TDR news No. 63 October 2000 1
Published by the UNDP/WORLD BANK/WHO Special Programme for Research and Training in Tropical Diseases (TDR)
No. 63 October 2000 Into the next 25 years: new strategy plans approved by TDR’s top governing body More than six months of intense discussions skills) into the market in TDR led to the outlining of a new TDR place more quickly. vision and strategic plan for 2000-2005. ‘Implementation re- This plan was approved by the Joint Coor- search’ is the main new dinating Board (JCB), TDR’s top govern- thrust of TDR’s Inter- ing body, in June. The strategy discussions vention Development took into account past TDR successes and and Evaluation area failures, using, as guidance, the recommen- and represents an im- dations of the 3rd External Review Commit- portant new role for tee. That committee had recommended, in TDR. 1998, that TDR fundamentally restructure The new philosophy in the interaction between research and con- capacity building that trol, develop a new philosophy in capacity has emerged is for building, and take up a stronger disease fo- closer synchronization cus in the management matrix of TDR. of Research Capability One conclusion that emerged during the dis- Strengthening (RCS) cussions was that TDR was cutting short with TDR research and its work on new tool development, was stop- development (see page ping its research when obtaining ‘proof of 2). Other future principle’ after ‘demonstrating the utility of orientations of RCS, the tools in their intended setting of use … approved by the JCB, and the initial exploration of the most ap- include a focus on propriate means of their application’ (2nd South-South coopera- WHO/TDR/Crump External Review, 1987-1988). So TDR be- tion and the plans for gan to define ‘implementation research’ (see evaluation of impact. TDRnews No 62), and to make a more de- As to the stronger dis- termined effort to work in the overlapping ease focus recom- area between research and control in order mended by the 3rd Ex- to get its ‘products’ (tools or knowledge or ternal Review, TDR Bednets: proven efficacy, but how to increase use?
Inside will now operate by both tor, and, for Basic and Strategic Research, • Basic and strategic research 2 functional area and dis- incorporation of Social, Economic and Be- • Strengthening research capability 2 ease, in a matrix manage- havioural research and a focus on the post • TDR allocates US$ 500 000 for TB 3 ment. New TDR disease genome agenda (see page 2). Other aspects • GLP handbook in preparation 3 coordinators have been of the new strategy approved by the JCB appointed (see Staff Up- include a ‘dynamic’ portfolio in which new • TDR consultation on new TB diagnostics 4 date, page 6). diseases will be incorporated if and when • Improving treatment of tuberculosis 5 the need arises or funds become available, • Advocacy for eliminating filariasis 6 Strategic plans for the other functional areas of and intensive use of information and com- • The ethics of biomedical research 7 TDR include, for Product munications technology. • Effort to conquer schistosomiasis in China 10 Research and Develop- JCB endorsed the strategy as forward-look- • Home management of malaria 11 ment, stronger interac- ing and directed towards the end-user of the • Dengue/dengue haemorrhagic fever 12 tions with the private sec- outcomes of TDR research. • Dutch registration for artemotil injections 13 2 TDR news No. 63 October 2000
Basic and Strategic Research: the changing profile
Basic and Strategic Research (STR) in TDR genomics to better understand the disease group that will facilitate discussions be- is evolving, in accordance with the new processes. ‘DNA technology has improved tween all parties interested and involved in TDR strategy. The team now comprises and opened new opportunities for devel- transgenesis, it’s potential applications, eth- three major units: opment of drugs, vaccines and diagnostics. ics and related policy issues. But we have to apply the technol- The committee bade farewell to Dr Boris ogy in order to better understand Dobrothokov, who has retired from TDR the physiological and biochemi- after managing the activities of the Com- cal activities in organisms and the mittee since it’s inception in 1994. host/parasite interactions in- Strategic Social, Economic and Behav- volved in the disease process. ioural Research (SEB) This will help us to identify new The first meeting of the newly established targets in the parasite or its life Steering Committee on Strategic Social, cycle and increase opportunities
WHO/TDR Economic and Behavioural (SEB) Re- for developing potential novel in- search was held in Geneva in September terventions’, says Doctor Ayoade 2000. This Committee was created follow- M. J. Oduola, Coordinator of ing recommendations from the Joint Coor- STR. dinating Board (JCB) in June 1999. SEB A. gambiae: Will changing mosquito genes help stop Molecular Entomology is located is STR to emphasize the im- malaria transmission? The Steering Committee on Mo- portance of the basic social sciences for identifying needs and opportunities for Pathogenesis and Applied Genomics lecular Entomology, at it’s seventh meeting held in September 2000, acknowl- improved prevention and control of TDR The Genome Committee, which for the past edged the achievement in mosquito diseases. Over the next several years, five years has devoted effort through net- transgenesis. The contributions of partici- SEB will focus on gaining a better un- works to sequencing, mapping and anno- pating scientists in the field were recog- derstanding of the implications of globali- tation of the genomes of trypanosomes, nized. The Committee also noted the po- zation and changing social, political and leishmania, schistosomes and filaria, has tential value of the advances in transgenesis civil structures for health equity and the merged with the Pathogenesis Committee in the control of vector borne diseases and persistence, emergence and resurgence of to form a new committee on Pathogenesis emphasized a need for careful approaches TDR diseases. and Applied Genomics. This Committee is in developing guidelines for future studies As a result of these changes, STR will be designed to take advantage of modern involving potential modified vectors. The better able to contribute to achieving the achievements in DNA technology and Committee resolved to organize a scientific overall objectives of TDR. TDR introduces a new tactic for strengthening research capability
In a new approach, TDR research capability line of reasoning taken during the TDR dis- ongoing projects are completed, more and strengthening (RCS) activities are being cussions on strategy for 2000-2005 – that more funds will be put into joint target work. tuned more closely to countries’ research there are new resources in the ‘South’ ready Thus there will be focused capacity build- capacity and to TDR research and develop- to be used for R&D priorities. In future there- ing, where joint capacity strengthening ac- ment (R&D) activities. fore, TDR will develop capacity building tivities are planned together with the R&D When TDR began, 25 years ago, there was based on selected initiatives, whereby RCS areas (Intervention Development and Evalu- far less research capacity in the ‘South’ than activities are funded according to R&D pri- ation, Product Research and Development, there is today, while well-equipped labora- orities in an operation known as RCS-Plus. and Basic and Strategic Research) of TDR. tories and trained scientists were almost en- RCS-Plus will work in the following way. For a start, RCS-Plus has two important tirely located in the ‘North’. Thus the two New capacity building initiatives will be emphases. Firstly, one on African trypano- priorities for TDR – R&D on tropical dis- jointly developed across TDR focusing on somiasis, it being a very neglected disease, eases, and RCS in tropical diseases in dis- the R&D priority areas and promoting ex- and, secondly, one on RCS for tuberculosis ease endemic countries – were taken up tensive involvement of institutions in devel- (see page 3). somewhat independently of each other. To- oping countries. The TDR Strategy Man- It is hoped that RCS-Plus will reinforce the day however, perhaps as a result of TDR in- agement Team (SMT) will decide which involvement of all TDR R&D areas in re- vestment in human resources and institution initiatives to fund. RCS will still work in search capability strengthening and, as well, development, there is ample research capac- the usual way – for example, supporting in- increase the participation of DECs across ity in the disease endemic countries that can vestigator initiated proposals in least devel- the whole range of TDR activities. contribute to the global effort for develop- oped countries where there is limited re- Fabio Zicker, RCS Coordinator, TDR ing tools for disease control. This was the search capability. But gradually, as many [email protected] TDR news No. 63 October 2000 3
TDR allocates US$ 500 000 for research capacity strengthening in TB high burden countries
The Director TDR has decided to ‘kick strengthening needs. The most important and difficult part of RCS start’ research capacity strengthening (RCS) In accordance with the new TDR strategy is sustainability, and for this, the most essen- in tuberculosis (TB) with the allocation of (see page 1), the Programme is beginning tial factor is support of the concerned gov- US$500 000 to this activity. to focus more on methods for field imple- ernment. So there is a need to sensitize political In September 2000, the first in a series of mentation of new tools and systems and on leaders to the importance of research and a need consultations was held aimed at develop- closer integration of its research activities to promote merit and excellence in research ing the initiative. It is expected that 26% of with control programmes. There was intense institutions. TDR can be pro-active in con- TDR operations will be devoted to TB re- discussion about whether or not control pro- fronting policy makers with these issues. search by 2005, and RCS will be a major gramme staff should themselves carry out TDR will be looking to develop partner- component. research investigations. However, all were ships with concerned organizations for At the consultation, various players in TB agreed that operational research should be meeting specific needs in RCS for TB and capacity strengthening, including repre- an integral part of control programmes, and coordinating with efforts in other diseases. sentatives of research institutions, aid that national TB programme managers It is expected that, after further consulta- agencies and national TB programmes, should manage the research process includ- tion with TDR management and national shared their experiences and information ing asking the right questions, so that coun- TB programme managers, selection and on current activities, to help TDR clarify try priorities could guide the development funding of TDR TB-RCS projects will be- its role and identify training and capacity of an RCS programme. gin by March 2001.
GLP handbook in preparation
TDR activities in the area of good labora- steps on how to implement GLP; and train- perimental biomedical investigations to tory practice – or GLP for short – have been ing and education packages. The handbook ensure quality and reliability of data, and generating a lot of interest. Laboratories aims to provide a useful tool for laboratories will include details of the resources, which practice GLP produce high quality in disease endemic countries that wish to im- methods, documentation and supervision data during pre-clinical studies. Drug regu- plement GLP. GLP is just one of several qual- required. As these guidelines will cover latory authorities in the ‘North’ have used ity standards in drug development that are all areas of biomedical research, not just GLP as a standard for over 20 years and it regulated; TDR is also working in the area of drug development, they will be further is hoped that, by taking ‘good practice’ to good clinical practice (GCP) (see e.g. discussed amongst WHO and other re- disease endemic countries, drug develop- TDRnews No. 62), which covers studies dur- search organizations and universities glo- ment studies conducted here will be up to ing the clinical stages of development. bally before becoming available. internationally acceptable standards and However, some areas of able to satisfy regulatory authorities every- drug development are not where. A developing country will then be regulated. These include able to market the products it has devel- discovery studies, studies oped in the rest of the world. on proof of concept, and The first TDR GLP workshops were held in studies to establish phar- Asia and Africa in 1999 (TDRnews No. 61). macodynamics effect and Another has now been held in Colombia and mechanisms of action. a further one took place in French speaking Also, studies on herbal African countries in October 2000. In addition, medicines are under-regu- national workshops, arranged by participants lated, particularly with re- from the original training sessions, have spect to the safety aspects taken place in South Africa and Thailand. (see TDRnews No. 62). As WHO/TDR/Crump Now a TDR handbook on GLP is taking a spin-off from the meet- final shape. It was discussed at a recent ing therefore, draft ‘good meeting in Geneva by, amongst others, rep- practice’ guidelines to resentatives of industrial GLP laboratories, non-regulated aspects of disease endemic countries, and drug regu- drug research and devel- latory authorities. The handbook will in- opment are being pre- clude the Organisation for Economic Co- pared. They will provide operation and Development (OECD) prin- general principles which Correct, detailed record keeping is an essential component ciples of GLP; a 24-month plan in eight can be applied to all ex- of GLP 4 TDR news No. 63 October 2000
TDR consultation starts the count-down to new TB diagnostics For more than a century, microscopic ex- greatly facilitate patient use of health care couraged. As new diagnostic tests become amination of a stained sputum smear has services and improve overall case detection, available, participants agreed that extensive been the central, and sometimes only, labo- even if such tests show less-than-perfect clinical trials will be necessary to determine ratory tool for the diagnosis of tuberculo- sensitivity.” the appropriate use for each type and to sis available in health clinics of disease Of the recent TB diagnostic advances, in- design diagnostic algorithms for their ap- endemic countries. Now, reaping the results cluding enhanced microscopy, improved plication. The TBDI agreed to lead coordi- of a decade of increased funding in tuber- serology and skin tests, alternative liquid nation of these trials to assure speed, qual- culosis basic research, a number of prom- ity, and comparability, and to minimize du- ising new diagnostic approaches are be- plication of effort. coming available. New tools are being de- Industry representatives highlighted the veloped for the detection of disease, for relative lack of data on the real costs of the determination of drug susceptibility, and for TB diagnostic process in disease-prevalent specific detection of latent infection with countries, and on the potential economic Mycobacterium tuberculosis. There is no value of better diagnostic tests. Public sec- consensus, however, on how these tools tor advocacy has focused on the poverty of
should best be used, how to surmount ob- WHO/TDR/Crump TB-endemic areas and the high benefit and stacles to continued test improvement, and low cost of conventional therapy. Such ad- how to ensure that only high quality prod- vocacy has tended to ignore the amount of ucts are put in wide use by national disease current spending and the value of rapid and control programmes. These questions were reliable diagnosis. In considering new di- the focus of a two-day consultation on “Di- agnostics, public health experts have, for agnosis of tuberculosis: Countdown to new their part, tended to compare new tests with microscopy performed in ideal study con- tools”, hosted by TDR, 29-30 June 2000, New diagnostics are needed to replace at WHO in Geneva. ditions rather than in real-life situations, sputum testing which is time-consuming when microscopy is often substandard, thus The meeting brought together experts from and cumbersome underestimating the benefits that might be the field, leading test developers and manu- brought by simpler tests with more repro- facturers, control programme directors and culture media, phage replication systems, ducible performance. other potential test users to discuss the state molecular probes, and antigen detection of the art in TB diagnostics and to review tests, none is ideal or answers the needs of The relatively high cost of several new TB the workplan of TDR’s Tuberculosis Di- all clinical settings. Tests with the greatest diagnostics mandates careful consideration of the role of such tools in TB control pro- agnostic Initiative (TBDI) and its partners. sensitivity tend to suffer from technical Experts at the meeting reminded partici- complexity and/or excessive cost. Some of grammes. However, industry representa- tives pointed out that the cost is likely to pants that the current diagnostic situation the simplest and most inexpensive tests, fall if production volume increases, and that is precarious, with understaffed and over- such as many of the serologic assays, func- the costs of diagnostic inefficiency seen with worked laboratories unable to keep up with tion poorly in HIV patients, one of the existing tests must also be taken into ac- demand, or to adequately discriminate - groups for whom improved TB diagnostics count. A large part of the market price of using existing tools - TB patients from those are most urgently needed. Meeting partici- tests may be unrelated to original sales cost with symptoms from other causes. The re- pants pointed out that tests which detect host and thus not addressable by the manufac- sult is both underdetection and response do not indicate severity of infec- turer, including shipping fees, import taxes, overtreatment, especially in countries tion - an important feature of smear distribution fees and local mark-up. where HIV is prevalent and both tubercu- microscopy that is built into the framework losis and non-tuberculous pulmonary or for TB control, targeting for treatment first An important product of the meeting was wasting disease are common. those patients that are most contagious. an inventory of leading laboratory and field research questions that need answering be- There is therefore considerable interest in Despite these drawbacks, a consensus fore the appropriate use of new diagnostics the potential of new diagnostic tools for TB, emerged that, as the ability to provide cura- can be fully understood. Participants en- especially in rapid tests that can be carried tive therapy improves in high burden coun- couraged further technical improvements of out in front of the patient and are appropri- tries, inadequate case detection becomes the new diagnostics and suggested a series of ate for use at district level. Dr. Daniel greatest obstacle to TB control. Diagnostic multidisciplinary studies to evaluate the Kibuga, Director of the National TB Pro- tests that improve case detection, either cost-effectiveness and potential health im- gramme in Kenya, reflected this when he through increased sensitivity, simplified use pact of their use in various settings. Mo- said “We are not going to improve the situ- or expanded patient access, would be a great mentum gathered for WHO and TDR lead- ation in regard to TB diagnosis until we boon to TB control efforts. More than one ership in the areas of test production qual- make the process more patient-friendly. type of tool will be needed, and the efforts ity assurance and assay validation, achiev- Current estimates of the cost of TB diag- by the TBDI to facilitate continued indus- able through maintenance of the Specimen nosis account for public costs only, and ig- try development of improved diagnostic Bank and network of field test sites and nore the substantial burden borne by pa- tools remain a high priority. The TB Speci- through development of a process for sys- tients having to return to the clinic multi- men Bank, formally launched at the meet- tematic evaluation of marketed tests. A full ple times in order to finally get a diagno- ing, is one feature of the TBDI effort, and meeting report will be available by Novem- sis. Reliable and rapid tests that simplify increasing the geographic and clinical rep- ber 2000 on the TDR website or on request the diagnostic process for the patient would resentation of the Specimen Bank was en- from TDR. TDR news No. 63 October 2000 5
Improving treatment of tuberculosis
For many years the world has been com- ery and development of a simple and afford- country for protecting the health of its placent about tuberculosis (TB) and the able treatment for TB by 2010. citizens. But for new anti-TB drugs, need for new treatment has not been suffi- TDR hosted the stakeholders of the Global regulatory approval is a time-consuming ciently recognized - no new anti-TB drug Alliance, formed earlier in 2000 (see process and a disincentive for industry. has been introduced into routine practice TDRnews No.62), at a meeting in Septem- So, owing to the urgent need for new in the last 30 years. But in fact, TB is one ber to review progress with its establishment anti-TB agents, TDR is leading measures of the most devastating infectious diseases and methods of working. The body will pro- to speed up the process of registering in the world today. A staggering one third of vide leadership, raise funds, advocate, and new anti-TB agents – and regulatory har- the global population is currently infected, coordinate efforts in developing new treat- monization was discussed in relation to and nearly 6000 die from it each day. Al- ments. Already it has appointed the initial new TB drugs and to fixed-dose combi- though the present multi-drug schedule of nations of four currently used TB drugs treatment (DOTS) has the potential to cure directors and scientific advisors, laid scien- tific plans, and raised considerable funds, at a meeting, in September, between 85% of cases, it lasts at least 6 months and WHO and the International Federation requires that several drugs are taken in the while its list of partners, from public and of Pharmaceutical Manufacturers Asso- right combinations and for the appropriate private sectors in both developed and de- ciations (IFPMA). duration. Because of this, only 25% of pa- veloping countries, continues to grow. It is tients actually receive full and effective treat- projected that the Alliance has a 60% chance The meeting was attended by over 60 rep- ment - treatment needs to be considerably im- of first registering a drug by 2010, with a resentatives from the pharmaceutical in- proved and preferably for less than 3 months. series of likely candidates in subsequent dustry and regulatory agencies. It is the in- Additionally, inappropriate treatment has led years. It will employ capabilities in endemic tention to: (i) develop a single harmonized to the emergence of multi-drug the discov- countries whenever appropriate. guideline to guide all actors (industry, in- ternational regulators, public health insti- tutions, individual scientists) in the devel- opment of new anti-TB agents; (ii) enhance the efficiency and speed of registering new anti-TB agents; (iii) incorporate ‘state-of- the-art’ science, e.g. surrogate markers, in the clinical development of new TB drugs; and (iv) develop a single international har- monized approach for the registration of fixed-dose combinations of four anti-TB drugs. Use of fixed-dose combinations of anti- TB drugs would help ensure that the vari- ous drugs are taken in the right combi-
WHO/TDR/Crump nations and for the right length of time. Fixed-dose combinations of four cur- rently used anti-TB drugs are already being produced by industry in response to WHO requests. Participants at the meeting agreed there is no need for ad- ditional safety and efficacy studies of these prior to their registration, but that DOTS is effective - simplifying treatment will improve compliance manufacture of starting material and fin- ished product should conform to good manufacturing practice (GMP) stand- At a subsequent meeting in New York, TDR resistant TB - some 2% of patients cannot ards, and, for first registration, Director Dr Carlos Morel was elected Chair- be cured with today’s cocktail of drugs. So bioequivalence of all four drugs should man of the Board of Directors. easier treatment, and new types of drug be established by each company com- which shorten the treatment and help pre- The Alliance was officially launched in Oc- pared to reference standards. TDR will vent the disease in those most at risk, par- tober 2000 in Bangkok, at the International lead preparation of reviews of clinical ticularly HIV-infected people, are very Conference on Health Research for Devel- studies on the efficacy and safety of the much needed. opment, when Dr GH Brundtland, Director individual drugs, and of the reasons be- Two recent meetings in Geneva have ad- General of WHO, delivered the keynote ad- hind the choice of dose of each. dressed these challenges. dress. The national regulatory authorities of 22 A global alliance takes shape: TDR hosts (See page 8 for Global Alliance funding op- high burden TB endemic countries and all formal meeting of stakeholders before portunities.) members of the International Committee launch Coordinating approaches to regulatory on Harmonisation (ICH) will provide in- The Global Alliance for TB Drug Devel- agencies on TB drugs put to the proposed guidelines on regula- opment, a public/private partnership in Regulatory approval of new drugs is a tory harmonization which, it is hoped, will which TDR is a partner, aims to accelerate process of paramount importance to each be finalized by the end of 2001. 6 TDR news No. 63 October 2000
Advocacy for eliminating filariasis Advoca Lymphatic filariasis has been targeted for should address the community or the indi- the individual – a change in behaviour (in elimination by 2020, the key strategy be- vidual. The scientists felt the former, and this instance, people taking the drug) can ing mass treatment with a single dose of the communications experts the latter. Ad- only be hoped for if the individual expects two-drug treatment (diethylcarbamazine dressing the community was core accord- some sort of personal benefit. Ultimately it was agreed to target the individual with the advocacy package. Another contentious issue was the actual content of the message. Researchers felt it should contain the main facts regarding lymphatic filariasis and its elimination, but the communications experts said it must be short and simple. The communications ex- perts felt the message should indicate that taking the drug would prevent disease in WHO/TDR/Chandran an individual, but the scientists insisted this was factually incorrect since taking the drug does not guarantee that the individual will not get the disease later – unless all indi- viduals in the community also take the drug. It was finally agreed that the core messages would be:
n Lymphatic filariasis can affect YOU!
Elimination will depend on most of the community knowing about the campaigns and n Get rid of lymphatic filariasis
taking active part n Take a single dose of DEC every year [DEC] plus albendazole, or ivermectin plus ing to the scientists because the strategy, These and other issues meant the discus- albendazole) each year for several years. being mass chemotherapy, will only work sions were intense and profitable. The four- For the elimination campaign to be success- if all individuals in a community take the day workshop concluded with the develop- ful, high coverages with treatment (over drug – if only a few take it, the disease will ment of a draft framework for advocacy for 80% of individuals in a community) must still circulate in the community as other in- lymphatic filariasis elimination in India, and be maintained. But recent independent dividuals, who do not take the drug, will a core protocol for a study to test the frame- evaluations in India have shown that it is continue to harbour the infection. Address- work and the advocacy package in several difficult to achieve more than 60% cover- ing the individual was core according to the districts where the current treatment pro- age in a routine campaign. How to achieve communications experts because, for a mes- gramme covers a population of some 4 mil- sufficient coverage with a disease such as sage to have an impact, it has to appeal to lion people. this, which does not kill, even though asso- ciated with significant morbidity? One hy- pothesis is that an intense and professional Staff update advocacy or marketing campaign might do the trick. Dr K. Bob Hata, Management Officer (Internetworking) in Programme Planning and Thus, to develop a package for advocacy, Management, who developed e-mail communication between scientists, managing TDR’s Task Force on Filariasis Interven- the tdr-scientists list and promoting its wide use in Africa, has retired. tion Research has commissioned a multi- Dr Mark Perkins has been appointed Manager, Diagnostics Discovery Research, in centric study on advocacy for lymphatic Product Research and Development. filariasis in India. To develop the research Dr Johannes Sommerfeld has been appointed Manager, Social, Ecomomic and Be- protocol and instruments for this study, a havioural Research, in Basic and Strategic Research. group of researchers, programme manag- In accordance with TDR’s new matrix management, the following have been appointed ers and communications experts from a va- disease coordinators: riety of sectors (social marketing, private advertising agencies and the government) n for malaria – Dr Rob Ridley, supported by Dr Kamini Mendis
met at a recent workshop in the Vector Con- n for tuberculosis – Dr Paul Nunn trol Research Centre, Pondicherry, India. n for lymphatic filariasis – Dr Hans Remme With experience ranging from selling soap n for leishmaniasis – Dr Philippe Desjeux to campaigning for family planning to pub- lic health and research, the discussions were n for schistosomiasis – Dr Janis Lazdins, supported by Dr Lester Chitsulo
bound to be lively. n for African trypanosomiasis – Dr Alvaro Moncayo, supported by Dr Felix Kuzoe
The scientists and communications experts n for onchocerciasis – Dr Hans Remme, supported by Dr Janis Lazdins had very different perspectives on every n for Chagas disease – Dr Alvaro Moncayo angle discussed. There was much debate on the ‘correctness’ of the core message, the n for dengue – Dr Howard Engers (acting) central issue being whether the campaign n for leprosy – Dr Paul Nunn TDR news No. 63 October 2000 7
The ethics of biomedical research: sustainable activities begin in Asia and the Western Pacific Review of research ethics by ethics com- ethical issues in behavioural and genetics ics is now being offered by Thammasat mittees is generally recognized to be inte- research, special problems of collaborative University as part of its regular activities, gral to the evaluation of research propos- research between developed and develop- thus placing the capacity building efforts als. It is essential to have a competent re- ing countries, and research integrity. on a solid, sustainable, institutional basis. view process in place. In this regard, a The core function of the Forum is to drive The University of Bergen is a partner in this number of significant developments in ca- a regional network through which resources – an agreement which will enable Masters pacity building have emerged in Asia and can be mobilized, information exchanged and Ph.D. training in research ethics. Such the Western Pacific during the past few (e.g. electronically), and activities coordi- university-university collaboration will ex- months. nated. In turn, the network collaborates with pand to involve other institutions in the re- In January 2000, The Forum for Ethi- gion within the next few months. cal Review Committees in Asia and The link between FERCAP and the Western Pacific (FERCAP) was universities, both inside and out- established, with the aim of foster- side the region, will ensure ing improved understanding and im- sustainability of activities and in- plementation of ethical review of bio- clusion of advanced training. medical research in the countries of These capacity building efforts this region (see TDRnews No. 62). are also linked to a three-year FERCAP is governed by a steering project funded by the European committee composed of members Commission which has the aim from different countries of the region, WHO/TDR/Chandran of developing course modules in headed by Dr. Vichai Chokevivat research ethics. These course from Thailand. modules will be field tested and Among other things, the Forum fa- used in the regional courses, al- cilitates training and education for lowing synergy between the dif- members of ethics committees, and, ferent efforts. in August, it sponsored a one-week The three components, i.e. the re- training workshop in research eth- gional network, the institutional involvement of universities, and ics review in Bangkok, in collabo- Obtaining prior informed consent from volunteers is fun- ration with Thammasat University damental the specific effort to develop rel- (Thailand) and the University of evant course material, are com- Bergen (Norway). In all, there were 57 par- established institutions, such as WHO (its plementary. They ensure (a) sustainability ticipants from 14 countries of the Asian/ regional offices in Asia and the Western of the network, (b) relevance to local con- Western Pacific region. Topics covered in- Pacific and headquarters in Geneva) and cerns, and (c) dissemination of products to cluded: informed consent, evaluation of the different universities, to implement its ac- those involved, at all levels in the region, risks and benefits of research, inducements, tivities. An annual course in research eth- in reviewing the ethics of research. Important progress in schistosomiasis vaccine development The Schistosoma haematobium vaccine Dr M. Tendler of FIOCRUZ, Rio de Ja- cently announced that the TPI-MAP he has project based on the worm enzyme glutath- neiro, Brazil, who is currently engaged in been working on can now be produced in ione-S-transferase (GST) has successfully the scaling up of Sm14, a fatty acid-bind- large amounts with standard batch-to-batch passed Phase I testing; the research group ing S. mansoni antigen. antigenic characteristics. This is the result lead by Professor A. Capron of the Pasteur The progress in schistosomiasis vaccine of work carried out at the Bachem Com- Institute in Lille, France, is now embark- development has been slow but steady - it pany, Los Angeles, USA, and the achieve- ing on Phase II clinical trials in Senegal has taken a few more years than anticipated ment will have widespread implications for and Niger. Meanwhile, the Schistosomia- to reach the point of clinical trials. The les- vaccine work in general. The technology sis Vaccine Development Programme sons learned include the absolute need to involving synthetic peptides is attractive (SVDP), based in Egypt and supported by form a good working relationship with in- since it permits the design of specific USAID (see TDRnews No. 56), is focus- dustry early on. The delays experienced immunogenic epitopes, but these constructs ing on two S. mansoni antigens: were mainly due to difficulties in the scal- have unfortunately been notoriously diffi- paramyosin, an invertebrate muscular pro- ing up of antigen production not fully ap- cult to scale up. The results amount to a tein, and a synthetic peptide construct con- preciated at the outset - standardized vac- breakthrough, particularly since the solu- taining multiple antigen epitopes (MAP) of cine-grade antigen production on a large tion found for the TPI-MAP can no doubt the schistosome triose phosphatase isomer- scale has so far only been achieved with be adapted to any other vaccine scheme ase (TPI). A third activity is promoted by Sh28-GST. However, Dr D. Harn has re- employing synthetic peptides. 8 TDR news No. 63 October 2000 t t t t t t Research needed
Chagas disease Task Force on Intervention Research on Global Alliance for TB Chagas Disease The Task Force will focus its activities on Drug Development TDR, World Health Organization the study of the population dynamics of non- Last February in Cape Town, South Africa, domiciliated triatomine vectors of Chagas 1211 Geneva 27 - Switzerland 120 representatives from academia, industry, disease present in the northern part of South Tel: (41-22) 791-3865/3903 Fax: (41-22) major development agencies, non-govern- America and in Central America. It is ex- 791-4774 mental organizations, and donors from pected that the entomological data gener- E-mail: [email protected] around the world gathered to discuss obsta- ated will assist the national control pro- cles and opportunities for the development grammes in adapting the vector control African trypanosomiasis of new drugs for tuberculosis. The main out- strategies that have proved very successful come of the meeting was a commitment to in interrupting vectorial transmission of 1. Assessment of the efficacy and cost-ef- create a Global Alliance for TB Drug Devel- Chagas disease in the countries of the South- fectiveness of using the CATT and CIATT opment during the year 2000. The Global ern Cone Initiative. for serodiagnosis at community level and Alliance’s vision is to provide new medicines, comparative evaluation. The research needs in this respect are as fol- accessible to all, for the treatment of tuber- lows: 2. Prospective cohort studies of sero-posi- culosis (see page 5). tive, parasitologically non-confirmed cases Mission statement: n Studies on triatomine distribution and to evaluate the epidemiological impact of Accelerate discovery and development of house/peridomicile infestation by non- treatment. cost-effective new TB drugs that will: domiciliated species. 3. Development of a network for monitor- n Shorten the duration of TB treatment or n Studies on the genetic structure of ing of drug resistance using simple tools populations of non-domiciliated tria- for detection and mapping. otherwise simplify its completion, tomines. 4. Development of decision analysis tools n Improve the treatment of latent TB in- fection, or n Studies on the sylvatic/domestic mobil- for the determination of a cost-effective ity of vector populations. sequence of diagnostic tests and case man- n Be effective against MDR-TB. agement. n Studies on the sensitivity of methods to Call for Letters of Interest detect infestation by non-domiciliated spe- Researchers interested in collaborating in The Global Alliance is currently seeking cies. the above activities should write to: projects in tuberculosis drug research and Dr Alvaro Moncayo, Manager, n Studies on the monitoring of insecticide development. The Alliance invites Letters efficacy. Task Force on Intervention Research on Af- of Interest from academic and industrial re-
n The effect of bioclimatic changes on rican trypanosomiasis search groups (including pharmaceutical domiciliated and non-domiciliated vector TDR, World Health Organization and biotechnology companies). Although populations. 1211 Geneva 27 - Switzerland projects in all phases of tuberculosis drug Researchers interested in collaborating in R&D are encouraged to submit Letters, the Tel: (41-22) 791-3865/3903 primary categories for consideration are: the above activities should write to: Fax: (41-22) 791-4774 Dr Alvaro Moncayo, Manager, n Tuberculosis drug discovery/pre-clini- E-mail: [email protected] cal projects
n Tuberculosis clinical drug development projects Projects that include public-private part- nerships and developing-country col- laborations are strongly encouraged to apply. Please visit the Global Alliance Web site at www.tballiance.org for in- formation required with Letters of Inter- est. The deadline for receipt of Letters is December 15, 2000. Please send Letters of Interest to: The Global Alliance for TB Drug Development, WHO/TDR/Mark Edwards 420 Fifth Avenue, 21st Floor, New York, NY 10018, Attn: Di Eckerle
Erratum In our article A suitable macrofila- ricide in TDRnews N0. 62, the photo- The CATT test is a useful tool for surveillance of African trypanosomiasis graph was of course of a microfilaria, and not of an adult worm, as indicated in the caption. TDR news No. 63 October 2000 9 t t t
t t t Steering Committee and Task Force Meetings
Meeting date Deadline for proposals
Basic and Strategic Research Pathogenesis and Applied Genomics Sep 2001 * Jul 2001 * Molecular Entomology (BCV) Sep 2001 * Jul 2001 * Social, Economic and Behavioural Research (SEB) 4-8 Jun 2001 23 Mar 2001 Immunology of Mycobacterial Diseases (IMMYC) Dec 2000 *
Product Research and Development Drug Discovery Research (DDR) 26-30 Mar 2001 26 Jan 2001 Vaccine Discovery Research (VDR) 28 May-1 Jun 2001 28 Mar 2001
Intervention Development and Evaluation (IDE) ** 1st Quarter 2001 * IDE Steering Committee Research on Drug Resistance and Policies (RAP) Severe Malaria (SEVERE) }1st Quarter 2001 * Malaria Home Management (HOME-MGT) Filariasis Intervention Research (FIL) Early May 2001 * Intervention Research on Chagas Disease (CHA) 2-4 May 2001 Intervention Research on African Trypanosomiasis (TRY) 4-6 Sep 2001 Chemotherapy of Leprosy (THEMYC) Feb 2001 *
Research Capability Strengthening Research Strengthening Group 12-16 Feb 2001 31 Oct 2000 Malaria Research Capability Strengthening 12-17 Mar 2001 30 Nov 2000 in Africa (MIM) ***
* Tentative ** IDE Task Forces may call for specific research proposals at any time of the year according to their workplans *** Progress reports and renewals only 10 TDR news No. 63 October 2000
Just published: an account of the last decade’s 153 million dollar effort to conquer schistosomiasis in China Schistosomiasis control has been a priority China added another dimension to the con- tional Reference Centre including provincial in China for 50 years. As a result, only the trol effort. The research programme was serum banks, preventive use of artemisin de- core regions with particular problems, such administered by a Joint Research Manage- rivatives, methods for the surveillance of cer- as the lands associated with the middle ment Committee (JRMC) which included cariae-infected water, cost-benefit analysis of reaches of the Yangtze river and the four advisors sponsored by TDR. JRMC different strategies, and the realization of a Dongting and Poyang lakes in central China focussed on projects where there were rea- national schistosomiasis survey to evaluate and certain mountainous areas in Sichuan sons to believe that results would be forth- the control project after the first five years. coming ‘here The increased interest in research reflects and now’ rather the sustained input from TDR in mobiliz- than in a distant ing and galvanizing scientists working in future. For this academic institutions and staff directly en- reason, drug gaged in control activities. development The overall outcome of the World Bank ini- was preferred tiative is likely to be of benefit at the inter- over vaccine national as well as the national level. Data research and and methodology emanating from interna- the develop- tional research were successfully merged ment and pro- with the national experience of schisto- duction of kits somiasis control, adding to JRMC’s legacy was favoured of a much improved network for schisto- WHO/TDR/Crump over research somiasis control in China. However, the on new diag- move forward might have been swifter had nostic antigens. there been closer interaction between con- In addition, trol activities and research efforts. In addi- geographical tion, progress was hampered in some of the information participating provinces due to slow and system (GIS)- uneven internal distribution of funds which related re- GIS systems for schistosomiasis developed in China are now being seriously constrained the overall pro- search received used for other diseases gramme. Despite this, although the road important sup- from ‘bench to field’ can be taxing and slow, and Yunnan, remain endemic. To get to grips port. Less visible, but of crucial imp ortance, a surprisingly rapid transfer of new control with the public health problem in these ar- was the influence of research moderniza- approaches took place. One reason for this eas, the World Bank provided a loan of tion and the improved capacity for high- could be the inclusion in JRMC of senior US$71 million from 1992 to 2000 with the level studies instituted by JRMC. Although managers and technical experts on schisto- stated objective of reducing prevalence and this did not make an immediate impact, somiasis control as well as scientists with intensity of schistosomiasis in humans and China is now well on the road to producing expertise in health economics, social medi- animals through interruption of transmis- a sizeable body of high-class research on cine and health education. In fact, the inter- sion by chemotherapy. As a reflection of schistosomiasis. During the time JRMC was disciplinary approach characterizing JRMC the seriousness of the situation and how it active, 245 projects were approved for led to an expansion of control expertise, is perceived at the highest political levels, funding out of more than 800 submitted, adding views and knowledge from related the Government of China and endemic most of them from the provinces. Seven fields which, in turn, changed the traditional provinces more than matched this funding, workshops and one symposium were spon- strong focus on biology to a broader ap- so the programme eventually received sored in order to help investigators formu- proach including research on the cost-ef- US$153 million. Mass chemotherapy was late better research proposals and improve fectiveness of strategies contemplated. instituted in regions of high prevalence, in their abilities to select suitable study top- JRMC thus contributed effectively to a some places together with mollusciding, and ics, design studies and assess outcomes. An move away from classical concepts towards selective chemotherapy in others. In spite exchange programme facilitated communi- interactive communication. The control of great environmental variations between cation and collaboration with foreign ex- programme will no doubt benefit further the eight endemic provinces, this simplified perts. By these activities, JRMC established from having strengthened research institu- strategy produced excellent results with ref- itself as a strong force and the operational tions and created experienced scientists. erence to morbidity. However, since trans- research arm of the consolidated effort to mission has been fundamentally changed, eliminate schistosomiasis as a public health Reference the re-infection of inhabitants and livestock problem. All in all, 278 theses were pub- Yuan, H.C, Guo, J.G., Bergquist, R., Tanner, is inevitable in a longer perspective. lished, 25 projects were awarded prizes, 7 M., Chen, X.Y., Wang, H.Z. (2000). The By setting about US$4.25 million of the projects generated patents, and new con- 1992-1999 World Bank Schistosomiasis Re- World Bank loan aside for operational re- trol tools were designed. Notable achieve- search Initiative in China: Outcome and Per- search and training, the Government of ments include the establishment of a Na- spectives. Parasitol Int. 49(3):195-207 TDR news No. 63 October 2000 11
Home management of malaria: linking with the formal health care system
Appropriate home management of malaria n Training identified community mem- both cases, drug use has to be monitored has been identified as a key practice that bers e.g. traditional healers, chemical/drug regularly. communities in Africa find beneficial for sellers, village health workers, village n Advocacy - to ensure that resources are their children’s health. But this practice health committees, to provide: public in- mobilized for supporting communities and cannot succeed on its own, without links to formation and education and serve as lo- individuals in home management, through the other actors in healthcare, particularly cal resource persons for the community; fostering of linkages with: all stakeholders the formal healthcare system. Thus the TDR store and dispense drugs for treatment; as- at the community level, non governmental Task Force on Malaria Home Management sist and advise on referral of complicated organizations, other ministries and depart- is exploring the specific inputs that the pub- and severe malaria cases; keep relevant ments, local authorities, traditional rulers, lic health system can make into improving records; and mobilize the community to and private health care providers. the home management of malaria. undertake preventive activities. n Providing an accessible and affordable
Despite the problems often associated with n Monitoring community resource per- referral system for cases of complicated and this sector, e.g. inefficiency, inadequacy of sons on a regular basis to ensure they are severe malaria, which means providing ad- supplies, and low staff morale, the govern- doing what they are supposed to do, peri- equate human resources and logistics. ment sector will have an essential role to odically organizing refresher courses for n Operational research, to support the play. The Task Force identified the follow- them, and providing them with the neces- implementation of home management and ing as among the roles to be explored: sary logistic support to enhance the success ensure that successful small projects are n Informing and educating families and of home management of malaria. scaled up. communities about: the prevention and n Monitoring drug use - drug availability The lessons learned from community di- treatment of malaria, especially the need to and supply being essential to the success of rected treatment of lymphatic filariasis seek early treatment from an identified home management. The formal health care (ComDT) will help in identifying these source, preferably the same day that a child system either serves as the source of drug roles. In ComDT, involvement of the health becomes sick; the importance of complet- supply and distribution or, where the pri- services in education, training, monitoring ing treatment; and how to recognize the vate sector is used for this, ensures that the and supervision was found to significantly signs and symptoms of severe and compli- distribution system is efficient and that the strengthen the implementation of this prac- cated malaria. drugs reach those who need them most. In tice (see TDRnews No.62).
Director TDR opens World Congress of Tropical Medicine and Malaria in Cartagena, Colombia
The Director of TDR gave the opening lec- poster sessions, the par- ture at the 15th International Congress of ticipants discussed the Tropical Medicine and Malaria held in state of the art of ma- Cartagena, Colombia, 20-25 August 2000. laria vaccine develop- At the opening ceremony, the President of ment and AIDS Colombia, Mr Adres Pastrana, inaugurated vaccines, as well as the the Congress with a vibrant speech that en- elimination of transmis- gaged his government in solving the prob- sion of Chagas disease, lems faced due to malaria and other tropi- onchocerciasis and po- cal diseases in the country. lio. In addition, there Dr Carlos Morel, Director TDR, presented were 4 satellite sympo- the new TDR strategy for 2000-2005, that sia and 7 special sym- stretches the activities of the Programme posia with 22 confer- towards implementation research and evalu- ences that dealt, nota- ation of programme results in the field. bly, with the emergency The Congress gathered some 3200 partici- caused by antibiotic re- pants together, of which more than 700 were sistance and with the international delegates from 96 countries. development of drugs In 55 symposia, 460 presentations and 34 against malaria. 12 TDR news No. 63 October 2000
Dengue/dengue haemorrhagic fever: a summary of research and control in South East Asia Contributed by WHO’s South East Asia Regional Office
Dengue fever/dengue haemorrhagic fever research in the area of diagnosis resulted in tive actions in the different environmental/ (DF/DHF) is gaining an ever-increasing the development of an improved serologi- epidemiological situations means that vec- foothold in countries of South East Asia1 - cal test, the IgM capture ELISA test, which tor control strategies may not be optimal. epidemics of DHF are now recurring in 3-5 has now become the standard test in labo- In this respect, WHO’s South East Asia year cycles in Indonesia, Myanmar and ratories all over the world. This research in Regional Office (WHO/SEARO) has devel- Thailand. This situation is a result of rapid Thailand led to the development of WHO oped guidelines to help strengthen preven- urbanization, population movement and in- guidelines for the clinical diagnosis and tion and control, and has organized reviews creased commercial activity consequent management of DHF where facilities are of the dengue control programmes in Indo- upon globalization. Whereas, all four den- minimal, in small hospitals at district level. nesia and Thailand with a view to strength- ening the national programmes. gue viruses circulate in all the endemic coun- For control of dengue in South East Asia, tries of this region, in some countries no in- the different countries have developed vari- Another line of research being followed vig- cidence of the disease has yet been reported; ous control strategies to reduce the disease orously in Thailand is aimed at developing an effective vaccine against DF/DHF. A these include the Democratic People’s Re- burden in their communities. Indonesia, tetravalent (effective against all four den- public of Korea, and Bhutan and Nepal in Myanmar, Sri Lanka and Thailand, for in- gue viruses), live, attenuated dengue vac- the Himalayan ranges where vectors of the stance, have organized formal national level cine has been successfully developed by disease have, however, been detected in programmes, whereas India, Bangladesh, towns located in the foothill regions. Mahidol University with the support of and Maldives have placed ad hoc arrange- WHO. Phase I and II clinical trials of this Research activities in South East Asia have ments under the responsibility of the na- vaccine in adults are now taking place. led to great strides in the case management tional vector borne diseases control pro- of DHF, including research carried out at grammes. The different approaches to con- WHO/SEARO, together with the WHO of- fice for the Western Pacific region, publishes Queen Sirikit’s Institute of Child Health in trol of dengue are largely community based; an annual bulletin - Dengue Bulletin – for Thailand, a WHO Collaborating Centre for they involve control of the vector through researchers and control staff in the region2. Clinical Management of Dengue. Results source reduction of breeding places. These from studies on pathogenesis and clinical activities have been found to be particularly 1. the countries included in WHO’s South East Asia region are: Bangladesh, Bhutan, Demo- management have been used effectively in successful when carried out by school chil- cratic People’s Republic of Korea, India, Indo- referral hospitals to reduce the case fatality dren and women’s organizations backed by nesia, Maldives, Myanmar, Nepal, Sri Lanka, rate from 10-15% (40% in some areas) in inter-sectoral support. Before developing Thailand. the early 1950s to less than 0.5% today. In local management methods using environ- 2. Interested readers may contact the Editor, VBC order to detect the severity of dengue early, mental interventions however, there is a Unit, Department of Communicable Diseases, other research in Thailand emphasized the need for research to identify and map the WHO South East Asia Regional Office, Mahatma identification of several critical clinical breeding sites in endemic areas; otherwise, Gandhi Road, New Delhi 110002, India, or events during the course of the disease. And lack of knowledge about the use of preven- [email protected], to obtain this bulletin.
Central American initiative for the elimination of Chagas disease: Progress in vector control and blood bank control The IIIrd Meeting of the Intergovernment Commission of the Central American Initiative was held in San Salvador, El Salvador, in July 2000. Important progress in vector control operations was reported from the Chagas disease control programmes in Belize, Costa Rica, El Salvador, Guatemala, Nicaragua and Panama. In all six countries, control plans are operational and the activities are budgeted with regular national funds. Cross sectional studies on the prevalence of Trypanosoma cruzi infection in schoolchildren and the distribution of triatomine vectors have been completed in all the countries, and the ministries of health are using the resulting information for planning and evaluation of vector control operations. The main advances reported at the meeting included the following: El Salvador: Screening in blood banks for T. cruzi-infected blood is now carried out in 100% of the blood banks in the country. Guatemala: Spraying activities have started in the departments of Zacapa and Chiquimula in a concerted programme involving the Ministry of Health, the University of El Valle and the Japan International Cooperation Agency (JICA). Honduras: The number of houses infested with Rhodnius prolixus, the main vector of Chagas disease and a domiciliated species, is 45 000 in the whole country. Since 1998, 13 222 infested houses have been sprayed, or 30% of the total. It is estimated that spraying of infested dwellings will be completed in 2001. The coverage of blood banks by screening is 100%. Nicaragua: Vector control activities, through insecticide spraying of infested houses, have been advanced to cover 97% of localities with houses infested by R. prolixus. There is still a substantial amount of work to be carried out on the implementation of vector control activities and blood bank screening in all the countries. However, the advances have also been very important and the responsible officers in the different national control programmes are confident of accomplishing the goal of interruption of transmission of Chagas disease in this sub-region in 2005, as planned. TDR news No. 63 October 2000 13
Dutch registration for artemotil injections Charles B. Lugt
On 22 May 2000, the Dutch registration early ring forms. In in vitro studies, is combined with mefloquine, and authorities approved two new artemotil in artemotil has been shown to be effective potentiation when artemotil is combined sesame oil products for the treatment of against parasite strains resistant to other with quinine. severe Plasmodium falciparum malaria by antimalarials, though this has not yet been There is, at present, no clinical information intramuscular injection. The registrations confirmed formally in clinical studies. as to the use of the drug during pregnancy are the result of a collaborative effort be- After intramuscular injection, artemotil and lactation. Pre-clinical studies have re- tween WHO/TDR, WRAIR and the Dutch is released slowly into the systemic cir- vealed embryotoxic effects, but no tera- company ARTECEF BV, that started in culation and attains peak concentrations togenic potential. Until more data become 1991 as the ‘Artemisia Project’. 3-12 hours later (Figure 2). The available, artemotil should not be used dur- majority of the drug is metabolized, ing pregnancy. by an oxidative alkylation in the Thus, artemotil is an excellent alternative to liver, to artenimol (formerly known quinine. It has clear advantages: it causes a as dihydroartemisinin). Fortunately, swifter decrease in parasite numbers, is sim- this metabolite has similar levels of pler to apply, and has far fewer undesirable antimalarial activity to artemotil. side effects. Artemotil has advantages too in Excretion is as the glucuronide of cases where the patient is not able to retain artenimol, principally in the faeces food, even though the malaria may not be and urine. severe. In particular, for small children in ar- Clinical studies in patients with eas poorly served by health services, treat- severe malaria were carried out ment with artemotil can save time and life, first in adults and later in children while, in better served areas, saving time is who could not be treated with oral relevant when a patient has to be transported medication, or who had critical to a central hospital. As to the cost of the drug, cerebral malaria, in Africa and it will be made available to developing ma- Thailand. No serious or inconven- laria endemic countries at the lowest possi- ient side effects were reported. ble cost, which is likely to be about half the current price of artemether. Figure 1 Although, with artemisinin com- pounds in general, degenerative Now that artemotil is registered in the Neth- Artemotil is a semi-synthetic derivative of neurotoxic effects have been reported erlands, a programme to extend regulatory artemisinin, a compound first isolated by during pre-clinical safety studies in ani- approvals to disease endemic countries is Chinese scientists from the plant Artemisia mals, these have occured at cumulative to be initiated. If initial experience is good, annua in 1972. Since then, a number of de- doses above 100 mg per kg body weight, then the drug will be considered for inclu- rivatives have been developed and regis- whereas, in clinical treatment with sion in WHO’s Essential Drugs List, and tered and have entered use in a variety of artemotil, the cumulative dose reached is would then likely be widely used by ma- countries. Artemotil is the first artemisinin 11.2 mg per kg. Also, throughout the laria control programmes. derivative to be registered as a single entity world, during treatment of millions of pa- according to European standards. It is indi- tients with vari- cated for patients with severe malaria. Un- ous artemisinin til now the only possibility for treatment of derivatives, no PPBR-982372 Artemotil- mean * (n=20) severe malaria, according to European neurotoxic effects 200 Artemotil standards, was through intravenous quinine, have been re- Dihydroartemisinin which currently remains the drug of choice ported. Nor has 150 ) in most parts of the world, despite its some- neurotoxicity been -1 times serious adverse effects. observed during
The solution of artemotil, 50 mg or 150 mg, controlled studies 100 in sesame oil (Artecef® 50 and Artecef® in volunteers and 150), is contained in ampoules and comes patients. Thus supplied with graduated needle/syringe com- there is no reason 50 binations, so is ready for immediate use in for restriction of the clinic. The product is indicated for chil- clinical use of Plasma conc. (ng. mL artemotil. 0 dren and adolescents up to the age of 16. 0 24 48 72 96 120 Administration, by intramuscular injection Pre-clinical para- over three days, is restricted to hospitals. sitological studies Artemotil (previously known as ß-arteether, with artemotil *: geometric mean Time (h) Figure 1) is the ethyl ether of artemisinin. have shown that It is a blood schizonticide active against all additive effects Figure 2: Mean plasma-concentration-time curves of artemotil and artenimol (dihydroartemisinin) in Thai children with severe P. falciparum malaria. stages of P. falciparum, including the very may occur when it
0 14 TDR news No. 63 October 2000
Global Forum for Health Research publication: Latin American Economic analysis of malaria control in sub-Saharan Africa. Catherine Goodman, Paul Coleman, Anne Mills - ISBN: 2-940286-00-0 triatomine network In this report, the cost-effectiveness and knowledge gaps and research priorities. economic benefits of a variety of malaria Achieving the recommendations of the re- created control interventions to countries in sub- port will require considerable capacity Saharan Africa are analysed, for the pur- building in Africa in the fields of econom- A Latin American Network for studies on poses of providing policy-makers with in- ics and epidemiology. triatomine control, or RELCOT (Red formation on the interventions which rep- This publication is available free of charge Latino Americana para el estudio de la resent the best value for money. from: Global Forum for Health Research, biología y control de triatominos), was The various interventions analysed include c/o World Health Organization, 20 Avenue created as a recommendation of the measures to prevent malaria in childhood Appia, 1211 Geneva, Switzerland. Meeting on Monitoring of Triatomine (insecticide treated nets, residual spraying, E-mail: [email protected] Resistence to Insecticides that was re- chemoprophylaxis) and pregnancy (chemo- Website: www.globalforumhealth.org cently held at the Center for Studies on prophylaxis, intermittant treatment), and Pests and Insecticides (CIPEIN), a WHO measures to improve case management of Collaborating Centre, in Buenos Aires, uncomplicated malaria (improving compli- Argentina. ance through: training providers, health edu- The meeting was attended by delegates cation for patients and care-givers, and pre- from Andean and Central American coun- packaging of chloroquine in unit doses; im- tries who had received laboratory and proving the availability of second and third field training at CIPEIN on techniques line drugs; changing the first line drug for for the detection of triatomine resistance, treatment; using combination therapies; in- troducing diagnostic tests). and who have established research work on this subject in their own countries. The The effectiveness of each intervention is meeting was also attended by the Direc- calculated in terms of disability adjusted life tor of the Argentinian Chagas disease years (DALYs) averted combined with in- control programme. formation costs to both governments and households. Results are stratified by epide- The participants decided to organize a miological zone, as far as possible, and by Latin American network for studies on economic zone (into very low, middle or triatomine control. The objectives and higher income brackets based on per capita WHO/TDR/Crump modus operandi of the network were gross national product - GNP). agreed upon and the decision taken to The report includes a review of the litera- invite as many interested laboratories and ture on the economic burden of malaria and control programmes on the continent as potential economic benefits to be derived possible, to work together in monitoring from improved control, concluding that triatomine resistance and recommending there is a general weakness in the existing use of insecticides for control of Chagas information. It reflects on the economic evi- Prepackaged antimalarials can improve disease vectors based on scientific fol- dence available to underpin WHO’s Roll compliance and slow down the appear- low-up of control activities. Back Malaria campaign, and identifies key ance of drug resistance
Ultrasound in Schistosomiasis: A practical guide to the standardized use of ultrasonography for assessment of schistosomiasis-related morbidity - TDR/STR/SCH/00.1 Ultrasonography has become an invalu- carried out in the same or different patients pared. This manual is now available and able extension of the clinical investiga- by various investigators, in various geo- it is hoped that it will contribute to the tion of patients with schistosomiasis, graphical locations, at different times in the gathering of further experience, particu- providing direct evidence of the patho- same patient, etc.) at a minimum, it was larly in the field of S. japonicum infec- logical changes associated with this in- felt that a system of yardsticks was needed. tion. It is expected that a final meeting fection. From the outset, due to the range To accomplish this, a manual was produced will be needed to finalize the work that of possibilities for use of the method and at a meeting held in Cairo, Egypt, in 1990. was started in Cairo in 1990. This meet- interpretation of its measurements, it was The experience gained with the use of this ing, tentatively planned for 2002, will evident that the application of ultrasound manual was discussed at a follow-up meet- focus on schistosomiasis in the Far East would need standardizing to permit use- ing in Niamey, Niger, in 1996, and a new but will allow adjustments to be made ful comparisons between the results of manual, incorporating recommendations with respect to examination of patients different examinations. In order to keep from the Niamey meeting and a later meet- with S. mansoni and S. haematobium in- variations in evaluation (of examinations ing in Belo Horizonte, Brazil, was pre- fections, if necessary. TDR news No. 63 October 2000 15
t t t Research needed t t t Maladie de Chagas logiquement non confirmés pour évaluer Alliance mondiale pour la l’impact épidémiologique du traitement. Le Groupe spécial sur la maladie de Chagas va 3. Création d’un réseau de surveillance de la mise au point axer ses efforts sur l’étude de la dynamique des pharmacorésistance à l’aide d’outils simples d’antituberculeuxbal populations de triatomes non domiciliaires, de détection et de cartographie. vecteurs à la maladie de Chagas dans le nord 10. Association de la cartographie des régions En février dernier, dans la ville du Cap en de l’Amérique du Sud et en Amérique centrale. d’endémie de la trypanosomiase africaine et Afrique du Sud, 120 personnes représentant On peut espérer que les données entomo- d’informations émanant d’autres programmes des universités, l’industrie, les principales logiques ainsi obtenues aideront les pro- comme ceux d’éradication de la dracunculose institutions de développement, des organisa- grammes de lutte nationaux de cette région à et d’élimination de l’onchocercose. tions non gouvernementales et des donateurs adapter aux conditions locales les stratégies de partout dans le monde se sont réunis pour de lutte antivectorielle qui ont si bien réussi à 4. Mise au point d’outils d’analyse décision- examiner les possibilités de mise au point de interrompre la transmission de la maladie dans nelle pour convenir d’une séquence rentable nouveaux antituberculeux et les obstacles à les pays du Cône austral. de tests diagnostiques et d’étapes de prise en surmonter pour ce faire. A la réunion, il a charge. été décidé de créer, au cours de 2000, une Al- Les recherches sont nécessaires dans le cadre liance mondiale pour la mise au point d’anti- de : Les chercheurs qui souhaitent collaborer aux activités énumérées ci-dessus sont priés de tuberculeux ayant pour dessein de mettre à n La distribution des triatomes et l’infestation s’adresser au : disposition de nouveaux médicaments, des maisons et de la proximité immédiate des accessibles à tous pour le traitement de la maisons par les espèces domiciliaires. Dr Alvaro Moncayo tuberculose. Administrateur n La structure génétique des populations de Enoncé de mandat triatomes non domiciliaires. Groupe spécial de recherche sur les interven- Hâter la découverte et la mise au point de tions de lutte contre la trypanosomiase n La mobilité sylvatique/domestique des nouveaux médicaments efficaces et populations de vecteurs. africaine économiques pouvant :
TDR, Organisation mondiale de la Santé n rendre plus courte la durée du traitement n La sensibilité des méthodes pour détecter l’infestation des maisons par les espèces non 1211 Genève 27 antituberculeux ou simplifier son achèvement domiciliaires. Tél : (41-22) 791-3865/3903 n améliorer le traitement de la tuberculose latente n La surveillance de l’efficacité des insecti- Fax : (41-22) 791-4774 n être efficaces contre la TB-MR. cides. E-mail : [email protected] n Les effets des changements climatiques sur Appel de lettres d’intérêt les espèces domiciliaires et non L’Alliance mondiale cherche actuellement domiciliaires. des projets de recherche et développement Les personnes intéressées sont sur les antituberculeux et invite les priées de réclamer le formulaire universitaires et groupements de recherche auprès de l’administrateur du industrielle (y compris les compagnies pharmaceutiques et les sociétés de Groupe spécial : biotechnologie) à soumettre des lettres Dr Alvaro Moncayo d’intérêt. Bien que les projets à toutes les Administrateur phases de R&D soient encouragés à Groupe spécial de recherche soumettre des lettres, on accordera la priorité sur les interventions de lutte aux catégories suivantes : contre la maladie de Chagas n Découverte d’antituberculeux/projets TDR, Organisation mondiale de d’étude préclinique la Santé n Projets de mise au point clinique 1211 Genève 27 d’antituberculeux Tél : (41-22) 791-3865/3903 Les projets comprenant des partenariats secteur public-secteur privé et une collabo- Fax : (41-22) 791-4774 ration avec des pays en développement sont E-mail : [email protected] vivement encouragés à faire une demande. Pour toute information ayant trait aux lettres d’intérêt, veuillez consulter le site de Trypanosomiase l’Alliance mondiale www.tballiance.org. Dernier délai de réception des lettres africaine d’intérêt : 15 décembre 2000. 1. Evaluation de l’efficacité et Prière d’envoyer vos lettres d’intérêt à :
de la rentabilité de l’utilisation WHO/TDR The Global Alliance for du CATT et du CIATT pour le TB Drug Development, sérodiagnostic au niveau 420 Fifth Avenue, communautaire et évaluation 21 st Floor, comparative. New York, NY 10018, Attn : Di Eckerle 2. Etudes prospectives de Studies of the distribution of triatomines such as cohorte sur des sujets Rhodnius prolixus are needed séropositifs mais parasito- 16 TDR news No. 63 October 2000
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