70034 PL 70034 OMS - WHO6 Global market report calls for TB diagnostics investment 8 Mobilizing research to halt dengue’s growth 12 Reducing infant deaths due to malaria 17 IVM for

Discovering ‘lead’ compounds with the potential tobecome usable drugs is a critical first step to ensuring asustainable global pipeline for innovative products (seeFigure 1).1,2 While the establishment of public-privatepartnerships (PPPs) has helped to stimulate productR&D for some neglected diseases,3 increased emphasisneeds to be placed on the high-risk early discoveryphase.4 TDR is helping to fill this gap through a coordi-nated initiative aimed at generating new lead com-pounds, which might result in more effective drugs for tropical diseases.1 Essential to this innovative TDR effort is the establishment of multi-disciplinarynetworks and partnerships between researchers inindustry and the public sector in both developed and developing countries.

A need for novel drugsThe need for new, effective and affordable drugsto treat parasitic diseases responsible for an enor-mous burden of disease in the developing world isone of the issues facing global health today. Avail-able drugs to treat these diseases, such as malaria,African sleeping sickness, Chagas disease, leishma-niasis, filariasis, onchocerciasis and schistosomiasis,are limited by factors ranging from parasite resis-tance to safety, compliance and cost. Productsrepresenting entirely new innovations in medicinalchemistry are presently lacking. More effectivediagnostics also are needed for these diseases –which often are misdiagnosed or diagnosed toolate.

A new generation of PPPs have provided one kindof response to these challenges by supportingaccelerated development and clinical testing forpotential new products already in the pipeline.These partnerships include TDR-initiated venturessuch as the Medicines for Malaria Venture (MMV),the Foundation for Innovative Diagnostics (FIND),as well as others such as the Drugs for NeglectedDiseases Initiative (DNDi), the Global Alliance for

TB Drug Development, and the Institute forOneWorld Health.5 Still, there remains a need for new chemical entities, or ‘lead’ structures, that have the potential to become innovativetreatments. New approaches to ‘drug discovery’for tropical diseases are required. “To develop a drug, you first have to discover it,” says Dr

Solomon Nwaka, who came to TDR from MMV about 18 months ago. Drawing upon a broadrange of experiences in academia, industry andPPPs, Nwaka hopes to position TDR at the fore-front of drug discovery for neglected diseases.

“While working at MMV, I recognized the paucityof quality lead compounds feeding the developmentpipeline for malaria, and made the decision to helpfill this gap, not only for malaria but for otherneglected diseases," says Nwaka, who trained as amolecular biologist. “Huge advances have beenmade in our understanding of the biology of manyhuman pathogens and their vectors, especially with the sequencing of many genomes.”

FEBRUARY 2007No. 77

CONTENTS Enhancing drug discovery forneglected tropical diseases

www.who.int/tdr

Innovation cycle

DEVELOPMENT

DELIVERY

DISCOVERY- Lead identification/

optimization- Basic research

4 Special JCB and stake-holder sessions support new TDR strategy and ten year vision:

“To foster an effectiveresearch effort on infectiousdiseases of poverty in whichdisease endemic countriesplay a pivotal role.”

6 Global market report calls for TB diagnostics investment

8 Mobilizing research to halt dengue’s growth

12 Reducing infant deaths due to malaria

17 IVM for VL elimination

18 Qualitative health research: a TDR collaboration

19 Building health economics capacity in Africa

20 Research ethics - training and guidance

21 Building capacity for public health product R&D

22 Seven years of MIM/TDR research on malaria

23 Research strengthening group meets in Nairobi

24 Good Laboratory Practice network launched

25 WHO/TDR at ASTMH

26 Grants

30 Publications

(continued on page 14)

Figure 1. The innovation cycle

Version_77.qxp: • TDRnews67b - copie 15.1.2007 15:56 Page 1

2 • TDRnews • No 77 • F E B R U A R Y 2 0 0 7

TDRnews

is published three times a year by the UNICEF/UNDP/World Bank/WHO Special Programme for Research andTraining in Tropical Diseases (TDR).

A PDF version of the newsletter isavailable on the TDR website. All mate-rial submitted to TDRnews undergoeseditorial review. Articles and illustra-tions published in TDRnews which arenot copyrighted may be reproduced,provided credit is given to TDR andprovided such reproduction is not usedfor commercial purposes. Articles donot necessarily reflect the views ofWHO.

Communications Manager Jamie Guth

Managing Editor Elaine Fletcher

Guest writer Angus Thomson

Design and Layout Lisa Schwarb

Production team Jocelyne Bruyère, Laurie Ingels

Fax (+41) 22 791 4854

E-mail [email protected]

Web www.who.int/tdr

Address World Health Organization

Avenue Appia 20 - 1211 Geneva 27Switzerland

TDR generates broad media interest in 2006The past six months have been a time of heightened interest in TDR for a number of reasons.

The development of a new 10-year strategy has drawn interest and involvement among an ever-widening circle of partners, collaborating scientists, and others who recognize the growingrelevance of research to disease prevention and control.

One of the key elements in TDR's new strategy is the enhancement of its stewardship andempowerment roles in research. Communications will be important to support this work, and plans are developing as to how best to complement TDR's technical work with effectivecommunications strategies. As part of our recent outreach efforts, we launched a readership survey on this newsletter. If you have not already responded to it, please go to our website at www.who.int/tdr and send us your thoughts.

The increased pace of recent TDR activity already has generated substantial interest in both gen-eral news and scientific media. In March and June, 2006, the governments of Nigeria and Ghanahosted high-level ministerial meetings in each of their countries, which TDR, the WHO RegionalOffice for Africa, and WHO country offices supported. Back-to-back with the second ministerialmeeting, the vice president of Ghana addressed our 29th Joint Coordinating Board (JCB) meetingin Accra. All of these events attracted widespread media interest across Africa and high visibilityfor TDR, its partners and collaborators (as reported in the recent Special Issue from Africa).

This summer and autumn, BBC World broadcast two special documentaries on our work as part of the highly rated Kill or Cure series. The first programme, aired in August, followed theevaluation research of syphilis diagnostic tests in Haiti, led by TDR diagnostics manager RosannaPeeling, in coordination with the WHO country office and Haitian health officials (pages 4-5).The second programme, broadcast in late November and early December, showcased a studyon home management of malaria in Nigeria, where TDR has funded local researchers to assesswhether local caregivers and drug distributors can provide new Artemisinin-based CombinationTherapy (ACT) drugs safely and effectively (pages 12-13). If you would like to receive copies ofeither programme, please email us at: [email protected].

At the end of October, TDR released a joint publication with the Foundation for Innovative New Diagnostics (FIND) that documented market opportunities for developing new tuberculosisdiagnostic tools (pages 6-7). The WHO-organized press conference at UN headquarters inGeneva generated unique stories in major media of the United States, United Kingdom, Chinaand Canada, as well as broad coverage through wire services across Europe, the Middle East,Africa, South America and the USA.

Our newsletter cover story, expansion of our discovery research networks that could help identify the next generation of new drugs for neglected diseases, also is attracting wider mediaattention. In November 2006, an article on innovative discovery research strategies for tropicaldiseases, co-authored by Dr Solomon Nwaka (the TDR manager of this initiative) and Alan Hudson, was published in Nature Reviews Drug Discovery. One of our pharmaceutical collabora-tors, Pfizer, described its contribution to this initiative in a worldwide press release in late October. And Dr Nwaka organized a session on the topic at the American Society of TropicalMedicine and Hygiene (ASTMH) November 14.

This year we will celebrate the 30th anniversary of our Joint Coordinating Board (JCB). We arecollecting stories about TDR's history and accomplishments, so if you have something that youwould like to share, please send it by email, fax or phone. As always, we would love to hear fromyou about any TDR-related activities and upcoming events. Please e-mail us at: [email protected].

Warm greetings from all of us at TDR.

Production moments of the BBC Kill or Cureseries profiling TDR-supported research on new strategies for malaria treatment inNigeria. Top: Dr Ikeoluwapo Ajayi explainsher research to producer Alex Gabbay and Dr Franco Pagnoni from TDR. Middle: MrsOlapeju Otsemobor of the Nigeria FederalMinistry of Health National Malaria ControlProgramme, discusses lessons learnt fornational scale-up. Bottom: Drs Grace Olusola Gbotosho and Ikeoluwapo Ajayi intheir laboratory.

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TDRnews • No 77 • F E B R U A R Y 2 0 0 7 • 3

We at TDR are deeply involved in the developmentof our new, ten year strategy, with the help ofinput and feedback we have received from so

many of you. My thanks to all for your support and assistance.

As you will read in this issue (pages 4-5), we held specialmeetings in October 2006 to review our proposal for a newstrategy. That led to an endorsement to move forward with a business and operational plan, to be reviewed at the nextJoint Coordinating Board meeting in June 2007.

The enhanced complexity of the research field, the intercon-nectedness of all our actions, and the commitment to buildingglobal research activity around the needs, capacity and aspira-tions of developing countries facing disease and associatedpoverty are all reflected in TDR’s core vision statement,namely: to foster an effective research effort on infec-tious diseases of poverty, in which disease-endemiccountries play a pivotal role.

TDR will work with and through others to realize this vision,using a three-pronged strategy that: provides a collaborativeframework and information service for research partners; 'em-powers' scientists from disease endemic countries as researchleaders; and supports research on neglected priority needs.TDR will play an enhanced role in knowledge management,fully utilizing our convening power and links to national andinternational agencies and programmes, to underpin ouractions and help provide a framework for the work of others.We term this 'stewardship'.

TDR's work in the context of this new strategy may take usinto new diseases and fields of endeavor in the coming decade.Diseases do not stand still. Science does not stand still. TDRmust move with the times while retaining its core values andcompetencies.

As TDR approaches its historic 30th anniversary as a UNICEF/UNDP/World Bank and WHO co-sponsored programme, I would like to mention some significant developments thatimpact on WHO, TDR, and global health research. WHO has a new director-general, Dr Margaret Chan. As formerAssistant Director General of WHO's Communicable DiseaseCluster, Dr Chan also served as WHO's Special ProgrammeCoordinator for TDR, with special oversight responsibility for our activities. In that capacity, Dr Chan helped steer TDR through important milestones of the last year, including a high-level meeting of ministers of health and a JCB meetingin Accra, Ghana in June of 2006. We warmly congratulate Dr Chan on her election.

Upon the acceptance of her new post, Dr Chan highlightedthe significance of science and research to WHO's mission,stressing the need for health initiatives to work collectivelyand in harmony with each other. She also indicated thatadvances in health in Africa and women's health will be priori-ty indicators of WHO’s global performance.

In early December, WHO convened an IntergovernmentalWorking Group on Innovation, Intellectual Property and Public Health, following upon a recent report by a WHOCommission on the same topic. Research for neglected tropi-cal diseases and research capacity strengthening in diseaseendemic countries will feature prominently on the agenda of this working group in the coming year.

While focusing on these high-level issues that are shaping global research agendas, it is important to remember the day-to-day activities and achievements of researchers worldwide,including those whom TDR supports directly. It is their workand efforts that generate progress in the field. This newsletterand our reports, combined with those of many other organi-zations, continue to demonstrate the remarkable innovation,progress and promise in tropical disease research. In the coming years we must maintain these advances by continuingour support both for institutions and for individual researcherswhose activities represent the fruit of, and inspiration for, our broader goals and strategies.

It is an exciting time for tropical disease research, with manypossibilities and strong interest and support. I look forward toworking with you in the context of TDR’s new vision so thatwe can continue to support new scientific advances thatimprove health in communities globally, and particularly inways that support alleviation of poverty.

Robert G. Ridley,TDR Director

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R O B E R T G . R I D L E Y

A letter from TDR’s director



Over a period of four days in October 2006, repre-sentatives of some 35 governments and numerousother institutions from around the world attendedtwo special meetings on TDR. The topic was thenew ten year vision and strategy under development.The meetings, scheduled at the request of the JointCoordinating Board (JCB) at its annual session inJune 2006, in Ghana, offered an opportunity forfocused review and discussion on the new strategy.

The new proposalFollowing an analysis of the changed landscape oftropical disease research, which assessed whereexisting emphases are being placed globally and what requires further engagement, TDR identifiedareas where it can add value to the global researcheffort (see the following diagram).

Building on this analysis and TDR's historical and current strengths, the following changes are beingrecommended:

Develop stewardship for research on infectiousdiseases of poor populations. This is a major newrole for TDR as facilitator and information providerto support needs assessment, priority setting andprogress analysis, and to provide a neutral platformfor partners to discuss and harmonize their activities.

Empower scientists and institutions from disease endemic countries. This moves beyond tradi-tional research training to build leadership at theindividual, institutional and national levels so that disease endemic countries can better initiate researchactivities and develop a stronger presence in interna-tional health research.

Conduct research on neglected priority needsnot adequately addressed by other partners, focusingon three strategic directions:

• Discovery and innovation for product develop-ment, emphasizing disease-endemic countryengagement and leadership.

• Development and evaluation of interventions in real life settings.

• Research that increases access to interventions.

The proposed strategy also recommends the devel-opment of a disease portfolio that is flexible, butremains focused on a limited number of well-definedactivities within this broader scope, and works more closely with regional leaders, organizations and countries.

Discussion and recommendationsDiscussions for input and feedback on the draft strategy began with a special stakeholder session, followed by a meeting of TDR's governing body, the Joint Coordinating Board.

The Stakeholder meeting was chaired by ProfessorChitr Sitthi-amorn, dean of the College of PublicHealth, Chulalongkorn University, Bangkok, Thailand.The meeting brought together over 100 specialistsfrom around the world, representing TDR's spon-sors, JCB members and observers from academicand research institutions, collaborating organizations,and governments.

This was followed by the JCB's special thematic session under the guidance of the JCB Chair, Dr BijanSadrizadeh, senior advisor to the minister of healthand medical education of the Islamic Republic of Iran.The new strategy and vision proposal was broadly

Special sessions support new TDR

From left, Professor Chitr Sitthi-amorn, Stakeholder Meeting Chair; Dr Bijan Sadrizadeh, JCB Chair; Dr Bill Kean, Executive Director,

Office of the Director-General of WHO.

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Figure 1. TDR Strategy Implications



supported. Representatives of the WHO RegionalOffices and TDR's sponsoring agencies offered tohelp TDR build a stronger regional presence andenhanced impact. Properly positioned, TDR couldbecome the infectious diseases research arm ofWHO and its co-sponsoring agencies. TDR was alsoencouraged to maintain and extend its collaborations– with co-sponsoring agencies, WHO regions andcontrol programmes.

The JCB emphasized that the new strategy will betterutilize the strong leverage role that TDR has throughits expanded range of partnerships. The JCB alsoencouraged TDR to work with research units andaffiliates of country-level ministries of health, to provide evidence to policy makers, involve them at

the outset of activities, help bridge the gap betweenhealth services and academia, and ensure politicalcommitment and recognition of the need to investin human resources for research.

Next StepsA complete business plan with detailed business linesand budgets will be presented to JCB(30) at its June,2007 meeting. In the meantime, there will be ongoingdialogue with major stakeholders to ensure contin-ued broad support and commitment.The currentportfolio will be phased into the new strategy, withexisting commitments honoured. Current commit-tees will continue until the new plan is finalized.

ten year vision

FOR MORE

complete details

and background,

visit us online at:

www.who.tdr

and select the

‘ten year vision and

strategy’ link.

TDR’s new vision statement:To foster an effective research effort on infectious diseases of poverty,in which disease endemic countriesplay a pivotal role.


A significant untapped global market exists for more effectiveand affordable tests to diagnose tuberculosis (TB) in low- andmiddle-income countries, where most cases occur. This is themajor finding of a new report, Diagnostics for Tuberculosis: GlobalDemand and Market Potential, released in October 2006 byWHO/TDR and the Foundation for Innovative New Diagnos-tics (FIND). The TB diagnostics market review is a milestonein TDR's expanding strategic effort to leverage cutting-edgeresearch, innovation and capacity-building in development, useand evaluation of diagnostics for neglectedtropical diseases. "Reliable diagnostics thatprovide rapid and accurate indicators ofdisease can be as important as drugs insavings lives and reducing morbidity,"notes Dr Rosanna Peeling, who heads upthe TDR diagnostic team’s effort.

Yet in the case of many diseases that TDRaddresses, both bacterial and parasitic,rapid and accurate diagnostic tools arelargely inaccessible or unaffordable to populations most at risk. In other cases, new tools are rapidly being developed, such asfor rapid malaria tests. However, clinicians and field managersrequire guidance to choose the best tests for their needs andgeographic location. In seeking to leverage action on theseissues, TDR's role is multi-faceted, involving:

• coordination of systematic reviews of knowledge and expertevaluation of developments in the diagnostics field, e.g.through the Diagnostics Evaluation Expert Panel (DEEP);

• guidance in evaluation and choice of appropriate diagnostics

through peer-reviewed publications such as the recentNature Reviews Supplement Diagnostics series (see bottom of page 7);

• research and capacity-building in more effective use anddelivery of diagnostics in clinical and field situations;

• collaborations with other public and private partners to spurdevelopment of new diagnostics or improve use of existingtools.

In the case of TB, the recent TDR co-sponsored report tookan innovative look at diagnostic needs fromthe market perspective. The report calls for new public-private collaborations andinvestment in improved diagnostic tools for low- and middle- income countries. The report concludes that such tests couldsignificantly bolster international TB control efforts and while responding to a clear mar-ket demand. Among other key findings andfacts:

• 1.7 million people a year die from TB, many because diagno-sis occurs too late or not at all.

• Most people who have TB, or who live in TB risk areas, do not have good access to rapid and accurate testing.

• One-third of the world’s population is infected with latentTB, at risk of developing the active disease. HIV is fuelling TB epidemics in many countries and multi-drug resistance is a growing threat.

• The global market for TB diagnostics is more than twice thatof the market for drugs for treatment. Worldwide, about


R E D U C I N G D I S E A S E T H R O U G H I M P R O V E D D I A G N O S T I C S

A large, untapped global market exists for improved TB diagnostic tests

BBC World's highly rated Kill or Cure television series trav-eled to Haiti with TDR's Diagnostics Coordinator RosannaPeeling last summer to document how TDR-sponsoredresearch into rapid diagnostic tests for congenital syphilishas helped prevent the disease from being passed on bypregnant women to their babies. The result was a half-hourdocumentary, aired by BBC in August 2006, following Peel-ing and the research team into remote areas where the testevaluations were being piloted. Globally, at least one-halfmillion babies are born with congenital syphilis every year,while at least one-half million stillbirths and miscarriagesalso occur due to congenital syphilis. There are often nosymptoms of syphilis among pregnant women, and the dis-ease is thus unknowingly transmitted to the unborn child.Syphilis diagnostic tests traditionally required electricity

and other laboratory infrastructure, so women in remoterural areas often did not get tested. There are, however,new rapid tests being marketed that do not need electricity,and TDR-supported positive evaluations of their efficacythus have very broad relevance. The use of properly evaluat-ed diagnostics already is saving lives now in Latin America,and holds the potential to save tens of thousands morelives if applied throughout Africa. After diagnostics evalua-tion has assessed the reliability of a new test, those with a positive evaluation can be put onto the WHO procurementlist so governments can purchase the tests at discountedrates. The success of research and evaluation of new rapiddiagnostics has led various governments to develop plans to eliminate congenital syphilis. Copies of the DVD can be requested from [email protected]

BBC Kill or Cure documentary on syphilis diagnostic tests

“Reliable diagnosticsthat provide rapid

and accurate indicatorsof disease can be

as important as drugs in saving lives...”


US$ 1 billion is spent on TB tests and evaluations,while about US$ 300 million is spent on drugs forTB treatment.

"The TB and HIV threat continues to grow in manyparts of the world, and governments need high-quali-ty diagnostics to help manage these epidemics," saidDr Robert Ridley, director of TDR, at the Genevalaunch of the report last October. "We need simpletests to accurately screen for active tuberculosis. Newtests are needed to monitor treatment response,identify bacterial drug resistance, and detect latentinfection in those at risk of progression to active TB."Of the estimated 9 million people who develop activeTB every year, most still do not receive a laboratory-confirmed diagnosis. Only about 2.2 million TB casesannually are diagnosed and reported with sputumsmear microscopy, the most widely available test.Other cases are diagnosed through an often ineffi-cient and sometimes wasteful combination of chestX-rays, bacterial cultures and guesswork. These testsmay fail to make critical distinctions between activeand latent TB, particularly in HIV-positive patients,the report notes, and between drug-sensitive anddrug-resistant forms of the disease. High-tech molec-ular and rapid culture diagnostics introduced indeveloped countries are too complex and costly formany settings where TB is most prevalent.

“The technology exists, and this report leaves nodoubt that there is a large global market. There isa huge opportunity for diagnostics developers toexpand their investments to meet this very realneed,” said Dr Giorgio Roscigno, Chief ExecutiveOfficer of FIND, a non-profit organization dedicatedto the development of improved diagnostics forpoverty-related diseases of developing countries. Compared to vaccines and medicines, the cost of developing new diagnostics is relatively low, thereport notes, at about US$ 1 to 10 million per tech-nology platform. The report projects demand forseven hypothetical products that could feasibly bedeveloped. Among those, a test that detects latentinfection and predicts progression to active disease

could have a potential available market of some 204 million patient evaluations a year. "Such a test, ifwidely implemented and accompanied by successfultreatment, could revolutionize TB control," thereport concludes. Large markets also exist for lessrevolutionary 'replacement' technologies for smear,culture, and drug susceptibility testing. Jean-Francoisde Lavison, President of the European DiagnosticsManufacturers Association, called the report"ground-breaking," adding, “it explains what kinds of improved diagnostic tools are needed and wherethey could have their greatest impact."

TDR’s global TB specimen bank is another directcontribution to TB diagnostics research, presentand future. Since its 1999 launch, the bank’sactivities have gradually expanded to includeapproximately 40,000 serum, sputum and urinespecimens from patients in a dozen countriesworldwide. The use of bank specimens can great-ly expedite the process of evaluating new TBdiagnostic tests, avoiding the need for expensivefield trials in the early stages of diagnosticsdevelopment. This, in turn, helps lower theiroverall cost.

Specimens are collected with full consent bothfrom patients infected with TB and from thosewho are not, as well as from those who are bothHIV-positive and negative. A 2006 collectionround has just been completed, which adds specimens from 1250 patients in diverse settingssuch as Viet Nam, Bangladesh, Kenya, SouthAfrica, Colombia and Peru. These specimens arecurrently stored in central repositories in Europeand the USA, and efforts are being made to create regional repositories. For details on thebank see the TDR website: www.who.int/tdr/diseases/tb/specimen.htm

TDR's TB specimen bank


TO KNOW MORE...

For the full TB

diagnostics report,

executive summary

and press release see:

www.who.int/

mediacentre/news/

releases/2006/

pr61/en/index.html

TDR CONTACT

Rosanna Peeling

[email protected]

FIND

media@

finddiagnostics.org

To order print copies

of the TB diagnostics

report please contact:

[email protected]

Nature Reviews Microbiology, in collaborationwith WHO/TDR, has launched a new supplementseries Evaluating Diagnostics to offer guidance in test-ing and selection of appropriate diagnostics for majortropical diseases that are a focus of TDR's work. Aimed at health policymakers, clinicians and field-workers, the guides represent a state-of-the-art syn-thesis of knowledge on diagnostic tools. First in theseries was The Malaria Guide, published in September2006, followed by the STI Guide on diagnostics forsexually transmitted diseases, published in December,

2006. Forthcoming supplements are scheduled to focus on diagnos-tics for dengue fever and for visceralleishmaniasis. The Nature Reviews Diagnostics Supplements series providethe results of expert review, consulta-tion and synthesis through TDR's Diag-nostics Evaluation Expert Panel (DEEP).The panel examines innovations in diag-nostic tests, bringing together best prac-tice and evidence.

Diagnostics take centre stage in Nature Reviews Supplement series



I M P L E M E N T A T I O N R E S E A R C H

Mobilizing research to halt exponential growth of dengue

Three new TDR initiatives aim to respond to the alarming worldwide resurgence of dengue virus (DV)infection. The efforts seek to enhance knowledgeabout vector surveillance and control; better ecosys-tem management; and finally, appropriate diseaseclassification and diagnostics that would supportmore effective treatment. The initiatives, all launchedover the past two years, come at a time when theglobal impact of dengue is being compared to that of diseases like tuberculosis and malaria.

At the same time, new research findings on dengueprevention, treatment and vector control offer hopethat new strategies emerging now can eventually bringthe epidemic under control. This was the messageemerging from an October, 2006 meeting of a globalScientific Working Group on Dengue, organized byWHO/TDR in Geneva and involving 60 experts ondengue research and control. A back-to-back WHOmeeting to update global dengue prevention and con-trol guidelines underlined the practical relevance oftoday's research agenda to disease control.

The global dengue burden has increased more thanfour-fold in the last 30 years, making it now the most common mosquito-borne viral disease. South-East Asia and the Western Pacific are most seriouslyaffected, but there also has been a rapid recentincrease in the Americas; it is endemic in all these aswell as in the Eastern Mediterranean and Africanregions.12

Along with this trend, there has been a rapid appear-ance of more virulent strains of the virus and a geographical extension of dengue vectors and diseaseacross the tropical and sub-tropical regions of theworld. This is thought to be due, at least in part, to major global demographic changes, especiallyuncontrolled population growth, mobility, and urbani-sation. As a result, epidemic outbreaks are occurringwith greater frequency and intensity, which can overwhelm unprepared healthcare systems. (See Fig. 1)

The challenges of dengueDengue disease poses a special research challengeinsofar as there is no effective drug treatment fordengue infection. Proper clinical management is com-plicated by difficulties in proper diagnosis and varia-tion in medical skills. The development of a vaccine, a promising approach to dengue control, has beenhampered by the immunological complexity of thehost response to the virus. Vector control, as well, isa special challenge. The Aedes mosquito which trans-mits the virus is well adapted to urban environments,where it breeds in the water accumulated in discard-ed debris, old tyres, and water storage containers.Some countries have instigated large programs ofurban cleanup or spraying to eliminate such mosquitobreeding grounds. However, these control measuresare difficult to sustain over a long period of time. Sowhile vector control, and particularly environmentalmanagement, may currently offer the best method of prevention of dengue virus infection, generalized

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4 to 6 Oct.2006, WHO/TDR Geneva,

in press.

Figure 1. Average annual number of dengue fever/dengue haemorrhagic fever cases reported to WHO and of countries reporting dengue



Dengue has increased exponentiallyin recent decades. Fueled by rapidurbanization, demographic change,large-scale migration, and travel, itis now endemic in more than 100countries and is a major internation-al public health concern.

Most dengue cases are not life-threatening; however, some can bedeadly, making diagnosis and treat-ment critical, alongside prevention.Patients initially develop fever, abright red rash, and often excruciat-ing bone and muscle pain andheadache. This explains why the dis-ease is sometimes popularly called“breakbone fever.” While this is usu-ally self-limiting, the infection mayprogress to potentially deadlydengue haemorrhagic fever andother severe forms which may causeinternal bleeding, organ failure andshock so that the patient may diewithin 24 hours without treatment.

Although there is no drug treatmentfor dengue infection, hospitalisationand proper clinical management ofcases leads to recovery in 99% ofcases. However, the fatality rate canexceed 20% without proper treat-ment. Half a million people are hos-pitalised each year with severeforms of dengue, many of whom arechildren.

The dengue virus cycles betweenhumans and the Aedes aegypti mos-quito, which prefers to live amongand feed upon humans. There areactually four serologically distinctsubtypes of the virus. While recoveryfrom infection by one confers life-long immunity, it paradoxically mayincrease the risk of severe diseasefrom a second infection by a differ-ent subtype. Thus people are atgreater risk in regions where thereare multiple dengue subtypes. InAsia, where all four dengue virusesare endemic, dengue has become aleading cause of hospitalisation anddeath among children in severalcountries.

About Dengue

control campaigns often have been inef-fective in reducing the relevant popula-tions of Aedes aegypti mosquitoes belowa threshold that could reduce denguevirus transmission.

The TDR responseWhile dengue has been part of the TDRportfolio since 1999, the recent initia-tives offer particular promise in respond-ing to the research gaps, and addressingthe growing public health importance ofthis disease. The TDR projects onimproving surveillance tools for vectorcontrol; examining the potential forecosystem management of dengue in amulti-disciplinary fashion to support pri-mary prevention; and testing diagnostictools to improve clinical case manage-ment, are reviewed below and describedin the figure on page 11.

Improved vector control throughpupal productivity surveysTDR is supporting multi-country studiesthat test the effectiveness of a new sur-veillance and control method that sur-veys and measures the “pupal productivi-ty” of dengue breeding sites in variousclasses of water containers.3 This surveymethod identifies the most importantbreeding grounds for the vector in agiven setting or community, and thentargets vector control and cleanup tothe most 'productive' containers orsites.4, 5, 6

Preliminary results from an initial ten-country study in Latin America, Africaand Asia, found that the pupal demo-graphic survey method identified epi-

demiologically important containers –e.g. containers that produce the mostmosquitoes for disease transmission, asopposed to those that were unimportantto disease transmission. In each of thestudies, moreover, the survey providedthe information necessary to create tar-geted control strategies.

“By doing studies in 10 different coun-tries we can identify common featuresand also provide recommendations thathelp health services to find their ownsolutions for their specific situation,”said Professor Axel Kroeger, TDR Dis-ease Research Coordinator for Dengue.Ongoing research still is needed todetermine if these interventions targetedat the most productive containers canalso be more effective in reducingdengue virus transmission over time.

At the same time, more selective chemi-cal and biologically-based vector controltools are being developed to controlAedes breeding sites. These includeimproved formulations of larvicides andinsect growth inhibitors that are safe and acceptable for use in drinking water.Insecticide treated window curtainsand water container covers have beenfound to reduce densities of dengue vectors and transmission in a recentWHO/TDR- co-sponsored cluster randomized-controlled trial conductedwith several partners in Mexico andVenezuela.7

Acknowledging the importance of community participation in any controlstrategy, TDR also has contributed to

The eggs of the dengue mosquito vector Aedes aegypti on the tip of a finger.

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the development of a step-by-step guide on socialmobilization and communi-cation for dengue preven-tion and control.

Ecosystem manage-ment interventions Effective dengue preven-tion increasingly isunderstood as a taskrequiring a multi-faceted arsenal of vec-tor control, environ-mental managementand community par-ticipation strategies.To examine more

holistically the biological, ecologi-cal and social ("eco-bio-social") factors affecting

dengue transmission, TDR and the InternationalDevelopment Research Centre (IDRC) in Ottawa,Canada have now embarked on a major research initiative focusing on Asian high-endemic countries.8

The initiative will include six research studies on theeco-bio-social aspects of dengue, located in countriesin South- and South-East Asia, including India, Indone-sia, Myanmar, Philippines, Sri Lanka and Thailand.Interactions will be examined between ecosystemfactors such as climate and the urban environment;biological factors such as vector density; social fac-tors; the functioning of vector control measures andother public services. The most effective interven-tions for specific ecosettings will be identified.

“This means looking, for instance, at dengue virustransmission in light of the dynamics affecting peo-ple's living conditions, their water storage behaviour,and urban services such as water supply and wastemanagement," explained Dr Johannes Sommerfeld,TDR's project leader of the initiative. The initiativealso will build a community of practice on dengueprevention, build research capacity, and support participatory ecosystem interventions for dengueprevention. The partnership has great potentialaccording to Dr Roberto Bazzani, Program Officer of IDRC's Ecosystem Approaches to Human Health(Ecohealth) Program Initiative based in Montevideo,Uruguay. “TDR has recognized experience embed-ding social sciences into biomedical and epidemiologi-cal studies and promoting community participation,”he said. “We strongly believe that this partnershipwill increase the potential for significant results and help build a multi-disciplinary dengue researchcommunity in Asia.”

The study follows the successful collaborationbetween TDR and IDRC in 2003-2005 on two pilotprojects examining some of the eco-bio-social factorsresponsible for the re-emergence of dengue in LatinAmerica. For instance, anthropologists, entomolo-

gists and policy researchers working together in the Brazilian citiy of Fortaleza found that poorerneighbourhoods had many more mosquito breedingareas than more affluent areas since the piped watersupply in the poor community was irregular, leadingto more water storage in containers. Projects in thisnew, and much broader, initiative will have both aresearch and an implementation evaluation stage.

Evaluating modified treatment strategiesand diagnostic tools Rapid diagnosis is essential for proper clinical man-agement of patients. However, there has been nosystematic validation of the many diagnostic testsavailable. A third new TDR-led initiative will evaluatefield performance of existing and new diagnosticsusing a network of dengue labs in Latin America andAsia. The Pediatric Dengue Vaccine Initiative (PDVI),a programme based at the International Vaccine Insti-tute (IVI) in Seoul, Korea, is the major partner in thisinitiative.9, 10

Appropriate clinical classification of dengue cases alsocan facilitate case management and thus save manylives – since dengue can manifest itself as both a relatively mild or very severe illness. However, TDRresearch found that current dengue classificationguidelines, developed over 30 years ago, are regardedby many clinicians as too complex.11 In response,TDR is now involved in a multicentre prospectiveclinical study in 7 countries to consolidate the cur-rent dengue case classification system and to betteridentify early warning signs of severe dengue acrossregions, age groups and nutritional levels. “We wouldlike to see evidence for a simplified classificationwhich will then be validated at different levels of thehealth system,” said Kroeger. This trial is funded bythe International Cooperation with DevelopingCountries (INCO) programme of the EuropeanCommission and TDR.

In a related effort, Professor Jeremy Farrar from theOxford University Clinical Research Unit based in Ho Chi Minh City, Vietnam, has been working closelywith TDR in the integrated multicentre network in 7 countries in SE Asia and the Americas to conductclinical research in dengue. He noted that “withoutTDR involvement, it would be impossible to bringclinical scientists from all these countries together in a collaborative way to address the real needs ofdengue. Bringing dengue research under the umbrellaof TDR has been a tremendously positive step whichwill enhance international collaboration on dengueresearch for years to come."

Future directions: vaccine preventionA dengue vaccine has been envisioned by manyresearchers as a more long term sustainable solutionto the worldwide resurgence of dengue. Yet specialchallenges exist in vaccine development, as well, sinceany dengue vaccine must provide very high level pro-tection against all four dengue strains to prevent pos-


FOOTNOTES:

1. DengueNet. WHO’s centraldatabase for global epi-demiological and virolog-ical surveillance of DF and DHF. Indicatorspresented here include:case fatality rates (CFR),frequency and distribu-tion of DF and DHF cases,number of fatalities andcirculating virusserotypes. www.who.int/denguenet/orwww.who.int/csr/disease/dengue/denguenet/en/index.html

2. Updates on dengue epi-demics can be found at:www.who.int/csr/don/archive/disease/dengue_haemorrhagic_fever/en/andwww.who.int/csr/don/archive/disease/dengue_fever/en/

3. Focks DA, Alexander N.Multicountry study ofAedes aegypti pupal productivity surveymethodology: findings and recommendations,Geneva, WHO/TDR, 2006.

4. Focks DA et al. Transmission thresholdsfor dengue in terms ofAedes Aegypti pupae perperson with discussion oftheir utility in sourcereduction efforts. American Journal of Tropical Medicine, 2000,62(1):11–18.

Dengue statistics

Some 2.5 billion people, two-fifths

of the world population is at risk.

There are 50 million infections

per year.

Up to 500 000 people annually con-

tract more serious cases of dengue.

An estimated 21 000 people die from

dengue-related illness.

Some 653 000 DALYs (disability

adjusted life years) are lost each

year.



FOOTNOTES (continued):

5. Focks DA. A review ofentomological samplingmethods and indicatorsfor dengue vectors.Geneva, WHO/TDR, 2003.

6. Detailed reports of manyof these studies havebeen recently publishedin a supplement to AnnalsTropical Medicine and Par-asitology(Vol 100, Supplement 1,April 2006).

7. Kroeger A, et al. Effective control ofdengue vectors with curtains and water con-tainer covers treated withinsecticide in Mexico and Venezuela: clusterrandomized trials. BMJ, 2006: 332:1247-1252. doi: 10.1136/bmj.332.7552.1247

8. More information on theIDRC Ecohealth Initiativecan be found at:www.idrc.ca/en/ev-3314-201-1-DO_TOPIC.html

9. www.pdvi.org/

10. Dengue diagnostics: proceedings of an interna-tional workshop.4-6 October, 2004. Geneva, WHO/TDR, Geneva, 2004.

11. Bandyopadhyay S, LumL, Kroeger A. Classifyingdengue: a review of thedifficulties in using theWHO case classificationfor dengue hemorrhagicfever. Trop Med Int Health 2006; 11, 1238-1255

12. More information on DV vaccines can be foundat the IVR website:www.who.int/vaccine_research/en/

sible vaccine-induced enhancement of disease.Responsibility for dengue vaccine development inWHO recently passed to the WHO Initiative for Vaccine Research, with whom TDR works closely.12

The most advanced strategy is production of liveattenuated vaccines. TDR also supports research into the pathogenesis of dengue virus infection which could assist the design and implementation of vaccines. “A vaccine will be a very important tool for dengue control in the future,” said Kroeger, “but it will still take some time to develop.”

All in all, dengue research is seeing important advances.Research is contributing to: the design and validationof new intervention packages; accelerated develop-ment of diagnostics, vaccines and drugs; and improved

dengue case management. New vector control toolsand approaches for vector surveillance are beingdeveloped and modern information technology isbeing tested for its cost and usefulness in supportingdistrict level decision-making, where vector controltakes place.

Dengue research is beginning to attract not onlyincreased funding from national and internationalsources, but also a diversity of young researchers –from molecular biologists to behavioural scientists.Admittedly the knowledge, tools and investmentneeded is still enormous. Yet the recent influx of talent and interest bodes well for the global effort tonot only halt dengue's epidemiological and geographicexpansion, but reverse the current trend.

TOOL DEVELOPMENT & EFFICACY TESTING IMPLEMENTATION RESEARCH

Ecosystem management & social mobilization*

Improved case classification & case management*

Support of vaccine developoment & evaluation

Targeted vector control*

Transgenic mosquitoes

New vector control tools & strategies*

High quality diagnostics*

Improved knowledge of pathogenesis*

Improved vector control

Improved case management

Improved primary prevention

Effective vaccine

Cost-effective

implementationstrategy*

Reduction of transmission & case fatality

* multi-country study in place or forthcoming

TDR and WHO research for improving dengue prevention and control



TDR CONTACT

Franco Pagnoni

[email protected]

TDR WEBSITE

www.who.int/tdr

in the malaria section

Reducing infant deaths due to malariaTDR implementation research to increase access to necessary drugs

An African baby dies from malaria every 30 seconds.At the end of each year, 1 million more babies areburied by their families – a scene that TDR is trying toprevent through its research into the innovative con-cept of home management of malaria intervention.

For many rural areas, there are no nearby health-care workers or facilities, so families have to walkmany miles and hours, and even then with nopromise of care at the end of their trip. So peopleoften do not even attempt to seek out care, andinstead used local remedies or just "wait it out". TDR began supporting research in 1998 for a decep-tively simple plan – train local mothers and othercommunity members to recognize fevers, provide

pre-packaged medications, and keep the medicinesproperly stored and recorded. The first results inEthiopia using chloroquine showed a 40% reductionin under-five child mortality, and were published inthe Lancet. Later, the work of Sodiomon Sirima andFranco Pagnoni showed that catching the malariaearly with prompt treatment stopped it from pro-gressing to a more severe and fatal form.

In 2002, the Ugandan government began teachingmothers how to recognize malaria symptoms, and to use a volunteer community medicine distributorfor diagnosis and treatment. The treatment providedwas HOMAPAK, a prepackaged combination ofchloroquine and SP specially developed for homecare. However, this medication no longer works inmany areas, due to parasites developing resistance to it. WHO now recommends artemisinin-basedcombination therapy (ACT), such as Coartem

“Early data suggests community members can be trained to administerthese new medications properly andavoid drug resistance, and this shouldtranslate into a substantial reduction in child mortality."Dr Franco Pagnoni, TDR research manager

Dr Franco Pagnoni reviewing records of local

drug distributors withNigerian investigators

Drs Ike Ajayi and Grace Olusola Gbotosho.

Accurate and rapid diagnosis of malaria is impor-tant not only to guide treatment at the point ofcare but also to avoid unnecessary treatment thatmay foster drug resistance and waste precioushealth resources. However, given the many diag-nostics on the market today, choosing the rightkit can be a challenge, and the best diagnosticoption may vary greatly from one setting toanother. Two resources below that can be helpfulinclude:

Malaria Diagnosis: new guidance in diagnostics evaluation A September, 2006 supplement to the journalNature Reviews: Microbiology, produced in coopera-tion with TDR, provides detailed guidance for clin-

icians and policymakers on how to evaluate diag-nostic tests for malaria.

The supplement can be downloaded free of chargefrom either the TDR web site: www.who.int/tdror from: www.nature.com/nrmicro/supplements/index.htmlPrint copies can be requested by e-mailing:[email protected]

The use of malaria rapid diagnostic tests (ISBN 92 9061 0883 3)

This simple 2004 guide for field managers coversthe basics of choosing and using rapid malariadiagnostics. It has recently been reprinted byWHO/TDR, and can be ordered, free of charge: [email protected]

Useful references and guides on malaria diagnostics

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(artemether-lumefantrine), but this medication isslightly more complicated to deliver and more expen-sive, and there is no evidence that ACTs will work in the home setting. In a WHO Bulletin article on the topic, Professor Umberto D’Alessandro from the Prince Leopold Institute of Tropical Medicine inAntwerp, Belgium, said, “There are no data availableon the effects of ACT when it is given by mothers totheir children without proper diagnosis. It shouldreduce mortality, but we simply don’t know if it does.”

So TDR is supporting research using these newermedications. Studies using ACTs in home manage-ment settings are underway in Benin, Burkina Faso,Cameroon, Ethiopia, Malawi, Nigeria, Uganda and the United Republic of Tanzania. Franco Pagnoni, the TDR coordinator of this project, says final resultswill be published in 2007, but early data are promising.In an article published in Tropical Medicine and Inter-national Health (TMIH) in July 2006, the researchersshowed that about 90% of caregivers in Ghana gavethe correct artemether – lumefantrine dose. The research is gaining attention (see list of publishedarticles and media attention), as could be expectedfor any intervention that could reduce the number of

children's deaths by 40%. “Early data suggests com-munity members can be trained to administer thesenew medications properly and avoid drug resistance,”Pagnoni said, "and this should translate into a sub-stantial reduction in child mortality."

RECENT REVIEWS ON HOME MANAGEMENT OF MALARIA (HMM)

Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia: a randomised trial.The Lancet, Vol. 356, August 12, 2000.

Tropical Medicine and International Health, July 2006:www.blackwellpublishing.com/journal.asp?ref=1360-2276

RealHealthNews, May 2006:www.globalforumhealth.org/realhealthnews/news%20analysis/may06_home_based_mm.php

WHO Bulletin, October 2006: www.who.int/bulletin/volumes/84/10/06-021006/en/index.html

BBC World Kill or Cure series, broadcast during November,2006 (see below).

Malaria research on the BBC

VIEW THE BBC

PROGRAMME ON

TDR-SPONSORED

RESEARCH

Copies can be

obtained free

from [email protected]

TDR-sponsored research into new home manage-ment and community directed models for malariatreatment was the recent focus of a BBC World doc-umentary. The highly rated Kill or Cure televisionseries programme aired five times in late Novemberand early December, 2006. Filmed on location inOyo State, Nigeria, the documentary profiles twoTDR-sponsored research projects that are examininghow to get new artemisinin-based combination ther-

apy (ACTs)to African chil-dren in ruralareas more effi-ciently. Coordinationbetween the local researchers at the University of Ibadan, the WHO country office, and the FederalMinistry of Health was highlighted as key to theeffort.

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But, he adds, "the critical element now is to be able to trans-late the insight gained from basic research into lead compounds that can form the basis for innovative treatment.This is part of our lead discovery efforts." Nwaka considers the fight against neglected disease a moral obligation; and sus-taining the availability of much-needed health products for thepoor despite all barriers is critical to the effort. Nwaka is fromNigeria and also has a Canadian citizenship. He did his earlystudies in Nigeria before moving to different countries inEurope, Asia and North America for further studies and train-ing. "It is this truly international experience that drives myprofessional and personal passion for this work." Nwaka hastaken his passion to TDR, where its Genomics and DiscoveryResearch Committees and team (GDR) are supporting severalnew networks for drug discovery involving developed anddeveloping country researchers, institutions and industry.These networks are interactive and cover different aspects ofthe process (see Figure 2).1

The networks include the following:

• Compound Evaluation Network – This network hasbeen the engine of TDR’s drug discovery effforts for severalyears, but it has been strengthened recently with increasedfunding and access to compound supplies through newindustry collaborations with TDR. The network currentlyhas the capacity to screen over 20 000 compounds per yearfor antiparasitic activity. The network consists of five cen-tres: the Swiss Tropical Institute (STI), Basel; the LondonSchool of Hygiene and Tropical Medicine (LSHTM); theNorthwick Park Institute for Medical Research (NPIMR),London; the Theodor Bilharz Research Institute (TBRI),Cairo; and the Laboratory for Microbiology, Parasitologyand Hygiene at the University of Antwerp (LMPH).

• Medicinal Chemistry and Pharmacokinetics Net-works – TDR recently established these collaborative

networks with the goal to further progress the ‘hits’ or‘leads’ identified through the compound evaluation network.The medicinal chemistry effort currently involves one largepharmaceutical company, Pfizer, and two biopharmaceuticalcompanies, Serono and Pharmacopeia. Academic institutionsinclude: the University of Cape Town, South Africa; the Uni-versity of Dundee, UK; and in the USA, the University ofNebraska, Ohio State University, and St. Jude Children’sResearch Hospital, Memphis. The pharmacokinetics/metabo-lism network, which provides essential pharmacology datafor medicinal chemists to help guide further synthetic work,includes Monash University, Australia, as well as Pfizer,Serono and Pharmacopeia.

• Drug Target Portfolio Network – This network is helping to create a globally accessible database containing a prioritized list of drug targets across the range of disease-causing parasites that are the focus of TDR research. Thiscapitalizes on the investment made in research on parasitegenome sequencing, and will help facilitate drug discoverybased on molecular targets. The database is thus expectedto become an important starting point in the search fornew drugs for neglected diseases, according to Dr WesleyVan Voorhis of the University of Washington in Seattle,who leads the TDR target network group. The databasealso will be "freely accessible," emphasizes Nwaka. The network includes groups at the University of Pennsylvania,USA; the Sanger Centre, Cambridge, UK; the Walter Elizaand Hall Institute for Medical Resarch (WEHI), Melbourne,Australia; and the Institute for Research in Biotechnology(UNSAM), Argentina.

• Helminth Initiative for Drug Discovery – This aims to support a network of academic and industry partners to develop new technologies in the search for new drugsagainst helminth infections such as schistosomiasis, oncho-cerciasis and lymphatic filariasis. This initiative is timely as it fills a gap created by a lack of a dedicated PPP for anti-helmintic product R&D. An informal consultation convened

(continued from page 1)

Figure 2. Integrated network/Partnership model



by TDR in 2005 identified the need for such an effort. Insubsequent meetings of global experts from industry, acade-mia and the donor community in 2005 and 2006, TDR wastasked with establishment and incubation of the initiative.

The multiple tracks of drug discovery How do we discover new drugs for tropical diseases? One ofthe fastest approaches is to examine how established drugs –for which there is already a body of clinical experience – mightbe used or adapted as treatments for parasitic diseases. Thisusually involves ‘whole organism’ screening of a known drugor compound against the parasite causing disease. TDR hashad important successes with this strategy. For example, thedrugs eflornithine and miltefosine have been developed forAfrican trypanosomiasis and visceral leishmaniasis from drugcompounds originally developed for cancer treatment.

Another approach is the ‘piggy-back’ strategy. This is mostuseful when a molecular target present in a parasite is also the focus of other commercial research, and thus provides achemical ‘starting point’ for investigation.1 For example, thehistone deacetylase inhibitor series developed for cancertreatment is now being explored in the context of anti-malari-al drug research.

A more long-term strategy involves ‘de novo’ discovery ofnew chemical entities based on protein or enzyme targets.Methods such as ‘high throughput’ screening; virtual screeninglinked to cheminformatics; and x-ray crystallography may bepart of this target-based, ‘rational’ approach. High-throughputscreening exposes a parasite protein or enzyme to thousandsof compounds in a highly automated process. Industry hasplayed a leading role in developing this technology, whichincreasingly is being applied in academic environments. Rational drug discovery can be challenging – but it arguably hasgreat potential for identifying drugs with novel modes ofaction.

Building capacity for drug discovery Through the TDR-led initiatives, developing country scientistsare now being trained in high-tech screening and medicinalchemistry techniques in industry settings. Collaboratiors so farinclude Pfizer, UK and Serono, a Swiss-based biotech compa-ny. Two research fellows from Brazil and Cameroon whotrained in drug screening at Serono recently returned to theirhome countries to put their new skills into practice. At bothindividual and institutional levels, the TDR networks arestrong instruments for capacity development and technologytransfer to developing countries.

"Ultimately, it is the countries suffering from the diseaseswhich need to play a leading role in searching for solutions,"observes Nwaka. "Developing countries need to participate indiscovering, developing and manufacturing their own drugs,and in establishing functional market mechanisms that suittheir own needs."

Dr Kelly Chibale, a medicinal chemist from the University ofCape Town, South Africa, who is one of the researchersworking with the TDR networks, underlines a similar theme."It is vital for African scientists to enhance drug discoverycapability in order to address the continent’s health needs,"

The TDR drug discovery initiative – and the potentialit holds to ease the critical bottleneck in the supplyof novel drug candidates for tropical diseases – wasthe focus of a special symposium at the 55th annualmeeting of the American Society of Tropical Medicineand Hygiene (ASTMH), 12-16 November, 2006.

The symposium, chaired by Dr Dyann Wirth of theHarvard School of Public Health, involved expertsfrom industry and academia as well as fromWHO/TDR. Presentations at the symposium under-lined the promise and initial results that are alreadybeing observed from an integrated drug discoveryapproach (see Fig. 2, page 14). Dr Solomon Nwaka,manager of Genomics and Discovery Research atWHO/TDR, discussed the gaps, needs and new oppor-tunities for drug discovery for tropical diseases. Healso described the promise of the network and part-nership model, involving academia, industry anddeveloping country institutions. Nwaka drew specificexamples from the work of TDR, public-private part-nerships (PPPs), and other organizations, emphasiz-ing the need for coordination and information-shar-ing among the various networks and collaborations.

A presentation by Dr Reto Brun of the Swiss TropicalInstitute highlighted how several lead compoundsinitially supported in the context of the TDR frame-work had been taken up by new PPPs for develop-ment, including synthetic peroxides for malaria, oral diamidines for human African trypanosomiasisand others. "This initiative, focused at the upstreamend of the R&D pipeline, presents a unique opportu-nity for neglected diseases," said Brun.

A presentation by Dr Michael Witty of Pfizer AnimalHealth, UK, described the progress made in estab-lishing collaborations between industry R&D groupswith high-tech research laboratories and chemicallibraries, TDR, and its international networks ofresearch institutes. Researchers in TDR-led networksare now making use of industry chemical compoundlibraries, such as Pfizer’s, to identify ‘hits’ and ‘leads’with potential for drug development.

A presentation by Dr David Roos, director of theGenomics Institute at the University of Pennsylvania,further highlighted how the TDR drug targets net-work is helping to facilitate drug discovery throughopen source database development.

ASTMH hosts symposium on TDR-led discovery research initiative



TDR CONTACT

Dr Solomon Nwaka

[email protected]@who.int

FOOTNOTES:

1. Nwaka S and Hudson A.Innovative lead discoverystrategies for tropicaldiseases. Nature Reviews Drug Discovery 5, 941-955,(2006).

2. Report of the Commis-sion on Intellectual Property Rights, Innovation and PublicHealth. World HealthOrganization (2006).

3. Nwaka S and Ridley RG.Virtual drug discoveryand development forneglected diseasesthrough public-privatepartnerships.Nature Reviews Drug Discovery 2, 919-928(2003).

4. Nwaka S and Widdus R.The research to development transitionfor candidate products to combat neglected diseases. In: Combating diseasesassociated with poverty:financial strategies forproduct development andthe potential role of pub-lic private partnerships(Widdus R and White K).Initiative for Public Private PartnershipsGeneva (2004).

5. For more information on these PPPs, see the websites: MMV: www.mmv.orgwww.mmv.orgDNDi: www.dndi.orgwww.dndi.orgFIND: www.finddiagnostics.orgwww.finddiagnostics.orgGlobal Alliance for TB drug development:www.tballiance.orgwww.tballiance.org

he says. "The ability of TDR to rapidly deliver promi-sing lead compounds through TDR-supportedscreening centres will enable medicinal chemists likemyself to start at a higher level in a more focusedmanner."

Cutting costs The process of creating a new drug is "long, riskyand expensive," Nwaka notes. It begins with the dis-covery phase where drug targets, lead compoundsand drug candidates are sought and identifiedthrough experiments in test tubes and animals, butcontinues into a development phase, in which drugcandidates are tested for safety and efficacy in ani-mals, and finally humans. The entire process cancost hundreds of millions of dollars and take wellover a decade. Along the way, the attrition rate issevere: only about one of thousands of compoundsscreened make it into a useable product. So system-atic coordination and collaborations between publicand private sectors can go a long way towardsreducing attrition and cutting costs.1

Results so far The TDR network and partnership model is alreadyyielding results. A vibrant portfolio of drug discov-ery projects have been developed and are beingmanaged with partners (see Fig. 3). Several new leadcompounds have been identified through the com-pound evaluation network and are now beingexplored further through the medicinal chemistryand other networks. In addition, the Drug TargetPortfolio has established an accessible database ofpotential drug targets. "This is perhaps the first timesuch an effort has been undertaken systematicallyacross a range of parasite causing diseases," Nwakastates. New collaborations with industry are helpingfacilitate drug discovery efforts, and supportingcapacity-building in parallel. "This is an exciting timefor drug discovery for tropical diseases. Ourapproach creates synergies with other organizations.As new drug leads are discovered, the technology istransferred elsewhere for further development."

Genomics High throughput screening (HTS)

Lead optimization

Preclinical development

Lead ID (Vitro/vivo test,

medical chemistry, pharmacokinetics)

Portfolio of drugtargets

and database

beingdeveloped

Walter Eliza and Hall Institute

for Medical Resarch (WEHI) 3 targets

Pfizer collaboration

Serono collaboration

Helminth initiative

Malaria 4 lead series

AfricanTrypanosomiasis

1 lead series

Leishmaniasis 1 lead series

Helminths 1 lead series

Histone Deacetylase

(HDAC)inhibition for

malaria

TDR 22093 with Medicines

for Malaria Venture (MMV)

Cyclodepsi-peptides

Figure 3.

Dr Solomon Nwaka explains TDR’s network initiatives.

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TDR CONTACT

Dr Axel Kroeger

[email protected]

Along with promotion ofmore effective drug treat-ments, effective vector control strategies are amongthe pillars of the campaignto eliminate visceral leish-maniasis (VL) on the Indiansubcontinent.

TDR, as a partner of the VL Eradication Initiative, issupporting research inBangladesh, India and Nepal,designed to provide newevidence on what are themost effective and efficientvector interventions in anintegrated vector manage-ment (IVM) framework.

A workshop and meeting in Kolkata in March 2006involving 15 government control experts andresearchers from all three countries drafted proposedterms of reference for the planned three-countrystudy on cost-effective integrated vector manage-ment as a contribution to visceral leishmaniasis elimination on the Indian subcontinent. The partici-pants were members of multidisciplinary researchteams who will carry out the research, with resultsexpected in the coming year.

In the case of Kala Azar, effective vector control maybe based on indoor residual spraying (IRS); use ofinsecticide treated netting materials (ITNs); environ-mental management strategies; or may combine twoor three of these interventions.

Areas of proposed focus for the research are toconsider the following gaps in knowledge: • vector ecology and efficacy of non-chemical

interventions; • efficacy of ITN curtains or bednets in reducing

vector densities; • cost, feasibility, acceptance and sustainability of

strategies using insecticide based vector controltools (IRS versus ITNs) or using non-chemical ecological interventions;

• cost and quality of conventional vector control(IRS) and options for increased efficiency, safetyand quality.

The Kolkata meeting included a brief review of thestudy designs developed by the five research teamsin the three countries; development of overarchingresearch questions along with questions specific toeach study site; outline of research instruments andforms; and proposal submission formalities. Theworkshop also was attended by representatives ofthe WHO Regional Office for South-East Asia, aswell as by WHO representatives from Nepal andIndia. WHO headquarters was represented by TDR and the Department for Neglected TropicalDiseases. A second back-to-back meeting also washeld with a group doing research into VL treatmentin Bihar.

Integrated vector management insupport of visceral leishmaniasis(VL) elimination on the Indiansubcontinent

Improved housing conditions can supportvisceral leishmaniasis

(VL) elimination, by targeting vectors

that live in the plasterof poorly constructed

homes.

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D E V E L O P I N G C A P A C I T Y I N S Y S T E M A T I C R E V I E W S

A TDR collaboration with the Joanna Briggs Institute

Res ipsa loquitur is a legal concept, essentially meaning, "the thing speaks for itself". For manyresearchers, the results of their work should speakfor the overall endeavour, and findings should beimplemented as a matter of course. In recent years,however, researchers have become more keenlyaware that proof of principle is not always sufficient,and a caveat to this maxim has thus been suggested:Res ipsa loquitur, sed quid in infernos dicet?" or "thething speaks for itself, but what the hell does it say?"

Clearly the uptake of research into practice will onlysucceed if findings are grounded both in sound scien-tific methods and in conclusions that can be broadlyunderstood. In the health and medical fields, evi-dence gathered through qualita-tive research methods is increas-ingly relevant to understandingthe social, cultural and economicfactors affecting disease transmis-sion, health status and healthcare. Rigorous norms, standardsand practices have, in fact, beendeveloped for the conduct ofqualitative health research, andfor its systematic review. Yetthese are less broadly familiar tohealth researchers – who stilltend to view the quantitativestudies, as epitomized by the ran-domized controlled trial – as theresearch "gold standard."

To address this gap in perception, knowledge andpractice, TDR is now collaborating with the JoannaBriggs Institute (JBI), a global network promotinggood practice in the design, dissemination and imple-mentation of systematic reviews of studies involvingqualitative research, economic research, and policyresearch.

Key to JBI's mission and strategy is the fostering ofinternational collaborations between collaboratingcentres, researchers and clinicians, and other healthgroups. There currently are 26 JBI CollaboratingCentres – primarily located in Europe, North Ameri-ca and Australia – participating in the internationaloutreach programme. The new TDR collaborationproposes to expand these networks and activitiesinto developing countries with an initial focus ontraining and certification of research groups in Africa."New disease control tools, as well as research find-

ings, are more likely to be scaled up and incorporat-ed into health systems if the endemic countriesthemselves participate in the evaluation of alterna-tives for prevention, control and treatment ofneglected infectious diseases,” notes Steven Wayling,manager of the initiative in TDR’s Research CapacityStrengthening team. “Expanding these kinds of net-works to include researchers from developing coun-tries can help that happen."

JBI was established a decade ago at Royal AdelaideHospital and the University of Adelaide in SouthAustralia. The Institute works closely with theCochrane Collaboration, which sets good practicemodels and standards for the meta-analysis of results

from randomized controlled trials;and with the Campbell Collabora-tion, which prepares, maintainsand disseminates systematicreviews of studies of social inter-ventions. In that array, JBI fills acomplementary niche, promotingsystematic review of research thatutilizes more integrated or alter-native approaches. JBI's activities,likewise, provide synergies withthe objectives of TDR's implemen-tation research and capacity build-ing programmes.

JBI has developed methodologiesand electronic systems to conductmeta-synthesis of both quantitative

and qualitative evidence for health care. In addition,the Institute has well developed programs in evi-dence translation, evidence transfer and evidenceutilisation.

Developing norms and promoting good practicestandards for such research is critical to the accep-tance of findings from studies that emphasize broad-er and more inclusive approaches to evidence. Such studies, in turn, may highlight critical associa-tions between population health and social, culturaland economic factors that quantitative research,alone, cannot yet identify. These same social, eco-nomic and cultural factors, in turn, are particularlyrelevant in the translation of research into healthcare practices in developing countries, and for popu-lations with diseases or conditions that are linked topoverty and health policy development.

TDR CONTACT

Steven Wayling

[email protected]

JBI CONTACT

Pr. Alan Pearson

School of Population

Health and Clinical

Practice,

The University

of Adelaide

and Executive Director,

the Joanna Briggs

Institute, Adelaide,

South Australia

alan.pearson@

adelaide.edu.au

www.joannabriggs.

edu.au

Rigorous norms, standards and practiceshave been developed

for the conduct of qualitative health

research and its systematic review. Yet these are less broadly familiar tohealth researchers.


"How much is this going to cost? How are we goingto pay for it? Should we pay for it?"

When officials in a ministry of health anywhere inthe world consider a proposed new policy or pro-gramme, the bottom line of costs and benefits, both financially and in terms of lives saved and illnessaverted, is a critical factor. The same questions areall the more relevant to developing countries, wherebasic health coverage and achievement of the health-related Millennium Development Goals dependsupon the efficient and equitable use of scarceresources.

Yet trained health econo-mists who can frame theissues properly, and then provide accurate answers,are in chronically short supplyin these same settings – and particularly in Africa. Accord-ing to one estimate, there areonly about 100 health econo-mists in all of Africa; talent isconcentrated in just a few coun-tries, and mostly in research andacademic centres, rather than inministries of health, where deci-sions are taken.1 One of the mostfundamental reasons for thedearth of health economists in the African contexthas been the lack of training opportunities. Thereare no dedicated health economics PhD programmesin African universities, and opportunities to studyhealth economics in the context of other PhD pro-grammes, while expanding slowly, remain very limited.

For nearly a decade, TDR has been involved in thecreation of master's level programs in health eco-nomics in Africa to respond to this identified need.Now, building upon these past efforts, involving awide range of partners, TDR is laying the ground-work for the development of a dedicated healtheconomics programme at PhD level at an Africanuniversity. One important milestone was an April2006 meeting of interested parties, convened byTDR, together with the University of Cape Town,Health Economics Unit. Participants in the April2006 meeting included former TDR PhD trainees inhealth economics; representatives of universitiesoffering some form of health economics training; theSwedish International Development Agency, SIDA(the leading bilateral agency providing support forhealth economics capacity development in Africa);the African Regional office of WHO; and Brunel

University, which has been assisting TDR in develop-ing new African master's level programmes in healthsocial sciences. TDR is now following up on this initial meeting with a dialogue involving other poten-tial partners in Africa and elsewhere, including the London School of Hygiene and Tropical Medicineand Sweden's Karolinska Institute.

The proposal for a doctoral level programme buildsupon a decade of TDR and partner involvement inbuilding health economics capacity. In the mid 1990s,TDR and the WHO Strengthening Health Services

programme were instrumental in thecreation of a Master's degree in HealthEconomics with the University of CapeTown.2 The only other Master's pro-gramme in Health Economics is inFrancophone Africa supported byCESAG (Centre Africain d'EtudesSupérieures en Gestion), Dakar,Senegal. In addition to dedicateddegree programmes, a growing num-ber of universities in Africa are nowoffering some other form of post-graduate health economics training,particularly as a module withinanother master’s programme(usually either a Master of Public

Health or Master of Economics).Increasingly, students in the generalist programmes,as well, are conducting their thesis research onhealth economics topics. Research institutions, suchas the Kenyan Medical Research Institute (KEMRI)and Navrongo Research Centre, also make animportant contribution by providing supervisory sup-port to master’s level students undertaking healtheconomics dissertation research in the field stationsof these institutions. Beyond the walls of academia,several other regional networks and initiatives alsoare playing an important role in strengthening capaci-ty among practitioners and researchers.

Among these are the Health Economics and PolicyNetwork in Africa (www.HEPNet.org), which linksministries of health, research institutes and academicinstitutions involved in health sector development. Another recent initiative is the establishment of the African Health Economics Advisory Committee(AHEAC) by WHO-AFRO. The primary purpose of this committee is to advise the African regionaldirector of WHO on issues relating to health eco-nomics. Through establishment of this committee,WHO and its regional offices, together with TDR,have demonstrated a commitment to placing healtheconomics on the policy agenda in Africa.

Strengthening health economicscapacity in Africa


TDR CONTACT

Steven Wayling

[email protected]

UCT CONTACT

Pr. Diane McIntyre

Health Economics Unit

University of Cape Town

[email protected]

www.heu.uct.ac.za

FOOTNOTES:

1. Data drawn from McIntyre D, Gilson L,Mutyambizi V (2005).Promoting equitablehealth care financing in the African context:current challenges andfuture prospects. Harare: Regional Networkfor Equity in Health inSouthern Africa(QUINET).

2. A similar programme was established with TDRsupport at ChulalongkornUniversity, Bangkok,Thailand.

A recent issue of the African Health Monitor, portrayed here, featuredhealth economics as thecover story, reflecting growing recognition of itsimportance to Africa’shealth sector.


National and international guidance in ethicalaspects of health-related research is typicallydeveloped within a biomedical paradigm. Suchguidance, however, often fails to reflect principlesand guidance drawn from social science research –which may be relevant and important to the ethicalconduct of qualitative health science research.

This was the central message emerging from therecent meeting of a new initiative being undertakenby the Ethics Committee of the Sao Paulo HealthDepartment in Brazil. The TDR-supported initiativeaims to review and analyze ethical principles rele-vant to qualitative or interpretative research inhealth sciences – and eventually issue guidance rel-evant to such research.

An initial meeting of the initiative in Guarujá,Brazil, 28 August to 1 September, 2006, wasattended by 30 national and international social

science experts representing leading academicresearch groups. Discussion was guided by five TDR-commissioned working papers highlighting differ-ences between the dominant 'biomedical positivist'paradigm for health research, and the 'interpreta-tive paradigm' in which social science and qualita-tive research is anchored.

Essential questions were posed and possiblemethodologies proposed as a framework for eventual guidelines. Key questions consideredincluded:

• How to assess the risk-benefit relationship forthe participants in research?

• What is the nature and process for obtaining afree-informed consent?

• Does the term “research” have the same meaningin different areas of knowledge?

Consultation on ethical review of qualitative health research


Teaching research ethics to healthsciences students in Brazil

Research ethics is a topic of growing interest indeveloping countries – due partly to the globalizationof research, as well as to the increasing emphasis onproduct development for populations suffering froma high overall burden of disease and socio-economicvulnerability. In light of these trends, the importanceof reinforcing principles of equity and respect forresearch participants is an ever more essential com-ponent in the training of research investigators.

The teaching of research ethics to research studentshas been the focus of a collaboration between TDRand Universidade de Brasilia, initiated in mid-2005. Fol-lowing the recommendations of the initial workshop, amajor meeting was held in Brasilia in May 2006.

The meeting was attended by research advisers andgraduate students of 10 postgraduate programmes inHealth Sciences and Tropical Medicine, as well as byresearch ethics committees of relevant public univer-sities and university hospitals in central and westernBrazil. It was held under the auspices of the Faculty ofHealth Sciences and Faculty of Medicine of the Uni-versity of Brasilia, and FLACEIS – Latin AmericanForum of Research Ethics Committees, with the sup-port of TDR, PAHO and the Brazilian Secretary ofScience and Technology of the Ministry of Healthhttp://www.unb.br/fs/eticaempesquisa/

The discussion revolved around a review of casestudies and working papers, with analysis of problems and challenges arising in different phases of the research process. The ways in which differentmethodological approaches may generate differentkinds of ethical issues was considered in an effort to elucidate key social, cultural, economic, health systems and policy-related questions. Issues relatedto science and technology development; national andinternational policies; priorities in health research;and the contribution of research ethics to a betterunderstanding of the social, ethical, legal and publicpolicy issues associated with health research all wereaddressed.

A new academic programme for the teaching ofresearch ethics, as well as an educational package for the public at large, was launched at the workshop.The programme curriculum, available on CD-ROM, isbeing made available free-of-charge through the TDRweb site (see Publications, page 31). The ongoing col-laboration between TDR, the universities, and theirresearch ethics committees is expected to supportcontinued strengthening of good research ethicspractices in the Americas, as well as improved rec-ommendations on research ethics guidance and regu-lation for national authorities, academic institutionsand ethics committees.

FOR MORE

INFORMATION:

Pr. Dirce Guilhem,

Universidade

de Brasilia

[email protected]

WHO/TDR CONTACT

Dr Fabio Zicker

[email protected]


• Would it be possible to establish a single stan-dard or guideline for the ethical review ofresearch in different areas of knowledge?

As a next step, a learning document is being prepared by an editorial committee. This will be circulated for wider review and consultation amonginstitutional ethics committees, prior to the propos-al of guidelines on the subject.

Institutions and organizations represented at themeeting included: the Brazilian National Council of

Ethics (CONEP); the Brazilian Society of CollectiveHealth (ABRASCO); the Secretary of Science andTechnology; Ministry of Health; the Brazilian Society for the Progress of Science; the FrenchNational Agency for Research on AIDS and ViralHepatitis (ANRS); the American Society of Psychology; and the journals: Public Health Journaland Reports in Public Health; Brazilian Society ofBioethics; and the National Societies of Research and Postgraduate in Psychology, Social Science andAnthropology.


Participants in the Guaruja, Brazil consultation.

Knowledge of pharmaceutical research and develop-ment is of increasing relevance to students of publichealth and health sciences. Particularly for studentsfrom developing countries, familiarity with commer-cial R&D processes can help train and empoweryoung professionals in both the assessment and evaluation of product R&D initiatives, as well as intheir management.

A month-long course offered by the University ofNagasaki Institute of Tropical Medicine in autumn2006 has provided one initial model for teaching sucha curriculum. The course was designed in collabora-tion with TDR, and along with experts from Japan,Colombia, Thailand, China and India. TDR also pro-vided financial support for students from a widerange of countries in Asia, Africa and Latin Americato attend. Along with supporting opportunities forstudents from developing countries to learn aboutthe whole process of pharmaceutical R&D, from reg-

ulatory to post-registration issues, the course pro-vides a platform for the development of professionalnetworks and even new products. Involvement offaculty from the private sector can open up newopportunities to students to pursue research activi-ties in collaboration with the pharmaceutical sector.One aim of TDR is to generate, from the Nagasakicourse model, momentum for the creation of a fullinternational diploma course at the MA level in Phar-maceutical Product R&D, tailored to meeting publichealth needs in developing countries.

A meeting held on 1-2 December 2006 at the Uni-versity of Tokyo, and sponsored by Nagasaki Univer-sity in collaboration with the University of Tokyo'sGraduate School of Pharmaceutical Sciences, TDR,and the Pharmaceutical Society of Japan, sought toprovide a framework for an initiative that could yieldsuch a diploma course, involving stakeholders fromdiverse cultures and geographical regions.

Building capacity in public health product research and development

TDR CONTACT

Dr Janis Lazdins

[email protected]

FOR MORE

INFORMATION:

Dra Iara Guerriero,

Secretaria Municipal

de Saúde de São Paulo

[email protected]

TDR CONTACT

Dr Fabio Zicker

[email protected]

From left, Dr Janis Lazdin,TDR; Ms Mary Alpa T Cornelio,course lecturer; Dr JuntraKarbwang, TDR; Prof KenjiHirayama, course director.


In a related effort, The MIM/TDR Task Force onMalaria Research Capability Strengthening organized a workshop to improve the quality of proposals submitted in response to the call for MIM grants for

2007. The workshop was the third stage of aprocess designed to identify research projects withpotential for significant contribution to reducing themalaria burden and capacity building.

Responding to a June 2006 TDR call, a total of 59 letters of intent were received from 14 Africancountries in the following areas: • improving access and rational use of artemisinin-

based combination therapy (9); • preventive treatment in children and pregnant

women (10); • bacteria co-infection in malaria (5);• role of parasitological diagnosis in management

of malaria in areas of high transmission (4);• improved prevention and management of severe

malaria (1);• effective delivery and use of available interventions

(9);


Immune responses in protectionagainst malaria: seven years ofMIM/TDR research

Capacity for malaria research and control in Africa is being strengthened significantly through the jointTask Force on Malaria Research Capability Strength-ening in Africa of TDR and the Multilateral Initiativeon Malaria (MIM). That was a message emerging from a symposium on research by this joint effort atthe 55th meeting of the American Society of TropicalMedicine and Hygiene (ASTMH) 14 November 2006in Atlanta, Georgia (see page 25).

The MIM/TDR collaboration, which is still ongoingtoday, supports multidisciplinary partnerships to

address specific research questions and develophuman resources in the field of malaria research andcontrol.

The model is founded upon partnerships linking scientists from developed countries with theirAfrican counterparts. Examples presented at thesymposium, attended by over 100 participants, drewupon the experiences in three MIM/TDR projectsfunded between 1998 and 2005, to demonstrate thisin action. Drs Dicky Akanmori (University of Ghana,Legon), Abdoulaye Djimde (University of Bamako,Mali), Anthony Holder (MRC London, UK) andRoseangela Nwuba (University of Ibadan, Nigeria)presented research findings on the role of hostimmunity in malarial anemia; response to chemother-apy; and propagation of the erythrocytic stages of P. falciparum. Along with a discussion of the implica-tions of this research for vaccine development, man-agement of malaria anemia, and drug resistant malariain Africa, the scientists also highlighted how north-south, south-south and multidisciplinary partnershipscontributed to the success of the projects. The sym-posium was co-chaired by Drs Lee Hall (NIH/NIAID)and Olumide Ogundahunsi (WHO/TDR).

TDR CONTACT

Dr Olumide Ogundahunsi

[email protected]

MIM/TDR proposal enhancement workshop (23 - 29 September 2006, Accra, Ghana)



The ResearchStrengtheningGroup (RSG) provides technical andstrategic adviceto TDR onengagement of developingcountries inscience andknowledge-based decision-making.

• improved vector control strategies (13); • other areas -including natural products (8).

Nineteen letters of intent were short listed fordevelopment into full proposals. Of these short-listedcandidates, seventeen investigators participated inthe workshop, including participants from: Burkina

Faso, Cameroon, Congo, Democratic Republic ofCongo, Ghana, Ivory Coast, Mali, Nigeria, Tanzania,and Uganda. Final proposals will be reviewed duringthe 10th meeting of the Task Force (26 - 30 March2007) at the African Regional Office of the WHO inBrazzaville, Congo.

The 30th meeting of the Research StrengtheningGroup (RSG) took place in Nairobi in March 2006,under the chairmanship of Dr Ana Rabello of theFIOCRUZ Institute, Brazil. RSG is a multidisciplinarygroup of scientists that provides technical andstrategic advice to TDR, supporting its unique man-date to engage developing countries in science andknowledge-based decision-making, as a pre-requisitefor sustainable development of appropriate tools for disease control.

Dr Peter Eriki, WHO Representative, Kenya, openedthe meeting, stressing the importance of promotingevidence-based health policy and supporting researchrelevant to public health goals. Dr Robert Ridley,director of TDR, presented a report on TDR'sprogress, challenges and future activities. The direc-tors of a number of international research organiza-tions in Nairobi, including the International LivestockResearch Institute (ILRI), International Centre ofInsect Physiology and Ecology (ICIPE), Institute of Primate Research (IPR), and the Trypanosomiasis

Research Centre (TRC) of the Kenya AgriculturalResearch Institute, gave overviews of their researchlines. For the first time, the principal investigators of institutional program-based grants made presenta-tions on their grant progress. The RSG reviewed 86 progress reports, and short-listed new applicationsfor institutional-based programme grants as well as 34 applications for research training grants. RSG-recommended funding totaled about US$ 1.6 million.

A joint session of the RSG and the MIM/TDR TaskForce, meeting the same week in Nairobi, also tookplace. Dr Fabio Zicker, TDR coordinator of ResearchCapability Strengthening, led discussions on: coordina-tion of projects and activities; support for projectplanning and development; and good practice standards for non-regulatory clinical studies. RCS’smentorship approach and its training of principalinvestigators in research project planning wereacknowledged as positively impacting the quality offunded proposals. A list of approved projects is post-ed on TDR’s website.

Research Strengthening Group(RSG) meets in Nairobi

TDR CONTACT

Dr Fabio Zicker

[email protected]

Drs Halima Mwenesi, Chair of MIM/TDR, Fabio Zicker from TDR and Ana Rabello, Chair of the RSG.



TDR's new Good Laboratory Practice(GLP)Network – facing the challenge of R&D in the south Along the pathway of developing effective drugs tocontrol diseases endemic in poor countries, the pre-clinical stage of tests constitutes a major, butoften unrecognized milestone – where a "GO" or"NO GO" decision must be made. Here, studiesrelating to the safety of the candidate drug are of critical importance. The importance of selecting theright candidate for exhaustive testing cannot be over-stated. As a result, it is critical that research anddevelopment studies designed to demonstrate thesafety of the drug candidate prior to launching clinicaltrials on human subjects be conducted in compliancewith a set of principles called "Good Laboratory Prac-tice" (GLP). Since regulatory safety studies are onlyacceptable internationally if they are performed incompliance with GLP, one means of building R&Dcapacity in disease-endemic countries is to facilitatetraining in Good Laboratory Practice.

Train the Trainers to deploy more rapidlyFollowing the recommendations of a GLP ScientificWorking Group in 2000, a TDR-sponsored trainingprogramme for GLP, together with a set of tutorialmaterials, was developed. Focused training was thenundertaken in a number of R&D institutes in Africa,Asia and Latin America. The next stage was thedevelopment of the TDR-sponsored GLP "Train the Trainer" initiative.

"The concept of ‘Train the Trainers’ was adopted so we could have a real impact on large numbers of

How did it happen? A group of committedresearchers selected from those already trainedthrough initial TDR courses were identified andinvited to be trained as future trainers. They areassisting TDR in the process of promoting theconcepts and principles of GLP and improving thequality of pre-clinical studies. These trainers havesince trained large numbers of researchers andGLP awareness is now becoming a more commonfeature of R&D in disease endemic countries.

Train the trainer sessionsthroughout the world

Good Laboratory Practice (GLP)meeting in Rio de Janeiro

GLP NETWORK FOCALPOINTS BY REGION

Latin AmericaDr Myriam Arevalo Herrera, Instituto deImmunologia del Valle,Calle 4B, 36-00, Cali, Colombia, Tel.: 57 2 558 1931, Fax: 57 2 558 1061, [email protected]

AsiaDr Sudhir Srivastava, Scientist-in-Charge, Division of Toxicology,Central Drug ResearchInstitute, Post Box 173,Lucknow, 226 001 India, Tel.: 91 522 21 411 418,Fax: 91 522 223 405, [email protected]

AfricaProfessor A. Walubo,Department of Pharma-cology, University of the Orange Free State,Post Box 339 (G6),Bloemfontein 9300,South Africa, Tel.: 27 51 401 3090Fax: 27 51 444 [email protected] [email protected]

If you are a researcher inthe field of non-clinicalsafety studies in a dis-ease endemic country,consider adopting GLP inyour institute. A TDR webforum on GLP is plannedfor the future. Thoseseeking information moreimmediately may contact:

Dr Deborah KioyTDR Pre-clinical [email protected]

Phot

o: D

ario

Zal

is

Members of TDR Network of GLP Trainers in Rio de Janeiro meeting.

researchers," says Dr Deborah Kioy, TDR coordina-tor for pre-clinical activities, who has led the GLPtraining initiative. Now, the initiative has launched athird phase of activities – and that is a new GLP net-work. Such a network can further reinforce expansionof the training effort, and assist in the practical imple-mentation of GLP principles.

The overriding aim is to bring laboratories in diseaseendemic countries up to international levels in theperformance of safety studies and thus promote theinternational acceptance of these studies, their dataand subsequently, the registration of new drugs. Thefirst organizational and planning meeting of the newGLP network, involving 21 experienced GLP trainers,was held in Rio de Janeiro, June 2006. Alongside thisevent, a group of 60 Brazilian scientists attended oneof the regular training workshops.



The annual conference of the AmericanSociety of Tropical Medicine andHygiene is one of the premier globalevents in the field of tropical diseaseresearch and control. A total of sevenTDR-sponsored symposiums, presenta-tions and posters were featured at therecent ASTMH meeting, which tookplace in Atlanta, Georgia, 12 -16November, 2006.

Major presentations were organized by TDR on: Innovative drug discoveryresearch for neglected diseases (seeTDRnews cover story); Rapid diagnosticstests for malaria, where do we go fromhere? (see pages 6-7); and Immuneresponses in protection against malaria:seven years of MIM/TDR research (seepage 22).

Presentations were also made on newresearch findings related to newArtemisinin-based Combination Thera-pies for malaria (ACTs) involving TDRresearchers in collaborations with arange of research institutions fromnorth and south. In all cases, what bringsthis diverse array of presentationstogether is the way TDR has used itsleadership and stewardship roles toleverage initiatives bringing togetherresearch and training institutions in

developed and developing countries andin the public and private sector to workfor common goals. See the ASTMH website:www.astmh.orgfor links to abstracts and papers.

Symposium 43Rapid Diagnostic Tests (RDTs) for malaria: where do we go fromhere?Chair: John W BARNWELl, Center for Disease Control and Prevention,Atlanta, GA, USA • Peter L. CHIODINI, Hospital for Tropical Diseases, London,UK • John W. BARNWELL, CDC,Atlanta, GA, USA • Qin CHENG, Australian Army Malaria Institute, Brisbane, Australia • David BELL, WHO Regional Office for the WesternPacific, Manila, Philippines.

Symposium 54Innovative Drug Discovery for Tropical DiseasesChair: Dyann WIRTH, Harvard School of Public Health, Boston • SolomonNWAKA, Special Programme forResearch & Training in Tropical Diseases(TDR), World Health Organization(WHO), Geneva, Switzerland • MichaelWITTY, Pfizer Inc., Sandwich, Kent, UK • David ROOS, University of

Pennsylvania, Philadelphia, PA, USA •Reto BRUN, Swiss Tropical Institute,Basel, Switzerland.

Symposium 68Immune Responses in ProtectionAgainst Malaria: Seven Years ofMIM/TDR ResearchChair: Lee HALL, National Institute of Allergy and Infectious Diseases,Bethesda, MD, USA • Abdoulaya A.DJIMDE, University of Bamako, Mali •Anthony A. HOLDER, National Institutefor Medical Research, MRC, London, UK • Roseangela Ifeyinwa NWUBA, University of Ibadan, Nigeria •Batholomew D. AKANMORI, NoguchiMemorial Institute for Medical Research,Legon, Accra, Ghana.

Presentations at Scientific session 32Artesunate (AS) plus amodiaquine(AQ) for treating falciparum malaria – assessing its efficacy andtolerability during six years of fielddeployment in Southern SenegalPhilippe BRASSEUR, IRD, Dakar, Senegal • Patrice AGNAMEY, Labora-toire de parasitologie/mycologie, Université Paris V, Paris, France •Moustafa CISSE, Centre Hospitalier,Oussouye, Senegal • Philippe ELDIN

WHO/TDR at ASTMH, 12-16 November 2006

What next?So far, over 1000 people in 10 countries (India, Thailand,Kenya, Benin, Congo, South Africa, Ghana, Nigeria, Colombia,Brazil, Tanzania) have been trained in GLP practices throughthe TDR-led initiative. In the June meeting of the new GLPnetwork, it was agreed that the network would have regionalbranches representing Asia, Africa and Latin America. TDR would retain an overall coordination function, while actu-al training operations would be outsourced as a non-profitactivity in the regions involved.

The proposed activities of the network include: • Continued training, organised regionally by the "outsourced"

network groups. This will be accompanied by constantreview and improvement of training materials already avail-able.

• Support for GLP implementation in disease endemic countrylaboratories by providing a forum for advice and aid in thepreparation of documentation.

• Encouraging national regulatory authorities to adopt GLPand set up monitoring bodies.

• Development of a web site for training and advice to insti-tutes wishing to implement GLP.

TDR network of GLP trainers

Africa branch Asia branch Latin America

branch

Ownership of GLP implementationsouth/south/north collaboration

Figure 1. Structure of the network



Latest grantsResearch in molecular entomologyNew grants These grants will be funded for one year only.

A60266Zakaria Bengaly • Centre International deRecherche Développement sur l'Elevage enZone Sub-humide, Bobo-Bioulasso, BurkinaFaso. Gene flow among populations of G. palpalisfrom the Comeo basin. US$ 19 050

A60311Nancy M. DuTeau • Colorado State University,Fort Collins, Colorado, USA. Biology of diseasevectors course – 2007. US$ 50 000

A60277Patrick M. Guerin • Université de Neuchâtel,Neuchâtel, Switzerland. Understanding hostseeking in tsetse fly vectors of African try-panosomiasis. US$ 36 000

A60312Winston A. Hide • University of the WesternCape, South African National Bioinformatics

Institute (SANBI), Bellville, South Africa.Mobilising tsetse genome information to addressdisease. US$ 25 000

A60345Jaroslaw Krzywinski • University of Texas atArlington, Arlington, Texas, USA. Identificationof sex determination genes in mosquitoes. US$ 28 653

A60262Maria Monastirioti • Institute of MolecularBiology and Biotechnology, Foundation forResearch and Technology-Hellas (FORTH), Crete, Greece. Development of transgenicAnopheles strains carrying a dominant female sterilizing allele. US$ 39 000

A60347Antonio Christophe Nkondjio • Organisationde Coordination pour la Lutte contre lesEndémies en Afrique (OCEAC), Yaoundé,Cameroun. Bionomics and genetic structure ofmalaria vectors An. moucheti and An. nili in SubSaharan Africa. US$ 35 856

A60169David A. O'Brochta • University of Maryland

Biotechnology Institute, College Park, Maryland,USA. Class II transposable element dynamics inAnopheles gambiae. US$ 30 000

A60278Loyce Martha Alungat Okedi • NARO/ Livestock Health Research Institute (LIRI), Tororo, Uganda. Human infective trypanosome transmission dynamics in the tsetse fly G. f.fuscipes from sleeping sickness foci in Uganda.US$ 26 800

A60258Susan Marie Paskewitz • University of Wisconsin, Madison, Wisconsin, USA. Lysozymeand development of Plasmodium falciparum inAnopheles gambiae. US$ 40 000

A60235Rosa Patricia Penilla • Centro de Investigacion de Paludismo, Instituto Nacional de Salud Publica, Tapachula Chiapas, Mexico.Molecular characterization of insecticide resis-tance in the malaria vector Anopheles albimanus.US$ 27 068

A60362Om Prakash Singh • National Institute of Malar-ia Research ICMR, New Delhi, India. Molecular

DE PECOULAS, Faculté de Pharmacie, Université de Caen, France • Jean-François FAUCHER, Service des maladies infectieuses, Besançon, France •Michel VAILLANT, CRP-Santé, Luxem-bourg • Oumar GAYE, Faculté deMédecine, Université Cheik Anta Diop,Dakar, Senegal • Walter (Bob) R. TAYLOR & Piero L. OLLIARO, SpecialProgramme for Research & Training inTropical Diseases (TDR), World HealthOrganization (WHO), Geneva, Switzer-land.

Artesunate + Amodiaquine (AS+AQ) for the treatment of uncom-plicated falciparum malaria: aninventory and systematic review of safety and efficacy data.Piero L. OLLIARO, Special Programmefor Research & Training in Tropical Diseases (TDR), World Health Organization (WHO), Geneva • MichelVAILLANT, CRP-Santé, Luxembourg •Revati PHALKEY, Université VictorSegalen Bordeaux, France • Jean-PaulGUTHMANN, Epicentre, Paris, France •Grant DORSEY, University of California

at San Francisco, USA • PhilippeBRASSEUR, IRD, Dakar, Senegal •Umberto D'ALESSANDRO InstitutPrince Leopold, Antwerp, Belgium •Pascal MILLET, Université Victor SegalenBordeaux, France • Walter (Bob) R.TAYLOR, Special Programme forResearch & Training in Tropical Diseases(TDR), World Health Organization(WHO), Geneva, Switzerland.

Poster Session A Confirmation of emergence ofmutations associated withMalarone® resistance in unexposedPlasmodium falciparum isolatesfrom Nigeria. Christian T. HAPPI, College of Medicine,University of Ibadan, Nigeria • Grace O. GBOTOSHO, College of Medicine,University of Ibadan, Nigeria • OnikepeA. FOLARIN College of Medicine, University of Ibadan, Nigeria • AkintundeSOWUNMIM, College of Medicine, University of Ibadan, Nigeria • Dyann F. WIRTH, Harvard School of PublicHealth, Boston, MA, USA • Ayoade M. ODUOLA, Special Programme for

Research & Training in Tropical Diseases(TDR), World Health Organization(WHO), Geneva, Switzerland.

Poster Session BSpatial analysis of spill-over effectsof insecticide-treated materials in a cluster-randomized trial againstAedes aegypti mosquitoes in Trujillo, VenezuelaNeal ALEXANDER, London School ofHygiene and Tropical Medicine, London,UK • Audrey LENHART, LiverpoolSchool of Tropical Medicine, Liverpool,UK • Elci VILLEGAS, Universidad de losAndes, Trujillo, Venezuela • MichaelLEVY, Emory University, Atlanta, GA,USA • Rana MOYEED, University of Plymouth, Plymouth, UK • AxelKROEGER, Special Programme forResearch & Training in Tropical Diseases(TDR), World Health Organization(WHO), Geneva, Switzerland; P. J.MCCALL, Liverpool School of TropicalMedicine, Liverpool, UK.

WHO/TDR at ASTMH (continued)



characterization of different q1 chromosomalforms of Anopheles fluviatilis. US$ 12 000

Renewed grants

A50363Christopher Bosio • Colorado State University,Department of Microbiology, Immunology andPathology, Fort Collins, Colorado, USA.Population genetics and vector competencefor dengue-2 virus of Aedes aegypti in Senegal.US$ 27 200

A50241George K. Christophides • Imperial CollegeLondon, London, UK. Effects of the Anophelesgambiae immune system on the transmission ofhuman malaria parasite Plasmodium falciparum.US$ 39 998

A50299Gabriella Irene Gibson • University of Green-wich, Natural Resources Institute, ChathamKent, UK. Field & laboratory investigation ofswarming and mating activities in the Anophelesgambiae species complex. US$ 40 000

A30328Elena A. Levashina • Institute of Molecular and Cellular Biology of CNRS, StrasbourgCedex, France. Recognition and signaling duringPlasmodium infection in the mosquito Anophelesgambiae. US$ 15 000

A50232Yvonne-Marie Linton • The Natural HistoryMuseum, Department of Entomology, London,UK. Molecular systematics and vector incrimination of the Oswaldoi group (Anophelesnyssorhynchus) in Latin America. US$ 39 800

A30346Thanasis Loukeris • Institute of Molecular Biology and Biotechnology, Foundation ofResearch and Technology-Hellas (FORTH), Heraklion, Crete, Greece. A study of Anophelesand Plasmodium proteases focusing onookinete/midgut interactions. US$ 24 250

A50256Jesus Martinez Barnetche • Instituto Nacionalde Salud Publica, Cuernavaca, Morelos, Mexico.Functional genomics analysis of Anopheles albi-manus immune response to infection with bacteria and Plasmodium vivax. US$ 40 000

A50303Mario Silva-Neto • Universidade Federal doRio de Janeiro, Instituto de Biofisica, Rio deJaneiro, Brazil. Phosphoproteome of malaria-infected mosquito midgut. US$ 9 500

A50340Kenneth D. Vernick • University of Minnesota,Center for Microbial and Plant Genomics, St. Paul, Minnesota, USA. Breeding and analysisof new malaria resistant lines of Anopheles gambi-ae. US$ 38 359

Research in pathogenesisand applied genomics

New grants These grants will be funded for 1 year only.

A60193Christine Clayton • Universitat Heidelberg,Germany. Proteomics and phage display forsleeping sickness diagnosis. US$ 35 000

A50314Malcolm Jones • Queensland Institute of Medical Research, Australia. A hidden antigenapproach to schistosomiasis vaccination. US$ 26 500

A60186Krister Kristensson • Karolinska Institute,Sweden. Genetic profiling in African trypanoso-miasis to determine the stage of neuroinvasionof the parasite. US$ 35 000

A60246Mariano Jorge Levin • Instituto de Investiga-ciones en Ingenieria Genetic y Biología Molecular, Argentina. Molecular immunology of protozoan infections. US$ 5 000

A60281Marcela de Freitas Lopes • Federal Universityof Rio de Janeiro, Brazil. Immunomodulation in Chagas disease and leishmaniasis: crosstalkbetween cell death signalling and cytokineresponses. US$ 25 400

A60291Paulo Pimenta • Centro de pesquisas ReneRachou - FIOCRUZ, Brazil. Vector saliva effecton the development of cutaneous leishmaniasisconsidering wild-caught and colonized sandflies.US$ 28 600

A60194Michal Shapira • Ben-Gurion University of Negev, Israel. The cap-binding complex of leishmaniasis as a novel drug target. US$ 30 000

A60314Chairat Uthaipibull • National Center forGenetic Engineering and Biotechnology, Thailand. Identification of antifolate resistantmutations on Plasmodium falciparum DHFR usingPlasmodium surrogate model. US$ 24 000

A60244Cristiana Valle • Institute of Cell Biology, Italy.The calcium channel hypothesis for the mecha-nism of action of Praziquantel. US$ 33 250

New south-south collaboration grants These multicenter grants will be funded for one year only.

A60265Marcus Oliveira • Federal University of Rio de Janeiro, Brazil. Hemozoin formation as a potential taget for chemotherapy of schistosomiasis. Pending finalization.

A60251Guilherme Correa de Oliveira • Centro de pesquisas Rene Rachou - FIOCRUZ, Brazil.Population genetics of schistosoma species inendemic areas of Brazil and Nigeria. US$ 40 000

Renewed grants

A50312Walderez Dutra • Universidade Federal deMinas Gerais, Brazil. Mechanistic analysis of therole of CD28+ and CD28-cells in human Chagasdisease: towards the understanding of pathologyUS$ 27 000

A40204Zahra Hasan • Aga Khan University, Pakistan.Chemokines as immunopathological markers in tuberculosis infections - pulmonary and extra-pulmonary. US$ 30 000

A40278Maria Susana Leguizamon • UniversidadNacional de General San Martin, Argentina.Differential expression of virulence factors andhuman infection by the main parasite lineales of Trypanosoma cruzi. US$ 20 000

A50354Daniel Masiga • Kenyatta University, Depart-ment of Biochemistry, Kenya. The developmentand improved production of a diagnostic forHuman African Trypanosomiasis. Pending reporton site visit.

A50230Anuja Mathew • University of MassachusettsMedical School, USA. Humanized SCID mice fordengue infection and immunity. US$ 35 000

A50304Leila Mendonca-Lima • Fundacão OswaldoCruz Bioquimica e Biología Molécula, Brazil.Mycobacterium bovis BCG moreau RJ: functionalgenomic studies applied to the improvement ofvaccine production. US$ 25 000

A50252Laura Ines Rutitzky • Tufts University, Department of Pathology, USA. Glycan residueson the Sm-p40 schistosome egg antigen: characterization and role in T cell response.US$ 34 500

A50098Sumalee Kamchonwongpaisan • NationalCenter for Genetic Engineering and Biotechnol-ogy, Bangkok, Thailand. Applications of transfec-tion technology for drug screening and immuno-logical studies in tropical parasitic diseases. US$ 19 150

Renewed grants in south-south collaboration

A50337Christian Happi • University of Ibadan, Collegeof Medicine, Ibadan, Nigeria. Molecular determinants of drug response and resistance in P. falciparum from Africa and South-Africa.US$ 50 000

A50271Mariano Jorge Levin • Instituto de Investiga-ciones en Ingenieria Genetic y Biología Molecu-lar, Argentina. Specific molecular mechanisms astarget of novel anti-parasitic drugs - pendingreport on site visit to partner lab in Kenya.



Research CapabilityStrengthening Programme grants

New grants

A50881Yewhalaw Delenesaw • Jimma University,Ethiopia. Malaria incidence and transmissionamong children near hydroelectric dam: baselinestudy to malaria control program. US$ 51 850

A51001Sambo Guemgo • Centre de Support en SantéInternationale de l'Institut Tropical Suisse auTchad. La tuberculose chez les chameliersnomades au Chari-Baguirmi/Tchad: prévalenceet facteurs de risque. US$ 44 380

A50845Stafford Nikulamba Kibona • National Institutefor Medical Research, Tabora Research Centre,Tanzania. Drug sensitivity of T.b. rhodesienseisolates and the role of domestic animals in epidemiology of HAT in Tanzania. US$ 35 000

Renewed grants

A20785Laura Arcos • Pontificia Universidad Católicadel Ecuador, Ecuador. Institutional capabilitystrengthening in tropical disease research andtraining at Catholic University, Quito, EcuadorUS$ 46 200

A20766Vinod Joshi • Desert Medicine Research Centre, India. Studies on dengue and denguehaemorrhagic fever in Rajasthan, India. US$ 17 100

A41486Grace Adira Murilla • TrypanosomiasisResearch Centre, Kenya Agricultural ResearchInstitute, Kenya. Capacity strengthening for try-panosomiasis research and control. US$ 50 000

A30930Nebie Issa • Centre National de Recherche etde Formation sur le Paludisme, Burkina Faso.Etude de l'activité antipaludique des plantes util-isées en médecine traditionnelle dans une régionhumide du BFA. US$ 41 900

A41490Omran Fadl Osman • University of Khartoum,Faculty of Science, Sudan. Transmission of vis-ceral leishmaniasis in eastern Sudan: studies onreservoir hosts and vectors. US$ 43 000

A41430Jean-Bosco Ouedraogo • Institut de Rechercheen Sciences de la Santé, Burkina Faso. Improve-ments of indirect haemagglutination assay as sustainable tools for schistosomiasis diagnosisand control. US$ 56 070

A30931Sadri A. Said • Institute of Marine Sciences,Tanzania. Discovery of new antimalarial drugsfrom marine invertebrates. US$ 46 000

Re-entry grants

New grants

A50904Collins Stephen Ahorlu • Noguchi MemorialInstitute for Medical Research, Ghana. Commu-nity intervention to reduce malaria-related morbidity and mortality in the Shime sub-districtin Ghana. US$ 16 700

A50839Luciana de Oliveira Andrade • UniversidadFederal de Minas Gerais, Instituto de CienciasBiologicas, Brazil. Study of the mechanism of T. cruzi entry and development in non-phagocytic cells. US$ 26 500

A50993Daniella Bartholomeu • Universidad Federalde Minas Gerais, Instituto de Ciencias Biologi-cas, Brazil. MASP gene family of Trypanosomacruzi: from in silico to wet-bench characteriza-tion. US$ 12 974

A50967Alia Benkahla • Institut Pasteur de Tunis,Tunisie. Global analysis of leishmania genesexpression using SAGE libraries. US$ 8 000

A50984Mawuli Dzodzomenyo • University of GhanaSchool of Public Health, Ghana. Inducible nitricoxide synthase 2 promoter polymorphism andmalarial disease severity in children in SouthernGhana. US$ 14 000

A50990Ana Lineth Garcia Orellana • UniversidadMayor de San Simon Facultad de Medicina,Bolivia. Peridomestic cutaneous leishmaniasistransmission in Cochabamba, Bolivia: evidence & implications for disease prevention/control.US$ 21 100

A50892Jonathan Kayondo • Uganda Virus ResearchInstitute, Uganda. Genetic structure, host seek-ing & feeding preferences in the main Anophelesgambiae malaria vectors across Uganda. US$ 21 225

A50987Guillermo R. Labadie • Instituto de QuímicaOrgánica de Síntesis, Argentina. Ergosterolbiosynthesis as target of antiparasitic agents.US$ 13 500

A50879Themba Mzilahowa • Malawi-Liverpool-Wellcome Trust Clinical Research ProgrammeMalaria vector breeding sites and assessing theirimpact on local malaria risk. US$ 16 410

A51005Ana Acacia Pinheiro • Universidad Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Brazil. Molecular mechanisms triggered by P. falciparum derived GPIs in cells of innate immune system: involvement of TLRsUS$ 19 000

A50982Hakim Sendagire • Makerere UniversityDepartment of Biochemistry, Uganda. Efficacy ofartemether-lumefantrine therapy & assessmentof possible molecular markers of resistance inUganda. US$ 18 350

A50880Rodrigo Pedro P. Soares • Centro de PesquisasRené Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Brazil. Role of L. chagasi & L. braziliensisLPGs & GIPLs in the innate immune response inmurine neutrophils & macrophages.US$ 18 500

Renewed grants

A41481Josiane Desiree Etang • Organisation de Coordination pour la Lutte contre les Endémiesen Afrique, Cameroun. Kdr-based insecticideresistance in Anopheles gambiae s.s. fromCameroon: origin, spread and levels of resis-tance. US$ 16 350

A41413Wamdaogo Moussa Guelbeogo • CentreNational de Recherche et de Formation sur le Paludisme, Burkina Faso. Génétiqueécologique et capacité vectorielle d'Anophelesfunestus au Burkina Faso. US$ 15 000

A41387Mo'Awia Mukhtar Hassan • Tropical MedicineResearch Institute, Sudan. Epidemiological stud-ies on sandflies and transmission of visceralleishmaniasis in Eastern Sudan. US$ 20 200

A30849Moses Lutaakome Joloba • Makerere University,Department of Medical Microbiology, Uganda.Evaluation of various methods for rapid detec-tion of multi-drug resistant tuberculosis. US$ 13 300

A41418Marcelo Tàvora Mira • Pontificia UniversidadCatólica del Ecuador, Ecuador. A study of hostgenetic risk factors for leprosy susceptibility.US$ 16 560

A41329Neelima Mondal • Jawaharlal Nehru University,India. Functional characterization of gyraseenzyme from Plasmodium falciparum. US$ 17 450

A41399Rintis Noviyanti • The Eijkman Institute forMolecular Biology, Indonesia. Molecular mechanisms of Plasmodium falciparum infection in severe malaria and pregnancy-associatedmalaria in Indonesia. US$ 17 500

A30848Clara Beatriz Ocampo Duran • Centro Inter-nacional de Entrenamiento e InvestigacionesMédicas, Colombia. Differential gene expressionin dengue-2 infected & non-infected midguts ofsusceptible & refractory strains of A. aegypti.US$ 13 000

A41403Lyda Elena Osorio • Centro Internacional deEntrenamiento e Investigaciones Médicas,Colombia. Population genetics of drug resistantP. falciparum in Colombia. US$ 18 000

A30891Edith Sanogo • Centre National de Rechercheet de Formation sur le Paludisme, Burkina Faso.Résistance des vecteurs du paludisme aux insec-ticides au Burkina Faso: mécanismes impliquéset facteurs favorisants. US$ 15 050

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Research training grantsA60114James Akazili • Ghana • M • PhDHealth sector reforms and its implications onequity, efficiency and quality of care (malaria).

A60157Hampate Ba • Mauritania • M • PhDContribution a l'étude d'An. gambiae s.l.et de la dynamique de transmission du paludisme, en bordure du Sahara Mauritanien.

A60158Nana Kwadwzo Biritwum • Ghana • M • PhDThe epidemiology and control of Lymphaticfilariasis in four districts in Ghana.

A60156Chhordaphea Chhea • Cambodia • F • PhDBehaviour changed communication and community participation in Tuberculosis controlin Cambodia.

A60118Jean Rousseau Djouaka • Benin • M • PhDAnalysis of behavioural & molecular changesinduced by petroleum products in Anophelesspecies with focus on changes.

A60168Sabelo Vusi Dlamini • Swaziland • M • PhDIn vitro analysis of effects of artemether-lumefantrine combination treatment on parasitesurvival & transmission of Pf.

A60120Ntoeila Mustafa Khalid • Sudan • F • PhDA study on the Taxonomy and molecular diver-sity of the subgenus phlebotomus phlebotmoussandfly species in Sudan.

A60122Pharath Lim • Cambodia • F • PhDMulti-drug resistance genes in Plasmodium falciparum in Cambodia.

A60170Abdelrafie Makhawi • Sudan • M • PhDVectoral capacity and molecular characterizationof malaria vectors in Eastern Sudan.

A60124Joao Soares Martins • Timor-Leste • M • PhDTo assess effectiveness of redeveloping malariacontrol program in Timor Leste.

A60125Nicholas Midzi • Zimbabwe • M • PhDDistribution of mixed infection from Pf, schisto& soil transmitted helminths in primary schoolsaged children.

A60133Clarisse Yafi Njua• Cameroon • F • PhDThe impact of intermittent preventive treatmentin pregnancy on maternal naturally acquired &transplacental immunity.

A60137Diana Iris S. Quelhas • Mozambique • F • PhDIntermittent preventive treatment in infants.

A60159Jane Jemeli Rutto • Kenya • F • PhDAssessment of the impact of land use & landcover on the epidemiology of sleeping sickness.

A60148Salazar Anita Villacis • Ecuador • F • PhDPhenotypic variation of Rhodnius ecuadoriensispopulations from Loja & Manabi provinces usingantennal sensilla patterns.

Social, Economic andBehavioural Research(SEB)

New grants

A60307Dr Peter Agyei-Baffour • Kwame NkrumahUniversity of Science & Technology, Kumasi,Ghana. Efficiency morphology of institutionalarrangements and their implications for improving contracts structuring in Malaria. US$ 34 820

A60450 Dr Duane Blaauw • Centre for Health Policy,School of Public Health, Witwatersrand Univer-sity, Johannesburg, South Africa. The efficiencyof institutional arrangements for tuberculosiscontrol in South Africa. US$ 41 000

A60192Dr Andrea Gazzinelli • Universidade Federalde Minas Gerais, Belo Horizonte, Brazil.Access to and utilization of schistosomiasischemotherapy and information in a rural andurban area in Brazil. US$ 40 000

A60334Dr Jessica Jitta • Child Health and DevelopmentCenter, Makerere University, Kampala, Uganda.Major factors affecting children's decision-mak-ing in response to infectious diseases in conflictareas in Uganda. US$ 10 000

A60449Dr Hamilton Moura Ferreira Junior • Institu-to de Saude Coletiva, Universidade Federal da Bahia, Salvador, Brazil. Institutional arrange-ments and efficiency of the tuberculosis controlprogram in the decentralization context inBrazil. US$ 37 700

A60451Dr Frank Kwadjo Nyonator • Ghana HealthService, Accra, Ghana. Migration of mid-levelhealth workers in disease control activities inthe Volta Region of Ghana. US$ 32 295

A60346Dr Loveday Anna Penn-Kekana • Centre forHealth Policy, University of the Witwatersrand,Braamfontien, South Africa. Exploring the inter-actions between foreign-trained doctors andmalaria control and treatment programmes inSouth Africa. US$ 39 300

A60152Dr Qiang Zhenhua • School of Humanities and Law, University of Science and Technology,Beijing, China. Access barriers for temporaryconstruction workers to TB care in China.US$ 26 200

A60331Dr Rajendra Surenthirakumaran • Universityof Jaffna, Jaffna, Sri Lanka. Infectious disease andhealth: the experience of children affected byconflict in Jaffna, Sri Lanka. US$ 14 485

Renewed grants

A40299 Dr Paul Wako M. Bukuluki • Makerere Univer-sity, Kampala, Uganda. Health seeking patternsof families with under-five children for malariatreatment in conflict areas: a case of Gulu district. US$ 16 090

A40300Dr Pablo Kreimer • Facultad Latinoamericanade Ciencias Sociales, Buenos Aires, ArgentinaGlobal dynamics, periphery & social actors: thelimits to development and access to diagnosisand treatment of Chagas Disease. US$ 16 400

A40153Dr Mariana Romero • Centro de Estudios de Estado y Sociedad (CEDES), Buenos Aires,Argentina. Decentralization policies and health system reform in Argentina: its impact on Chagas vector prevention and control. US$ 14 312

A50384Dr Susilowati Tana • Center for Health Policy and Social Studies, Yogyakarta, IndonesiaUnderstanding factors contributing to theresiliency of Aceh health workforce. US$ 64 458

A40099Dr Shaokang Zhan • Fudan University, Shanghai,China. Globalization and TB in migrant popula-tions in China. US$ 19 750

A30298Dr Xiao-Nong Zhou • National Institute of Parasitic Diseases, Shanghai, China. Biosocial &environmental risks related to disease burden of schistosomiasis in the Yangtze River Basin,China. US$ 32 200

A reader notesThe picture on page 12 of TDRnews No. 76was mistakenly identified as the photo ofProfessor Awa Marie Coll Seck. In fact, it is the photo of Dr Dorothy Djeuma, rector of the University of Yaounde I, Cameroon.TDRnews apologizes for any error.

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HOW TO OBTAIN

TDR PUBLICATIONS:

All TDR publications

can be downloaded

from the TDR website:

www.who.int/

tdr/publications

or are available

free of charge from:

TDR Communications

World Health

Organization

20, Avenue Appia

1211 Geneva 27

SWITZERLAND

Fax: (+41) 22 791-4854

[email protected]

Publications

• Diagnostics for tuberculosis: global demandand market potential206 pp., 2006 (ISBN 978 92 4 1563307)

A significant untapped global market exists for moreeffective and affordable tests to diagnose tubercu-losis in countries where the disease is most preva-lent. This report by WHO/ TDR and the Founda-tion for Innovative New Diagnostics (FIND) is thefirst time an international network of researchersand policy experts has made a comprehensivereview of the TB diagnostics market; it calls forgreater industry investment in diagnostics tar-geted to low and middle income countries.

• Diagnostics evaluation series No.1Laboratory-based evaluation of rapidsyphilis diagnostics Results from 8 SDI Sites, 40 pp., 2003(TDR/SDI/DE/03.1) reprint

This is the first in a series of laboratory-based eval-uations assessing rapid syphilis tests and identifyingcandidates for further evaluations in field settings.Six rapid treponemal tests were evaluated in eightSDI laboratory sites. All showed reasonable relia-bility and were considered easy to use. Four testshave been selected for further evaluations of testperformance and utility in field settings.

• Social, economic and behavioural (SEB) research,report series No. 3Gender and tuberculosis: cross-site analysisand implications of a multi-country study inBangladesh, India, Malawi and Colombia 97 pp., 2006 (TDR/SDR/SB/RP/06.1)

More than half a million women annually die fromTB, and gender-related barriers to TB-related con-trol and treatment persist. The findings of thismulti-country study suggest specific strategies forimproving TB control through gender-sensitive andlocally appropriate community action, clinic opera-tions, programme monitoring and action-orientedresearch for TB control.

• Multicountry study of Aedes aegypti pupalproductivity survey methodology - findingsand recommendations 56 pp., 2006 (TDR/IRM/DEN/06.1)

Dengue fever is a fast-growing public health prob-lem worldwide. Reducing vector populations indomestic and peri-domestic water containers is

the main strategy used toreduce transmission. TDRfinanced a multicountrystudy involving nine LatinAmerican, Asian, andAfrican countries to evalu-ate a new pupal demo-graphic survey method,and determine whether itcan consistently identifyand classify categories ofcontainers where thedengue vector, Aedes aegypti (L.), breed most pro-ductively, providing a reference base and guidancefor targeted control strategies.

• The use of rapid syphilis tests 28 pp., 2006 (TDR/SDI/06.1)

Syphilis is a curableinfection caused by abacterium, Treponemapallidum. Yet syphilisinfection often is notdiagnosed and treated,and along with beingtransmitted sexually, itcan be passed from moth-er to fetus in pregnancy,leading to stillbirth, prematurity, and neonataldeath. As a cause of genital ulcers, syphilis also hasbeen associated with an increased risk of HIVtransmission and acquisition. This bookletdescribes the use of rapid syphilis tests importantto early detection and treatment. In press butavailable on: www.who.int/tdr/publications/publi-cations/rapid_syphilis.htm

• Recherche concernant les maladies tropi-cales: progrès de la recherche 2003-200498 pp., 2005 (TDR/GEN/05.1)

Now available in French: the 17th ProgrammeReport of the Special Programme for Research &Training in Tropical Diseases (TDR). The reportdescribes in detail the main projects and achieve-ments of TDR during the 2003-2004 biennium.

Now available from TDR



www.who.int/tdr/publications

• Quality informationin field research: training manual onpractical communica-tion skills for fieldresearchers and project personnel134 pp., 2005(TDR/IRM/PCT/05.1)

This manual is the outcome of a training process developedat the Kenyan Medical Research Institute (KEMRI)-Well-come Trust Collaborative Research Programme in Kilifi, Kenya, a centre for multidisciplinary research focusingon prevention and treatment of severe childhood malaria.The aim of the training was to build upon the communica-tion skills of the field workers collecting the data, and thusimprove the quality of the information they gathered.

• TDR summary report 2004-2005 16 pp., 2006 (TDR/GEN/06.4)

Available in English, Arabic, French, Spanish and Portuguese.The report covers achievements of the 2004-2005 bienni-um and aims for 2006-07. Key activities covered include:visceral leishmaniasis elimination, halting congenital syphilis;treatment safety for river blind-ness; and ethical guidelines for clini-cal research. There is also a briefreview of: new knowledge genera-tion; new and improved tools andstrategies; and capacity building.Also addressed are TDR's struc-tures of governance, partnerships,financial contributions, key publica-tions and strategic performanceindicators.

• Evaluating diagnostics: the malaria guideNature Reviews Supplement: MicrobiologyVol. 4, No. 9, September, 2006

Effective, quality-assured diagnostics are important forpatient management and disease control. This supplement,produced in a collaboration between TDR, the WHORegional Office for the Western Pacific region (WPRO) andNature Publishing Group, is the first in a series of user-friendly operation guides explaining how to design and con-duct evaluations of diagnostic tests for infectious diseasesthat are of public health importance to developing coun-tries. Available free on the TDR website and at:www.nature.com/nrmicro/supplements/index.html

• Evaluating diagnostics: the STI guideNature Reviews Supplement: MicrobiologyVol 4, No. 12, December, 2006

This second supplement inthe new Nature Reviews sup-plement series on diagnos-tics evaluation focuses ondiagnostics for the bacterialsexually transmitted infec-tions: syphilis, chlamydia and gonorrhoea. Takentogether, these are respon-sible for an enormous burden of morbidity andmortality, particularly inwomen in developing coun-tries. Available free on the TDR website and at: www.nature.com/nrmicro/supplements/index.html

• CD-ROM – Bioethics and research ethics: academic and extension programmes. 2006. In Spanish and Portuguese

This tutorial CD-ROM is the product of a pioneering initiative developed by the University of Brasilia, in partner-ship with Anis – Institute of Bioethics, Human Rights andGender and the Latin American Forum of Research EthicsCommittees in Health – FLACEIS. The initiative is supportedby WHO/TDR, the Ministry of Health of Brazil andUNESCO. The CD-ROM provides academic programmeson research ethics for undergraduate and graduate studentsand the public-at-large, including lecture plans, cases studies, discussion questions; reference and regulatory background;slides; and bibliography. Available free at: www.nature.com/nrmicro/supplementsFor CD-ROM copies contact: Prof Dirce Guilhem, Universidad de Brasilia, at [email protected]

In collaboration with others

• Control of human parasitic diseasesAdvances in Parasitology, Volume 61, 2006 (ISBN: 0-12-031761-3)

A state-of-the-art source on parasitic disease control, thisvolume covers latest developments in methods for controlof eleven parasitic infections, including all the parasitic dis-eases that TDR addresses. The impact of recent researchfindings on control strategy, and the health policy implica-tions of these findings, are emphasized, as are controlstrategies of extremely low cost and high efficacy – many of which currently fail to reach the poorest populationsmost afflicted by these parasites. Price: US$ 169.95. To order see: http://www.books.elsevier.com

Publications available from elsewhere


D E A D L I N E S

Call for courses/applications

• Implementation research on drug delivery strategies for 28 February 2007lymphatic filariasis elimination in urban areas in Africa

• Implementation research on validation of 28 February 2007improved dengue clinical guidelines

• Cours de spécialisation en immunologie, vaccinologie et biotechnologie appliquées aux maladies infectieuses 23 mars 2007

• Advanced course on immunology, vaccinology and biotechnology applied to infectious diseases 27 April 2007

• 10th International Dengue course: 20 years strengthening capacities May 2007

In addition, grant applications and research proposals relevant to TDR's scientific work plansare reviewed by TDR Steering Committees at their regular meetings. To guarantee review, docu-ments should be received by TDR in Geneva at least two months before the meeting date.For more information see: www.who.int/tdr/grants


30 years of TDR activitiesWe are celebrating the 30th anniversary of the establishment of TDR's Joint Coordinating Board(JCB). If you have any stories about TDR-supported research that made a difference to public healthand to TDR history, please send us your contributions for consideration in special anniversary weband print publications. The stories should be 500 words or less and clearly describe 1) the TDR link2) the work or personality in question and 3) the broader relevance to public health and tropicaldisease research in the setting of a particular community, a country, a region or globally. We apolo-gize that we cannot individually acknowledge every contribution. E-mail: [email protected]

Establishing the effectiveness of community-directeddistribution of ivermectin to control onchocerciasis(river blindness) – one of many TDR successes.

Global health research activities atthe Wellcome Trust: support for developingcountry researchers

Fellowships and programmesin Public Health and Tropical Medicine are nowbeing offered, targeted toresearchers from developingcountries at various profes-sional and career stages,and including: - Master's- Training- Intermediate and - Senior Fellowships.

For details see: www.wellcome.ac.uk/international

TDRWorld Health Organization

Avenue Appia 201211 Geneva 27

SwitzerlandTel: (+41) 22-791-3725Fax: (+41) 22-791-4854

E-mail: [email protected]: www.who.int/tdr

TDR is sponsored by:

UNICEFUNDP

World BankWHO

Photo: WHO/TDR/Crump


Documents

70034 PL 70034 OMS - WHO6 Global market report calls for TB diagnostics investment 8 Mobilizing research to halt dengue’s growth 12 Reducing infant deaths due to malaria 17 IVM for