r1.html11Shenoy RK et al. Antifilarial drugs, in the doses employed in mass drugadministrations by the Global Programme to Eliminate Lymphatic Filariasis, reverselymphatic pathology in children with Brugia malayi infection. Annals of TropicalMedicine and Parasitology. 2009, 103:235-247.12Cotreau MM et al. The antiparasitic moxidectin: safety, tolerability, andpharmacokinetics in humans. The Journal of Clinical Pharmacology, 2003, 43:1108-1115.13Report on an informal meeting assessing the feasibility of initiating the first phase II studyof moxidectin tablets in subjects infected with Onchocerca volvulus, Accra, Ghana, 5-6May 2005. Geneva, World Health Organization, 2008. Available from www.who.int/tdr/svc/publications/tdr-research-publications/moxidectin14Nwaka S and Hudson A. Innovative lead discovery strategies for tropical diseases.Nature Reviews Drug Discovery, 2006, 5:941-955.15Agüero F et al. Genomic-scale prioritization of drug targets: the TDR Targetsdatabase. Nature Reviews Drug Discovery, 2008, 7:900-907.16Mboya-Okeyo T et al. The African network for drugs and diagnostics innovation.Lancet, 2009, 373:1507-1508.17Whitworth JA et al. Strengthening capacity for health research in Africa. Lancet,2008, 372:1590-1593.18Reviving research in Liberia. TDRnews, 2009, No. 82:19-23. Available from www.who.int/tdr/svc/publications/tdrnews/pdf/TDRnews-issue-82.pdf19Giving a voice to health researchers in disease endemic countries. TDRnews, 2007,No. 78:26-29. Available from www.tropika.net/editorial/gv/giving_voice.pdf202008 Global Ministerial Forum on Research for Health. Commentary and analysis:Strengthening Research for Health, Development and Equity, 17-19 November2008, Bamako, Mali. TropIKA.net website. Available from www.tropika.net/svc/home/bamako200821Evaluating diagnostics: the CD4 guide. Nature Reviews Microbiology, 2008, Nov. Vol6, issue 11s.22Evaluating diagnostics: the VL guide. Nature Reviews Microbiology, 2007, Nov. Vol 5,issue 11sNineteenth programme report | TDR 2007-200839

ResourcesGovernancePartnershipsFinancial40“ TDR’s unique positionderives... from the breadth ofthe consensus through whichit operates in partnershipwith hundreds of scientists,institutions and networks all overthe world, and by the manner inwhich it is governed. ”“ TDR is a partnershipprogramme, bringing peopleand groups together to identifyresearch gaps, advocate forincreased research, and worktogether to support research andbuild research capacity. ”

PART IIIKey publications and resourcesTDR-funded research has led to199 articles in peer-reviewedscientific journals in 2007 and207 in 2008 (a total of 406 for thebiennium). These articles are alllisted in the publications section onthe TDR website. Encouragingly, thepercentage of first authors from DECshas been increasing over the years;for 2007 and 2008 this percentagewas approximately 59% and 71%respectively.The 3 times a year TDRnews wasredesigned in 2007 to better meetresearcher and stakeholder needs.The TDR website was redesigned in2008 to reflect the new strategy, andis drawing approximately1000 visitors a day – 40% of themfrom disease endemic countries.TDR also produces scientific andtechnical reports, guidelines andmanuals. These are classified asWHO publications, and have anISBN number. Below is a list of themajor publications for 2007 and2008; these are freely accessible inthe publications section of the TDRwebsite (www.who.int/tdr/svc/publications).Published in 2008Community-directed interventionsfor major health problems in AfricaA report outlining the results froma CDI study carried out in sevenresearch sites in three countries(Cameroon, Nigeria and Uganda).Evaluating diagnostics: the CD4guide. Nature Reviews Microbiology(Volume 6, issue 11, Suppl)A guide on evaluating CD4immunodiagnostics published incollaboration with Nature Reviews.Framework for operations andimplementation research in healthand disease control programmesA collaborative document with theGlobal Fund for Malaria, HIV/AIDS andTB, aiming to standardize the practiceof operations research (OR) acrossthe international health communityand to stimulate the integration of ORinto health programs. This documentis available in English, French andSpanish.Genomic-scale prioritization ofdrug targets: the TDR targetsdatabase. Nature Reviews DrugDiscovery (Volume 5, pp. 900-907)A review of the development ofthe TDR Targets database (www.tdrtargets.org), which facilitates theidentification and prioritization ofcandidate drug targets for pathogens.Laboratory-based evaluation of19 commercially available rapiddiagnostic tests for tuberculosis.Diagnostics evaluationseries No. 2A report on a WHO/TDR sponsoredevaluation of commercially availablerapid TB tests.Strengthening health-economicscapability in AfricaA summary and the outcomes of aregional consultation of experts andpolicymakers.The social context of schistosomiasisand its control: an introductionand annotated bibliographyA book presenting a micro as well asa macro view of schistosomiasis.The use of visceral leishmaniasisrapid diagnostic testsA user guide to the proper use ofrapid diagnostics tests for visceralleishmaniasis.Nineteenth programme report | TDR 2007-200841

Key publications and resourcesPublished in 2007Applied social sciences for publichealth (ASSPH): Higher degreetraining for implementationresearch on tropical diseasesA report presenting the backgroundon the training needs in ASSPH insub-Saharan Africa, with an overviewof related courses and programmesavailable locally and internationally.Effective project planning andevaluation in biomedical researchA set of three booklets to accompanya course on effective project planningand evaluation in biomedicalresearch, including a step-by-stepguide, a training manual and a trainthe-trainerguide. The first two are alsoavailable in French.Ethical challenges in study designand informed consent for healthresearch in resource-poor settingsA review by Patricia Marshall (inSocial, Economic and BehaviouralResearch, Special Topics No. 5).Evaluating diagnostics: the VLGuide. Nature Reviews Microbiology(Volume 5, issue 11, Suppl)A guide on evaluating diagnostics forVL published in collaboration withNature Reviews.Lessons learned in Home Managementof Malaria: Implementationresearch in four African countriesA guide on the home managementof malaria, which focuses in particularon Burkina Faso, Ghana, Nigeria andUganda.Neglected diseases: A humanrights analysisA review by Paul Hunt (in Social,Economic and Behavioural Research,Special Topics No. 6).Recommendations of the Informalconsultation on Issues for clinicalproduct development for HumanAfrican TrypanosomiasisWHO report following an informalconsultation on the development ofclinical products for Human AfricanTrypanosomiasis. Also available inFrench.Report of the expert consultationon immunotherapeutic interventionsfor tuberculosisA report following expert consultationon immunotherapeuticinterventions for tuberculosis.Reporte sobre la enfermedadde ChagasReport on Chagas disease. In Spanish.Scientific working group reporton dengueA report from the 2006 meeting ofthe Dengue Scientific Working Group.Special issue focusing on thehelminth drug initiative in expertopinion on drug discoveryA documentation of the rationale forthe TDR Helminth Drug Initiative andreportings coming out of this.42

PART IIITDR governanceTDR is governed formally through three bodies:• The Joint Coordinating Board (JCB)• The Standing Committee• The Scientific and Technical AdvisoryCommittee (STAC)TDR operates under the legal auspices of WHO as itsexecuting agency and within a broad framework ofintergovernmental and interagency cooperation andparticipation.More details about these bodies are given inthe next few pages.The TDR governing bodiesJoint Coordinating Board (JCB)Standing Committee(UNICEF, UNDP, World Bank, WHO)Scientific & TechnicalAdvisory Committee (STAC)Executing Agency (WHO)TDR OrganizationNineteenth programme report | TDR 2007-200843

GovernanceThe Joint Coordinating Board (JCB)TDR’s top governing body is the Joint CoordinatingBoard (JCB). The JCB meets annually to review TDR’sstrategic direction and activities, evaluate progress andplans, determine the budget and approve arrangementsfor the Programme’s financing.The new vision, strategy and its six year businessplan (2008–2013) were endorsed by the JCB at the30 th anniversary session held in Geneva in June 2007.At the 31 st session of the JCB, which took place inJune 2008 in Rio de Janeiro, the JCB provided furtherguidance to TDR on matters related to the implementationof TDR’s new strategy and business plan thatstarted on 1 January 2008. The Board is stronglysupporting TDR’s work in strengthening the pivotalrole of disease endemic countries’ in leading healthresearch and setting priorities.Composition of the JCB12governments(selected byTDR resourcecontributors)6cooperatingparties (selectedby JCB)4co-sponsors(UNICEF, UNDP,World Bank, WHO)12governments(selected byWHO regionalcommittees)Standing Committee44

PART IIIThe JCB consists of 34 members: TDR’s four co-sponsoringagencies (UNICEF, UNDP, the World Bank andWHO); 12 contributor governments or constituencygroupings of contributor governments selected byresource contributors to TDR; 12 governments representingthe six regions of WHO and selected by the sixregional committees of WHO; and 6 other cooperatingparties of TDR selected by the JCB itself. The tablebelow shows the membership of governments in theJCB during the period under report.Professor Rolf Korte, Senior Health Policy Advisor forthe German Agency for Technical Collaboration inGermany acted as JCB chair in 2007 and 2008, whileDr Frank Nyonator, the Director of Policy, Planning,Monitoring and Evaluation for the Ghana HealthService acted as vice-chair in 2007 and ProfessorRodrigo Corrêa-Oliveira, Director, René RachouResearch Centre at Fiocruz from Brazil acted as vicechairin 2008.2007 200812governments(selected by TDR resourcecontributors)12governments(selected by WHO regionalcommittees)6cooperating parties(selected by JCB)BelgiumCanadaDenmarkGermanyIndiaJapanMexicoNetherlandsNigeriaNorwaySwitzerlandUnited Kingdom of Great Britainand Northern IrelandBangladeshBrazilCentral African RepublicChadCubaDjiboutiGreecePhilippinesSyrian Arab RepublicThailandUzbekistanViet NamChinaGhanaIran (Islamic Republic of)LuxembourgSwedenUnited States of AmericaBelgiumCanadaChinaGermanyIndiaJapanNetherlandsNigeriaNorwaySwedenSwitzerlandUnited Kingdom of Great Britainand Northern IrelandBhutanBulgariaBrazilChadComorosCosta RicaLibyan Arab JamahiriyaPapua New GuineaSyrian Arab RepublicThailandUzbekistanViet NamCubaGhanaIran (Islamic Republic of)LuxembourgPanamaUnited States of AmericaNineteenth programme report | TDR 2007-200845

GovernanceThe Standing CommitteeThe Standing Committee oversees the management andfinancing of TDR and comprises the four co-sponsors– UNICEF, UNDP, the World Bank and WHO. It hasmet three times each in 2007 and 2008, providingadvice and guidance to TDR on issues related to TDR’smanagerial oversight mandate.In order to enhance the coherence and coordinationbetween TDR’s governing bodies, the Chair and Vice-Chair of the JCB as well as the Chair of STAC have alsoparticipated in the meetings of the Standing Committeeon an ex-officio basis. During the period of the elaborationand launch of TDR’s new strategy, participationin the Standing Committee was further extendedto two JCB representatives from disease endemiccountries and one from an Organisation for EconomicCo-operation and Development (OECD) country.The Scientific and Technical AdvisoryCommittee (STAC)The STAC – consisting of 21 leading health scientistsselected on the basis of their professional and scientificexpertise in the endemic countries - meets on anannual basis to oversee TDR’s scientific activities inaccordance with its three major functions:• Review, from a scientific and technical standpoint,the content, scope and dimensions of TDR,including the diseases covered and approaches to beadopted;• Recommend priorities within TDR, including theestablishment and disestablishment of ScientificSteering Committees, Task Forces and WorkingGroups, and all scientific and technical activitiesrelated to TDR;• Independently evaluate the scientific and technicalaspects of all activities of TDR.46

PART IIITDR partnerships 2007-2008TDR is a partnership programme, bringing people andgroups together to identify research gaps, advocate forincreased research and work together to support researchand build research capacity where it’s needed in low andmiddle-income countries. We work with governmentsaround the world, multilateral and bilateral donors, andmany programmes, services, partnerships and organizationsinvolved in health research and delivery. Here we providesome examples from the last two years of the types of stakeholdersand partners that we have worked with, and givea brief overview of their role in TDR activities. This sectiondoes not attempt to list all the many groups and organizationsthat we work with, but instead provides insight intohow some of our interactions with partners increase ourpotency and leverage and help us work toward our goal.Academic institutions and researchinstitutionsTDR has a long-standing history of working in partnershipwith academic and research institutions throughout theworld, in both developed and developing countries. During2007-2008 we continued to develop such partnerships. Forinstance, our research activities on innovative vector controlinterventions involved partnership with the University ofTokyo (contributing to the sequencing of Glossina morsitansmorsitans genome), the Wellcome Trust Sanger Institute(helping sequence the Glossina m. morsitans genome), andpartners contributing to the mobilization of research andcontrol communities – including the Kenyan AgriculturalResearch Institute (KARI), the Tanzanian TrypanosomiasisResearch Institute (TTRI), and the Ugandan NationalLivestock Research Institute (NaLIRI).National, regional and global health initiativesand programmesIn drug development and evaluation for helminths andother neglected tropical diseases, our main partners werethe African Onchocerciasis Control Programme (APOC),the lymphatic filariasis elimination programmes, schistosomiasiscontrol programmes and national dengue, Chagasdisease and African trypanosomiasis control initiatives.These stakeholder groups are well established and can, forinstance, highlight research needs and gaps, provide uswith links to key national institutions (such as nationaldrug regulatory agencies) and help us advocate forincreased funding.Pharmaceutical companies andpublic-private partnershipsTDR is, in many ways, the originator of today’s publicprivatepartnership (PPP). From its early days, it hasbrought together pharmaceutical companies withgovernments and research organizations to help developnew drugs for diseases of poverty, and over half of allnew drugs in tropical diseases developed since 1975 area result of TDR partnering with industry. Many PPPsand PDPs (public-private development partnerships)have been launched since then (some initiated by TDR).During 2008 TDR worked closely with several PPPs,including the Medicines for Malaria Venture (MMV), theDrugs for Neglected Diseases initiative (DNDi) and theGlobal Alliance for TB Drug Development. MMV andTDR, for example, acted as partners and co-funders oftwo antimalarial drug discovery projects – one at Pharmacopeiaand a second project together with University ofCape Town. Meanwhile, pharmaceutical companies suchas Pfizer, Bayer, GlaxoSmithKline (GSK), Sanofi-Aventis,Merck-Serono, Chemtura, Wyeth and many otherscontinue to support TDR research efforts.Nongovernmental organizations,non-profit organizations and fundersPartnership with groups such as the Stop TB Partnershiprepresent an unprecedented opportunity for research tobe integrated. Such an alliance provides strong leveragefor resources and global consensus for action. Ourrelationship with donors has also formed at differentlevels and often involves more than receiving funds forof our activities. For instance, in 2008 a frameworkand guidance to countries for implementation researchin health and disease control programs was developedin association with The Global Fund to Fight AIDS,Tuberculosis and Malaria (GFATM), with the goal ofincreasing this type of research within the GFATMgrants to countries.Nineteenth programme report | TDR 2007-200847

TDR financial information 2007-2008This 2007–08 programme progress report spans twobudgetary bienniums: 2006–2007 and 2008–2009.At the beginning of 2008 TDR reorganized itsprogramme and adopted a new strategy, incorporatinga business line structure. These factors, together witha move to a new accounting system, mean that it isdifficult to provide detailed information about expenditurefor the cross-biennium period 2007–2008RevenueTotal revenue for the period 2007–2008 was US$ 74million (US$ 36.4 million in 2007 and US$ 37.6 millionin 2008). Details are shown in the table on the nextpage.ExpenditureFor 2007–2008, actual total expenditure wasUS$ 83.7 million. This was higher than revenue inthis period due to the use of some of the budgetcarryover from the previous period.For illustrative purposes, budgeted expenditure by thenew strategy’s business lines is presented in the diagrambelow.For 2008-2009, the JCB approved an expenditurebudget of US$ 121 million.Special researchinitiatives 8%Programme relatedsupport 16%Stewardship 8%Empowerment 11%Community-basedinterventions 2%Visceral leishmaniasiselimination 2%Antimalarial policy/access 10%Lead discovery for drugs 8%Innovation research 1%Vector Control interventions 8%Drug development forhelminths /NTDs 10%Evidence for treatmentof TB/HIV 9%Quality assured diagnostics 9%48

PART IIITDR financial contributions 2007-08 in US dollarsCONTRIBUTOR 2007 2008TOTAL2007-2008Belgium 1,075,263 1,464,129 2,539,392China 770,995 55,000 825,995Cuba 4,975 5,000 9,975Denmark 1,901,141 2,109,705 4,010,846Finland 192,788 -- 192,788Germany 1,030,411 1,230,529 2,260,940Ghana 14,972 -- 14,972India 25,000 25,000 50,000Iran (Islamic Republic of) 20,000 10,719 30,719Ireland 288,184 314,465 602,649Italy 66,667 3,573,746 3,640,413Japan 400,000 400,000 800,000Luxembourg 1,333,333 1,891,074 3,224,407Malaysia 24,978 25,000 49,978Mexico -- 10,000 10,000Netherlands 1,173,770 1,173,770 2,347,540Nigeria 95,238 101,865 197,103Norway 4,413,843 3,565,368 7,979,211Panama 7,000 7,000 14,000Spain 73,108 -- 73,108Sweden 3,338,172 3,140,704 6,478,876Switzerland 1,500,000 1,962,661 3,462,661Thailand 21,752 23,607 45,359Turkey 5,000 5,000 10,000United Kingdom of Great Britain and Northern Ireland 6,021,275 1,988,072 8,009,347United States of America 1,640,000 2,481,250 4,121,250African Programme for Onchocerciasis Control (APOC) 695,610 700,000 1,395,610Bill & Melinda Gates Foundation (USA) 3,228,410 1,173,209 4,401,619ExxonMobil Foundation 500,000 500,000 1,000,000Global Fund to Fight AIDS, Tuberculosis and Malaria 292,000 292,000International Development Research Centre (CAN) 482,901 765,938 1,248,839International Federation of PharmaceuticalManufacturers & Associations (IFPMA)-- 1,000,000 1,000,000International Vaccine Institute, Republic of Korea (PDVI) 175,000 100,000 275,000Medicines for Malaria Venture (MMV) 3,731,872 174,434 3,906,306Miscellaneous 11,841 -- 11,841Oswaldo Cruz Foundation (Brazil) 149,960 -- 149,960University of Heidelberg (funds from CEC), Germany 36,400 27,095 63,495World Bank 2,000,000 1,900,000 3,900,000World Health Organization -- 1,789,000 1,789,000Wyeth -- 3,600,000 3,600,000TOTAL CONTRIBUTIONS FOR TDR 36,449,859 37,585,340 74,035,199Nineteenth programme report | TDR 2007-200849

Notes

Notes

All pics from WHO/TDR/Craggs, except:Page 4: WHO/Chris Black – 8: WHO/TDR –12: WHO/TDR/Craggs – 14: WHO/TDR/Crump –18: WHO/TDR/Gomes – 19: WHO/TDR/Pagnoni – 20: WHO/TDR/Ghalib – 26: WHO/TDR/Fisher – 28: Olivier Asselin – 30: Simon Fenwick (map) – 31: WHO/TDR/Kuesel – 32: OlivierAsselin and WHO/TDR/Karbwang – 33: WHO/TDR/Remme – 35-37: Olivier Asselin –46: WHO/TDR/Schwarb.

TDR/World Health Organization20, Avenue Appia1211 Geneva 27SwitzerlandFax: (+41) 22 791-4854tdr@who.intwww.who.int/tdrFor research ondiseases of povertyUNICEF • UNDP • World Bank • WHOThe Special Programme for Research and Training in TropicalDiseases (TDR) is a global programme of scientific collaborationestablished in 1975. Its focus is research into neglected diseasesof the poor, with the goal of improving existing approaches anddeveloping new ways to prevent, diagnose, treat and controlthese diseases. TDR is sponsored by the following organizations:World Bank