No. 84 - D e c e m b e r 2 0 0 9

TB or not TB? The latest in TDR’s research from diagnosis to disease treatment | PAGE 14

Also in this issue M e et i n g s 32 • Quality management PAGE ar4 Rese ch briefs • New tools for VL elimination 4 7 TDRbriefly 33 • Community-based interventions 11 Stewardship 34 • Strategic alliances Targeting 22 MIM Pan-African conference 35 • Empowerment visceral 24 ANDI leishmaniasis 25 Global Health Histories • Diagnostics 28 Artemisinin’s discovery 36 • Tropical medicine conventions eradication 30 World of TropIKA.net 37 Publications Editor’s corner

The meaning of meetings

Take the interview by one of the Chinese scientists pagepage hen I set off 244 for Dar es Salaam who was a leader in the international development to write about TDR of the first artemisinin combination therapy, the research into earlier fastest-acting antimalarial available today. initiation of anti-retroviral In an interview on page 28, Professor Zhou Yiqing re- therapy in HIV-positive TB pa- counts how a TDR-organized 1981 meeting in Beijing tients, I had no idea that I would was the turning point that introduced artemisinin be spending so much of my time in the tropics in an to the world. over-air-conditioned hotel conference room. From there, the rest is history. But along with field visits to hospitals, laboratories and clinics, our group of clinical trial team members In 2009 and 2010, TDR’s Stewardship function is convening meetings all over the world to take a fresh page28 from four countries also sat for several days in a 28 darkened room exhaustively reviewing slide presen- look at target diseases and thematic issues with tations. The team analysed in painstaking detail the critical relevance to control of infectious diseases Communications critical steps related to good clinical practice (GCP) most prevalent in poor countries (see article, page 11). manager Jamie Guth and good clinical laboratory practices (GCLP) that This series of meetings adds another dimension to are essential to any clinical trial. Managing editor the discussion of research gaps and priorities. Elaine Fletcher While meetings in some instances can be perceived On the eve of each meeting of these “disease and Contributing writers as bureaucratic encumbrances, in fact they have im- thematic reference groups”, an even wider range of Julie Reza, portant consequences, and can shape what happens stakeholders gathers. Representatives of govern- scientific editor in health research and hospital services. ment, NGOs, the private sector and academia Patrick Adams, meet with the expert group to share knowledge reporter While the glamour of research may be associated page and views about the diseases or themes being Design and 31 with huddling over a microscope or a field sample of examined. coordination insect vectors, meetings are important too. They are LisaCommunications Schwarb manager essential for training and improving field services There, history is yet to be written. Perhaps the JamieLayout Guth and procedures, as well as for sharing knowledge next artemisinin will emerge from one of those Simon Fenwick Managing editor and discoveries among expert peers. meetings. ElaineProduction Fletcher team Patricia Codyre, webDesign editor PelthiaLisa Schwarb Makgatho, Layoutadministration CopySimon editor Fenwick ProductionVallaurie Crawford team Pelthia Makgatho Elaine Ruth Fletcher Ali Bhanpuri Cover photo: Managing Editor, TDRnews TB(intern) diagnostic samples Copyawait analysiseditor at VallaurieMuhimbili CrawfordNational Hospital Laboratory Coverin United photo: Republic of ATanzania. rapid malaria Photo credit: diagnosticMuhidin Issa in MichuziAfrica. CoverCredit: Foundationbox photo: TDR’sfor Innovative Soumya New SwaminathanDiagnostics. in Goanpura village, Bihar, India, as part of a joint TDR-Indian health services exploration of research initiatives to support VL elimination. Photo credit: Greg Matlashewski Letter from TDR’s director No. 84

Innovation in action

Innovation is the first time that you put a new idea Meanwhile, innovation in health into practice – that was a theme sounded in the systems and in access to health service recent Global Forum for Health Research meeting delivery are other topics receiving in- Forum 2009 in Havana, Cuba. creasing focus within WHO and among donor agencies. The term innovation typically conjures up im- ages of new tools, new products and new patents. Major donors such as the GAVI However, our understanding of the concept as it Alliance (Global Alliance for Vaccines applies to global health has become much more and Immunisation) and the Global broad in recent years. Fund to fight AIDS, Tuberculosis and Malaria are examining how they In fact, there can be many different facets of might direct new resources into innovation. health systems strengthening. As our cover story reflects, TDR has been on the cut- ting edge of efforts to develop and assess new forms Here too, TDR is involved. We are work- of TB diagnosis and treatment. Some of these involve ing with others in WHO to organize new tools, such as the use of light-emitting diode the first Global Symposium on Health (LED) microscopes in TB diagnosis. Some efforts test Systems Research, 16-19 November 2011 3 strategies for the improved use of existing tools – for in Montreux, Switzerland. instance, the earlier initiation of ARV therapy for HIV- In the widening discussion around innovation, the positive TB patients. competition can at times become intense between Innovative institutional networks and groupings can diverse groups pitching for innovative new tools; also be part of the innovation drive. Over the past approaches to networking and knowledge manage- year, TDR has been involved in the development of ment; and investments in health systems innovation. a new African Network on Drugs and Diagnostics In TDR’s view, the entire continuum of innovation is Innovation (ANDI), which held its second stakehold- important and should be viewed holistically. Those ers’ meeting on 4-7 October in Cape Town, South actors concerned with R&D and those concerned Africa. Inspired by ANDI, a new China Network on with health systems and access are working Drugs and Diagnostics Innovation (China-NDI) held together towards a mutual goal – the elimination its initial meeting, 24-25 October, in Shanghai. of diseases of poverty and the improved welfare of These are both important contributions to the Global people globally. Strategy on Public Health, Innovation and Intellectual Property approved at the World Health Assembly in 2008.

Dr Robert Ridley TDR Director No. 84

Research briefs

• New TB smear diagnostic procedures on the horizon • Shorter, easier visceral leishmaniasis treatment shows promise • Vector control can play critical role in visceral leishmaniasis elimination • Researchers uncover DNA blueprint of Schistosoma mansoni • TDR initiates model public health PhD programmes

TB DIAGNOSIS becoming popular in developing country VISCERAL LEISHMANIASIS settings. Expert review, as well as More rapid and accurate controlled trials, indicates that the LED Shorter, easier treatment smear microscopy microscopes make the analysis of TB shows promise in India smears faster and easier. New techniques to make diagnosis of For nearly a century, the standard TB much faster and easier in developing The Scientific and Technical Advisory treatment for visceral leishmaniasis (VL), countries have shown good results in Group of WHO’s STOP TB Department or kala azar, has been a painful 30-day TDR-supported trials, and are likely to reviewed experiences with both course of intramuscular injections with be endorsed soon by WHO. front-loading and LED fluorescence sodium stibogluconate. In addition to the prolonged regimen, the treatment One procedure is a new “front-loading” microscopy in a November meeting 4 and will issue findings shortly. Nearly is associated with serious side effects smear sampling technique that would including pancreatitis, myalgia (muscle half of suspected TB patients do not get permit same-day TB smear diagnosis pain) and cardiac failure. with two sputum smear samples. a confirmed TB diagnosis currently. A Currently, sampling over two or three major factor is the dropout rate of poor Over the past decade, TDR and days is required, imposing a burden patients who cannot afford the travel partners in India successfully brought not only on laboratories but on patients and time off work for repeated clinic to registration a 28-day oral drug, having to make repeated clinic visits. visits. (See TB update, p. 14). miltefosine, for VL. The only existing oral treatment, miltefosine has proven TDR also recently sponsored clinical trials highly effective in both children and of low-cost LED (light-emitting diode) FOR MORE INFO adults. However, at roughly US$ 72 per fluorescent adapters to microscopes. Dr Andy Ramsay: [email protected] treatment, miltefosine is costly. LED fluorescence microscopy is rapidly Now it appears that a shorter, easier and lower-cost treatment for VL may be on the horizon. Preliminary results of a TDR-sponsored clinical trial of Gilead’s AmBisome® (liposomal amphotericin B) followed by 14 days of oral miltefosine

WHO/TDR/Crump treatment are very promising. Publication of final results is expected in 2010.

The trial, led by Banaras Hindu University and Rajendra Memorial Research Institute of Medical Sciences, is being conducted in two sites in India, one in Varanasi and the other in Patna. The latter is the capital of Bihar, where close to 50% of the Indian subcontinent’s VL cases occur.

According to TDR scientist Byron Arana, combining one injection of AmBisome® with the 14-day miltefosine course appears highly effective as a treatment. This regime also improves patient adherence to the therapy, which helps stave off parasite resistance to the new VL drugs. “Patients tend to feel much better after a short time of taking miltefosine – and then they often stop taking the pills. That’s a recipe for resistance,” Arana says, Microscopic examination of a TB specimen at St Peter’s TB Clinic, Addis Ababa, Ethiopia. “and the patient is never cured.” No. 84

and Nepal, while IRS plus the renewed insecticide treatment of bednets in Bangladesh (where bednet coverage exceeds 90 percent in endemic districts) has the best potential there for rapidly reducing insect bites. WHO/TDR/Matlashewski The next stage of studies aims to help national vector control programmes administer IRS spraying of homes more effectively.

“In ideal conditions when our researchers spray, you can say this works well. In real-life situations, the challenges are very different,” observes Examining a patient for VL during a November 2009 joint TDR and Indian VL officers’ visit to villages near Patna, in India’s Bihar region, where the disease is endemic. Axel Kroeger, one of the study’s co- authors and a professor of International Community Health at Liverpool A shorter miltefosine course would be less The study, a cluster randomized control University. “A vector control programme costly and would reduce gastrointestinal trial carried out in villages in Bangladesh, may spend millions of dollars and then side effects often experienced with the India and Nepal, found that all three wind up spraying water on the walls, 28-day oral miltefosine regime. vector control interventions tested had if, for instance, the insecticide is sold very significant impacts on reducing Still, as VL researchers know too well, illegally to farmers. Or spraying may not sandfly vector densities – but IRS spraying no single drug regime is a cure-all for happen because the monsoon comes too either with DDT (in the case of India) or this neglected disease of poverty. Active early or there are elections.” pyrethroids (Nepal and Bangladesh) had case detection efforts as well as improved the most pronounced effect. Along with the health and ecological access to care, disease surveillance, impacts of long-term reliance on IRS integrated vector management and Environmentally-friendly wall plastering particularly with regards to DDT, insects social mobilization all are critical. “There of homes with lime as well as the use of 5 may also develop resistance if it is used are many pieces to the leishmaniasis long-lasting insecticide treated bed nets over a prolonged period. puzzle,” says Arana. “This combination (LLIN) also had very good outcomes. In treatment is a big one. But it’s only one.” sites where the lime had an appropriate “So IRS is always best used in a acidity, the plastering, a traditional campaign period, while a combination FOR MORE INFO practice in festival seasons, had a of measures would always work particularly strong effect in reducing better over the long-term,” Kroeger Dr Byron Arana: [email protected] sandfly densities. concludes.

The study was part of a WHO/TDR implementation research program VISCERAL LEISHMANIASIS FOR MORE INFO designed to support elimination of VL Vector control critical by 2015 on the Indian subcontinent For link to the article see: www.biomedcentral.com/ to VL elimination through integrated vector management. 1741-7015/7/54 Achieving lasting vector control in The authors conclude that IRS should Dr Axel Kroeger: [email protected] poverty-stricken areas, where poor be strengthened immediately in India sanitation and housing facilitate insect breeding, is a goal that has long eluded visceral leishmaniasis (VL) disease control programmes.

In parts of South-East Asia, VL was virtually eliminated with DDT fifty

years ago, only to return once mass Dinesh Mondal/ICDDRB spraying campaigns ended. Indoor residual spraying (IRS) with DDT is still practiced in India while in Bangladesh, vector control is largely reliant on use of bednets.

A TDR-supported study published in October in BMC Medicine illustrates how a renewed vector control effort could potentially make an enormous impact on sandfly vector breeding sites around homes. Effective vector control could thus make a critical contribution to the elimination by 2015 of VL, a disease that affects some 500 000 people on the Indian subcontinent. Impregnating bednets with insecticides in order to prevent VL transmission from sandfly bites. No. 84

Shistosomiasisc the parasite known as a miracidium, which universities. CARTA builds upon past develops from eggs passed in the urine or TDR collaborations within Africa Researchers uncover faeces of infected people. that successfully built master’s-level parasite’s DNA blueprint programmes in epidemiology, health An estimated 400 million people economics and health social sciences. An international research consortium led worldwide are at risk of schistosomiasis These laid the groundwork for the by University of Texas researchers and infection. Because existing drugs don’t doctoral-level programmes. supported over the years by TDR has confer lasting protection, many of those sequenced the genome of Schistosoma people will likely become re-infected. Steven Wayling, the TDR representative mansoni, a parasite that infects some 200 However, for unknown reasons, others on the CARTA consortium, says: “CARTA million people in 76 countries as one of will not. The research team seeks to is an example of how TDR works with the major agents of schistosomiasis. identify the genes responsible for severe other groups with similar objectives to infections in some groups and the raise money for capacity development, As reported in the cover article of Nature’s development of immunity in others. and how TDR leverages its intellectual July 16 edition, the sequencing of resources to benefit a wider audience.” S. mansoni is the largest of any parasite The project is supported in part by to date. Although associated with low the National Institute of Allergy and “TDR will provide technical guidance and mortality, S. mansoni causes severely Infectious Diseases of the USA-based contribute materials central to the training debilitating illness in populations National Institutes of Health, the John programme,” Wayling said. “Each cohort of throughout Africa, the Eastern E Fogarty International Center for students will come together every academic Mediterranean, South-East Asia and Advanced Study in the Health Sciences, year to be trained in skills not always eastern South America, constituting a the Burroughs Wellcome Fund and TDR. taught in formal academic programmes. public health burden second only to This may include grantwriting, publication malaria in terms of parasitic diseases. FOR MORE INFO and negotiating skills.” Berriman M et al, Nature, 2009; see Peer-reviewed publications, p. 39 CARTA is led by Alex Ezeh, executive director of the African Population and Criscione CD et al, Genome Biology; Health Research Centre in Kenya. Sharon 30;10(6):R71. www.ncbi.nlm.nih.gov/ pubmed/19566921 Fonn, dean of the School for Public Health, University of Witwatersrand, South 6 TropIKA.net: www.tropika.net/svc/ Africa, is CARTA’s deputy director. Fonn is news/20090703/Chinnock-200900703- Macmillan Magazine Ltd News-schisto-genome a member of TDR’s Research Strengthening Group and of TDR’s Scientific Advisory Committee for integrated community- AFRICAN INSTITUTIONS INITIATIVE based interventions. TDR improving public health TDR also is involved in a second doctoral programmes consortium being supported by the African Institutions Initiative – the TDR is helping initiate model doctoral Research Institute for Infectious Diseases programmes in Africa in public and of Poverty (IIDP) Consortium, directed by population health in collaboration with Margaret Gyapong in Ghana. a new African Institutions Initiative. The TDR Director Robert Ridley says, “The £30 million programme, funded and According to Phil LoVerde, professor African Institutions Initiative is aligned spearheaded by the Wellcome Trust, is of biochemistry and pathology at the with TDR’s focus on ensuring researchers designed to strengthen health research University of Texas Health Science Center and institutions in disease-endemic capacity on the continent through the at San Antonio and a coauthor of the countries play a pivotal role in shaping creation of seven pan-African consortia. article, the DNA mapping of S. mansoni health research agendas. We are looking A meeting to launch the initiative was provides a window on the genetic forward to contributing to this important held 6-8 October in Arusha, United mechanisms behind schistosome-host new programme.” Republic of Tanzania. interactions. Comprising more than fifty universities FOR MORE INFO “Knowing the organism’s genetic sequence and research institutions from eighteen Dr Alex Ezeh: [email protected] should help researchers develop better African countries as well as partners medication for infections, a diagnostic field Dr Sharon Fonn: outside Africa, the consortia will advance test and even a vaccine,” says LoVerde, [email protected] the development of viable research hubs who co-authored the paper featured at African universities through new in Nature. “It opens a new door for academic programmes, networks and development of better control regimens.” other strategies. Schistosomiasis, also known as bilharzia Members of the seven consortia will or snail fever, often occurs in areas where be responsible for focus areas such

dams and irrigation schemes have been WHO/TDR/Craggs as networking, research capacity constructed for energy or agriculture. strengthening and training while also Snails, S. mansoni’s intermediate host, breed working towards common goals. in these waters and release a larval form of the parasite (known as cercariae) that TDR is a member of the Consortium penetrates human skin, threatening anyone for Advanced Research Training in who enters the water. The snails themselves Africa (CARTA), which plans to develop become infected by another larval stage of doctoral programmes in nine African Dr Margaret Gyapong. No. 84

• Global Forum for Healh • Former TDR grantees Research meets in Cuba recognized for research • EcoSoc ministerial meeting • TDR veterans receive high TDRbriefly • CRIMALDDI initiative spurs honours antimalarial drug R&D • Poverty Related Diseases College opens

supported African Network for Drugs and Diagnostics Innovation (ANDI). n Olivier Asselin For complete Forum 2009 coverage: TropIKA.net at: http:// meeting.tropika.net/cuba2009/ For more on the Global Forum: www.globalforumhealth.org/ TDR contact: Jamie Guth, [email protected]

Focus on global public health: a first for ECOSOC Due to the global economic crisis, 7 some 23 African countries may not meet a single Millennium Forum 2009 assembles in Havana, Cuba. Development Goal, including goals for reducing child mortality and improving Forum 2009: ‘Innovation is Other key speakers to explore maternal health (MDGs 4 & 5) and implementation’ the theme included José Ramón for combating HIV/AIDS, malaria and Balaguer Cabrera and Chen Zhu, other diseases (MDG 6). Invention is coming up with a health ministers of Cuba and China new idea; innovation means respectively. Local polyclinics and Sudan issued that somber warning on implementing it for the first time. research centres also were opened for behalf of the world’s least-developed This was a key message sounded by site visits by meeting attendees. countries (Group of 77) at the annual Carlos Morel, director of the Center United Nations Economic and Social for Technological Development in Cuba is highly regarded for its ability Council (ECOSOC) in Geneva. The Health at Brazil’s Oswaldo Cruz to provide high-quality health care meeting was the first ECOSOC annual Foundation, speaking before the despite poverty and limited access to session to make global health issues Global Forum for Health Research in resources. Cuban authorities use health the leading topic of a high-level Havana, Cuba. research to identify population needs; ministerial review. these are addressed with a network of The Forum 2009 meeting, polyclinics and family doctors at the The global health review, conducted 16-20 November, drew some community level. These policies have over the first four days of the 6-31 July 800 participants from more than meeting, focused on how policy-makers resulted in one of the world’s lowest 70 countries to discuss what might attain international goals and infant mortality rates: 4.7 per innovation means to health research commitments related to the 1948 1000 live births. and how to encourage more of it, “health for all” declaration of the particularly to address diseases of Stephen Matlin made his final speech International Conference on Primary poverty in developing countries. as the Global Forum’s executive Health Care at Alma Ata, in what is now Kazakhstan. “In global health, innovation director at the meeting; he had previously announced his retirement may mean better, cheaper or WHO Director-General Margaret Chan at the year’s end. Anthony Mbewu will more practical products to treat charged that the global economic begin his term as executive director in diseases,” said the chair of the system is failing to address critical January; he has served as South African Forum’s Foundation Council, Gil health issues, and that poorer nations Medical Research Council president and Samuels, in an opening address. Just are bearing the brunt of financial, a visiting professor in cardiology and as important, she stressed, were environmental and health-related crises. better delivery systems to make internal medicine at the University of interventions cost-effective and Cape Town, South Africa. He also serves “Globalization has not turned out to accessible to all. on the Task Force of the new TDR- be the rising tide that lifts all boats. No. 84

Instead, wealth has been created and accessing leprosy treatment than men. make an impact upon the millions spread in waves that lift the bigger TDR-supported scientists also have needlessly dying from this disease boats but swamp or sink many smaller used socioeconomic analysis in field each year. Antimalarial drug research ones,” Chan said in her keynote speech. trials to improve access to health tools and development programmes such as antimalarials and bednets. are in operation across Europe and Neglected tropical diseases, throughout the world, but too often noncommunicable diseases and TDR recently initiated a series of these initiatives are uncoordinated, and maternal health all were discussed as disease and thematic reference time and money are spent going over factors impacting attainment of the groups to examine emerging needs old ground.” MDG goals. in research on neglected diseases. A Global report for research on infectious CRIMALDDI will survey the current Other topics included ways to improve diseases of poverty, planned for 2011, state of antimalarial research across health systems and retain health will synthesize these findings with Europe. A roadmap for antimalarial workers in developing countries, particular reference to health systems, drug discovery efforts there and a inequities in health among and within biotechnology and the environment. n five-year action plan for delivering countries (including gender inequality), on the roadmap will be based on the the importance of technologies in TDR contact: Dr Garry Aslanyan, survey’s findings. An expert advisory improving health outcomes and the [email protected] group will provide external validation role of philanthropy and public-private and ensure that the plans are practical partnerships in global health. and appropriate. CRIMALDDI also will formulate strategies to better ECOSOC brings together ministers CRIMALDDI to coordinate coordinate R&D, to remove barriers and government officials, UN malaria drug search to drug development and to facilitate organizations, non-governmental The European Commission is funding dissemination of results. organizations (NGOs) and others to a two-year, US$ 800 000 project to discuss international economic, social, Ward explains that this streamlining coordinate European and international 8 humanitarian and environmental issues. will improve the use of limited research to develop new malaria drugs. antimalarial funding. “Coordinating “This year’s focus reflected a growing Led by the Liverpool School of Tropical research will mean that resources perception among policy-makers of Medicine (LSTM), the CRIMALDDI are better directed towards faster health’s relevance to sociopolitical project (Coordination, Rationalisation development of drugs to treat and and economic agendas,” said Meinrad and Integration of Antimalarial eliminate malaria. We will look at Studer, TDR external relations Drug Discovery and Development the global status of antimalarial coordinator. Initiatives) brings together key players drug discovery to ensure that the research agenda for antimalarials “Due to the recognition that health in antimalarial drug discovery. These in Europe over the next decade is and sustainable development are include WHO/TDR, the Medicines for properly aligned with what’s going intrinsically linked, health policy-makers Malaria Venture (MMV) and Europe’s on elsewhere in the world.” n are shifting towards a more holistic leading research organizations. approach to health,” Studer observed. LSTM Deputy Director and Professor “Ministries of health must work closely For more info: www.liv.ac.uk/ Steve Ward is CRIMALDDI’s scientific with ministries of finance, food and lstm/about/communications/ coordinator. He explains the project’s agriculture, foreign affairs, environment press_releases/crimalddi.htm mandate thus: “New drugs to prevent, and development. Health NGOs must TDR contact: Dr Solomon Nwaka, treat and eventually eliminate malaria work with development NGOs.” [email protected] are desperately needed if we are to Along with participating in forums such as ECOSOC, TDR engages politicians and policy-makers through a range of other stewardship, strategic STOCKBYTE alliance and advocacy activities.

“TDR is in a position to lead the way on such intersectoral cooperation in light of the fact that its co-sponsors (UNICEF, UNDP, the World Bank and WHO) are key actors in various aspects of development,” Studer said.

TDR has long been a leader in research on socioeconomic aspects of neglected diseases. For instance, socio-economic research has shed light on why women may have greater difficulty in No. 84

Another outstanding scientist, Lizette Koekemoer, has been awarded

WHO/TDR the Southern African Association for the Advancement of Science (S2A3) British Association Medal (Silver) for 2009.

Koekemoer is director of the Vector Control Reference Unit at the National Institute for Communicable Diseases in Johannesburg, where she investigates the molecular basis of insecticide resistance in malaria vector mosquitoes including Anopheles funestus and An. gambiae complex. Her work has Dr Jean Paul Chiron, Secretary General of the National Academy of Pharmacy of France (left), extends demonstrated that the resistance award to Dr Abdoulaye Djimdé (right). In the middle: Dr Djimdé’s wife, Mama Assa Diba-Djimdé. mechanism is metabolic and she has identified two genes that are Past TDR grantees Tunisia, Guizani has made significant unregulated in resistant individuals. contributions to the understanding recognized for research Koekemoer discovered two species of the pathogenesis and population excellence of Anopheles mosquitoes, a rare feat genetics of leishmaniasis at the given the century of in-depth research Abdoulaye Djimdé, a researcher with the molecular level. on the genus. She has introduced Malaria Research and Training Center new technology to vector research, at Mali’s University of Bamako and a Taking a “gene-to-patient” approach, including a multiplex PCR assay to former TDR grantee, was named Best her research has resulted in several identify fiveAn. funestus mosquitoes in 9 Pharmacist in the Francophone World milestones: the development of a Africa. The assay is now the standard by the National Academy of Pharmacy bioinformatic tool kit for in silico method for identification of this group of France in May. Presented during characterization of potential targets; of mosquitoes worldwide. the 62nd World Health Assembly in validation of an antigenic leishmania Geneva, the award recognized Djimdé’s target, LeIF protein; and development As principal investigator on TDR- outstanding contributions to anti- of a prototype diagnosis kit based on funded projects for biological control malarial therapeutics development. DNA chips using targets identified of vectors and MIM/TDR malaria by comparative genomics. Over her Djimdé began his career by researching research, Koekemoer was recognized 20‑year career, Guizani has received herbal medicines traditional healers for “high-quality science, with a sound several TDR grants, served on TDR’s used to treat jaundice in his native Mali. background and straightforward Research Strengthening Committee Several years later, he served as principal analytical methodology.” She also is and published more than 30 peer- investigator on a Multilateral Initiative a member of the TDR Empowerment reviewed articles. She is a founding n on Malaria (MIM)/TDR Antimalarial Research Strengthening Group (RSG). member of the Tunisian Women and Drug Resistance Network in Mali. Science Association and a founder One of the world’s leading experts and African coordinator of the TDR- TDR contact: Dr Glenn Laverack, on the molecular characterization sponsored South-South Initiative for [email protected] of malaria parasite resistance to Tropical Disease Research. antimalarial drugs, Djimdé has published 38 peer-reviewed articles and oversees 12 scientists at the University of Bamako. (see also: www. edctp.org/Announcement. 403+M52f6b37568e.0.html).

Elsewhere in the Francophone world, Tunisian scientist Ikram Guizani, also a former TDR grantee, was awarded a prize for Best Female Scientific Researcher by the President of the Republic of Tunisia in recognition of her contributions to leishmaniasis control.

As head of the Laboratory of Epidemiology and Ecology of Parasitic Dr Ikram Guizani, on right, receives her award for Best Female Scientific Researcher from Leila Ben Disease at the Pasteur Institute of Ali, wife of the President of the Republic of Tunisia. No. 84

Poverty Related Diseases College opens doors

A first-of-its-kind international programme in biomedicine and development has opened at Cameroon’s University of Yaoundé I.

The Poverty Related Diseases College (PRDC) offers students from developed and developing countries an educational curriculum that bridges biological sciences, Dr Adetokunbo Lucas , second from left, at Sussex ceremony. health and development, according to Professor Wilfred Mbacham, a TDR veterans receive Another TDR veteran, CP Ramachandran, former TDR trainee and University of high honors has recently been named professor Yaoundé public health biotechnology emeritus by the University of expert who is coordinating the new Former TDR Director Adetokunbo Lucas Science, Malaysia (USM) in Penang. programme. was awarded an honorary doctor of Ramachandran, a pioneering medicine degree by the University of researcher into lymphatic filariasis The programme is the first such Sussex in the United Kingdom at a (LF), served for ten years as professor initiative to be led by an African ceremony in July. It was the first such and dean of USM’s School of Biological institution under the auspices of the honorary degree in medicine following Sciences, overseeing a period when 7th Framework Program (FP7) of the the university’s establishment of the the school developed into a major European Commission Directorate 10 Brighton and Sussex Medical School. research institution. After joining General for Research, a major European Lucas, a medical doctor and senior TDR in 1975, Ramachandran became Union funding instrument for health policy expert in Nigeria, served as head of the Research Capacity international research. TDR’s second director from 1976-1986, Strengthening Unit. “Effectively, I guiding the new programme at a time became a salesman for TDR,” he The PRDC is targeted at PhD when discoveries in biology, genetics recalls. “In Southeast Asia my name candidates or post-doctoral and immunology transformed medicine. went from ‘CP Ramachandran’ to researchers worldwide. The college’s ‘TDR Ramachandran’.” inaugural class comprises 24 advanced Under Lucas’s leadership, TDR set out PhD students and post-docs, with 12 to translate those discoveries into From 1985 until his retirement in from Africa and 12 from Europe. Via a tangible benefits for the victims of 1996, Ramachandran was secretary of curriculum-based scientific exchange neglected diseases. Lucas later served TDR’s Filariasis Steering Committee, program, the students will participate as chair of the Carnegie Corporation’s where he was instrumental in in three intensive courses at research Strengthening Human Resources initiating the Global Program to and university centres in Uganda, in Developing Countries grant Eliminate Lymphatic Filariasis. South Africa and Cameroon. programme; chair of the Global Forum He continues to serve as a Global for Health Research and professor of Alliance for the Elimination of While based in Cameroon, the international health at the Harvard Lymphatic Filariasis executive group PRDC involves a partnership with School of Public Health. On 2 December, member as well as chair of the Makerere University in Uganda, Lucas presented at WHO in Geneva on Mekong Plus Program Review Group the International Centre for Genetic TDR’s early history and achievements, and chairperson of the Pacific Island Engineering and Biotechnology in as a guest speaker of the Global Health Countries Programme Review Group South Africa, the Tropical Diseases Histories series (see p. 25). for Elimination of LF. n Research Centre in Zambia and the Mbeya Medical Research Programme in the Republic of Tanzania. The college’s collaborating European partners include Sweden’s Stockholm University, Germany’s Max Planck Institute, Italy’s National Research Council and the Academic Medical Centre at the University of Amsterdam, Netherlands. n

For more info: www.prd-college.eu and www.uy1.uninet.cm. Dr CP Ramachandran, on right, receiving his award from the King of Malaysia. Articles | Stewardship No. 84

Global report for research on infectious diseases of poverty Country-led dialogue guides review of issues

Since its founding in 1975, TDR has convened expert groups to stimulate action on critical research agendas. Now, TDR is expanding and enhancing this effort in the context of its Stewardship function and a new European Commission partnership. Ten expert groups are preparing reports on specific areas of neglected disease research. A Global report for research on infectious diseases of poverty is to be launched in 2011. Underlying these reports is a new emphasis on broad dialogue among stakeholders and more active leadership by developing countries.

Co-chairs of the TDR-sponsored expert reference groups “The challenge is to make our report rigorous enough met 2-4 September in Geneva to agree on a framework to function as a one-stop repository of up-to-date infor- for the planned disease and thematic reference group mation, yet flexible enough to permit the exchange of (DRG/TRG) report series. They also discussed how the novel ideas,” said Felipe Guhl, co-chairman of the group series would contribute to the subsequent Global report (continued on page 13) > for research on infectious diseases of poverty, to be published 11 in mid-2011. The reference group reports are intended to be “unique, authoritative, and credible overviews” of the status of research in a particular area, highlighting top-level research priorities, while the global report should be an “action-oriented report, identifying areas useful for accelerating development and applications of interven- tions,” said Catherine Davies, Global report scientific coordinator. AFRO The reports also are a key element in a new European AMRO Commission-TDR partnership to provide an overview EMRO and top-level, stakeholder-endorsed strategic recom- EURO mendations on priorities for research on neglected dis- SEARO eases, notes Ayoade MJ Oduola, coordinator of TDR’s WPRO Stewardship function, which is leading this effort. Currently, less than 10% of the global health research Disease refrence groups (DRGs) and thematic reference groups (TRGs) budget of both the public and the private sectors is ear- hosted in WHO country o ces (WCO) marked for health problems in developing countries and DRGs/TRGs to be developed only 2% of global R&D funding is allocated to research on major communicable diseases, according to data published by the European Commission1.

Six TDR-sponsored reference groups are addressing dis- DRG 1: Malaria – WHO Regional O ce for Africa (AFRO), Republic of Congo ease-specific areas of research in which TDR has been DRG 2: TB, leprosy and Buruli ulcer – WHO country o ce, Philippines engaged for over 30 years, while four more groups ad- DRG 3: Chagas disease, human African trypanosomiasis and leishmaniasis – dress cross-cutting research themes particularly relevant WHO country o ces, Sudan & Brazil DRG 4: Helminth infections & Ivermectin Resistance Initiative – African Programme to diseases of poverty: social sciences and gender; inno- on Onchocerciasis Control (APOC), Burkina Faso vation and biotechnology platforms; health systems and DRG 5: Dengue and emerging viral diseases of public health importance – implementation research; and environment, agriculture WHO country o ce, Cuba and infectious diseases. DRG 6: Zoonoses and marginalized infectious diseases – WHO Regional O ce for the Eastern Mediterranean (EMRO), Egypt Each DRG/TRG report will stand alone. The Global TRG 1: Social sciences and gender – WHO country o ce, Ghana TRG 2: Innovation and biotechnology platforms for health interventions – report will focus on three cross-cutting themes – bio- WHO country o ce, Thailand technology and innovation, health systems and access, TRG 3: Health systems and implementation research – WHO country o ce, Nigeria and environment/climate change. TRG 4: Environment, agriculture and infectious diseases – WHO country o ce, China No. 84 Articles | Stewardship

Box 1. Better environmental management can reduce climate change impacts on diseases, experts at Shanghai meeting conclude

Case studies of how climate change may impact infectious diseases prevalent in agricultural areas were a focus of the “We forecast an expansion of October meeting of TDR’s Thematic Reference Group (TRG) schistosomiasis transmission into currently on Environment, Agriculture and Infectious Diseases. non-endemic areas in the north, with 2 Presentations included a review of how better ecosystem an additional risk area of 783,883 km management could aid in prevention and control of snail-borne by 2050, translating to 8.1% of the schistosomiasis, avian influenza, mosquito-borne dengue, the surface area of China. Our results call for foodborne trematode clonorchis sinensis and echinococcosis, rigorous monitoring and surveillance of a disease transmitted to shepherds via livestock and dogs. schistosomiasis in a future warmer China.”*

The second annual stakeholder consultation and meeting of *Xiao-Nong Zhou et al, Potential impact of climate change on experts, 26-28 October in Shanghai, China, was hosted by the schistosomiasis transmission in China. American Journal of Tropical National Institute of Parasitic Diseases, Chinese Center for Medicine and Hygiene, 78(2), 2008, pp. 188–194 Disease Control and Prevention (China CDC), in collaboration with the WHO Representative Office in China and the Shanghai Municipal Government. Experts at the meeting reviewed linkages between environment, agriculture and disease for a range of parasitic diseases and viral infections, including schistosomiasis, dengue fever, and avian influenza.

Modeling of climate change trends by Chinese scientists, including Transmission area TRG members, has led to forecasts that the transmission Present zone of the parasite Schistosoma japonicum will 2030 expand by some 783 883 km2 by 2050, due to the 12 2050 northward shift of the “freeze line” – where January temperatures exceed 0ºC. Rising temperatures are expected to promote the development of snails that are intermediate hosts of S. japonicum. However, climate change impacts can be mitigated through disease control, surveillance and ecosystem measures, said Li Shizhu and Qian Yingjun, of the National Institute of Parasitic Diseases, China CDC. These include surveillance N of snail populations, of the parasite in human populations and reduction of snail habitats through the design of water carriers that inhibit snail breeding 0 500 1,000 km and mobility.

In a keynote address, Cris Tunon, acting WHO representative The potential transmission area of S. japonicum will be in China, noted that the TRG’s work responds to the increased 662,373 km2 in 2030 and 783,883 km2in 2050, if average interest in environmental health issues among both national temperatures increase by 0.9°C and 1.6°C respectively. and UN agencies in China. China CDC Vice Director-General Weizhong Yang underlined the need for further research into the control of environmentally-induced infectious diseases. Case studies reviewed by the TRG will contribute to a report on Environment, agriculture and infectious diseases, planned for 2010. The TRG’s work, in turn, will also contribute to the Li Shizhu/Qian Yingjun, China CDC Yingjun, Li Shizhu/Qian Global report for research on infectious diseases of poverty, said TDR’s Johannes Sommerfeld, who is responsible for coordinating the group. “The case studies are concrete examples of how we can prevent disease by managing the environment better,” Sommerfeld said. n

Further info: www.who.int/tdr/svc/topics/environment TDR contact: Dr Johannes Sommerfeld, [email protected] Retention tanks inhibit snails’ spread via water carriers. Articles | Stewardship No. 84 examining Chagas disease, human African trypanoso- Contributing to WHO/TDR miasis (HAT) and leishmaniasis in an integrated man- ner, something rarely done although the same family research agendas of trypanosomatidae parasites cause all three diseases. The Global report will be the first in a planned series of All three diseases are strongly associated with poverty: biennial reports on top-level priorities for research on “In addition to severe health impact, they have enormous neglected infectious diseases of poverty, including: socioeconomic impacts,” said Guhl, who is director of • identification of the most pressing public health the Center for Research in Microbiology and Tropical priorities in developing countries; Parasitology (CIMPAT) in Bogota, Colombia. • recommendations for high-impact, targeted science/ “Knowlege about the trypanosome genome and the dis- implementation research. ease-transmitting vectors (triatomine bugs for Chagas, tsetse flies for HAT and sandflies for leishmaniasis) has The report’s focus is on three themes currently resonant greatly expanded in recent years,” he adds. “But this has in international policy dialogues: health systems, inter- not translated into more effective tools for prevention play between the environment and neglected diseases, and treatment. and potential impact of biotechnology/innovation. “The reasons for this include the one-dimensional sum- It will build upon key findings from the DRG/TRG re- ming up of scientific developments in different sectors ports as well as taking a fresh look at the issues, Davies of activity, ill-defined stakeholder roles and very narrow said. approaches to the identification of priority research areas and gaps,” Guhl said. “These are the challenges we want The TDR report is expected to contribute to the World to address.” Health Report 2012, which will be dedicated to the topic of research for health for the first time in WHO history. Stakeholder and DEC involvement Its analysis will also contribute to European Commis- sion strategies around funding for infectious diseases Great emphasis is being placed on encouraging the active of poverty. 13 leadership of scientists, decision-makers and institutions from disease-endemic countries (DECs) in the formula- “The Global report, along with the disease and thematic tion of recommendations. report series, comprise key elements in TDR’s aim of Each DRG/TRG, while international in membership, is building a platform for dialogue and debate about re- being hosted in a developing country and co-chaired by search priorities,” Oduola said. The other element in this national experts from that country or region (see map neutral platform is the TropIKA.net knowledge manage- p. 12). Corresponding WHO country or regional offices ment portal designed for sharing research information. serve as partners coordinating the overall effort. “Together, these resources should establish an effective Each DRG/TRG expert group also has been launched framework for continuous assessment of research and with a broad consultation forum of government officials, control needs, progress analysis and provision of infor- industry leaders and representatives of civil society and mation useful to foster coherence, collaborations and NGOs, who discussed the relevance of the initiative and effective action on priorities amongst stakeholders on issues important to their work. infectious diseases of poverty,” Oduola said. “All are being encouraged to provide input to the frame- “These reports should frame recommendations in a way work and activities of the disease and thematic reference that is relevant to countries, to those working in the field, groups so that the reports will be useful to their work,” and to those making decisions on funding,” Davies said. said Oduola. “And when the work is finished, they’re “They will set out ‘options for actions’ illustrating how encouraged to utilize those reports.” agreed priorities might be taken forward.” y In his presentation to the co-chairs of the DRG/TRGs in Geneva last September, TDR Director Robert Ridley stressed the importance of stakeholder involvement in the review process – as evidenced by a number of past 1. Global Forum for Health Research, as reported in: Health and poverty findings in neglected diseases research. reduction in developing countries, Communication from the Commission to the Council and the European Parliament (COM, 2002) 129 final. For instance, when insecticide-treated bed nets were first Brussels, Commission of the European Communities, 22.03.2002. marketed for malaria prevention, they were uniformly (access at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri= white. That changed, Ridley noted, when it was reported COM:2002:0129:FIN:EN:PDF) that in some cultures white is strongly associated with death, as it is the colour of a shroud. For more information: “Each DRG/TRG report will have to resonate with a www.who.int/tdr/svc/stewardship/research-think-tank particular community of both experts and stakehold- ers,” he observed. At the same time, the global report should paint a “big picture” that can resonate with the Contact: Dr Ayoade MJ Oduola, [email protected] worldwide community of scientists and policy-makers. No. 84 Cover story | TB update

TB or not TB? Closing the gap between evidence TB is one of the world’s most widespread infections – one of every three people is a carrier. Over the past two decades TB resurged worldwide, along with TB co-infections with HIV/AIDS and drug-resistant TB. Daunting gaps in knowledge about how to manage the new epidemic left TB diagnostic and treatment practices in dire need of improvement, and health services overwhelmed. Yet new evidence generated by TDR is making a major difference in TB diagnosis and treatment.

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Dar Es Salaam, United Republic of Tanzania: better recovery rates and overall health than those who At a busy TB clinic, Freddie waited to pick up his drug only receive TB drugs. prescription for the next two weeks. The Tanzanian mili- After a few soul-searching conversations with the nurses tary band member was leaving to perform in Zanzibar, and his brother, Freddie decided to brave the HIV test, and wanted to make sure he would not miss a dose. which turned out to be positive. The upside was that he A tall man who looks much younger than his 44 years, was registered for the TB-HAART trial, which he credits Freddie (his nickname) just a few months ago was mostly with restoring his health. bedbound and coughing up blood. Married with two In fact, Freddie still does not know if he has been receiv- children, ages 25 and 9, he knew his life was at risk. ing ARV drugs right from the start or a placebo for the Then he was referred to Dar es Salaam’s Mwanan-Jamala first six months plus the TB course (after the first six Hospital TB clinic, which is collaborating with TDR months everyone receives ARVs and is guaranteed a life- on a trial to improve treatment of TB patients infected time supply). But he has observed a rapid and remarkable with HIV. change in his overall health. A sputum smear was positive for TB. But at the same “My weight has gone up from 65 to 75 kilos and my CD4 time the clinic staff started him on TB drugs, they also blood cell count [a measure of immune systems strength] invited Freddie to be tested for HIV as part of an in- rebounded from 400 to 500 [cells/mm3]. Overall, I am novative TDR-supported trial. The trial, TB-HAART, is feeling much better, so I am convinced that I am already testing whether HIV-infected TB patients who also begin receiving ARVs along with my TB treatment,” he said. antiretroviral (ARV) therapy together with TB treatment, “I have hope and have been able to resume my normal and much earlier than ARVs typically are offered, have life” (see Freddie, p.16). Cover story | TB update No. 84 and practice

15 All pictures: Muhidin Issa Michuzi All pictures:

While the data has yet to be unblinded, rebound stories counts of 350 or lower. WHO guidelines noted, however, like Freddie’s provide strong indications that initiation that the quality of evidence regarding that threshold is still of ARVs simultaneously with TB treatment is not only only “moderate” – relying largely upon one randomized safe but also can improve patient survival and overall control trial in Haiti and one post-hoc analysis of data health. As a result, there may be interim review of from another trial.1 patient data from the four participating countries in Beyond the current WHO recommendation, the TB- late 2010, according to Philip Onyebujoh, coordina- HAART trial is testing if TB-infected HIV patients with tor of TDR’s Evidence for TB/HIV Treatment Policy CD4 counts higher than 350 – people like Freddie – also business line. might benefit from earlier initiation of ARV therapy. If Ultimately, the trial holds the potential to significantly evidence reflects a significant benefit, the case for raising influence TB/HIV treatment policy and even HIV treat- the threshold even further could be made. ment – particularly since evidence is scant on when “All in all, the thresholds we have right now still lack to begin ARV therapy for HIV-infected populations in evidence about optimal treatment for developing country developing countries. populations, who also are frequently malnourished and Many African countries, including Tanzania, begin ARV beset with other parasitic, bacterial and viral infections,” treatment after CD4 count falls below 200 – although says TDR’s Mahnaz Vahedi, a medical doctor and TB- HAART project manager. the Ministry of Health is considering an upward shift of that threshold in line with worldwide trends. On Vahedi’s polite demeanor belies an intellectual intensity 30 November, WHO issued guidelines recommending and professional drive that has led her to ply the air routes that ARV treatment be offered for anyone with CD4 between Geneva and Africa countless times over the past No. 84 Cover story | TB update

Freddie: ‘I am proud to be an advocate’ for HIV testing

“When I was first supposed to get tested, I left the clinic and ran away, I was so afraid,” Freddie says. “I went to my brother’s house and talked with him; he convinced me that I should go through with it. ‘Better to know and to get treated than not to know,’ he said. ‘There are drugs now to treat HIV.’ ” Freddie returned to the TB clinic at Mwanan-Jamala Hospital TB clinic, talked with the nurses there, and braved the test. The United Republic of Tanzania recently instituted a policy of offering HIV tests and ARVs free-of-charge to HIV-positive people with CD4 counts of 200 cells/mm3 or below. But since Freddie’s initial CD4 count was higher, he would not have been eligible. As a member of the study he is now assured of receiving anti-retroviral drugs after six months, but he is convinced that he is already receiving them now. He has meanwhile become a quiet advocate for getting tested among his relatives and his friends. (His wife has tested negative for HIV, and they are now careful to use condoms). At a recent military festival, he spoke to many people at the AIDS testing booth. “I feel so sorry for the former generation of Tanzanians who died of AIDS without having access to such treatments,” he says. “Now people are less afraid of being tested and finding out. There are the drugs for treatment and the stigma has been reduced. Until now, I had read about the stories of others who have become advocates for getting tested,” he adds. “I am proud now to have become an advocate.” n

16 two years to ensure the trial’s smooth progression. Large- um. The last of the 1836 volunteers were completing ly due to such efforts, the trial has nearly reached its treatment at the end of 2009 with analysis forthcoming halfway point in recruitment. in 2010 (see TDRnews 82, p. 4). • “Fixed-dose” drugs: This trial tests TB treatments Value-added TB research that combine multiple drugs into a single-dose pill. The addition of TB to TDR’s portfolio of neglected diseases Already on the market in many countries, these fixed is relatively recent. In 1998, in response to rapid world- dose combinations had not previously been evaluated wide surge in TB cases, TDR’s governing body decided to for safety and efficacy. A single-blinded randomized develop a targeted series of research activities. clinical trial involving 1000 patients in Ethiopia and Nigeria is to end in 2010 (see TDRnews 78, p.16). “TDR does not aspire to be the lead actor on either TB or HIV/AIDS,” Director Robert Ridley said. “We are working • More rapid and accurate smear microscopy: New alongside the STOP TB Partnership and the Global Fund ways to speed up smear diagnosis of tuberculosis are to Fight AIDS, TB and Malaria as well as with WHO’s likely to be recommended by WHO following large STOP TB Department. TDR-led multi-country clinical trials of “front-load- ing” methods. Front-loading means that two sputum “We identify needs for new evidence, and then make smears are collected and analyzed on the same day. optimal use of our networks and experience in field set- Currently, patients must return to a clinic over two tings to fill these critical gaps.” Key areas of TDR focus or three days to provide sputum samples, and many so far have included: do not receive treatment due to patient drop-out. • TB-HAART (highly active anti-retroviral treatment): The four-country trial has enrolled 720 of a planned • LED fluorescence microscopy for easier diagnosis: 1800 patients. The halfway mark – 900 patients TDR also has been a leader in testing light-emitting having undergone at least six months of treatment – diode (LED) adapters for microscopes, another new should be reached in 2010. At that point, the trial’s technology likely to be recommended soon by WHO. safety oversight committee might decide to review The use of LED causes bacilli to glow in specially- preliminary results, which are ugently needed as stained smears. This makes them appear larger than evidence for treatment policies. usual, considerably reducing the time required for examining each smear. • TB treatment in four months: Cutting treatment time from six to four months with a gatifloxacin- • A rapid TB blood test: Not one commercial TB blood containing TB drug combination is the focus of a piv- test on the market performs as well as smear micros- otal TDR co-sponsored Phase III trial. This research copy. However, a combination of antigens identified is under way in collaboration with the national TB in a systematic review by TDR and partners last year control programmes of Senegal and Benin, research shows promise. These will be evaluated in the coming institutions in Guinea, Kenya and South Africa, and year to see if a truly revolutionary rapid blood test for the European Commission-funded Oflotub Consorti- TB could be developed. Cover story | TB update No. 84

TDR’s training and coordination roles “We have almost hit our halfway point for enrolment,” he adds. “By late 2010, we might be in a position to Before the TB-HAART trial started, it took up to two generate preliminary findings that can support policy weeks to get a sputum sample from a peripheral site recommendations. to the national laboratory in Dar es Salaam, according to Saidi Egwaga, manager of the Tanzanian National “But to do that, it is critical that every single aspect of Tuberculosis and Leprosy Programme (NTLP) and a the trial be conducted strictly according to internation- principal investigator of the TB-HAART trial. al GCP and GCLP standards, and that any review will confirm the robustness of the data. “Now we can speak about same-day delivery of smear samples to the laboratory,” Egwaga said. He was leading “Not only that, but there is a need to ensure procedures an August visit to the Muhimbili National Hospital Labo- are the same across all countries so data are completely ratory by members of TB-HAART research teams. This comparable. This trial, if you look at any aspect, must mixed group of investigators, clinical trial coordinators, pass any kind of audit or inspection. The data have to trial managers and monitors came from the four country be clean – completely clean.” sites – Zambia, Uganda, South Africa and Tanzania. The tour of the hospital laboratory was part of a “re- From field site to laboratory fresher course” in good clinical laboratory practices The ensuing three days are filled with presentations on (GCLP) and good clinical practices (GCP), organized step-by-step trial recording, reporting and data manage- by TDR’s Vahedi for the country teams. The four-day ment processes, as well as related issues of patient safety, course was a step-by-step review by safety physi- particularly adverse events. Sessions are highly interac- cians, trial monitors, TDR staff and the participants tive and led by clinical monitors, safety physicians and themselves of all aspects of procedure. country trial staff as well as by Vahedi and Onyebujoh. “Pressure to generate data from this trial is enormous,” Every link in the diagnostic and treatment chain is stated Onyebujoh, speaking to the group on the first discussed: from the procedures for taking and labeling day of the week-long session. Bulky and spectacled, sputum or blood samples to microscopy examination in 17 Onyebujoh has a presence that is a cross between ac- field sites. Other topics include packaging and transport, ademic-physician and artist. He never met Freddie in follow-up cultures in reference laboratories, reporting person, but he shares his love of jazz, and a keen per- back, treatment processes, patient records and discrep- sonal appreciation for how the TB and HIV epidemics ancies, and adverse events. have ripped through Africa’s best and brightest. He approaches his clinical trial teams like a coach urging players to score a goal against death. Getting the patient data right “Globally, there are four trials ongoing looking at optimal Misrecording data is not just a matter of a technical error timing for the start of ARV therapy,” he says. “But this – it can be a life-changing event for the patient, accord- trial is large enough to make a stratified analysis of out- ing to Getnet Yimer. The young Ethiopian doctor who comes among patients with different CD4 blood counts. is a roaming clinical monitor in the trial recalls how

Members of the four TB-HAART clinical trial teams meet in August in Tanzania for a GCP and GCLP refresher session. No. 84 Cover story | TB update

the wedding engagement of a young man he knew was and people feel that they are being backed by WHO/ cancelled due to an incorrect report of an HIV diagnosis. TDR at headquarters.” Yimer reviewed some of the common problems in re- cording that can be encountered from field site to labo- Ensuring patient safety ratory. Those include issues such as transcription errors Vahedi expresses satisfaction that the trial has improved in case record forms; lack of proper transport logs for sample movements; inconsistencies between patient de- patient care at participating clinics, which observe a tails in laboratory reports and source documents; and strict routine of follow-up appointments for 24 months, documents that are not filed, signed or followed-up including contacting those who miss appointments. properly (see Yimer below). Underlying strict observance of trial procedures, is a Yimer devotes countless hours traveling from one clinical concern for the patient, points out Catherine Magezi trial site to another throughout Zambia, Uganda and Tan- Muwonge, the trial’s chief safety physician, speaking zania. There he will sit for hours, paging through docu- at the GCP refresher course. ments with a registered nurse or a clinical trial associate, So while it is important to report a serious adverse event and making detailed notes and corrections where needed. within 24 hours to clinical trial investigators and spon- Vahedi oversees the trial with daily calls to trial monitors sors as per GCP standards, even more critical is the and other staff. Every few weeks she also arrives at the health of the person involved, she points out. far-flung trial sites to provide a double quality control. “If you have abnormal results, the issue is not just “If you are not there, you just do not really see the picture,” about rapid reporting. It really is about the safety of she says. “If you are there, you can overcome roadblocks, the individual, another human being. So you have to

18 Yimer: “Get the signature right” Mosquitoes hover around Getnet Yimer in a tiny airless room at the Mwanan-Jamala Hospital TB clinic. He is checking hundreds of pages of clinical trial ‘case record forms’ (CRFs) against original ‘source forms’ that were filled in during patient visits. He is hunting for discrepancies, often tiny, in the transcription of dates, times and blood counts. He also observes the real-time intake of patients by TB- HAART clinical trial associate Maliwaza Mganga. The issues he notes are illustrative of the level of detail that must be addressed in order for the trial Dr Getnet Yimer, TB-HAART clinical trial monitor, reviews case to reflect international standards. records with clinical trial associate Maliwaza Mganga. Yimer says a common problem is slight inconsistencies between signatures, particularly in the cases of illiterate patients. In the latter case, an accompanying witness is supposed to co-sign the consent form, alongside the patient’s “identifying mark.” “Consent is a major component of a clinical trial,” he notes. “See here, the trial associate has been writing the date on the consent form for those who cannot read and write. I am telling her that it is the witness who should be writing in the date, not herself, because that witness is, in effect, signing in the place of the patient.” Yimer peers at the source form again. In the initial physical exam, the associate had noted the patient’s musculo-skeletal condition as “normal.” However, there is no such exam in the TB trial, so Yimer shows her how she should put “not applicable” and sign with her initials. “Height,” he says, “if you did not get it the first time, you can catch it on the next visit. It is not a variable that will change. However, if you missed weight the first time, you cannot fill it in later. “Date and month of birth: if they do not know, then put 99/99. Don’t guess.” And then, there is the issue of the signature. “When you have to sign the bottom of the form, write your full signature, not just initials,” he instructs her, “that is, unless you really do use your initials as your signature.” “And if you are going to change that practice from an initial to a full signature, then please make a note for the file!”n Cover story | TB update No. 84

relate the abnormal results to the clinical condition. • rapid transfer of samples from clinics to laboratory; You have to manage the patient, to treat them.” • quality control in laboratories, external and internal; All in all, the bottom line is to adopt a critical, question- • supply of materials like reagents for analysis and tests; ing stance vis-a-vis data – and particularly abnormal data, concludes Onyebujoh. • documentation of samples. “If a patient’s blood count upon treatment was normal “TB-HAART has helped us develop standard operating and then it becomes abnormal, clearly something is procedures for reporting. People now appreciate more wrong. So you have to ask: are we dealing with a sam- the importance of reliable and accurate source data. The ple that was too long in the laboratory or a meaningful study also has helped us build confidence that we can pathological situation? undertake other clinical trials,” Egwaga says. Muhimbili Hospital’s experience shows how TB-HAART “You ask that question and you review the information is more than a clinical trial: it “embeds” a culture of holistically, in context. You need to be thoughtful, you research into national disease programmes. need to be a clinician. That is what it is all about.” Essentially, says Onyebujoh, the strategy works on three levels to strengthen health systems: Embedding research culture in • It builds improved laboratory and treatment proce- TB control programmes dures in key national health laboratories and hospi- Muhimbili Hospital’s TB laboratory is one of three ref- tals, such as Muhimbili, which can then introduce erence laboratories in Tanzania. It is the laboratory to those same practices elsewhere. which samples are sent from all four TB-HAART trial • It involves national TB programme managers directly sites in the country. in the research creating confidence in findings and The laboratory is tucked into a cramped series of support for adoption of new practices. rooms on the hospital’s third floor and demand on • Opportunities to participate in research can be a pro- 19 its facilities is heavy. Every tenth TB sputum sample fessional stimulus for health workers in developing nationally is supposed to be referred for a follow-up countries, where “brain drain” is a chronic problem. culture; in reality, only about one sample out of 100 is thus confirmed. “Not only does this trial provide people with an addi- tional allowance, it opens up opportunities for continu- This is the first time that the laboratory has participated ing education – and this improves staff motivation and in such a major piece of research, and good practices retention, which we know is a major problem in Africa,” adopted for the trial have extended to routine work, says Egwaga observes. Egwaga. He cites improvements as follows: “I now have my eye on future opportunities for us to • specimen quality as a result of capacity-building in become involved in other such trials. This way, everyone periphery; knows that there is something new coming along.”

TB slides awaiting microscopic examination. No. 84 Cover story | TB update

Doulla: ‘You have to know how to talk to people’

Basra Doulla is a hospital laboratory coordinator who organizes the day-to-day logistics of sample pickup and reporting back of diagnostic results. She escorts visiting TB-HAART teams through the laboratory and speaks about how procedures have improved, but also about how a personal touch is important in getting good results. “In this day of the cell phone, we can call or SMS, and that usually works better than e-mail. We can ensure that results are reported straight back from the central office to the site and used more actively in case management. “But you have to know how to talk to people, how to make them feel good about their efforts. “Prior to the start of the TB-HAART trial, the transit time for a specimen from the periphery to the central laboratory here could be two weeks. Why did it take two weeks when the bus takes seven hours? It would sit in an office somewhere,” she says. “Today, it is possible to talk about same-day delivery in Dar, and outside of Dar two to three days.” The urban delivery system is based upon “runners” who move Dr Catherine Magezi Muwonge, on left, and Basra easily through the city by motorcycle. In the rural areas, bus Doulla, center, review procedures at the Muhimbili 20 National Hospital TB laboratory. drivers have been sensitized to more readily accept specimen loads, which are carefully packaged so as not to break. “As a result of the systems improvements we have made in TB-HAART, it is possible today to document properly the samples and to trace the movement of samples and to provide timely feedback on results. These experiences we can carry into our routine work,” Doulla says. “We still have our bumps; we sometimes still get an empty specimen container... but we now have procedures in place to check those things out.” n

New LED microscopes shed light “We believe that very considerable gains in TB case detection could be achieved with existing laboratory One new tool aiding performance of clinics in outlying staffing levels and the addition of this low-cost equip- areas, says Egwaga, is light-emitting diode (LED)-based ment,” Ramsay says. He cites a recent TDR study that fluorescence for TB microscopy. This includes purpose- modeled how LED-based microscopy could improve built LED fluorescent microscopes or ordinary light existing TB services in Malawi.3 microscopes converted to LED with adapters. TDR has led testing of the inexpensive adapters. Based partly on these studies, LED fluorescence microscopy ‘Front-loading’ smear microscopy may soon become a recommended procedure, follow- “Front-loaded” sputum specimen collection – making ing a meeting in November 2009 of the Scientific and possible a same-day smear diagnosis of TB – is another Technical Advisory Group (STAG) of WHO’s STOP TB procedure likely to be recommended soon. TDR recently Department. completed a large multi-control trial of the approach, Conventional fluorescence microscopes are expensive, tested earlier in a small study conducted by the Liverpool 4 and their mercury vapour lamps are both short-lived School of Tropical Medicine . and toxic. LED-based fluorescence is simple, non-toxic The TDR study, funded by the Bill and Melinda Gates and can be operated on solar-powered batteries. Foundation and the USA’s Agency for International De- “It’s the same kind of light that campers often wear on velopment (USAID), found that a single-visit, two-spec- bands around their heads,” says Andy Ramsay, a TDR imen approach is as effective as a diagnosis that requires scientist who is also secretary of the Stop TB Partnership’s two visits and two or three specimens. The results were Working Group on New Diagnostics.2 presented to WHO in late 2009. The use of LED causes bacilli to glow in specially-stained For patients, making multiple visits to a TB clinic for di- smears. This reduces examination time and increases agnosis is the costliest part of TB treatment, largely due sensitivity of the diagnosis. to the travel and lost work time involved (see graphic). Cover story | TB update No. 84

It is thus a huge burden on patients who are poor and a 87% of costs 85% of costs factor in high rates of patient dropout. incurred before incurred before treatment treatment “A same-day, patient-centered approach would signifi- 180 cantly increase the numbers of people who get treated, particularly among the poor,” says Ramsay. 160 $21

Future research needs and aims 140 Yet even with more optimized smear microscopy serv- ices, as many as half of those with active TB still may 120 never get a smear-positive diagnosis, Ramsay points out.

So the search continues for a “point-of-care” test sim- 100 ple enough to be administered by a lay person. A 2008

TDR-supported evaluation of commercially available US$ 80 rapid diagnostic tests (RDTs) for TB revealed that none $146 performed sufficiently well to do the job.5 60 However, a combination of antigens identified in a sys- tematic review by TDR and partners in early 2009 show 40 promise, says Ramsay.6 These antigen combinations are $6 being incorporated into an RDT format that will be evaluated with TDR support in 2010. 20 $34 TDR is also working with the Foundation for Innovative New Diagnostics (FIND) to systematically identify other 0 Bangalore Yangon candidate antigens – using high-tech analysis of most of the nearly 4000 proteins in the M. tuberculosis proteome.7 21 Cost during Cost before “We are not only dealing with diagnostics that can give treatment treatment incremental gains but also participating in the quest for diagnostics that could revolutionize TB care,” he says. For TB patients, cost of diaagnosis is typically the costliest element of A TB drug treatment that does not generate adverse in- care, as this study in South-East Asia indicates – due to travel and work time lost for clinic visits. (Graphic by Knut Lönnroth, WHO/STB) teractions with second-line ARV therapies used by HIV patients is another urgent need, Onyebujoh says. waiting lists. However, early initiation of ARVs may also “The current standard TB course is much less effective generate savings for health systems – delaying the time in HIV-positive patients who are on second-line ARVs when HIV-positive patients need to go on more expensive because of drug interactions,” says Onyebujoh. “In par- and difficult-to-tolerate second-line ARV drugs. ticular, the TB drug rifampicin interacts.” “This issue cuts across everything we are doing,” Onye- Vahedi, meanwhile, is leading a TDR effort on research bujoh observes. “If we look at TB-HAART, or use of into new TB biomarkers; the focus of a joint TDR-Euro- new biomarkers in studies, or at the replacement of pean Commission expert consultation in 2008.8 rifampicin with rifabutin for TB patients already on “Not only blood samples, but also sputum and other second-line ARVs, we have to be able to say that it is not fluids, may contain biomarkers that are easy to collect only safe and effective, but also feasible and cost-effective and can give us valuable information regarding the – particularly for a developing country.” y progress of TB treatment,” she says. – Reported and written by Elaine Ruth Fletcher Cost-effectiveness of new interventions is another is- from Dar es Salaam, photos by Muhidin Issa Michuzi sue Onyebujoh would like to address more deeply. For instance, there is clearly a cost associated with the rais- For more information: ing of CD4 thresholds, adding tens of millions more www.who.int/tdr/svc/research/evidence-treatment-tb-hiv HIV positive people to the already long ART treatment www.who.int/tdr/svc/research/quality-assured-diagnostics

1. Rapid advice: Antiretroviral therapy for HIV infection in adults and 5. Laboratory evaluation of 19 commercially-available rapid diagnostics adolescents, Geneva, WHO, 30 November 2009. www.who.int for tuberculosis. Geneva,WHO/TDR, 2008. (www.who.int/tdr/svc/ 2. www.tbevidence.org publications) 3. Ramsay A et al. New policies, new technologies: modelling the 6. Steingard KR et al. Performance of purfied antigens for serodiagnosis potential for improved smear microscopy services in Malawi. PloS ONE, of pulumonary tuberculosis, a meta-analysis. Clinical and Vaccine 2009, 4:11.2009. doi:10.1371/journal.pone.0007760.t00 Immunology, 2009, 16(2):260-276 4. Ramsay A et al., Front-loading sputum smear microscopy services: an 7. For more information: www.finddiagnostics.org/media/newsletters/articles/ opportunity to optimize smear-based case detection of tuberculosis issue13_tuberculosis_point_of_care.html in high-prevalence countries. Journal of Tropical Medicine, Vol. 2009. 8. Joint TDR/EC expert consultation on biomarkers in tuberculosis, doi:10.1155/2009/398767 Expert group report. TDR and the European Commission, 2008. 143 pp. (www.who.int/tdr/svc/publications) No. 84 Articles | Malaria

5th MIM convenes in Kenya Access to treatment and parasite resistance lead agendas WHO/TDR/Guth

22 Nairobi, Kenya – Eradicating malaria is the goal. To get there, research is essential. That was the main message from the 5th Multilateral Initiative on Malaria (MIM) Pan-African Conference. From 1-6 November, some 2000 researchers and policy-makers reviewed the latest in disease control issues and research needs.

“We all know why this meeting is so important,” said A pre-conference field trip also allowed journalists Robert Newman, WHO Global Malaria Programme to witness two related clinical trials in Uganda led director, in his plenary speech at the 5th Multilateral by TDR-supported scientists. Makerere University’s Initiative on Malaria (MIM) Pan-African Malaria George Pariyo is assessing mortality impact, cost- conference in Nairobi. effectiveness, and acceptability of integrated commu- nity-based treatment of fevers with antimalarials and “In 2008, there were an estimated 232 million malaria antibiotics. cases and 841 000 malaria deaths, with close to 90% of those occurring in sub-Saharan Africa,” he noted, At Iganga-Bugiri, site of an integrated malaria and pneu- declaring: “We have an unfinished agenda.” monia trial managed by Makerere’s James Tibenderanat, journalists had a chance to observe epidemiology in ac- Despite the fact that some 80 countries now recom- tion, as researchers tracked malaria cases via household mend artemisinin combination therapy (ACT) as first- interviews. line treatment for malaria, few malaria patients in sub- Saharan Africa are treated with ACTs. The challenge of increasing access to ACTs, which are the fastest-acting Combating parasite resistance antimalarials available, was a key focus of sessions. Paradoxically, while promoting access to artemisinin In a symposium co-sponsored by UNICEF and TDR, combination therapies (ACTs) in Africa was high on TDR scientist Franco Pagnoni led with a review of how the agenda, an equally hot topic was the reports of TDR-supported research on home management of ma- widening plasmodium parasite resistance to artemisinin laria (HMM) is modeling scaled up access to antimalar- in Asia. ials. This is also combined with use of rapid diagnostic Recent reports of such resistance along the Thai-Cambo- tests (RDTs) so that drugs are not used unnecessarily. dia border region are a sobering reminder that without Then, scientists from Senegal, Ethiopia, Ghana, Uganda, adequate regulatory structures and surveillance, today’s and the WHO Regional Office for Africa presented re- most effective antimalarial drug could go the way of chlo- search testing strategies for integrated community case roquine. This would rob malaria control programmes of management of malaria, pneumonia and diarrhoea. To- their most powerful weapon – which, as the Gates Foun- gether, these childhood illnesses cause three-quarters of dation’s Regina Rabinovitch put it, “is a panic-inducing mortality in children under five years of age. prospect that we simply cannot afford.” Articles | Malaria No. 84

“Strengthened surveillance is one important response,” Genetic modification said TDR scientist Andrew Kitua in a press conference on the resistance issue. Against these gloomy reports, genetic modification of mosquitoes offers one entirely new tool for vector con- Kitua called for greater surveillance of uncontrolled use trol. TDR scientist Yeya Touré discussed how genetically- of artemisinin, citing recent reports that less than 25% modified (GM) Anopheles gambiae mosquitoes may soon of artemisinins used worldwide are in fact combination begin field trials. The trials would likely involve sterile 1 therapies (ACTs) – designed to blunt resistance. Counter- insect strategies long employed with agricultural pests, feit antimalarials also flood developing country markets. but with a GM twist. Currently, a GM-modified mosquito “We need to have regulations and enforcement of regula- is being tested, in which the GM male would be released tions in order to prevent this,” said Kitua. “The community to mate in the wild and pass on a fatal genetic defect to must be educated and the media must play a role.” offspring (see TDRnews 81, p. 30). Certain aspects of GM development and deployment lie Mosquito resistance to insecticides beyond the scope of existing national or international regulatory schemes. With the support of the Gates The growing resistance of Anopheles mosquitoes to insec- Foundation and the USA-based Foundation for the Na- ticides used in the impregnation of bednets and in other tional Institutes of Health (FNIH), TDR is collaborat- vector control operations looms as another huge threat, ing with scientists in Brazil, Kenya, India and Mexico meeting participants noted. to develop guidelines on safety and efficacy testing. Since 2001, the proportion of African households owning TDR also recently initiated a network of biosafety an insecticide-treated bednet (ITN) has increased by more centres and courses for developing world scientists than 30% across the continent. Most nets are impregnated (see TDRnews 82 p. 32). with pyrethroids, a class of insecticides with particularly low toxicity. Yet now, mosquito resistance to pyrethroids is a growing problem in parts of the developing world. Strengthening African research In comparison to the first MIM conference in 1997, in- 23 “We have too many of our eggs in one basket,” said New- volving only 100 African scientists, the size of the turn- man. “And we don’t have any alternatives in the pipeline out to this year’s event was perhaps one indicator of how for the near term.” scientific capacity on the continent is growing. In a pre-conference press tour to a Burkina Faso field The new African Network for Drugs and Diagnostics study on mosquito resistance, journalists observed sci- Innovation (ANDI) aims to bolster capacity in a related entists documenting insect resistance to two common arena – R&D that would produce marketable pharma- pyrethroids – permethrin and deltamethrin. The research was subsequently presented at MIM. ceutical products. TDR’s Solomon Nwaka, coordinator of ANDI, led a MIM symposium that described ANDI’s The study is being conducted by the Centre National de plans to increase collaboration among African R&D in- Recherche et de Formation sur le Paludisme (CNRFP), stitutions and to establish a major endowment fund for based in Ouagadougou. CNRFP is part of a TDR-sup- product development (see ANDI, p. 24). ported network studying insecticide resistance in Angola, Benin, Chad and Sudan, as well as Burkina Faso. Meanwhile, TDR’s longstanding contributions to MIM were recognized in awards presented to Director Rob- Most mosquitoes still remain susceptible to the carbamate, ert Ridley as well as to TDR/MIM coordinator Olumide bendiocarb, and to the organophosphate, fenitrothion, net- Ogundahunsi – for promoting develoment of young work coordinator Hilary Ranson of the Liverpool School African researchers. Plans to move the MIM secre- of Tropical Medicine, reported to the Lancet’s Adele Ba- tariat from Tanzania to the University of Yaoundé 1, 2 leta. Those chemicals, however, have greater toxicity and Cameroon, in January 2011 also were announced. ecosystem impacts than pyrethroids. Selected from an open competition, the site’s central Use of dichlorodiphenyltrichloroethane (DDT) among African location and bilingual university facility will farmers poses another dilemma for vector control efforts, position MIM at the crossroads of East and West Af- observed Sodiomon Sirima, interim director of CNRFP. rica, and strengthen outreach to Franco­phone African researchers. Professor Rose Leke at the University’s The Stockholm Convention, which came into effect in Biotechnology Centre will serve as secretariat chair. y 2004, outlawed the farm use of DDT, while permiting continued vector control use for public health – until alternatives can be found. However, illicit DDT use in – Reported and written by Patrick Adams agriculture in the developing world remains widespread, and Jamie Guth from Nairobi contributing to mosquito resistance. For more information: www.mimalaria.org 1. According to the findings of a new study co-sponsored by the London School of Hygiene and Tropical Medicine and Population Studies International. Contact: Dr Olumide Ogundahunsi 2. Insecticide resistence threatens malaria control in Africa.The Lancet, Vol. [email protected] 374, Issue 9701, 7 November 2009. pp 1581 - 82. No. 84 Articles | Cape Town

Initial call for projects in 2010 Business plan endorsed for African innovation network (ANDI) Some 300 high-level researchers and policy-makers endorsed an ambitious business plan, including a proposal for a US$ 600 million endowment fund, for the new African Network for Drugs and Diagnostics Innovation (ANDI) at the second stakeholders’ meeting in Cape Town.

The ANDI network aims to support and promote research available – venture capitalists or ‘business angels’,” she by African institutions for new drugs and diagnostics to added. “The establishment of ANDI will help us deal address the diseases most affecting Africans. The con- with the crisis in R&D for neglected diseases and develop cept was launched by several African institutions, through human capital for sustainable development.” TDR, in October 2008 in Abuja, Nigeria. Following the 2008 meeting, an ANDI Task Force was The turnout at Cape Town, South Africa, reflected the formed to develop a strategy and the new business plan. support for the ANDI initiative that has since developed The Task Force is led by Ambassador Tom Mboya, of among governments, research institutions, Africans in the Permanent Mission of the Republic of Kenya to the the diaspora, and international and multilateral agen- United Nations Office in Geneva. cies, including the African Development Bank and the While TDR has provided seed monies, endowment sup- European Commission. 24 port is now being recruited from multiple donors. Negotia- Currently, there is a “valley of death” between product tions are being conducted with the African Development R&D and the marketplace where most innovation falters, Bank to host the fund. The call for funded projects is antici- said South Africa’s Minister of Science and Technology, pated in 2010, with a third stakeholders’ meeting planned Naledi Pandor, in a keynote address at the 4-7 October in October as a formal launch of the network. event, attended by several health and science ministers. The ANDI Task Force estimates a need for an additional “That’s where innovation needs the most support, US$ 2.4 billion investment in R&D for health products and where it is least likely to get it from the only agents for Africa just to reach the median of global expenditures. Africa bears a disproportionate 25% of the global disease burden; it has only 15% of the world’s population. China initiates Asian innovation network A TDR-supported analysis in 2008 of African R&D ef- forts underlined the fragmented nature of existing initia- Inspired by the ANDI experience, some 150 Chinese research leaders tives. Most African-based researchers are better linked held the first meeting of a Chinese Network on Drug and Diagnostics Innovation (China NDI) – the first spin-off of the TDR-fostered concept in with Europe and North America than within Africa. another region. ANDI will stimulate more intra-African collaboration, The 24-25 October Shanghai gathering involved 48 institutions working enhancing leadership, ownership and sustainability of on drug, diagnostics and vaccine R&D for bacterial, viral helminthic and African R&D, said Solomon Nwaka, TDR coordinator protozoan infections, as well as vector-borne diseases. of the initiative. ANDI also will faciliate networks, IT The meeting involved high-level representatives from China’s Ministry of infrastructure development, and management of intel- Science and Technology, Ministry of Health, Centres for Disease Control lectual property rights. and Prevention, and TDR’s Director Robert Ridley. “The new China NDI initiative is the first step in a vision of building a “We need African-based solutions with African-based broad-based Asian innovation network,” Ridley told the meeting of institutions,” said Anthony Mbewu, president of the professionals from universities, academic and research institutions and South African Medical Research Council, which hosted the private sector, working from upstream to downstream R&D. and organized the event with support from TDR and Plenary sessions covered trends in tropical diseases drug development, the Government of South Africa. Mbewu, an ANDI Task needs and challenges in diagnostics and international collaborations. Force member, also recently became head of the Global Over two dozen technical sessions covered topics such as new drugs and vaccine development for schistosomiasis, malaria, and tuberculosis as Forum for Health Research (TDRbriefly, p. 7). y well as drug target screening and computer-aided drug design. A working group of 28 experts was charged with developing a five-year workplan. They included representatives of the National Institute of More about the ANDI meeting: Parasitic Diseases, National Center for Drugs Screening, Second Military http://meeting.tropika.net/andi2009/ Medical University, Fudan University, Pfizer Pharmaceuticals, Beijing www.who.int/tdr/svc/news-events/news/andi-endorsement Holley-Cotec Pharmaceuticals, Sichuan Maker Science & Technology, Ease Medtrend Technology and Tigermed Consulting. n Contact: Dr Solomon Nwaka, Link to China-NDI at: www.asiandi.org/china [email protected] Articles | Global Health Histories No. 84

Global Health Histories seminars frame contemporary research in a long-term perspective

From Patrick Manson, the 19th-century Scottish physician who discovered that a parasitic disease could be carried by insects, to Carlos Chagas, the 20th-century Brazilian researcher who discovered the disease that bears his name, tropical disease research has had a long and distinguished history of bravery and boldness, rigorous science and serendipity. Examining the past in the light of contemporary health issues is the goal of the Global Health Histories series, co-sponsored by WHO, the Wellcome Trust and the Wellcome Centre for the History of Medicine at University College London.

The Wellcome Trust-WHO history collaboration began Bhattacharya, adding: “It has even brought together people in 2008 as part of the events surrounding WHO’s 60th in WHO who might not normally interact!” anniversary. That series was co-organized by Thomson Bhattacharya is now hoping that tropical diseases will Prentice, former editor of the World Health Report, whose become the focus of a Wellcome Trust-sponsored series interest helped ensure its continuity beyond the lifespan of Witness Seminars, to begin in 2011. In the popular of the WHO anniversary year. Witness format, experts gather to exchange views on a 25 Bringing together a diverse group of medical historians, specific theme; the sessions are recorded and proceed- policy-makers and researchers, the 2009 series focused ings are printed and then distributed in book form as on themes in tropical disease research and control. It was well as on the Internet. co-organized by TDR along with WHO’s Department of Neglected Tropical Diseases. He and WHO colleagues are now also planning a 2010 series on “emerging issues and trends in global health The series highlighted how interchange between social and disease control.” Plans call for a focus on climate scientists and scientists can lead to new ways of looking change, environment and health in 2011. at disease control challenges – identifying issues from the past with modern-day relevance. Past meets present across disciplines From the Wellcome Centre side, Sanjoy Bhattacharya has been another key driving force in the initiative. Along with seizing a compelling theme, the 2009 series on tropical diseases broadened its appeal through use “The series is a wonderful way of getting social scientists of new internet technology. and scientists involved with policy management,” says Seminars were broadcast live as “webinars.” This permitted researchers around the world to tune into WHO in Geneva, the ‘nerve centre’ of global health,

WHO/TDR hear world-class presenters, and then fire questions at them live. The webinars are now being converted to podcasts. The tropical disease sessions also had a unique format. Each involved two speakers – one an academic historian or social scientist, and the other a scientific expert fluent in current issues of research and control. Often, the historian chose to speak his or her mind on topical policy themes, while WHO research and policy fig- ures demonstrated their fluency in historical retrospective. No doubt the inherent drama of the material also helped. From the practice of research volunteers self-infecting with malaria and yellow fever, to the combing of swamps Research capability strengthening in TDR’s early days: Laboratory and deserts to collect insect vectors of disease, the philo- practice during a 1978 TDR-sponsored workshop on enzyme-linked immunosorbent assays (ELISA) at the Institute of Parasitic Diseases, sophical, ethical and scientific layers of dialogue offered Chinese Academy of Sciences, China. a welcome step-back perspective. No. 84 Articles | Global Health Histories

The 2009 seminar series began in March with a focus on and socioeconomic development virtually eliminated the leprosy and a historical examination of the political and disease from these regions. social forces that drove the elimination campaign. The series then moved onto dracunculiasis (guinea worm), Current malaria control efforts, however, focus mostly trypanosomiasis (sleeping sickness), onchocerciasis on drug treatment, bednets and chemical vector control. (river blindness), malaria, Chagas disease, leishmaniasis A key history lesson – that malaria control and effective (kala azar) and tropical disease vectors (see p. 27). vector control succeeded as a result of an integrated package of approaches that also emphasized environ- Former TDR director Adetokunbo Lucas was one of two mental management and socioeconomic development guest speakers to close the 2009 series, presenting on – needs to be reinforced in modern-day programmes, the changing role of pharmaceuticals in world health at both Packard and Kroeger emphasized. a 2 December session. Lucas, director from 1976-1986, spoke of the innovative role that TDR played in research Other speakers highlighted the dynamic nature of dis- on new drugs and diagnostics – a quest so successful ease control, even in the so-called “elimination phase”. that it overtook, in some cases, the quest for vaccines. In his presentation on the history of sleeping sick- “Three major advances occurred in response to WHO/ ness, Jean Jannin, coordinator in the Department of TDR initiatives,” Lucas said. “Global networks of scien- Neglected Tropical Diseases, noted that elimination is tists generated new knowledge, with a noticeable im- not a static state. Sleeping sickness was thought to have pact. New models of collaboration with the pharmaceu- been virtually eliminated in the 20th century, only to tical industry demonstrated the value of public-private rebound again. partnerships for product develoment, and pharmaco- History’s lesson, Jannin observed, is that even when philanthropy emerged as a new phenomenon.” “elimination” is reached, “what-next” scenarios need to be examined, new tools honed and strategies planned to History’s value to research today maintain the achievement. 26 Despite massive advances in technology, transport, com- History has also underlined how political stability is an munication and education, the series has highlighted how essential ingredient of disease control – time and time contemporary scientists face many of the same challenges again, control campaigns suffered major setbacks after as their predecessors. Author Aldous Huxley’s comment civil war or strife created conditions in which the parasitic on history seems to sum it up: “From age to age, nothing vectors of disease could once again thrive. changes and yet everything is completely different.” Such defeats, however, can contain lessons – if they are In particular, lessons learned from history are not always studied and absorbed, notes Hooman Momen, WHO remembered. That was all too evident in a November ses- focal point for the seminar series: “Failure is not bad for sion on the topic of vector control for tropical diseases, research; in many instances more can be learned from co-presented by Randall Packard, Institute of the His- failure than from success.” tory of Medicine, Johns Hopkins University, and Axel Kroeger, a Liverpool School of Tropical Medicine scientist Yet while failure can teach a great deal, success is better. working in TDR. In his presentation on the campaign against river blind- Packard noted that malaria was widespread in southern ness (onchocerciasis), Janis Lazdins-Helds focused on England, the southern USA and Italy until agricultural how the campaign to control and eliminate onchocerciasis achieved many of its goals due to the constant interaction between control officers and researchers who tested and refined strategies for treatment and distribution of the drug, ivermectin, via community-based channels. Not only that, but Africans led much of the contemporary research and control effort. “I wonder if the success of the oncho control programme also then had something to do with the African perception

Private collection of Dr Uwe Brinkmann collection Private of the past,” he later asked. The ex-colonial era medical officers involved in modern- day onchocerciasis control also were keenly aware of his- tory, adds Jesse Bump of Harvard University, who spoke about the colonial and post-colonial forces that thrust on- chocerciasis onto the international stage. “Key programme advocates, including ex-French and British colonial staff who were core advocates to the international agencies in the early days of the global programme, were aware of

Onchocerciasis control field work in the early days of the global how previous control efforts had failed and were eager to partnership to control and eliminate river blindness, Mali. overcome those barriers.” Articles | Global Health Histories No. 84

Seminars in the series

Leprosy: Why is elimination so elusive? 100 years of Chagas Disease: A continuing public • Michael Worboys, director, Wellcome Unit for the health challenge History of Medicine, University of Manchester, UK • Simone Kropf, professor of history, Oswaldo Cruz • SK Noordeen, former director, WHO Leprosy Foundation, Brazil Elimination Programme and former president of the • Gabriel Adrián Schmunis, formerly of Communicable International Leprosy Association, India Diseases Unit, WHO American Regional Office, USA

End of the ancient dragon? Eradicating guinea worm Kala azar: Can visceral leishmaniasis ever be controlled? disease • Robert Killick-Kendrick, honorary research fellow, • Anne Marie Moulin, research director, Centre Imperial College, UK National de la Recherche Scientifique, France • CP Thakur, emeritus professor of medicine and • Dirk Engels, coordinator of preventive chemotherapy, former health minister, India Department of Control of Neglected Tropical Diseases, WHO, Switzerland Tropical disease vectors: Identification and control

Sleeping sickness: The controversy continues “How malaria became a vector-borne disease” • Guillaume Lachenal, lecturer, History and Philosophy • Randall Packard, chair and William H Welch professor of Science, University of Paris Diderot, France of history of medicine, Institute of the History of • Jean Jannin, coordinator, Innovative and Intensified Medicine, Johns Hopkins University, USA Disease Management, Department of Control of • Axel Kroeger, professor of international community Neglected Tropical Diseases, WHO, Switzerland health at the Liverpool School of Tropical Medicine, UK, and scientist, TDR, Switzerland River blindness: The keys to control 27 • Jesse Bump, fellow, Harvard University, USA Essential and inessential medicines: The changing role of • Janis Lazdins-Helds, former coordinator of drug pharmaceuticals in world health development, TDR, Switzerland • Jeremy A Greene, assistant professor, Harvard University, Brigham & Women’s Hospital and Malaria treatment and control: A cultural history of Harvard Medical School institutions, methods, and metaphors • Adetokunbo Lucas, former director, TDR, Switzerland, • Peter Brown, professor of Anthropology and Global and former professor of international health at the Health, Emory University, USA Harvard School of Public Health. n • Andrea Bosman, scientist, WHO Global Malaria Programme, Geneva, Switzerland

A subjective past Learning from each other In the early days of tropical disease campaigns, elimina- Free exchange stimulated by the Histories series has per- tion strategies and surveillance expeditions often were mitted a fresh look at such records, and debate around shadowed by colonialist goals, laced with a certain sen- conventions that evolved. timent of European cultural superiority, and organized Guillaume Lachenal, of the University of Paris Diderot along the lines of military campaigns. who spoke about the politics of international health, Historical records and archives often reflect the biases of commented: “The seminars provoke, allowing us to hear cultural, socio-economic and political forces dominant fresh things about global health – which has sometimes at the time, Bhattacharya notes. the tendency not to question its words and categories.” Even maps, sometimes used as a comparison point for Added Bump, “I came to provide perspectives in river contemporary research, were often created with po- blindness control. I left with a much deeper appreciation litical agendas in mind. “When carrying out research of the science and personalities involved. The dialogue now, such subjectivity must be re-visited,” Bhattacharya between historians, policy-makers, scientists and prac- points out. titioners is as valuable as it is rare. The organizers of this wonderful forum are to be commended for their vision.” y As Simone Kropf, who spoke about Carlos Chagas, observed: “The neglected disease debate can only gain For more information: www.who.int/global_health_histories/ from exploration of how certain health topics have been seminars/2009/en/index.html given varying degrees of political and social relevance over time, depending on national contexts and interests WHO contact: Hooman Momen, involved.” [email protected] No. 84 Interview | Malaria WHO/TDR/Crump

28 How TDR helped transform an ancient Chinese anti-fever cure into a modern malaria drug

Processes for artemisinin extraction from the Artemisia annua plant are tested at the University of Geneva in the early days of artemisinin’s development as an antimalarial drug.

Professor Zhou Yiqing, the Chinese scientist who led the development of artemisinin, credits TDR for calling global attention to Chinese research on the topic in the 1970s – research which otherwise might have been ignored. Zhou was interviewed by the WHO Bulletin after he and his team won the 2009 European Inventors of the Year award (in the non-European countries category) for developing the first internationally-registered artemisinin-based combination therapy (ACT) for malaria, Coartem®.

What was your first experience of malaria? Is that what spurred you to do research to find anti­ malarial drugs? Prof. Zhou: In the battle to cross the Yangtze River in 1949, I contracted the disease for the first time and suf- Prof. Zhou: While I worked as a battlefield doctor, one fered recurring bouts. No effective medicine was avail- thing bothered me most: wounded soldiers begging me able. The pain left a sharp impression on me. I received to save their lives, but sometimes I just could not help an arsenic injection and, later, Atabrine (quinacrine) them. However, my official participation in the research pills. The pills made me turn bright yellow. Although project stemmed from the Viet Nam War... I witnessed the side-effects were serious, I survived. rampant malaria that reduced the combat strength by Interview | Malaria No. 84

half, sometimes by up to 90% when the soldiers became ill. There was a saying, “We’re not afraid of American Zhou: “Essays caught the eye of WHO” imperialists, but we are afraid of malaria,” although in fact the disease took a huge toll on both sides. Later, we submitted a report to China’s Central Military Commit- tee stressing the importance of developing China’s own antimalarials. Taking our advice, the central government European Patent Office Patent European set up a panel of more than 500 medical military and civilian experts to develop new anti­malarial treatments for stricken soldiers. This was classified as a top-secret state mission named Project 523 after the date, 23 May 1967, when it was established.

What made you and your team think of using artemisinin to treat malaria? The son of peasants, Zhou was born in 1929 and joined the Eighth Route Army (later part of the People’s Prof. Zhou: Project 523 included two groups engaged Liberation Army) at age 16. During the Sino-Japanese in antimalarial drug development: one to devise chemi- War and the War of Liberation (Chinese Civil War) he cal medicines, another to examine traditional Chinese served as head of a nursing squad, physician assistant and eventually doctor-in-charge. In 1960, he graduated medicines. The latter group included researchers as well from medical school and later became a researcher as traditional Chinese medicine doctors, who as part at the Institute of Microbiology and Epidemiology of Chairman Mao’s barefoot [doctors] scheme scoured of the Chinese Academy of Military Medical the nation to collect folk remedies. Experts screened Sciences. His comments to interviewer Cui Weiyuan a list of herbs and folk remedies, a few of which were about the critical role played by TDR in convening an international conference in Beijing in 1981 on found to have a curative effect against malaria. In the “Artemisinin and its variants” are excerpted here. end, Artemisia annua was chosen for further research. Combining knowledge of traditional and modern In the early 1970s, a Project 523 team first isolated medicine, Professor Yiqing Zhou and his team at the 29 artemisinin from the plant. Clinical trials confirmed Institute of Microbiology and Epidemiology in Beijing its antimalarial effects. Between 1976 and 1978, the developed Coartem®, a potent antimalarial drug. n molecular structure of artemisinin was identified and more artemisinin derivatives were developed. In 1979, artemisinin-based antimalarial drugs were first used in the battlefield in the Sino-Vietnamese War (the people outside China. Yet I knew it could cure patients Third Indo-China War). and bring hope and health back to those suffering from malaria. How could I watch such a good medicine die What role did the World Health Organization silently in the laboratory and do nothing about it?...I (WHO) play in the early development of ACT? went to the Ministry of Science and Technology, which introduced me to China International Trust and Invest- Prof. Zhou: In the early 1980s it seemed that ment Corporation (CTIC). With the state’s approval and antimalarial research was over for good. Fortu- CTIC’s help, we were introduced to Novartis [which nately, essays published by Project 523 sci- co-sponsored the drug’s development]. entists caught the eye of WHO. In around 1979, TDR expressed interest in coopera- Looking back, you must be proud of your achievement. tion on antimalarial research. But after Prof. Zhou: I am proud of what we achieved with our Project 523 was disbanded in 1981, there partners. To date, Novartis has provided over 250 mil- was no one to negotiate the issue. lion treatments at cost to patients in the developing In 1981, TDR held the first international conference world, helping to save an estimated 630 000 lives. The in Beijing on artemisinin and its variants. The next year, credit goes to my country and the thousands of scien- thanks to WHO/TDR’s efforts, the National Chinese tists, researchers and barefoot doctors – some of them Steering Committee for Development of Qinghaosu [sweet died before they could see the great things Coartem® wormwood] and its Derivatives was set up under the could do – together with government officials and our Ministry of Health to replace Project 523. The project partnership companies and organizations. Coartem® was saved. Although the cooperation between the Na- would not have been possible without them. y tional Committee and WHO and TDR was suspended, they continued to provide support. This Q&A is excerpted with permission from the complete Why did you introduce ACT outside China? interview available in the October 2009 issue of the WHO Bulletin (vol. 87, no. 10) at www.who.int/bulletin/ ® Prof. Zhou: Today, our discovery, Coartem , has proven volumes/87/10/09-051009/en/index.html. to be highly effective and well tolerated, with high cure For more on TDR’s historical role in the development of artemisinin rates of over 95%, even in areas of multi-drug resistance. see the 30th anniversary TDR history book, Making a difference – But in an emerging economy like China, nobody has the 30 years of research and capacity building in tropical diseases, money to support development of a medicine that has (WHO, 2008) available online at: www.who.int/tdr/about/history_ no domestic market and is mostly consumed by poor book/anniversary_book.htm The world of TropIKA.net TropIKA.net is a web portal that aims to foster innovation and knowledge application relating to research on infectious diseases of poverty. Recent selections are presented here.

As we mark TropIKA.net’s as a whole as well as on the second year, considerable issues presented in blogs, progress has been made commentaries, and meeting towards our goal of forums. Suggestions will becoming the leading be incorporated into our web portal for research development plans. n on infectious diseases of poverty. Knowledge hubs This progress is due in large part to contributions TropIKA.net’s “knowledge Patrick Adams and Dr Onikepe Folarin reporting for the MIM from a growing circle of hub” initiative provides knowledge hub in Nairobi. contributors, web browsers opportunities for participants and forum/meeting to contribute more effectively The Forum 2009 meeting, malaria researchers, control to large health forums. People 30 participants. 16-20 November, was managers and decision- who are not at the meeting attended by some 800 makers, involving some We will continue to dedicate can use the knowledge hub to scientists, policy-makers, 2000 participants. During ourselves to the task of be virtually present. health care workers, funders the conference week, the bringing different research and other stakeholders. Its number of visits to TropIKA. constituencies together Visit the TropIKA.net theme was “Innovation for net nearly doubled due to to share knowledge and knowledge hub’s coverage the health of all”. Highlights the interest generated in the dialogue. We hope that the of three major meetings in 2009. The most recent of the comprehensive meeting fora. wide range of new content was Forum 2009, the annual TropIKA.net coverage in all website sections TropIKA.net interviewed meeting of the Global Forum included an interview with will stimulate further ten MIM delegates on their for Health Research, 16-20 the Global Forum’s next participation in this exciting malaria research endeavours. November in Havana, Cuba. executive director, Anthony venture while our expansion High-profile delegates The 5th Multilateral Initiative Mbewu. continues. on Malaria (MIM) Pan-African interviewed included: Rose Carlos Morel, director of the A key element of the Malaria Conference was held Leke, chair of the new MIM Center for Technological TropIKA.net initiative is 2-6 November in Nairobi, secretariat at the University Development in Health at interactivity. Every item Kenya, and the 2nd Meeting of of Yaoundé I Biotechnology FIOCRUZ in Brazil, also was appearing on TropIKA.net the African Network for Drugs Centre in Cameroon, Sanjeev interviewed. He said Cuba’s includes a “comment” facility and Diagnostics Innovation, Krishna from St George’s innovations in technology for feedback. We welcome in Cape Town, South Africa, Hospital in London and can be exported to other comments on the portal 4-7 October 2009. Pedro Alonso of the Malaria developing countries, Eradication Research Agenda with adjustments made (malERA). for differing levels of infrastructure development. MIM-related guest blogs included contributions from The diversity of topics Roma Chilengi, head of discussed in Havana is clear clinical trials at the KEMRI/ from such TropIKA.net Wellcome Trust Research articles as “What will happen Programme in Kilifi, Kenya; to primary care in Cuba Ashley Birkett, director of when the US embargo comes pre-clinical development down?” and “Digital health at the PATH Malaria Vaccine care in rural India: the costs Initiative; and Kevin Marsh, and benefits of broadband.” director of the Wellcome- Readers can comment on all KEMRI-Oxford Collaborative session reports. Research Programme. We The Multilateral Initiative on welcome invitations to create Malaria (MIM) conference, TropIKA.net Knowledge Hubs 2-6 November, was the at upcoming health fora or TropIKA.net knowledge hubs: the next best thing to being there. largest-ever gathering of scientific conferences.n TropIKA.net No. 84

Reports Profiles Reports by global health Twenty experts have been agencies and institutions are profiled since the project’s another important source launch. We chose a diverse of information on new range of interviewees from developed and developing health and health research Matlashewski WHO/TDR/ developments. TropIKA. countries, including net has so far summarized specialists in industry, and commented on 60 such academia and global health reports. Recent examples agencies. For example, include the joint UNICEF/ Many visceral leishmaniasis victims in Asia and Africa are children. Professor Brian Greenwood WHO report, Diarrhoea: – probably Why children are still dying the southern Sudan and West O riginal articles best known for and what can be done, Africa’s largest-ever dengue his pioneering These items are especially WHO/TDR and a report from the fever outbreak. Claims from work against written for the site. For International Federation of expert groups that the most malaria – example, the TropIKA.net Red Cross and Red Crescent neglected of all infections of spoke about team examined recent Societies on the damage poverty are pneumococcus the neglect reports on fake and done by infectious disease and Haemophilus influenzae B of two major substandard medicines, epidemics in the South. A were also covered in TropIKA. infectious killers of the poor, describing the huge report from a workshop net. Not all of the news is meningitis and pneumonia. numbers of these products held by the UK Academy bad; genetic mapping of And Professor Wen Kilama in circulation as a “neglected of Medical Sciences, Global Schistosoma mansoni has of the African epidemic of poverty. “ health diagnostics: research, opened new opportunities Malaria Network Trust development and regulation, for research into We hope to expand the WHO/TDR also appeared in our reports schistosomiasis. Encouraging number of original articles (AMANET) section. n new reports suggest the we publish. Contact TropIKA. talked of North–South research gap is net if you would like to write the pressing need for narrowing. for us. n N ews more African 31 New initiatives reported have scientists on the front lines TropIKA.net aims to provide included the African Leaders of research. timely reports on key news Malaria Alliance and a new Editor’s choice in research on infectious effort to combat neglected and blogs Other recent interviews: diseases of poverty. The more tropical diseases in Latin • Professor Alan Fairlamb than 400 stories published in Something new appears on America and the Caribbean. of Dundee University (UK) TropIKA.net News also relate the TropIKA.net blog nearly to news of disease outbreaks; The Centenary anniversary every day. The blog offers • Larry Geiter and for example, the new since the discovery of Chagas readers an opportunity to Charles Wells of Otsuka epidemic of leishmaniasis in disease was also featured. n comment on TropIKA.net Pharmaceuticals articles and on developments • Michael Gottlieb, head elsewhere. The blog editorial of the Grand Challenges team also alerts readers to F rom the journals project at the Foundation interesting items they have for the National Institutes TropIKA.net has highlighted nearly 400 published spotted on the internet. The of Health (USA) medical articles in the form of summaries and blog includes an “Editor’s • Professor Ogobara commentaries. choice” section highlighting Doumbo of Mali’s Malaria content added to the website Some examples of the diversity of articles: Research Training Centre - Barriers to the effective treatment and prevention of and new developments, • Professor Christopher malaria in Africa: a systematic review of qualitative studies. sometimes controversial. See, Plowe of the University of - Prevalence study of yaws in the Democratic Republic of for example: A time to honour commitments; Too many Maryland (USA) Congo. organizations, too much talk; All - Genomic diversity and evolution of Mycobacterium • Awa-Marie Coll-Seck, controversy is good controversy executive director of ulcerans revealed by next-generation sequencing. …perhaps. n the Roll Back Malaria - Decreased motivation in the use of insecticide-treated Partnership nets in a malaria-endemic area in Burkina Faso. - Cost of dengue cases in eight countries in the Americas • Jimmy Whitworth, head and Asia: a prospective study. The future of international activities at the Wellcome Trust (UK) - Mapping the health research landscape in sub-Saharan Looking ahead, new initiatives Africa: a study of trends in biomedical publications. are planned to enrich your • Professor Rose Leke, visit to TropIKA.net. These As well as articles reporting new findings, we have include the publication of the highlighted reviews, discussions and opinion articles, TropIKA Reviews – rigorous WHO/TDR including: assessments of the available - The global burden of trachoma. evidence on key research - Malaria and vitamin A deficiency in African children: questions and issues relating Contacts: a vicious circle? to policy and practice on Dr Ayoade MJ Oduola, - Access to antimalarial therapy: accurate diagnosis is meeting challenges of [email protected] essential to achieving long term goals. the infectious diseases of of Cameroon’s University of Ms Edith Certain, poverty. n Yaoundé I n [email protected] No. 84 Meetings | Quality management • Visceral leishmaniasis

developed. This would assist TDR in Quality management advisory identifying opportunities and goals for committee recommends ‘quality improvement, QMAC members stated. council’ and manual Quality manual The committee also recommended that a TDR quality manual be developed, in- cluding a description of programmatic policies, quality objectives and instruc- tions regarding processes and practices.

Such a manual would be useful not only for the quality management team, but across TDR as a whole. It should reflect a broad-based sense of ‘ownership’, and be perceived as speaking ‘on behalf of’ research teams to whom it is addressed.

Mihai Mihut Organizational commitment Quality management in action: a Good Clinical Practice refresher course for clinical monitors, held in July 2009 under the auspices of TDR and the WHO/TDR Clinical Coordination and Training Center, Thailand. Openness, transparency and communi- cations are essential for an effective qual- TDR’s Quality Management Advisory Positioning ity management process, as are effective Committee (QMAC) recommended that and timely feedback, the committee A TDR “quality council” would facilitate a TDR ‘quality council’ be established members emphasized. 32 buy-in and ownership of QM processes, and a quality manual be developed to driving continuous improvement and pro- Indeed, quality management is best prac- help provide oversight and monitoring viding direction on strategic quality issues, ticed as a positive feedback loop driven by of TDR’s quality managment activities. QMAC members stated. the achievement of clearly-defined goals. The QMAC met 14-15 September in Geneva. The proposed council, composed of TDR The need to allocate appropriate resourc- members, would both reflect and reinforce es, autonomy, authority and accountabil- Quality management aims to enhance a broad-based organizational commit- ity to the quality management team was the quality of TDR-supported scien- ment to continuous quality improvement. also underlined. tific research. The concept embodies elements of quality assurance, quality Such a group could identify actions and It was noted that TDR’s senior manage- control and quality improvement. specific quality management initiatives to ment is committed to quality manage- be implemented across the research pro- ment, including simplicity, consistency In practical terms, this translates into gramme’s activities, as well as monitoring with goals and objectives, and emphasis accountability for the quality of both and reporting on quality management- on outputs and outcomes. y research processes and deliverables related aspects of performance. – including issues such as patients’ protection during clinical trials and The proposed council should also de- quality-assurance of data and research velop a feedback cycle, using evidence Contact: Dr Juntra Karbwang, findings. and quality indicators that would be [email protected]

Based on these elements, a comprehen- SAC discusses new tools for visceral sive VL elimination approach can be de- veloped. This can be specifically tailored leishmaniasis elimination to highly endemic areas where the ma- jority of VL cases occur, in line with rec- Efforts to eliminate visceral leishma- The SAC noted that new tools have made ommendations by national programme niasis (VL) on the Indian subcontinent the ground ready for more active case managers and principal investigators in are at a pivotal moment, thanks in detection efforts supported by the rapid the target countries: Bangladesh, India large part to TDR-supported develop- diagnostic test rK39. Clinical trials also and Nepal. ment and evaluation of new drugs are underway of a potential new com- and diagnostic tools. That was the bination treatment of miltefosine and As these new tools are deployed, research consensus of the Scientific Advisory AmBisome® (liposomal amphotericin should also monitor their effectiveness Committee (SAC) on Elimination of vis- B). Quality-assured vector management in reducing VL caseloads as well as the ceral leishmaniasis (BL 10) at the group’s was also discussed as another important number of cases of post-kala azar dermal second meeting 6-8 July in Geneva. dimension of strategies. leishmaniasis (PKDL) following treatment. Meetings | Community-based interventions No. 84

The presence of asymptomatic VL infec- tions, which remain untreated, would be another important focus, SAC members recommended.

SAC members underlined that VL elimi- WHO/TDR/Matlashewski nation, and subsequent maintenance of very low levels of parasite transmis- sion, would not be possible without a better understanding of the role of both PKDL and asympto­matic individuals in VL transmission.

With regard to vector control, the SAC recommended that efforts should build on existing capacities and opportunities in country health systems, especially in A traditional caregiver (Asha) discusses visceral leishmaniasis and other common health problems with a the field of malaria control and other TDR and Indian health services team visiting Goanpura village, Bihar, in November 2009. vector-borne diseases. To guide these efforts, the SAC urged the development view of the huge challenges posed by • support close coordination among na- of a monitoring and evaluation manual tional, district and local programme and detailing standard operating procedures vector-borne diseases in the region, health personnel; on key project elements. The document the SAC recommended that a vector should be developed jointly by research biologist should be included on the • involve the private sector; teams and programme managers, and committee. • enhance current passive case detection; its use should be supported by a training Turning its attention to case detection, • incorporate geographic information; 33 programme. the SAC reiterated the need for better di- • establish and utilize standardized case As recent research shows that impreg- agnostic tools, particularly for PKDL. The definitions; committee also endorsed formulation nated bednets can serve as a strong • Include mechanisms for data analysis of diagnostic criteria for asymptomatic complimentary intervention to indoor and timely feedback to public health infection and urged support for imple- residual spraying (IRS) in endemic ar- and vector control programmes and eas, the SAC recommended research mentation research using geographic in- local health facility personnel. y examine combining IRS with either formation systems (GIS) data. Finally, the long-lasting insecticide-treated nets SAC recommended the strengthening of Contact: Dr Greg Matlashewski, and/or environmental management kala azar and PKDL surveillance. Overall, [email protected] through lime plastering of walls. In the SAC urged that TDR’s VL research:

Analytic framework for community-based interventions (CBI) should be developed

An analytic framework for ‘community- poor, rural communities in Africa can dra- based’ health interventions (CBI) should matically improve access to antimalarial be developed to see how various strat- treatments and bednets when given the egies, including school-based health means to direct the the distribution of an WHO/TDR/Crump programmes and other social marketing integrated package of health treatments. approaches, relate to the Community di- The approach, dubbed community- rected interventions (CDI) strategy tested directed interventions (CDI), was tested in by TDR in onchocerciasis-endemic areas communities that already had experience of sub-Saharan Africa. with such annual distribution of ivermec- This was a key recommendation from tin treatment to combat onchocerciasis. the Strategic and Scientific Advisory TDR’s BL 11 has since been spearheading Committee (SAC) meeting of TDR’s new research on guidance and tools for Community-based interventions business the scale-up of the CDI approach. While line (BL 11), 23-25 June, in Geneva. CDI should remain TDR’s main focus, an Community-directed distribution of ivermectin to combat river blindness in Mali: A community In a major research milestone, a TDR study analytic framework examining the wider distributor records the number of tablets given published in 2008 demonstrated that range of community-based interventions to each member of the household. No. 84 Meetings | Strategic alliances

would help place the range of available Along with proposing the analytical deferred pending availability of funds strategies and experiences into a more framework, the SAC also reviewed and and further development and testing holistic context, the SAC said. That would refined qualitative and quantitative in- of interventions in African settings. dicators to measure the impact of inte- help guide coherent future research The SAC also urged BL11 to strengthen grated community-based interventions. directions. collaborations with other TDR research These would include: The SAC recommended that the new teams whose activities make use of • improved health delivery (increased CBI-type approaches or might benefit analytic framework also include a section access to health services); from using such methods in the future. devoted to ethical issues relative to pub- These include TDR business lines in: lic health practices in disease-endemic • empowerment of communities; drug development and evaluation for countries. • evidence of inclusion of CBI in health helminths and other neglected tropical Resources on this topic would be drawn policies, strategies and guidelines. diseases (BL 6); evidence for antimalar- ial policy and access (BL 9); and research from the disease and thematic reference While integrated community-based to support the elimination of visceral group reports to be published in 2010 interventions have been effective in leishmaniasis (BL 10). y (see Stewardship, p. 11). The committee different settings, the SAC has so far recommended that all future calls for advised that TDR activities be limited to proposals issued by BL 11 call attention Africa for the time being. Decisions on Contact: Dr Soumya Swaminathan, [email protected] to ethical issues in public health research. expansion to other regions should be

Strategic Alliances Advisory Group recommends moves for strengthening TDR partnerships 34 A newly formed Strategic Alliances outreach to the media should be ex- Geographical outreach: The Middle Advisory Group (SAAG) has called for de- panded. Stories collected from people East, China, Africa, Eastern Europe and velopment of a specific framework and whose lives have been changed by TDR- the Americas were all seen as areas communications strategy as initial steps supported activities will help partners where TDR should expand interactions. towards enhancing TDR’s partnerships appreciate the value of work undertaken. Researchers, academics, non-govern- with external bodies. Documentary film/video production can mental organizations, federal bodies, United Nations agency heads and min- The multidisciplinary group’s broad range be an important vehicle, highlighting isters of health also were highlighted successes as wells as gaps in funding and of expertise – spanning medicine, law, as groups with which TDR should build political decision-making. government, business, corporate and in- stronger links, depending on the region. ternational relations, innovation, journal- Potential partners: The SAAG experts Assisting countries in communicating ism and artistic creativity – is expected highlighted venture philanthropy and the research results through symposia and to build alliances that will increase the important role that the private sector (in- other supportive efforts, and helping to sustainability, effectiveness and growth cluding non-pharmaceutical commercial ‘sensitize’ political leaders about science of TDR-backed initiatives. Key recom- organizations and private academic and were also seen by the group as valuable mendations from an inaugural meeting in research institutions) can play in helping activities. SAAG encouraged TDR to take Geneva (8-10 June 2009) covered a broad TDR meet its goals both through funding advantage of existing regional and sub- range of topics, including: and advocacy. As charities, foundations regional initiatives in building these suggested links. y Partnership tools: Communications is and individuals can also aid in TDR’s ac- central to building new partnerships. tivities, TDR should continually scan the Communication of ‘challenges and im- horizon for ways to develop partnerships Contact: Dr Jane Kengeya Kayondo, [email protected] pacts’ should be emphasized and TDR with these potential sources of support. WHO/TDR/Schwarb

Contact: Jane Kengeya-Kayondo, [email protected] Meetings | Empowerment • Diagnostics No. 84

Empowerment SAC endorses new moves to address inequities in health research TDR needs to strengthen ties and share ex- periences on empowerment of develop- ing country researchers within WHO as well as with outside institutions and agencies. WHO/TDR/Schwarb This was a key recommendation emerging from the Strategic and Scientific Advisory Committee (SAC) of the Empowerment function, at a 2-3 July meeting in Geneva.

As part of this effort, TDR should strive to work more closely with the Council on Health Research for Development (COHRED), the Global Forum on Health and less experienced colleagues also were some cases, continues to manage, and to Research and other organizations, with encouraged. Workshops and guidance review the characteristics of such networks which TDR shares common aims and goals. on the writing of grant proposals also (in terms of portfolio, best practices, etc.). were suggested as tools that would help This will allow Empowerment to find ways In terms of practical support for research, empower researchers. that the networks can work together to training, networks and leverage, SAC also advance research leadership development. issued the following recommendations Training: Decentralization of high-quality to the Empowerment function: courses met with committee approval, Leverage: SAC endorsed Empowerment’s although SAC recommended that MSc/ new strategic leverage function, which Research: Progress in this area was wel- PhD and short course programs run for allows TDR to capitalize on its knowledge 35 comed, with the committee being par- and by disease endemic countries should and expertise to secure resources and ticularly encouraged by inter-country be examined for excellence, relevance commitments for effective, high-quality research collaborations such as the and inclusion of key scientific standards. global research on infectious diseases of South Africa-Zimbabwe collaboration SAC also encouraged institutional coop- poverty. SAC also urged the business line to strengthen capacity in entomology. eration on training initiatives between to identify pivotal individuals or institu- Looking ahead, Empowerment should developed and developing countries as tions that can create conglomerates of identify new institutions and health re- this can increase training efficiency and leaders with those in other developing searchers with which to partner. It also benefit candidates from small countries. countries, and so help reduce inequalities should develop a list of potential funders in health research. y and their areas of interests – so as to help Networks: The committee encouraged match researchers with potential fund- Empowerment to analyse the nature and ing sources. Development of mentorship extent of TDR’s relationship with the vari- Contact: Dr Glenn Laverack, [email protected] schemes between established researchers ous networks that it has fostered and, in

advocacy brochures) be enhanced in or- Diagnostics SAC recommends der to improve awareness of the activity expanded advocacy effort and its impact. Concretely, the SAC approved a new With validated rapid diagnostics tests In terms of regulatory issues, there is a project to develop a set of “assured” prod- now available for a number of major trop- need for more effective regulation of di- uct specifications for new diagnostics in ical diseases, TDR’s diagnostic activities agnostics at the country level in order to various disease specific areas. The test have leveraged impressive results with prevent these markets from being domi- specifications, endorsed by international modest investment, according to the nated by cheap and unreliable products and scientific and medical communities, Strategic and Scientific Advisory group that discourage quality manufacturers. would then be made widely available to (SAC) on Accessible, quality-assured diag- The committee recommended that the test developers via the TDR website and nostics (BL 7). Diagnostics BL should explore with key other communications channels. SAC countries options for providing quality also approved a proposed study of the Along with ongoing work to advance standards and improving the regulation health impact of bad diagnostics to be testing and evaluation of more rapid of diagnostics tests. undertaken by the London School of diagnostics for a range of diseases, the Hygiene and Tropical Medicine (LSHTM). cross-cutting issues of regulation and In terms of advocacy, there is a need advocacy need to be addressed in the to raise the profile of TDR’s diagnostics In terms of disease-specific issues, the coming two years, the SAC stated in a work. The committee recommended SAC reviewed the progress of diagnostics meeting 2-3 September in Geneva. that communications (e.g. web portal, research in a range of areas. No. 84 Meetings | Tropical medicine conferences

These includeed: schistosomiasis, tuber- to single tests) comprised of new tools testing continue and that the business culosis (TB), malaria, visceral leishmania- such as light-emitting diode (LED) fluo- line support further R&D for those tests sis (VL), human African trypanosomiasis rescence microscopy and “front-loaded” deemed promising. (HAT), dengue and other diseases, in- smear microscopy. Both strategies have Leprosy and cholera – The SAC sup- cluding influenza A (H1N1), leprosy and recently been found by TDR to improve ported a proposal to evaluate two new cholera and sexually transmitted infec- accuracy and reliability of diagnosis, and leprosy tests being developed by the tions. Among the recommendations front-loading can also facilitate one-day Infectious Diseases Research Institute in were the following: diagnosis with just two smear samples. Seattle, USA, and also expressed support Schistosomiasis – The SAC expressed sup- Malaria – The SAC assessed the results of for a possible TDR-led evaluation of rapid port for funding of a grant renewal submit- the first round of the WHO and Foundation diagnostic tests for cholera. ted by the National Institutes of Parasitic for Innovative New Diagnostics (FIND) Sexually-transmitted infections – Diseases in China. The funding would sup- evaluation of 41 malaria rapid diagnostic Activities supported by a three-year port five new provincial reference centers tests (RDTs). Satisfied with the quality of grant from the Bill & Melinda Gates on schistosomiasis diagnosis by providing that study, the committee recommend- Foundation, were reviewed and ap- quality assurance, quality control and ex- ed continuation with Round 2 as well proved for 2010. These include projects ternal quality assessment to build on the as the establishment of a WHO malaria related to the testing and field evaluation experiences of previous studies. specimen bank. of rapid diagnostics for sexually-transmit- TB – Exploring new diagnostics for pedi- VL – BL7 is currently coordinating a head- ted infections, and research on how to atric TB and the continued optimization to-head comparison of seven diagnostic scale up their use, particularly in Africa. y of smear microscopy as a diagnostic tool tests, four of which are widely available for TB in adults were among the directions on commercial markets in endemic coun- recommended. The SAC also proposed tries. The SAC reviewed the tests selected, operational research to determine the im- the evaluation sites and the research Contact: Dr Francis Moussy, [email protected] 36 pact of diagnostic packages (as opposed methods, recommending that product

Tropical medicine meetings highlight TDR-related presentations at ASTMH • Pre-referral rectal artesunate in rural African LATE health equity and access communities: experience in use; Chair, BREAKING Melba Gomes, TDR & Co-chair Malcolm NEWS Molyneux, Liverpool School of Tropical Early treatment of severe malaria in the than village health workers,” Gomes said. Medicine, UK community with rectal artesunate is most The symposium examined the challenges • Rapid diagnostic tools in theory and practice; effective when carried out by mother co- Chair, Jane Cunningham, TDR & Co-chair, of making the drug available in remote ordinators, according to the results of a Rosanna Peeling, London School of communities, addressing the percep- Hygiene and Tropical Medicine, UK new TDR-sponsored study presented at tions of patients (or their parents) about • Getting a rapid TB diagnosis: What can we the 58th annual meeting of the American the need for hospitalization after receiv- do with what’s available? Chair, Luis Cuevas, Society of Tropical Medicine and Hygiene TDR ing a suppository, and the intervention’s (ASTMH) 18–22 November in Washington. • A systematic review of the accuracy of rapid cost-effectiveness. diagnostic tests for malaria in endemic areas; Presenter, Piero Olliaro, TDR Widely considered the premier forum for Earlier, TDR scientists also participated in advances in tropical medicine and glo- • Parasitological impact of one-year preventive the 6th European Congress on Tropical mass chemotherapy on soil-transmitted bal health, the meeting explored links Medicine and International Health in helminthiasis and schistosomiasis in northern between global health and the safety, Verona. With its theme of Equity, human Rwanda; Presenter, Piero Olliaro, TDR security and economic performance of rights and access to care, the meeting For further information: www.astmh.org/ Abstracts_and_Education.htm countries around the world. Sessions were 6-10 September addressed topics rang- devoted to the relationship between nutri- ing from ethical challenges in clinical TDR-related presentations at the tion and infectious disease; new malaria research to gender-based violence in European Congress on Tropical diagnostics and treatments; the spread of refugee populations. Medicine & International Health pandemic influenza A (H1N1) and infec- • Home/near-home treatment: is this the way The meeting culminated in the Verona tious diseases’ socioeconomic impacts. forward? Moderator, Franco Pagnoni Declaration – calling for stronger European • Translating research into practice: using In a special symposium on rectal artesu- policies to address social determinants of systematic reviews in policies, guidelines nate, TDR scientist Melba Gomes described health, and in particular, risks to migrants and influencing change(Cochrane Infec- tious Diseases Group); Chairs, Paul Garner, the multi-country study of treatment at the and refugees “that directly or indirectly put Liverpool School of Tropical Medicine, UK community level by: village health work- at risk the life of migrant people and ham- & Piero Olliaro, TDR ers, traditional healers, mother coordinators per their access to health.” The declaration • Antimalarial treatments: registration & beyond, Chair, Piero Olliaro, TDR and a mix of the three. “The results show also asked donors to place the strength- that providing early treatment through ening of health systems at the centre of For further information: www.festmih.org/verona2009/ mother coordinators was more successful global health initiatives. y No. 84

Print and multimedia publications now available from TDR

Handbook: Good laboratory practice All TDR publications may be downloaded (2nd edition) from the TDR website: Quality practices for regulated non-clinical research www.who.int/tdr/publications and development 328 pp., 2008 (ISBN 978 92 4 154755 0) To order hard copies free of charge, please fax DOI 10.2471/TDR.09. 978-924-1547550 or mail us the attached publications order

SECOND form, or e-mail your request to: [email protected] EDITION Good laboratory practice (GLP) is HANDBOOK the recognized rules governing

GOOD LABORATORY the conduct of non-clinical Good laboratory practice training PRACTICE (GLP) Quality practices safety studies. They ensure the for regulated non-clinical research and development manual: Trainee (2nd edition) quality, integrity and reliability A tool for training and promoting good laboratory of study data. practice (GLP) concepts in disease-endemic countries 268 pp., 2008 (ISBN 978 92 4 154757 4) This 2nd edition handbook is designed to aid countries upgrading their

Special Programme for DOIResearch & Training 10.2471/TDR.09. 978-924-1547574 in Tropical Diseases (TDR) sponsored by UNICEF/UNDP/World Bank/WHO laboratories to GLP status. Based on the Organization

SECOND EDITION

Special Programme for Research & Training in Tropical Diseases (TDR) sponsored by This manual provides resource UNICEF/UNDP/World Bank/WHO for Economic Cooperation and Development (OECD) TRAINING MANUAL material for good laboratory principles of GLP, the handbook provides laboratories 37 practice (GLP) training. It is GOOD LABORATORY and trainers in disease-endemic countries with PRACTICE (GLP) based on the Organisation for technical information necessary to implement GLP TRAINEE Economic Cooperation and programmes. Development (OECD) principles Now available in hard copy, or for download at: of good laboratory practice, www.who.int/tdr/svc/publications/training-guideline- which are recognized as the publications/good-laboratory-practice-handbook international standard. The manual is designed to be used by trainees at TDR-GLP training workshops. It contains an introduction which highlights the history and fundamental points of OECD principles of GLP. O perational research in support of anti-retroviral therapy scale-up: Now available in hard copy, or for download at: Lessons learned workshop and product www.who.int/tdr/svc/publications/training-guideline- development team meeting publications/good-laboratory-practice-manual-trainee 44 pp., 2009 (ISBN 978 92 4 159876 7) DOI: 10.2471/TDR.09.978-924-1598767 Good laboratory practice training manual: Trainer (2nd edition) Scale-up of ART treatment is A tool for training and promoting good laboratory a major goal of African health practice (GLP) concepts in disease-endemic countries services. However, fears of social 268 pp., 2008 (ISBN 978 92 4 154756 7) stigmatization, as well as other

Special Programme for DOIResearch & Training 10.2471/TDR.09. 978-924-1547567 in Tropical Diseases (TDR) sponsored by UNICEF/UNDP/World Bank/WHO factors, may inhibit access to

SECOND EDITION available testing, treatment and Special Programme for Research & Training This manual is aimed at trainers in Tropical Diseases (TDR) sponsored by UNICEF/UNDP/World Bank/WHO follow-up counseling. This report TRAINING MANUAL of good laboratory practice (GLP) and is a companion manual summarizes the studies and GOOD LABORATORY PRACTICE (GLP) to the GLP trainee manual. findings of operational research TRAINER Distribution of hard copies, projects undertaken in Uganda, complete with CD-ROM, is Malawi, Burkina Faso, Zambia and the United Republic of strictly limited to those who have Tanzania to support anti-retroviral therapy (ART) scale-up. undertaken the TDR-GLP training It reviews lessons learned and reflects on how to take of trainers workshop or who are already GLP experts. operational research forward in the area of ART scale-up, and more generally. Now available in hard copy, or for download at: www.who.int/tdr/svc/publications/training-guideline- Available for download at: www.who.int/tdr/svc/ publications/good-laboratory-practice-manual-trainer publications/tdr-research-publications/op-research-hiv No. 84

Dengue: guidelines for diagnosis, In cooperation with others treatment, prevention and control

Pathways to better diagnostics for 160 pp., 2009 (ISBN 978 92 4 154787 1) tuberculosis: a blueprint for development Since the second edition of 125 pp., 2009 (ISBN 978 92 4 159881 1) Dengue haemorrhagic fever: diagnosis, treatment, prevention This publication offers a structure and control was published by to guide researchers through the the World Health Organization different phases of tuberculosis in 1997, the magnitude of the (TB) diagnostic development dengue problem has increased – from the discovery of new dramatically and has extended techniques and tools to their geographically to many delivery in neglected markets. previously unaffected areas. Described here are TB diagnostic This new edition represents a concise source of approaches and tools available information of worldwide relevance on dengue for today, and in the pipeline. The publication can help TB health practitioners, laboratory personnel, vector diagnostics researchers work more effectively with health control officers and other public health officials. The services as well as academics and industry professionals. guidelines provide updated information on clinical Available for download at: www.who.int/tdr/svc/ management, vector management, diagnostic publications/tdr-research-publications/tb-blueprint tests, surveillance, emergency preparedness and response. New and promising avenues of research and guidance on specialist areas related to dengue also 38 A vailable through others are discussed. Available for order (CHF 48.–/24.– for developing Global health risks, mortality and burden of countries) or download at: diseases attributable to selected major risks www.who.int/neglected_diseases/en/ 125 pp., 2009 (ISBN 978 92 4 156387 1)

A response to the need for Treatment Action Group 2009 comprehensive, consistent and pipeline report comparable information on health 70 pp., 2009 (ISBN 978 0 9819863 2 6) risks at global and regional level. Global health risks provides detailed Treatment Action Group global and regional estimates of (TAG) is an independent premature mortality, disability research and policy think tank and loss of health attributable focusing on antiretroviral to 24 global risk factors, ranging treatments, HIV basic science from environmental factors such as unsafe water and and immunology, vaccines sanitation to behavioural factors such as smoking and and prevention technologies, sedentary lifestyles. Many diseases and injuries are caused hepatitis and tuberculosis. by more than one risk factor. For example, the infectious This year’s TAG pipeline agent, Mycobacte­rium tuberculosis, is the direct cause report shows, in brief, a lull of tuberculosis. However, crowded housing and poor in anti-HIV drug development, an alarming stasis in nutrition also increase the risk. In turn, most risk factors hepatitis B treatment research, renewed activity (after are associated with more than one disease, and targeting a gap of almost 40 years) in TB drug development, those factors can reduce multiple causes of disease. For agonizingly slow and incremental progress in TB example, reducing smoking will result in fewer deaths and diagnostics research, very preliminary human studies less disease from lung cancer, heart dis­ease, stroke, chronic of several new TB vaccine candidates, a back-to- respiratory disease and other conditions. By quantifying basics mood in the HIV vaccine research community, the impact of risk factors on diseases, evidence- renewed hopes for efficacy in microbicide and pre- based choices can be made about the most effective exposure prophylaxis, and no dramatic developments interventions to improve global health. in immune-based therapies or therapeutic vaccines for HIV. Available for order or download at: www.who.int/healthinfo/global_burden_disease/global_ Download or order hard copies from: health_risks/en/ www.treatmentactiongroup.org/publication.aspx?id=3212 No. 84

Diagnostics TDR in the scientific press Ramsay A et al. New policies, new technologies: TDR-supported research leads to the publication of modelling the potential for improved smear microscopy hundreds of articles in the peer-reviewed press every year. services in Malawi. PLoS ONE, 2009, 4(11): e7760. In 2008, 212 articles were published with TDR support. Of doi:10.1371/journal.pone.0007760. those, 149 were by first authors from disease-endemic Scolari PS et al. Quality and reporting of diagnostic countries. A complete listing is posted on the TDR web accuracy studies in TB, HIV and malaria: evaluation using site at the end of each year (see the 2008 list at: www. QUADAS and STARD standards. PLoS One, 2009, 4:e7753. who.int/tdr/svc/publications/peer-reviewed-articles). PMID:19915664 doi:10.1371/journal.pone.0007753

During the year, peer-reviewed publications in each For other diagnostics articles, see: TDR area of work also are posted on the TDR web www.who.int/tdr/svc/research/quality-assured- site as they are identified. Examples of recent 2009 diagnostics/peer-reviewed-articles publications are noted below with links to more recent peer-reviewed publications by area of work. If you are a Drug development for helminths and TDR-supported researcher who has published an article neglected tropical diseases in a peer-reviewed journal and we do not know about it Sirima SB et al. The efficacy and safety of a new fixed-dose yet, you are welcome to send a link or PDF of the article combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium to: [email protected]. falciparum. Malaria Journal, 2009, Mar 16; 8:48. PubMed PMID: 19291301; PubMed Central PMCID: PMC2662869 Drug discovery doi: 10.1186/1475-2875-8-48. Nwaka S et al. Advancing drug innovation for neglected Olliaro P, Darley S, Laxminarayan R, Sundar S. Cost- diseases: criteria for lead progression. PLoS Neglected effectiveness projections of single and combination Tropical Diseases, 2009,3(8):e440. PMID:19707561 therapies for visceral leishmaniasis in Bihar, India. Tropical 39 doi:10.1371/journal.pntd.0000440 http://clinicaltrials. Medicine and International Health, 2009, 14:918-925 ploshubs.org/article/info:doi%2F10.1371%2Fjournal. Epub 2009 Jun 28. PMID:19563434 doi:10.1111/j.1365- pntd.0000440 3156.2009.02306.x

For other drug discovery articles, see: For other drug development articles, see: www.who. www.who.int/tdr/svc/research/lead-discovery-drugs/ int/tdr/svc/research/drug-development-helminths-ntds/ publications-resources publications-resources#_Peer-reviewed_articles

Innovative vector control Visceral leishmaniasis (VL) elimination Berriman M, et al. The genome of the blood fluke Mondal D et al. Visceral leishmaniasis elimination Schistosoma mansoni. Nature, 2009, 460:352-358. programme in India, Bangladesh, and Nepal: reshaping PMID:19606141 doi:10.1038/nature08160 the case finding/case management strategy. PLoS Neglected Tropical Diseases 3(1): e355. Tun-Lin W et al. Reducing costs and operational doi:101371/journal.pntd.0000355. constraints of dengue vector control by targeting productive breeding places: a multi-country non- Joshi AB et al. Chemical and environmental vector inferiority cluster randomized trial. Tropical Medicine and control as a contribution to the elimination of visceral International Health, 2009, 14:1143-1153. PMID:19624476 leishmaniasis on the Indian subcontinent: cluster doi:10.1111/j.1365-3156.2009.02341.x randomized controlled trials in Bangladesh, India and Nepal. BMC Medicine 2009;7:54 10.1186/1741-7015-7-54 For other vector control articles, see: www.biomedcentral.com/1741-7015/7/54. PMID:19804620 www.who.int/tdr/svc/research/vector-control- doi:10.1186/1741-7015-7-54 interventions/publications-resources For other articles on VL research, see: Antimalarial policy www.who.int/tdr/svc/research/visceral-leishmaniasis- Simba DO, et al. Factors influencing elimination/publications-resources adherence to referral advice following pre-referral treatment with artesunate suppositories in children in C ommunity-based interventions (CBI) rural Tanzania. Tropical Medcine and International Health, Diawara L et al. Feasibility of onchocerciasis elimination 2009, 14:775-783. PMID:19497077 with ivermectin treatment in endemic foci in Africa: first doi:10.1111/j.1365-3156.2009.02299.x evidence from studies in Mali and Senegal. PLoS Neglected Tropical Diseases, 2009, 3(7):e497. doi:10.1371/journal. For other articles on antimalarial policy, see: pntd.0000497. www.who.int/tdr/svc/research/antimalarial-policy-access/ publications-resources#_Peer-reviewed_articles For other articles on CBI, see: www.who.int/tdr/svc/research/community-based- interventions/publications-resources No. 84

is published three Celebrate the discovery, times a year by the Special Programme for Research and combat the disease Training in Tropical Diseases (TDR), sponsored by UNICEF/UNDP/World Bank and WHO.

Both html and PDF versions of the newsletter are available on the TDR website. All material submitted to TDRNews undergoes editorial review. Articles and illustrations published in TDRNews which are not copyrighted may be reproduced, provided credit is given to TDR and provided such reproduction is not used for commercial purposes. Articles do not necessarily reflect the views of WHO.

To our readers: We want to hear from you. Please send us your feedback, as well as letters and ideas on possible stories for TDRNews and on TDR-related tropical disease research issues, events, “Carlos Chagas’ 1909 discovery was a unique achievement in biomedical science and institutions, publications and showed that this brilliant scientist was more than a ‘microbe hunter.’ The description of personalities. Thank you! 40 Trypanosoma cruzi, its life cycle, vectors, domestic and sylvatic reservoirs and corresponding human disease, was both remarkable scientifically and in terms of its relevance to human health and well being. However, decades were required for international recognition of the profound impacts of Chagas disease in Latin America – and beyond. Today, a hundred years later, approximately 12-14 million people remain infected in 18 Latin American countries and an unknown number throughout the world. This silent ‘neglected disease’ progressively ruins lives. On the centennial of Chagas’ discovery, we call for a renewed effort to sustain and expand policies for continuous transmission control. We call for research into new and more effective means of preventing and eliminating Chagas as well as better treatments for already-infected individuals, who lack adequate therapies and diagnosis.” A ddress TDR World Health Organization – Joseli Lannes-Vieira, Maria de Nazaré Correia Soeiro, Tania C. de Araújo-Jorge, Paulo Gadelha, and Rodrigo Corrêa- 20, Avenue Appia Oliveira - Coordinators of the Fiocruz Program for Research and Technological Development on Chagas Disease (PIDC) 1211 Geneva 27 and organizers of the International Symposium on the Centennial of the Discovery of Chagas Disease, 8-9 July 2009, Oswaldo Switzerland Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. Fax: (+41) 22 791-4854 For more on the FIOCRUZ Centennial, see: www.fiocruz.br/chagas100 [email protected] www.who.int/tdr

TDR grant awards in 2009

In 2009 TDR awarded grants for post-graduate in 45 countries across funding are determined 104 grants to promote and research training. all WHO regions – with on the basis of TDR the vision of “fostering Africa and the Americas stewardship and Research grants include research on infectious being the most heavily priority-setting exercises. grants to institutions and disease of poverty in represented, followed Research projects are individuals in developed which disease-endemic by South-East Asia, the accompanied by TDR and developing countries countries play a leading Western Pacific, the coordination, monitoring on TDR priorities. role.” Eastern Mediterranean & evaluation, as well as These also may involve communications. For Empowerment and European regions. collaborations with details on TDR’s 2009 grants include grants governments, industry The awards ranged from grant awards, see: to developing- and networks for clinical small field studies to www.who.int/tdr/svc/ country scientists trials and drug R&D. high-tech collaborations grants/grants-awarded and institutions for on drug discovery. leadership training, The 104 grant awards For information on calls programme and career approved by TDR scientific Grant awards are only for grant applications development and skills- committees in 2009 were one component of please see: www.who.int/ building, as well as disbursed to recipients TDR’s work. Areas of tdr/svc/grants

ISSN 1028-5911 DOI: 10.2471/TDR.09.TNL.84.1028-5911