Loa Loa: a New Rapid Assessment Tool

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No. 66 October 2001 TDR UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR)

CONTENTS KEYNOTE ARTICLE

3 TDR participates in major WHO initiative Loa loa: A new rapid 4 The filariases: TDR studies help define parameters for control assessment tool

5 Biosocial research and the TDR agenda Rapid development of

WHO/TDR an urgently needed 8 Does inequality matter? tool puts onchocerciasis control operations 9 Multilateral Initiative back on track in cen- on Malaria in Africa (MIM) tral Africa.

10 Dengue update

10 Dr Remme of TDR awarded the Eijkman Medal

11 TDR co-worker awarded for contribution to A simple method that can be used to rapidly An interviewer mine how heavy (or ‘intense’) TB control assess which communities are at risk of develop- asks about history Loa infection is, and so a sim- of eye worm. ing severe adverse reactions following treatment ple method was sought. 11 TDR research with ivermectin for onchocerciasis, due to co- Earlier studies2 had indicated collaborator honoured infection with ‘eyeworm’ (or Loa loa), has been that a correlation exists between intensity of substantiated in a TDR multicountry study. After infection and prevalence, that there are preva- analysis of the results at a workshop in Septem- lence thresholds above which the risk of severe 12 Awards in Basic and ber 2001, the method was immediately taken up reactions becomes too high for routine treat- Strategic Research by the African Programme for Onchocerciasis ment with ivermectin. High-risk villages, where Control (APOC) for use alongside community adverse reactions may be anticipated, were indi- 16 Staff news: directed treatment with ivermectin (CDTI). cated to be those where there is more than 20% comings and goings The need for such a method was urgent. In some prevalence of Loa infection, or more than 5% areas of Cameroon where both diseases prevalence of heavy Loa infection (more than 17 Chagas Disease (onchocerciasis and loiasis) are endemic, the use 8000 microfilariae/ml blood). The current study, of CDTI, and hence onchocerciasis control, had carried out in over 100 villages in Nigeria and virtually come to a standstill because of the risk Cameroon, confirmed that a very clear correla- 18 Publications of severe adverse reactions. The reactions occur tion does indeed exist between prevalence and in persons heavily infected with loiasis and intensity of infection. 19 Net news include potentially fatal degenerative effects in A number of different rapid assessment the brain.1 However, under field conditions it is procedures (RAPs) for determining prevalence 20 Deadlines not at all practical to do blood surveys to deter- were compared, including history of > (next page)

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... A new rapid assessment tool

(continued)> eyeworm (whether worms moving along the white of the lower part of the eye have ever been experienced) and Calabar Swelling (whether swellings under the skin which change position or disappear have ever been experienced). All RAPs showed correlation with level of endemicity of Loa, although the best performance was with the RAP based on eyeworm. A prevalence of 40% or more of eyeworm in a community, confirmed by showing a photograph of a worm in the lower part of an eye, was identified as the threshold above which there is a high risk of adverse reactions during CDTI; conversely, where history of eyeworm is less than 40%, there need be no worry concerning mass treatment with ivermectin. The procedure, called RAPLOA, is 100% sensitive and more than 90% specific. This simple method is effective because eyeworm is such a well known infection in endemic communities that they have their own local names for the condition. As recommended by APOC, TDR is now developing standardized guidelines for the application of RAPLOA, and APOC intends to apply the TDRnews RAPLOA method soon in several areas where CDTI is planned and where Loa loa is potentially endemic. Further research will aim at devel- is published three times Loa loa worm a year by the UNDP/World moving along the white oping a rapid mapping method, possibly through combining RAPLOA with Bank/WHO Special of the eye. an environmental modelling system under development by the Liverpool Programme for Research School of Tropical Medicine. Due to the rapid development of RAPLOA and Training in Tropical (a mere nine months went by between the protocol development work- Diseases (TDR). shop and application of the results in practice), onchocerciasis control Full article text available operations in Central Africa can soon go full speed ahead again. on the TDR website. All material submitted to TDRnews undergoes edito- Correlation between history of eye worm rial review. Articles and and prevalence of Loa loa illustrations published in TDRnews which are not copyrighted may be repro- duced, 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.

Managing editor Nina Mattock Production team Andy Crump Cathy Needham Design and layout Lisa Schwarb Eastern Cameroon Western Cameroon Cross River Nigeria Tel. (+41-22) 791-3725 CONTACTS 1 Fax Gardon J et al. Serious reactions after mass (+41-22) 791-4854 Dr Hans Remme treatment of onchocerciasis E-mail with ivermectin in an area TDR [email protected] endemic for Loa loa infection. Lancet, July 5 1997, Web Tel: (+41-22) 791-3815 350(9070): 18-22. www.who.int/tdr Fax: (+41-22) 791-3737 2 Boussinesq M et al. Address Relationships between the TDR E-mail: [email protected] prevalence and intensity of World Health Organization Loa loa infection in the Cen- tral province of Cameroon. Avenue Appia 20 Annals of Tropical Medicine 1211 Geneva 27 and Parasitology, 2001, Switzerland 95(5): 495-507.

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RESEARCH CAPACITY STRENGTHENING TDR participates in major WHO initiative

WHO and six of the Free internet access to would like to par- biggest medical jour- top international medical ticipate in this initia- nal publishers tive, and how you announced an journals–WHO invites would make the important initiative medical schools and most of your partic- in July 2001. Medical research institutes in low ipation. There is no schools and research income countries to seize restriction on the institutes in low number of institu- income countries the opportunity tions that can par- are to get free (or ticipate, so please low cost, depending on GNP per also suggest other organizations in capita) full-text access through the your country and region that might Internet to nearly 1500 top interna- benefit from this chance too. tional medical journals. “It is per- To be eligible, you/your institute haps the biggest step ever taken must exist in a low income country towards reducing the health infor- and be working in the area of health mation gap between rich and poor or biomedicine, e.g. you will likely countries” said Dr Gro Harlem be from a: Brundtland, Director-General of • school of medicine, nursing, CONTACTS WHO, at the signing of the State- public health, pharmacy, Mrs Barbara Aronson ment of Intent by senior executives biomedical sciences, or social WHO information and of the publishers. sciences. library services It is planned that the initiative will • university (particularly one offer- begin in January 2002, and that ing graduate studies in biomedical Tel: (41-22) 791-2034 progress will be monitored for disciplines). Fax: (+41-22) 791-4854 three years. TDR will help in imple- • research institute. E-mail: menting the initiative (known as • government office. [email protected] Health InterNetwork Access to This initiative is expected to have Research Initiative, see TDRnews implications that extend beyond No. 64) because of its commitment access to information. It is envi- Steven Wayling to capacity building. sioned that better and timely infor- Manager–Research Thus WHO would be interested to mation will increase the capacity of Training hear from any of you, our collabora- scientists and health care workers tors, who could make use of this from low income countries to par- WHO/TDR opportunity. We would like to ticipate in the global research agen- Tel: (41-22) 791-3909 know how you/your institute would da, to better set national research Fax: (+41-22) 791-4854 ensure the widest possible access to and health care priorities, and to E-mail: the journals. We need to know increase countries' self-reliance in what your institute can provide and developing evidenced-based strate- [email protected] what it lacks. Perhaps you already gies and tools for the prevention, have high-speed Internet access, and control and treatment of disease. possibly a LAN, as well as the neces- We look forward to hearing from sary hardware (e.g. computers, you. For further information, printers, toner, paper). Perhaps you need training for trainers on Inter- please see WHO press net and information management release at: skills, or on scientific writing and http://www.who.int/ publishing. Whatever your needs inf-pr-2001/en/ and aspirations, please contact us by e-mail to let us know that you pr2001-32.html

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INTERVENTION DEVELOPMENT AND IMPLEMENTATION RESEARCH The filariases: TDR studies help define parameters for control

TDR research is helping to elic- Simulation model gives sentative, so further analysis was it answers to a number of ques- new insights into optimal made of patterns of infection by tions posed by filariases control age. The most common pattern treatment strategies programmes. was that of a plateau, not a In onchocerciasis, for example, for filariasis, and simple decline, in prevalence after a cer- where control programmes are foot care is shown to be tain age; thus Pondicherry was making headway towards elimi- a sustainable and cost- found to be an exception rather nating the disease through com- than the rule. In addition, a very munity directed treatment with effective way of preventing clear and different picture ivermectin, the main research filarial fever emerged between the age of questions are how to monitor maximum prevalence in Africa progress and how to identify (about 40 years) and Asia (15-20 communities who are not receiving sufficient years), with an overall higher prevalence in Africa treatment coverage. A study undertaken by a than in Asia. These findings are being integrated national coordinator for onchocerciasis control 1 into the LYMFASIM model. and supported by TDR, showed that monitoring Another question in lymphatic filariasis is whether of schoolchildren for ivermectin treatment by foot care is effective and sustainable in communi- schoolteachers gave a good indication of popula- ties. Foot care consists of using soap and water CONTACT tion coverage among the community. A much (and occasionally topical ointments containing Dr Hans Remme closer indication, in fact, than the figures for antibiotics) to treat and prevent acute attacks of TDR/IDE treatment coverage reported by district health adenolymphangitis (ADL, or filarial fever). For one services. Now, a larger study is being undertaken year, 140 filariasis patients in India were super- Tel: (+41-22) 791-3815 to validate the findings under routine operational vised and instructed in foot care, after which they Fax: (+41-22) 791-3737 conditions covering several health districts. were advised to continue the simple measures E-mail: [email protected] In lymphatic filariasis, where national control without supervision. One year later, the patients programmes to eliminate this disease are being were interviewed and examined. Most had been initiated, one of the main questions is how many able to maintain the treatment and the severity of treatment rounds will be needed to achieve elim- ADL episodes was considerably less than before ination under different conditions of population (95.2% of patients had either no ADL or ADL of coverage, drug of choice, frequency of treatment, reduced severity); they abstained less from work etc. The computer simulation model LYMFASIM and for a much shorter period. Thus their quality is being developed to address these questions. of life had improved. Foot care is therefore seen Preliminary sensitivity analysis has been complet- to be a most cost-effective method for preventing ed using the current LYMFASIM model, which is ADL attacks, which can be sustained by patients based on the situation in urban Pondicherry, themselves. India (on the results of a vector control trial com-

bined with chemotherapy data from various drug Required treatment coverage and duration trials). Some of the results are shown in the fig- to achieve LF elimination in India ure. If, for example, an area has a lymphatic filaria- (LYMFASIM model predictions)

sis prevalence of 7%, and 70% of a population is Isolines for 99% probability of elimination covered by each round of treatment, then five 100 treatment rounds will be sufficient to achieve 90 elimination; if the disease prevalence is 10%, then 80 six rounds will be required. 70 Another question concerns the effect of age and 60 immune factors on the prevalence and intensity of 50 40 1 Dr Richard Ndomugyenyi, lymphatic filariasis. In the LYMFASIM model quan- (%) coverage Treatment Number of treatment rounds Ministry of Health, tified for urban Pondicherry, prevalence of the 123456789101112 National Onchocerciasis Prev. 7% Prev. 8.5% Prev. 10% Control Programme, disease declines after the age of 30 years. There Uganda. was concern that this pattern may not be repre-

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BASIC AND STRATEGIC RESEARCH Biosocial research and the TDR agenda

Paul Farmer* and Mercedes Becerra** present an overview of biosocial research now being taken up by TDR

What is biosocial research? screening practices mean rising rates of Ameri- can trypanosomiasis, it is an anthropology of TDR is in the unique position of developing new blood banking and bloodbankers, rather than research strategies in order to respond to new scrutiny of patients’ notions, that is called for. problems–or to old problems that have wors- This list of emerging research topics is long and ened in novel ways. Social, economic, and behav- involves each of the TDR diseases. What is clear, ioural research (SEB) is a small but important in contemplating such problems, is that truly part of TDR, as it seeks to bring a broad array of biosocial research necessarily draws on a broad social-science methodologies to bear on the chief range of disciplines and methodologies and can- causes of morbidity and mortality among the not be conducted without ample time and sup- world’s poorest and most marginalized people. port. For years, confusion as to the nature of such research has reigned. Many of those working in What methodologies does the laboratory to develop new vaccines, diagnos- biosocial research use? tics or drugs saw social science research as con- cerned chiefly with elucidating the “beliefs” of In seeking to characterize the more ambitious those living in areas in which the diseases are research agenda that has emerged in SEB in endemic. Others thought that such research recent years, some have referred to “upstream” focused on the burden of stigma. The quest in research: inquiry that, in addition to describing * Professor Paul Farmer is chairperson of the TDR either case was to better understand the “cul- local cultural beliefs, would seek to understand Steering Committee on ture” of “target” populations. Often, a cognitivist the distribution of infectious diseases and also Social, Economic and anthropology of belief resulted, leading to a large their outcomes in broader social context. Such Behavioural Research, and author of the award-winning number of “knowledge, attitudes, beliefs, and an exercise involves large surveys, demographics, publication Infections and practices” (KABP) surveys that may or may not laboratory assistance (for example, for serologic inequalities: the modern prove relevant in piloting new tools. studies), and also deep knowledge of local cul- plagues, University of California Press, Berkeley, In considering the community of researchers tures and of the cultures of the research and USA, 1999. committed to TDR diseases, it is easy to discern funding communities. a stark division between social scientists and Biosocial research is thus likely to draw on both ** Dr Mercedes Becerra, an infectious disease epidemiol- other researchers when no such division is war- qualitative and quantitative methods. Among the ogist, is director of research ranted. The phenomena that concern us–epi- former are ethnographic methods (including for the Program in Infectious demic and endemic disease–are not solely bio- long-term participant observation, which takes Disease and Social Change, Harvard Medical School, USA. logical; neither are they purely social. Yet con- years), case histories and biographies, network ventional studies typically rely on disciplinary analysis, and focus groups. Quantitative methods approaches and fail to reveal the full complexity important to biosocial research include conven- of these epidemics. tional and molecular epidemiology, biostatistics, Only by embracing a transdisciplinary, biosocial economics, and demographic studies. Political approach can we hope to describe fully these economy and history are necessary to any com- epidemics, and intervene successfully. For exam- prehensive account of shifting disease determi- ple, when yet another hydroelectric dam alters nants. One might also argue that the sociology rates of schistosomiasis or filariasis, we must also of science has a special role to play in sorting out study the “behaviour” of policymakers at devel- “scientific debates” that arise as often in anthro- opment agencies if we are to understand the dis- pology, say, as they do in particle physics. tribution and outcome of schistosomiasis and filariasis. When recurrent drug stockouts charac- A biosocial view of emerging terize a tuberculosis control programme, the drug resistance “knowledge, attitudes, beliefs and practices” of patients may have only limited relevance to the The emergence of strains of malaria, pathogenic emergence of drug resistance, whereas fluctuat- bacteria, viruses, and mycobacteria resistant to ing drug prices, tariffs, and poor drug quality our therapeutic arsenal could be thought of as might prove determinant. When poor blood- classic biosocial problems. There is > (next page)

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Biosocial case study: primary or acquired drug resistance?

Haiti bears one of Latin 21-year-old student. The taking care of Jean were been positive the whole America’s greatest TB way Jean recalls it, his sure that he was “non- time. I stopped taking burdens. Approximately family’s problems began compliant” and said as them and went to an 10 000 new cases of tuber- when he started to cough. much to his parents. herbalist (dokte fey) for a culosis are reported each At first he sought to treat Towards the end of the few weeks.” At the herbal- year; the true number is his persistent hack with year, Jean’s fears were ist’s, Jean was treated with thought to be closer to herbal teas. But when his heightened by an episode various concoctions con- 50 000. The Joseph family cough worsened, he began of hemoptysis. “I knew I taining the bark and leaves might be termed a typical to think he might have was getting worse, so I of trees held, he said, to lower-middle-class Haitian something other than a went to a pulmonologist.” cure “tuberculosis and family, if not for mul- banal cold. In the second The specialist referred Jean other lung disease.” But tidrug-resistant tuberculo- month of his illness, with to the national TB sanato- his symptoms persisted, sis (MDR-TB). They were a new back pain and a fever, rium in January, 1998. and when he again began large family crowded into a Jean took himself to a TB There Jean was found to to cough up blood, he small house in a poor hospital in Port-au-Prince. be floridly smear-positive returned to the sanatori- neighbourhood in the “It’s not that I thought I and admitted for further um. Again he was pre- sprawling capital. Mme had tuberculosis,” he therapy. Jean was an inpa- scribed the same first-line Joseph sells wares in the recalled in an interview. tient for almost three drugs, including rifampin streets; her husband is an “Not at all. It’s rather that months, during which he and isoniazid. During that irregularly employed con- I knew they could take a received directly observed time, he recalls, he was struction worker. Although chest x-ray.” But Jean did therapy with the same placed in an open ward they live in poverty by any indeed have TB, and he drugs he had received pre- with other patients, many standard, theirs was a was started that day on a viously. He remained of them, he knew, with household in which it four-drug regimen that smear-positive throughout drug-resistant disease. might be expected that all included not only rifampin, his time there. “I was dis- “None of them were get- eight children would but also streptomycin, a couraged, I wanted to stop ting better,” Jean recount- attend school; one or two drug that is injected intra- [taking the medications]. I ed. “They started talking of them might even be muscularly. “I took all my was sure these medicines about other medicines that expected to find jobs. medications,” he recalled wouldn’t do anything for were better, but they said One of their most talented anxiously, “but I kept me, since I had taken that the government either children is Jean, in 1997 a coughing.” Some of those them for over a year and didn’t have the medicines

(continued)> simply no way to understand the Social, economic, and dynamics of emerging drug resistance without an behavioural research and understanding of both microbial and human the “outcome gap” “behaviour.” Quotation marks are appropriate because the term behaviour tends to focus The goal of TDR is to perform research that attention on those afflicted with the diseases, meets the highest scientific standards in order whereas we must clearly cast our net much to respond to a dozen diseases that kill mil- wider if we seek firm analytic purchase on what lions and blind or maim millions more. Most of might prove to be the Achilles’ heel of new drug these afflictions are thought of as “tropical” development. diseases but they are in truth more linked to Allow us to give an example from our own work social class than to latitude. Those who work on the emergence of resistance to antitubercu- with TDR are called to go “from blackboard to lous drugs. Those who study this field have bench to bedside” to bring new diagnostics, classed resistance in two categories: acquired vaccines, and drugs to the population bearing and primary. A patient with a history of previous the greatest disease burden. tuberculosis treatment is said to be sick with The “upstream” research mentioned above has acquired drug resistance when drug-susceptibili- already revealed a rising tide of social inequality testing of an isolate of Mycobacterium tubercu- ty, which makes it increasingly difficult to bring losis shows resistance. Acquired resistance is research to the bedside (in fact, many do not very often attributed to patient non-compliance. sleep in beds, but on mats or worse). This ris- But the story can be much more complex, as a ing outcome gap may well prove the biggest more biosocial example–drawing on comple- challenge facing TDR in the coming decades. mentary methodologies–reveals. That is, as we develop new tools–vaccines and other preventives, diagnostics, drugs–our fail- ure to distribute them equitably means that the poor will do worse than ever. This has been seen starkly as regards tuberculosis and many other TDR diseases: although the diseases occur in many settings, virtually all

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or wasn’t going to distrib- medicines, and so I had to dren did not get better on work, they began therapy ute them.” stop. I became positive first-line drugs, their and became smear-nega- The names of these drugs: again.” providers assumed, once tive within two months. kanamycin, cycloserine, Jean soon had fevers every again, “non-compliance.” However, “genetic finger- ethionamide, and night, and drenching Maryse threatened to never printing” of their samples ciprofloxacin. They are far sweats. He coughed inces- return to clinic after a suggests that the family more expensive, more santly, and lived in fear of heated exchange with the was infected with a single toxic, and less effective hemoptysis (he learned doctor in charge of the strain of drug-resistant than are rifampin and iso- during his sanatorium stay facility. The national TB tuberculosis, and that niazid. Little reason, then, that this symptom could programme dutifully regis- empiric therapy with first- to take them–unless you prove rapidly fatal). But tered all the Joseph sib- line drugs–following inter- have the misfortune to the situation, Jean reports, lings as having acquired national recommenda- have MDR-TB. In that case, was to become even worse. drug resistance. The Hait- tions–led to a worsening such “second-line” drugs “Even though I had ian government could not of their drug-resistance often hold the only real stopped coughing blood, buy the drugs for patients profiles. Likely infected hope of cure. Once Jean’s my sister Maryse began with MDR-TB, but did refer with a strain resistant to parents had the names of coughing in about October, the Joseph family for cul- isoniazid, rifampicin, and the drugs, and a prescrip- and then she started ture and drug-susceptibili- streptomycin, members of tion from one of the pul- coughing up blood.” One ty testing. “I never got the the Joseph family subse- monologists, they started by one, the Joseph chil- results. I kept going back quently “lost” ethambutol selling off assets–furni- dren became ill. After every couple of weeks, and and ethionamide in the ture, a parcel of land–in Maryse, the oldest, came they kept telling me to course of empiric regimens order to buy the medica- Myrlene, who had for years come back again in a cou- recommended by both poli- tions. “I started taking suffered with sickle-cell ple of weeks.” cy makers and their physi- [second-line] medicines anemia. Then came Kenol, Eventually, in November cians. Among the Joseph inside the sanatorium, and the youngest. Finally, Shel- 1999, all of the Joseph family, non-compliance I was soon [smear-]nega- la started coughing. siblings were sent to a cannot be shown to have tive. In July, I went home. And one by one the Joseph referral facility with pre- played a role in either the But after five months of siblings began treatment sumptive diagnoses of acquisition of drug-resis- treatment, my parents with first-line drugs. acquired MDR-TB. Follow- tant tuberculosis or in the couldn’t buy any more Because the Joseph chil- ing the requisite laboratory initial poor outcomes.

CONTACT Dr Johannes Sommerfeld TDR/STR research that could help us to pilot new tools Tel: (+41-22) 791-3954 is called for if we are to diminish the outcome gap. That research will draw upon the Fax: (+41-22) 791-4854 biosocial work that seeks to define the E-mail: dynamics of disease persistence, emergence, [email protected] and re-emergence. But neither biosocial nor operational research will amount to much if there are no new vaccines, drugs, or diagnostics to distribute. Those working on Strategic Social, Economic, Intrafamilial transmission of and Behavioural Research are grateful to be M. tuberculosis is common in part of the TDR community. All of the dis- endemic settings. In this family, tardy diagnosis of a eases under the TDR aegis are known to be father with smear-positive “social” diseases and many in both the basic pulmonary tuberculosis led sciences and public-health communities note to infection in his children, of whom four developed the need for new and more comprehensive active disease. analyses of these persistent plagues. We know from experience that biosocial research takes time and resources, and thus appreciate the understanding of our colleagues in the basic sciences. It also requires the patience of our colleagues in the field, deaths are registered among the poor. This is and of the populations we, too, hope to true for tuberculosis, malaria, and HIV as well. serve. Many of us believe that genuinely From an equity perspective, the situation has biosocial research will help us fill gaps in gotten worse since new tools were developed. analysis and allow us to turn our attention to A worsening outcome gap has led some closing the outcome gap–a task likely to researchers away from developing new tools. emerge as the pre-eminent challenge to trop- This is, in our view, a mistake. New operational ical disease researchers in the 21st century.

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Does inequality matter?

Erik Blas, TDR Programme Manager

This question–does inequality matter?–was • Epidemiologists and health systems posed a few months ago on the front page of The researchers can best help equity-oriented Economist, a leading international news magazine. health policy-makers take advantage of the The magazine further devoted its main editorial present climate by developing an evidence to discussing the topic.1 It argued: in good eco- base concerning intervention options for nomic times, even the poor feel better off. In bad reaching the poor effectively. ones, the rich may lose the most money, but the Gwatkin further states that, although resear- poor lose their jobs, their houses, even their chers have contributed valuable conceptual families. The editorial goes on to state that help- frameworks for approaching these issues, they ing the truly poor is a much worthier goal than have not yet reached the heart of the matter, merely narrowing the inequalities. If the rich get namely the identification of measures that can poorer, some people may feel pleased, but few deal effectively with the inequalities that have are better off. If the poor get richer, the whole been uncovered. country will benefit.1 It concludes by saying that TDR is committed, through its Strategy 2000- helping the poor is not just something to do sim- 2005, to developing solutions to public health ply on humanitarian grounds but is also some- problems, having defined its end-users as poor thing that should be done to ensure stability and and marginalized populations in disease endem- continued economic growth of the society. Here ic countries who do not have access to appro- there is a shared interest with the humanists, priate and cost-effective means to prevent and who use the ethical concept of equity as a syn- treat their neglected infectious diseases. This onym for social justice and fairness. Inequities are commitment is guiding the Programme in its CONTACT inequalities that are judged to be unfair, i.e. both efforts to discover and develop new drugs, vaccines, and diagnostics, and to realize the Erik Blas unacceptable and avoidable.2 Equity in health care need of extending TDR research beyond proof means that health care resources are allocated TDR Programme Manager of principle into implementation research. according to need, health services are received However, there are still gaps in our under- Tel: (+41-22) 791-3784 according to need, and payment for health ser- standing of why inequities in access to health Fax: (+41-22) 791-4854 vices is made according to ability to pay. It care exist, how they relate to various policy implies a commitment to ensuring high standards E-mail: [email protected] reform elements, and how these inequities can of real (not only theoretical) access, quality, and be overcome. The recently established TDR acceptability in health services for all.3 Steering Committee on Social, Economic and During the 1990s, there was growing concern Behavioural Research (SEB) has put these that the efficiency-driven health reforms being questions high on its agenda. Already in 1998, implemented in many poor countries, using TDR, in collaboration with the International instruments such as direct user-payments, Clearinghouse for Health System Reform Initia- exemption mechanisms, various insurance tives in Mexico and with funding from the gov- 1 [Anonymous] schemes, privatization, decentralization, might Does inequality matter? ernment of Norway, had commissioned 18 The Economist, London UK, lead to decreased social justice and fairness as studies on health sector reform and equity. 16 June 2001:11-12. well as add to instability and eventual slow down These studies have now been completed and of economic growth in the poorest countries. In 2 Whitehead M. are being prepared for publication in an inter- 4 The concepts and principles a recent article, Davidson R Gwatkin of the national peer-reviewed journal. At the same of equity and health. Inter- World Bank calls for a new wave of health sec- time, policy briefs targeting policy-makers are national Journal of Health tor reforms, that are equity-oriented, and con- Services, 1992, 22:429–445. being prepared, presenting the main findings of ceived and executed with even more passion the research and highlighting the policy implica- 3 Braveman P. and determination than the efficiency-directed tions. These policy briefs will be posted on the Monitoring equity in health – reforms of the 1990s. He presents three argu- TDR website at a policy-oriented approach in low- and middle-income ments to support his call: http://www.who.int/tdr/topics/social- countries. Geneva, World • Significant reforms will require changes that research/policy/ over the next few months. In Health Organization, 1998. are far deeper than commonly recognized in addition to providing the results and recom- 4 Gwatkin DR. policy circles. mendations, each brief will also carry the con- The need for equity-oriented • Current movement toward debt relief in poor tact details of the research groups who under- health sector reforms. countries is creating a climate that is potential- took the research in the hope of stimulating International Journal of Epidemiology, 2001, ly more favourable to deeper change than was networking among researchers interested in 30:720-723. the climate of the recent past. this type of study.

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UPDATE Multilateral Initiative on Malaria in Africa (MIM)

A new cycle of research projects

A call for letters of intent was issued by the Multilateral Initiative on Malaria (MIM)/TDR initiative to promote partnership in research capacity for malaria in Africa. Fifty-four letters were submitted by scientists from 16 African countries by the deadline of 15th July 2001. The letters covered broad areas of malaria research, the most popular being studies on different aspects of antimalarial drug resistance. Other proposals were in the areas of epidemiology, community based interventions, insecticide resistance, socioeconomic and behavioural research, pathogenesis of severe malaria, genomics applications, and health policy. Twenty-six of the letters were selected by an external panel of experts to be further developed into full proposals. These will be submitted to the MIM/TDR Task Force, sched- uled to meet in Uganda, March 2002. The MIM/TDR Research Capacity Strengthening grants for malaria in Africa are intended to promote sustainable human resource development by supporting research activities in partnerships and global collaborations as instruments for capacity strengthening. The objective is to develop or CONTACT strengthen core African basic and/or applied science research groups and networks in developing effective control tools for malaria and improving Dr Olumide Ogundahunsi relevant health policy strategies. Funds are intended to support institution Scientist, MIM/TDR or research group development programmes, rather than independent or Research Capability isolated research projects. Multidisciplinary approaches and research net- Strengthening, works in specific areas, constituting shared African resources and facilities for research and training, are encouraged. Tel: (+41-22) 791-13597 Fax: (+41-22) 791-4854 E-mail: Antimalarial drug resistance network [email protected] A network of MIM/TDR-funded research groups in six African countries will be conducting studies to systematically define the characteristics and levels of Plasmodium falciparum resistance to antimalarial drugs currently used in Africa. This is one of four networks emerging from MIM/TDR research projects (see TDRNews No. 65). The ultimate goal of the drug resistance network is to gain better understanding of drug resistance in malaria parasites, and provide useful information to malaria control programmes for policy-making. The research groups will focus on the following four criteria for defining and identifying drug resistant P. falciparum infections: • Clinical treatment outcome following adequate antimalarial drug therapy. • In vitro susceptibility profile of malaria parasites. • Determination of antimalarial drug blood levels to confirm adequate plasma concentration of drug during treatment. • Presence of molecular markers confirmed and associated with clinical resistant infection. Dr Wilfred Mbacham, from the University of Yaounde, Cameroon, has been designated network manager as from November 2001, and will facilitate the planning, implementation and follow-up process.

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UPDATE Dengue

CONTACTS An unprecedented 1.3 million cases of cases of Typical of post-epidemic periods, dengue activi- Dr Howard Engers dengue fever and dengue haemorrhagic fever ty was much lower in the year after the pan- were reported to WHO in 1998, including over demic, but the number of reported cases TDR/PRD 3500 deaths. The pandemic largely affected the increased to over 0.5 million in 2000. Prelimi- WHO Regions of the Americas (AMR), South- nary data for the year 2001, up to September, Tel: (+41-22) 791-3736 east Asia (SEAR) and the Western Pacific for two of the three regions (AMR and SEAR), Fax: (+41-22) 791-4854 (WPR). More than 55% of the cases, mostly of show a further, large increase of reported cases dengue fever, and only 2% of the deaths, were (>525 913 cases) with nearly 500 deaths. These E-mail: [email protected] reported from AMR. However, in this region, data suggest a level of activity comparable in dengue fever and dengue haemorrhagic fever magnitude with that of 1998. are reported separately, whereas in SEAR and Dr Michael Nathan WPR the data are aggregated and the great For further information see: CPE/PVC majority of reported cases are hospitalized http://oms2.b3e.jussieu.fr/DengueNet/ cases of dengue haemorrhagic fever. The bur- WHO Report on global surveillance of epidemic-prone infectious Tel: (+41-22) 791-3830 den of severe disease remains proportionately Diseases. Chapter 6: Dengue and dengue haemorrhagic fever. WHO/CDS/CSR/ISR/2000.1 Chapter 6 can also be found at: much greater in the affected Asian and Pacific Fax: (+41-22) 791-4869 www.who.int/emc-documents/surveillance/docs/ countries. whocdscsrisr2001.html/dengue/dengue.htm E-mail: [email protected]

Cases of Dengue Fever and Dengue Haemorrhagic Fever Reported to WHO 1998-2001* 1998 1999 2000 2001*

WHO Region Cases Deaths Cases Deaths Cases Deaths Cases Deaths

Western Pacific 356 554 1 470 64 066 112 45 603 167 NA NA South-East Asia 218 859 2 075 55 405 471 57 997 542 119 707 452 Americas (DF) 708 146 0 317 040 0 394 847 0 400 875 0 Americas (DHF) 12 426 83 5 216 98 5 667 92 5 331 44 Americas (total) 720 572 83 322 256 98 400 514 92 406 206 44 Eastern Mediterranean No dengue cases reported to WHO (several countries are affected, including Pakistan, Somalia, Sudan) African No dengue cases reported to WHO World 1 295 985 3 628 441 727 681 504 114 801 525 913 496

* Provisional data to Sept. 2001 NA - data not available Only the Americas countries report DF and DHF separately

AWARD Dr Remme of TDR awarded the Eijkman Medal

* For full profile, see: www.who.int/ We are pleased to The Eijkman Medal The aim of the Foun- announce that Dr Foundation was estab- dation is to encourage tdr/topmenu/staff/ Hans Remme has been lished in 1923 in hon- research in tropical remme.htm awarded the Eijkman our of Christiaan Eijk- medicine, and the Medal for his contribu- man, former professor Eijkman Medal is tion to tropical medi- of hygiene at the awarded every two cine, specifically for his University of Utrecht, years to those scien- work in the field of The Netherlands. tists who have made epidemiological Renowned for his a major contribution research and control research in the former to this field. of onchocerciasis. Dr Dutch East Indies Dr Remme is to Remme has worked in (now Indonesia), which receive the medal TDR for ten years and led to elucidation of on the 12th October is currently coordina- the cause of beri-beri, 2001 during a meeting Dr Hans Remme. tor of lymphatic filaria- Christiaan Eijkman of the Netherlands sis and onchocerciasis received the Nobel Society for Tropical research activities.* Prize for Physiology Medicine. and Medicine in 1929.

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AWARD TDR co-worker awarded for contribution to TB control

Dr Akihiro Seita, its most effective ing the inaugural Regional TB Advisor means of controlling session of the 32nd and TDR counterpart the current tuberculo- IUATLD World for TB at the WHO sis epidemic. Dr Sty- Conference on Lung Eastern Mediter- blo's work made it pos- Health, 1 November ranean Regional sible for developing 2001, Paris, France. Office (EMRO), has countries to make real Dr Seita has worked been awarded the progress against TB - closely with TDR's Karel Styblo Public such as industrialized Research Capability Health Prize for 2001 countries made 40 Strengthening pro- by the International years ago–only at a gramme since joining Union Against Tuber- much lower cost. His EMRO, particularly in culosis and Lung Dis- strategy (now called promoting TB Dr Akihiro Seita. eases (IUATLD) for DOTS or Directly research in the east- his contribution to Observed Treatment - ern Mediterranean between research and tuberculosis control. Short Course) has region and as a secre- control can be found in The award was named been adopted by over tariat member of the TDRNews No. 65, June in honour of the for- 90 countries in the last EMRO/TDR/Roll Back 2001. TDR extends its mer scientific director few years as a response Malaria Small Grants warm congratulations at IUATLD, Dr Karel to tuberculosis becom- Programme, which to Dr Seita and his col- Styblo, following his ing the largest infec- funds control-related leagues in the Region death in 1998. Dr tious killer of youth research in the with whom he gener- Syblo is credited with and adults. The award Region. Dr Seita's ously shares the hon- providing the world will be presented dur- thoughts on the links our.

AWARD TDR research collaborator honoured

Lenore Manderson award- intended to help retain her to many countries and their relationship ed the prestigious Aus- Australian researchers worldwide while, at to culture and social tralian Federation Fellow- in Australia, and to home, her contribu- networks has the ship bring others back tions have been potential to change home; a total of 125 towards improving significantly the way in Professor Lenore are to be awarded Australia’s capacity to which health care is Manderson, member over the next five deliver health services delivered even to the of the TDR Steering years. Professor Man- to its culturally and most disadvantaged Committee for Strate- derson is among 15 ethnically diverse com- communities. gic Social, Economic beneficiaries munity. Her current Professor Manderson and Behavioural announced in the first research examines has served for many Research (SEB), has round. how individuals per- years on various TDR been awarded the Professor Manderson ceive themselves and steering committees most prestigious, pub- is one of the world’s how these perceptions and task forces and is licly-funded fellowship leading medical are re-shaped by expe- co-author of several ever in Australia. The anthropologists. She is riences of serious ill- TDR publications, award was announced currently Director of ness and trauma. Since among them a review by Mr Howard, Prime the Key Centre for many of the factors on community partici- Minister of Australia, Women’s Health in which affect adjust- pation and several on 25 September Society, Department ment to chronic dis- methods guidelines for 2001. of Public Health, Uni- ease and disability are social research on Professor Manderson versity of Melbourne. social, relating to fami- tropical diseases. is one of the first Her anthropology and ly and community, the recipients of the Fel- public health research emphasis on different lowships, which are activities have taken patterns of resilience

TDRnews • No 66 • OCTOBER 2001 • 11 // g

LATEST GRANTS Awards in Basic and Strategic Research

* www.who.int/tdr/ From now on, TDR will publish This is a joint initiative between ‘renewed’ grants were funded grants/awards regularly, in the newsletter and TDR’s Pathogenesis and in 2000 and are now being on its website,* details of all Applied Genomics Committee renewed for a further year fol- approved and renewed propos- and the Research Capability lowing the successful progress als. We hope this will lead to Strengthening unit of TDR, and made towards meeting the better dissemination and is in line with TDR’s strategy of objectives during the first year. awareness of the work that involving researchers and insti- TDR is engaged in at any given tutions from disease-endemic Project Development moment, and to increased countries in all areas of Grants in Pathogenesis transparency of our activities, research and development and Applied Genomics helping researchers interested (know as ‘RCS-Plus’). • A10323 SUNGAE CHO, in similar areas to make contact TDR is pleased to acknowledge Yonsei University Medical with each other and ensuring the collaboration of Burroughs Center, Department of that the scarce resources for Wellcome Fund, USA, the Microbiology, 134 Shinchon- research in tropical diseases are Malaria Research and Refer- dong, Seoul 120-752, used as efficiently as possible. ence Reagent Resource Centre the Republic of Korea. Evalu- In this issue of TDRnews, we (MR4), the National Center for ation of cell mediated are pleased to announce details Biotechnology Information immune responses (CMI) of of recent awards in the area (NCBI), the National Institute TB and leprosy patients to of Basic and Strategic Research. of Allergy and Infectious Dis- define mycobacterial antigens eases (NIAID), and Oswaldo (budget: US$ 10 000) Training in bioinformat- Cruz Foundation (FIOCRUZ) ics and applied genomics Brazil, in supporting the Inter- • A10337 MAURO national Workshop on Training TEIXEIRA, Instituto de Cien- TDR is supporting the estab- of Trainers of Bioinformatics, cias Biologicas, Departamen- lishment of three Centres for held in FIOCRUZ, May/June to de Bioquimica e Imunolo- Training in Bioinformatics and 2001. gia, Universidade Federal Applied Genomics, in Africa, de Minas Gerais, Avenida Asia and Latin America. The Research in pathogenesis Antonio Carlos 6627, 31270- centres, selected from among and applied genomics, 901-Belo Horizonte Pampul- 18 applications received from and in molecular ento- ha MG, Brazil. Evaluation of disease endemic countries, will mology the pathophysiological role of provide facilities for annual MIP-1in human schistosomia- regional training workshops on The TDR Committee on sis: A biomarker of worse bioinformatics for young inves- Pathogenesis and Applied prognosis tigators, and will facilitate the Genomics, and the Committee (budget US$ 10 000) development of networks on on Molecular Entomology, met • A10355 JOSEPH OKAO the applications of genomics in in Tunisia, October 2001, to OLOBO, Makerere Universi- tropical diseases in endemic deliberate and recommend ty Kampala, Immunology Lab- countries. projects for funding by TDR. oratory, Unit PO Box 7072, The centres are: The projects listed below were Kampala, Uganda. • South African National Bioin- selected from among a large The role of selected formatics Institute (SANBI), number of applications cytokines and chemokines in Cape Town, South Africa received from investigators the pathogenesis of TB in • Departamentos de Para- worldwide. Each project listed contacts sitologia et Ciência da Com- under ‘new grants’ will be fund- (budget: US$ 10 000) putação, University of Sao ed for one year in the first Paulo (USP), Brazil instance, and for an additional • A10324 OTAVIO • International Centre for year if sufficient progress is HENRIQUE THIEMANN, Genetic Engineering and made in the first year towards University of Sao Paulo, Biotechnology (ICEGEB), reaching the scientific objec- Physics Institute of Sao India. tives. Projects listed under Carlos, Brazil. Structural

12 • TDRnews • No 66 • OCTOBER 2001 // g

approach in search for novel • A10256 HAGAI DAVID Analysis of genomic variation targets for chemotherapy GINSBURG, Hebrew Univer- among natural populations based on the Leishmania sity of Jerusalem, Institute of of P. falciparum in Africa: a major genome project (bud- Life Sciences Department of chromosomal dissection get: US$ 10 000) Biological Chemistry, Terra approach Sancta Bldg, 91904 Jerusalem, (budget: US$ 35 000) • A10339 HENG WANG, Israel. Maintenance and School of Basic Medicine, • A10308 ANA RODRIGUEZ, upgrading of a web site dedi- Peking Union Medical New York University School cated to blood stages of College, 5, Dong Dan 3 Tiao, of Medicine, Department of Plasmodium falciparum PUMC, Rm. 562, 100005 Bei- Parasitology, 341 E. 25th St., (budget: US$ 8 100) jing, the People’s Republic of New York 10010, USA. Role China. Proteomics approach • A10328 MARY GWO-SHU of dendritic cells in malaria- to identify novel antigens on LEE, New York University induced immunosuppression the surface of malaria infect- School of Medicine, Depart- (budget: US$ 35 000) ment of Pathology, 550 First ed erythrocytes (budget: US$ • A10325 EUZENIR NUNES Avenue, New York NY 10 000). SARNO, Fundacao Oswaldo 10016 USA. Functional Cruz, Laboratorio de Hanse- genomics of African try- New grants in Pathogene- niase, Av. Brasil 4365- Man- panosomes – proteins traf- sis and Applied Genomics guinhos, 21045-900-Rio de ficking in Trypanosoma brucei Janeiro RJ, Brazil. Exploita- • A10311 HANNAH (budget: US$ 35 000) AKUFFO, Karolinska Insti- tion of novel genetic and tute, Microbiology and • A10306 ROBERT LAZARUS molecular approaches to Tumour Biology Center, Box MODLIN, University of Cali- understand nerve damage in 280S-17177, Stockholm, fornia School of Medicine, leprosy (budget: US$ 35 000) Division of Dermatology, 52- Sweden. Innate immunity to • A10440 WORACHART 121 CHS, 10833 Le Conte human leishmaniasis and its SIRAWARAPORN, Mahidol Avenue, Los Angeles CA influence on vaccine outcome University, Faculty of Science, 90095-1750, USA. Analysis (budget: US$ 35 000) Department of Biochemistry, of genomic toll-like receptors Rama VI Road, Bangkok • A10349 HANNAH in mycobacterial infection by 10400, Thailand. P. falciparum AKUFFO, Karolinska Insti- functional genomics (budget: dihydropteroate synthase tute, Microbiology and US$ 35 000) (pfDHPS): optimization of Tumour Biology Center, • A10350 INGRID MÜLLER, enzyme expression in Box 280S-17177, Stockholm, Imperial College of Science, E. coli and development of a Sweden. The role of apopto- Technology and Medicine, bacterial scr sis in the pathogenesis of Department of Immunology, (budget: US$ 35 000) human leishmaniasis Norfolk Place, London W2 (budget: US$ 35 000) • A10340 JULIO SCHARF- 1PG, UK. Influence of toll STEIN, Univ. Federal de Rio • A10422 ROBERTO like receptor (TLR) activation de Janeiro, Instituto de on the innate immune DOCAMPO, University of Biofisica Carlos, Chagas response to Leishmania major Illinois, College of Veterinary Filho Bloco G- C.C.S.- Ilha (budget: US$ 35 000) Medicine, Dept of Pathobiol- do Fundao, 21944-900-Rio ogy, 2001 South Lincoln • A10322 PAMELA MARIE de Janeiro RJ, Brazil. Activa- Avenue, Urbana IL, 61802 PENNINGTON DE tion of kinin-receptors by USA. Polyphosphate metabo- SANCHEZ, Universidad del Trypanosoma cruzi: a modula- lism in Trypanosoma brucei Valle de Guatemala Centro tory role for kininase in and Leishmania major de Estudios en Salud, Institu- cardiovascular pathology (budget: US$ 35 000) to de Investigaciones, 18 (budget: US$ 35 000) Avendida 11-95, Zona 15, V. • A10329 CHRISTIAN • A10318 HG H.III Guatemala 82, 01901 DANIEL DOERIG, Institute STUNNENBERG, University Guatemala. Genetic variabili- National de Sante et de la of Nijmegen, Department of ty of Trypanosoma cruzi as a Recherche Medicale Molecular Biology, NCMLS determinant of myocardial (INSERM), INSERM Unite 191, P.O. Box 9101, Toer- tropism 511 CHU Pitie-Salpetriere, nooiveld 1, NL-6500 HB (budget: US$ 18 705) 91 Boulevard de l'Hopital, Nijmegen, Netherlands. 75013 Paris, France. A • A10375 STEPHEN RICH, Proteomic approach to ‘chemical genetics’ approach Tufts University, Division of identify novel drug targets for the functional study and Infectious Diseases, 200 and vaccine candidates in validation of malarial protein Westboro Road, North the human malaria parasite kinases (budget: US$ 35 000) Grafton MA, 01536 USA. (budget: US $35 000)

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• A10332 THEODORE F. Renewed grants in tors in macrophage respon- TARASCHI, Thomas Jeffer- Pathogenesis and Applied siveness to protozoan son University, Dept of Genomics derived GPI-anchors Pathology, Anatomy and Cell (budget: US$ 35 000) • A00644 PEDRO M. Biology, 1020 Locust Street, ALZARI, Institut Pasteur, • A00645 EMANUELA Philadelphia PA, 19107-6799, Unite de Biochimie Struc- HANDMAN, Walter and USA. Evaluation of role of turale, Departement d'Im- Eliza Hall Institute for Med- the Plasmodium falciparum AP munologie, France. Structural ical Research, Melbourne, endonuclease, pfApel, in Studies of the Trypanosoma Australia. Characterization of DNA base excision repair cruzi trans-sialidase rational mucin-like proteo-phospho- (budget: US$ 35 000) design on inhibitors glycan, a potential Leishmania • A10419 MARIE TERESA (budget: US$ 20 000) major amastigote virulence TELLEZ-INON, Instituto de factor (budget: US$ 35 000) • A00521 LENA ASLUND, Investigaciones en Ingenieria Department of Genetics and • A00532 SEYED HASNAIN, Genetica y Biologia, Molecu- Pathology, Uppsala, Sweden. Centre for DNA Fingerprint- lar (INGEBI-CONICET), 2nd Functional analysis of ing, Nacharam, India. Molec- floor, Vuelta de Obligado Trypanosoma cruzi: expres- ular genetics and functional 2490, 1428 Buenos Aires CF, sion profiling on cDNA genomics of M. tuberculosis Argentina. Biological func- microarrays of gene from patient isolates in India tions and role in cell division genome projects (budget: US$ 35 000) of TzCRK1 and TzCRK3 and (budget: US$ 15 000) their associated cyclins • A00571 HECTOR (budget: US$ 18 350) • A00509 ALFRED CORTES HERNANDEZ, Tufts CLOSAS, Papua New Guinea University School of Medi- • A10342 ESTHER VON Institute of Medical cine, Boston, USA. Strategies STEBUT, Johannes Guten- Research, Amdang, Papua for reducing pathology burg University Mainz, New Guinea. Molecular in schistosomiasis Department of Dermatology, mechanisms involved in the (budget: US$ 35 000) Langenbeckstrasse 1, 55131 protection of ovalocytic indi- Mainz, Germany. Vaccination • A00508 KRISTER viduals against cerebral against experimental cuta- KRISTENSSON, Karolinska malaria (budget: US$ 27 200) neous leishmaniasis with pro- Institute, Stockholm, tein antigen-transduced den- • A00561 THOMAS Sweden. Trypanosoma brucei- dritic cells EGWANG, Med Biotech trafficking across brain (budget: US$ 35 000) Laboratories, Kampala, endothelial cells Uganda. Protein prenylation (budget: US$ 35 000) • A10456 STEVEN in Onchocerca volvulus as a WILLIAMS, Smith College, • A00547 MARIANO JORGE possible biochemical drug Clark Science Center, Filarial LEVIN, Instituto De Investi- target (budget: US$ 35 000) Genome Project Resource gaciones En Ingenieria Center, Dept. of Biological • A00550 ANA MARIA C. Genetica Y Biologia, Argenti- Sciences, Northampton MA FARIA, Universidade Federal na. Pathophysiology of trans- 01063, USA. Use of microar- De Minas Gerais, Belo Hori- genic mice expressing hu rays and proteomics to study zonte, Brazil. Role of ageing chronic Chagas heart disease the effects of Wolbachia elim- in immunity to schistosome anti-p antibodies ination on gene expression in infection in humans and mice (budget: US$ 35 000) Brugia malayi (budget: US$ 35 000) • A00492 PENG LI, Institute (budget: US$ 62 000) • A00486 ALBERTO of Medical and Veterinary • A10418 ROBERT ALAN FRASCH, Instituto de Inves- Science, Adelaide, Australia. WILSON, University of tigaciones Biotecnologicas, Role of infected York, Department of Biolo- Buenos Aires, Argentina. macrophages in dengue virus gy, P.O. Box 373, York Y010 Mucin surface cover of pathogenesis – induction of 5YW, UK. A proteomic Trypanosoma cruzi: regulation permeability in primary approach to define the mole- of expression and interaction human endothelial cells cular structure of the schis- with the immune system of (budget: US$ 35 000) tosome tegument surface, the host • 990510 KEITH the site of immune evasion (budget: US$ 33 000) MATTHEWS, Victoria Uni- (budget: US$ 35 000) • A00477 GIOVANNI versity of Manchester, UK. GAZZINELLI, Universidade Life cycle regulation of the Federal De Minas Gerais, proteome of Trypanosoma Belo Horizonte, Brazil. Study brucei (budget: US $6500) on the role of toll-like recep-

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• A00527 SARA MELVILLE, Molecular and cytological Aedes aegypti from Cuba Cambridge University, Cam- characterization of Anopheles (budget: US$ 26 000) bridge, UK. Development of gambiae molecular forms and • A10406 MICHAEL single nucleotide polypmor- evaluation of their role as LEHANE, University of phism (SNP) markers for malaria vectors Wales, UK. Optimisation of high-throughout genotypic (budget: US$ 38 000) RNAi in mosquitoes (budget: analysis of phenotype variants • A10390 MARTIN AKOG- US$ 15 000) (budget: US$ 35 000) BETO, Centre de Recherche • A10360 DOUGLAS NOR- • A00552 GUILHERME Entomologique de Cotonou, RIS, Johns Hopkins Universi- CORREA DE OLIVEIRA, Benin. Etude des relations et ty, USA. Population and Centro De Pesquisas Rene des divergences écologiques genomic approaches to insec- Rachou Fiocruz, Belo Hori- des formes moléculaires et ticide resistance in Anopheles zonte, Brazil. The use of chromosomiques d'Anopheles gambiae s.l. in Mali microsatellites to assess of gambiae s.s. (budget: US$ 39 857) genetic variation in Schistoso- (budget: US$ 12 530) ma mansoni • A10410 ANN SODJA, • A10442 AHMED (budget: US$ 28 460) Wayne State University, HASSANALI, International USA. Isolation and character- • A00480 NING QUAN, Centre of Insect Physiology ization of an antenna-specific Ohio State University and Ecology, Kenya. Isolation gene in Aedes aegypti Research Foundation, Ohio, and identification of behav- (budget: US$ 39 099) USA. Role of imflammatory iourally active semiochemi- cytokines in the pathogenesis cals from human foot odour of neurodegeneration for African malaria vectors Renewed grants in induced by the infection of (budget: US$ 33 600) Molecular Entomology Trypanosoma brucei • A10429 GUIYUN YAN, • A00399 ADALGISA (budget: US$ 35 000) State University of New CACCONE, Yale University, • A00557 PATRICK J. York, USA. Assessing the USA. Molecular genetics SKELLY, Harvard School of spread rate of introduced studies of malaria vector Public Health, Boston, USA. genes in Anopheles gambiae heterogeneity Inhibition of cathepsin gene (budget: US$ 40 000) (budget: US$ 27 500) expression in schistosome • A10402 LAURENCE • 990488 MARIO COLUZZI, using RNA1 ZWIEBEL, Vanderbilt Univer- Universita di Roma ‘La (budget: US$ 35 000) sity, USA. Isolation and char- Sapienza’, Italy. Oviposition • A00524 JONATHAN acterization of odorant behaviour of Anopheles gambi- KWEKU STILES, Morehouse receptor genes from Aedes ae complex malaria vectors School of Medicine, Atlanta, aegypti mosquitoes (budget: US$ 36 200) USA. Chemokine mediators (budget: US$ 36 750) • 980619 MARIO COLUZZI, of cerebral malaria • A10420 ADAM RICHMAN, Universita di Roma ‘La (budget: US$ 35 000) University of Maryland at Sapienza’, Italy. Isolation and • A00505 ANDREW PAUL College Park, USA. Ectopic molecular characterization WATERS, Leiden University midgut expression of a of salivary gland-specific Department of Parasitology, cecropin transgene in promoters from Anopheles Netherlands. Investigation of Anopheles: effect on gambiae (budget: US$ 32 000) the biology of gamete surface Plasmodium viability • A00401 FOTIS KAFATOS, proteins of Plasmodium (budget: US$ 36 000) European Molecular Biology belonging to the 6 cyc • A10424 ANA MARIA PER- Laboratory, Germany. A domain gene superfamily ALTA DE MERIDA, Universi- method for inducible in vivo (budget: US$ 35 000) dad del Valle de Guatemala. dsRNA inhibition in anophe- Population genetics of Aedes lines. Application for the New grants in aegypti in Chiapas (Mexico) study of a serpin gene com- Molecular Entomology and central America plex (budget: US$ 37 000) • A10454 BARRY BEATY, (budget: US$ 29 113) • 990476 TOVI LEHMAN, Colorado State University, • A10405 JUAN BISSET LAZ- Centers for Disease Control USA. Biology of Disease CANO, Instituto de Medicina and Prevention, USA. Popula- Vector course 2002 Tropical ‘Pedro Kouri’, tion genetics of immune res- (budget: US$ 50 000) Cuba. Molecular characteri- ponse genes to identify genes • A10435 ALESSANDRA zation of insensitive acetyl- determining susceptibility of DELLA TORRE, Universita di cholinesterase mediated Anopheles gambiae to patho- Roma ‘La Sapienza’, Italy. insecticide resistance in gens (budget: US$ 39 140)

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• A00914 Christos Louis, • 990501 ROBERT SINDEN, • A00407 JOSEPH VINETZ, Institute of Molecular Imperial College of Science, University of Texas Medical Biology and Biotechnology, Technology and Medicine, Branch, USA. Expression of Greece. AnoDB, the UK. Natural role of xan- a Plasmodium falciparum Anopheles database thurenic acid in regulation chitinase-neutralizing single (budget: US$ 35 000) of malarial gametogenesis: chain antibody within the a logical basis for novel Anopheles gambiae midgut • A00398 CHRISTIAN chemotherapy? (budget: US$ 33 500) MATHIOT, Institut Pasteur (budget: US$ 46 830) de Dakar, Senegal. Rôle 1 Detailed information d'Aedes aegypti dans l'interac- • 990484 SARALA SUB- on funding and how tion des cycles selvatique BARAO, Indian Council of to apply for support from this Committee et épidémique de dengue 2: Medical Research, India. can be obtained at the aspects génétiques et Population genetic analysis of website www.who.int/ moléculaires Anopheles culicifacies species tdr/grants and from Dr Yeya Touré, Manager, (budget US$ 22 245) A (budget: US$ 22 500) Molecular Entomology Committee: [email protected] TDR expresses sincere gratitude to members of the Steering Committees and to external reviewers 2 Detailed information for their critical assessment and contributions to the selection process. on funding and how TDR would also like to thank those investigators who were not funded. A large number of projects to apply for support from this Committee were reviewed but only a few selected due to the highly competitive selection process. TDR wishes can be obtained at the to encourage these investigators to continue their good work and to re-compete next year. website www.who.int/ tdr/grants and from The next deadline for submission of new applications for consideration by the Committee on Molec- Dr Ayoade Oduola, ular Entomology is 21 June 2002.1 Coordinator, Basic and Strategic Research: The next deadline for submission of new applications for consideration by the Committee on Patho- [email protected] genesis and Applied Genomics is July 2002.2

Staff news: comings and goings

In the last 18 months, the fol- • Dr JOHANNES lowing staff have joined TDR: SOMMERFELD, who is Manager of the Steering • Dr LESTER CHITSULO, who Committee on Social, joined Research Capability Economic and Behavioural Strengthening to become Research. Programme Grant Manager. He is also Disease Research • Dr YEYA TOURÉ, who is Coordinator for Schistoso- Manager of the Molecular miasis. Entomology Committee. • Mr MICHAEL McCUL- and the following have LOUGH, who is Technical departed: Officer, Programme Planning and Management. • Dr WIN GUTTERIDGE, Coordinator of Product • Dr CATHY NEEDHAM, who Research and Development, joined the Communications who retired. Unit to become TDR’s Web Editor. • Dr PAUL NUNN, the erst- while focal point for all dis- • Dr MARK PERKINS, who is ease research coordination Manager, Diagnostics activities in TDR, who has Research and Development. returned to WHO’s Stop • Dr ROB RIDLEY, who is TB programme. Coordinator, Product Research and Development.

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INTERVENTION DEVELOPMENT AND IMPLEMENTATION RESEARCH Chagas disease intervention development and implementation research: transfer to the WHO regional office for the Americas

TDR is placing a lot of emphasis on working of the Pan-American Health Organization closely with disease control programmes, both in (PAHO, which acts as WHO Regional Office for WHO and in countries. The aim is to ensure the Americas). that proven products and procedures are imple- PAHO staff have been working very closely with mented successfully and contribute as much as national control programmes in research and possible to reducing disease burden. Although implementation of new tools, and in all activities newly developed products and procedures may and initiatives pertaining to interruption of Cha- be effective, their implementation is often not so. gas disease transmission, including participation But by using research to tackle the problems in Expert Committee and Task Force meetings. encountered during implementation, we can Dr Felipe Guhl (Director, Tropical Parasitology achieve an impact on control. History shows us Research Centre-CIMPAT, Universidad de los that research should be an important part of all Andes, Bogota, Colombia) was temporarily phases of operations, from planning to imple- recruited by TDR, and, together with Dr Zaida CONTACT mentation and evaluation. Yadon (PAHO/HCT), has worked out a smooth Dr Zaida Yadon Research activities in Chagas disease, supported transition for moving Chagas disease research PAHO/HCT by TDR in several countries, have increased our activities from TDR to PAHO, and a future Tel: (+1-202) 974-3856 knowledge on several aspects of disease control workplan. and stimulated ministries of health to implement Based on the TDR strategy for 2000-2005, the Fax: (+1-202) 974-3688 control activities that have resulted in interrup- PAHO research agenda will include priority lines E-mail: tion of transmission of this disease. Two coun- of research as proposed for Chagas disease by [email protected] tries have already been declared free of trans- an Expert Committee meeting held in Brasilia, mission: Uruguay (1997) and Chile (1999). In Brazil, November 2000 (see TDRnews no. 64). addition, 12 of the 19 endemic provinces of These lines of research have been assigned to Argentina were declared free of vectorial trans- the new TDR Proof of Principle and Implementa- mission in 2000/01. In Brazil, infection rates are tion Research Steering Committees (more also very low and, in 2001, available data indicate details of these committees in the next issue of that vectorial transmission has been interrupted TDRnews). All research activities related to Cha- in 10 of the 12 endemic states. Current data on gas disease in other TDR areas (Basic and Strate- house desinsectation, coverage of blood banks gic Research, Product Research and Develop- screening, and serology in younger age groups, ment, Research Capacity Strengthening) will con- indicate that Bolivia and Paraguay are also mov- tinue at TDR in Geneva. ing towards the goal of interrupted transmission. Surveillance programmes are in action in these Southern Cone countries in case of possible re- infestation. In view of the achievements in reducing transmission of Chagas disease in the countries of the Southern Cone Initiative, and the improvement in control activities in some of the countries under the initiatives of the Andean and Central American countries, the momentum was consid- ered appropriate for transfer of TDR Interven- tion Development and Implementation Research activities to the Communicable Disease Program

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www.who.int/tdr/publications

• Handbook. Good laboratory practice • Handbook: Quality standards (GLP): Quality practices for regulated in biomedical research non-clinical research and development TDR/PRD/QSBR/01.1 TDR/PRD /GLP/01.2 A draft document prepared for TDR by the The third in the TDR series on good laborato- Scientific Working Group on Good Laborato- ry practice (see TDRnews No. 64 for the first ry Practice, this handbook addresses quality two volumes), this handbook addresses the issues in basic research investigations and issues of regulatory safety studies which are proposes general standards for laboratories covered and governed by the Organisation for working to explore and discover substances Economic Co-operation and Development with potential for developing into new drugs (OECD) Principles of GLP. The OECD series and other products. This stage of product on GLP and compliance monitoring is present- research and development is not covered by ed in its entirety in the annexes. These are pre- any officially recognized quality standards ceded by an overview of GLP – the fundamen- (such as those issued for good laboratory tal points and history of GLP, training, practice [GLP] and good clinical practice resources, documentation, quality control, and [GCP]). stepwise implementation. The handbook is The standards cover the way basic discovery designed to help those who wish to upgrade research and any other laboratory based their laboratories to GLP status, providing lab- research is organized and carried out (e.g. oratory staff and trainers in disease endemic how to keep records and store data), but not countries with the necessary technical aid for the content of the research. The intention is HOW TO OBTAIN implementing GLP programmes. to help speed up the discovery process and PUBLICATIONS make it more cost-effective, because, when All TDR publications are quality standards are followed, the data arising from basic research will be universally accept- available to download from able and credible, and when the basic underly- the TDR website: ing conditions of the experimental set-up are www.who.int/tdr/ clear and well documented, there will be no publications/publications doubt as to the validity of the knowledge gen- erated and its contribution to science. or on request from This draft handbook is intended to serve as a TDR Communications working document, and to be circulated inter- nationally to scientists and researchers involved in basic biomedical research. So, if you work in this area of research, please request a copy of the draft document and send us your comments.

• Report of the fourth TDR/IDRI meeting on second-generation vaccines against leishmaniasis TDR/PRD/LEISH/VAC/01.1 1-3 May 2001, Universidad Autónoma de Yucátan, Mexico. (See TDRnews No. 65 [June 2001] for summary of this meeting)

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Posters:

• Onchocerciasis October 2001.

• African trypanosomiasis November 2001.

• Dengue December 2001.

Co-publications with Trends in Parasitology (formerly Parasitology Today).

Net News/grant writing tips

'You know your research is stimulating, exciting and groundbreaking; the only thing you need to do now is to convince those holding the purse strings.'1 Whether you are applying for research funds CONTACT from the NIH, the Wellcome Trust, TDR, or elsewhere, good grant writing skills are essential for success. Cathy Needham, There are a number of resources on the web that can help. A useful collection of resources and TDR Web Editor tips on successful grant writing is available on Science's Next Wave website: Tel: (+41-22) 791-3786 http://nextwave.sciencemag.org/cgi/content/full/1999/09/20/2 Fax: (+41 22) 791-4854 Published on these pages are some 25 articles on subjects ranging from 'expository writing skills' E-mail: to 'how to get a bit of NIH's billion-dollar funding pie'. Included also is the series 'how not to [email protected] kill a grant application', which gives practical advice aimed at improving your chances of being awarded research funds. Various funding organizations, research centres and universities also provide information The theme for the next and links to grant writing tips on their websites (e.g. www.paho.org/English/HDP/HDR/ 'net news' (TDRnews hdr-rgp.htm, www.umass.edu/research/ora/dev.html). Often tailored to suit specific needs, No. 67) will be public- these can also contain useful general tips–e.g. the NIH 'grant writing tips sheets' page private partnerships. (http://grants.nih.gov/grants/grant_tips.htm) and the recently updated 'how to write We welcome suggestions a research grant application' (www.niaid.nih.gov/ncn/pdf/howto.pdf). and feedback.

1 Mohan-Ram, V. How not to kill a grant application, part 6: developing your research plan. 2000, Internet communication of 11 Aug 2000 at website http://nextwave.sciencemag.org/cgi/content/full/2000/08/09/3

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DEADLINES Steering Committee meetings

TDR Research proposals and reports submitted to TDR are reviewed by the relevant commit- World Health Organization tees. To guarantee review at a given meeting, your proposal should in general be received in Avenue Appia 20 Geneva two calendar months before the date of the meeting, or earlier in the case of 1211 Geneva 27 Research Capacity Strengthening. Proposals received later than this may be reviewed at the Switzerland following meeting of the relevant committee. When preparing your research proposal, it is Tel: (+41) 22-791-3725 important to bear in mind that TDR supports goal-oriented research and that your proposal Fax: (+41) 22-791-4854 should be consistent with the plans of the relevant committee. Therefore please study the E-mail: [email protected] priorities of the relevant steering committee before submitting your proposal and, if you are Web: www.who.int/tdr applying for the first time, please contact the relevant research manager in TDR with an out- line of your proposed research before developing a full proposal.

Meeting date Deadline BASIC AND STRATEGIC RESEARCH • Molecular Entomology Sept 2002* 21 June 2002* • Pathogenesis and Applied Genomics 4-9 Sept 2002* 21 June 2002* Working Group on Applied Genomics for Drugs and Diagnostics 19-21 Sept 2002* 22 July 2002* • Social, Economic and Behavioural Research 3-7 June 2002* 22 Mar 2002*

PRODUCT RESEARCH AND DEVELOPMENT • Drug Discovery Research 25-28 Mar 2002 25 Jan 2002 • Vaccine Discovery Research May 2002 Mar 2002* • Diagnostics Research 18-20 Sept 2002 18 July 2002

INTERVENTION DEVELOPMENT AND IMPLEMENTATION RESEARCH • Implementation Research Steering Committee 8-10 April 2002 to be annouced 16-18 Oct 2002 • Proof of Principle Steering Committee 10-12 April 2002 to be annouced TO OUR READERS 14-16 Oct 2002 We are unfortunately These two steering committees met for the first time in October 2001; unable to accept for incoroporated into their activities are those of the previous IDE task publication in TDRnews forces (Malaria Home Mangement; Severe Malaria; Research on Drug announcements (for Resistance and Policies; Filariasis Intervention Research; Intervention meetings, new pro- Research on Chagas Disease; Intervention Research on African Trypanaso- grammes, institutions, miasis; Chemotherapy of Leprosy). publications, etc.) which readers send us. Further information to be found in the next issue of TDRnews, and, as it Announcements which becomes available, at the TDR website. relate to research on tropical diseases would RESEARCH CAPACITY STRENGTHENING clearly be of interest to • Research Strengthening Group 11-15 Feb 2002 our readers. However, Feb 2003* 31 Oct 03* because of limited space in the newslet- • Malaria Research Capacity Strengthening ter, we regret that we in Africa 11-15 Mar 2002 can publish only those Mar 2003* Nov 2002* concerning events in which TDR is directly * tentative involved.

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