Malaria Research Capability Strengthening in Africa

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1 July 2005 UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases (TDR) Multilateral Initiative on Malaria (MIM) Malaria Research Capability Strengthening in Africa INTRODUCTION The Multilateral Initiative on Malaria (MIM) was launched to "strengthen and sustain, through collaborative research and training, the capability of malaria endemic countries in Africa to carry out research required to develop or improve tools for malaria control". Since 1998, MIM through the UNICEF / UNDP / World Bank / WHO Special Programme for Research & Training in Tropical Diseases (TDR), the U.S. Department of Health and Human Services, National Institutes of Health ( and a broad range of partners including international research institutes and councils, has applied a multi-pronged approach to achieve this goal. For example, better access to information, Internet connectivity as well as technical support for research collaboration is funded by the National Library of Medicine through MIMCom ( The National Institute of Allergy and Infectious Diseases also funds the Malaria Research and Reference Reagent Resource Center (MR4, The MR4 provides investigators with access to research reagents and standardized protocols and information as well as workshops and training in malaria research. Other partners and collaborations both within and outside Africa contribute additional expertise and technology transfer, training and mentorship. Competitive grants awarded every year through a process managed by the MIM/TDR Task Force, provide opportunities for research partnerships, collaboration, technology transfer, equipment upgrade and training including support of individuals enrolled in Ph.D and M.Sc. programs within the context of focused research projects. Promote research intended to stimulate development and improvement of tools against malaria. Health policy, system and services To develop core groups of African investigators and institutions engaged in high quality malaria research through partnerships To optimize the incorporation of research results into malaria control policy and practices The Task Force promotes opportunities for collaboration and reinforces interaction among research scientists, institutions and control managers within the Ministries of Health in malaria endemic countries of Africa. In the past 7 years, the Multilateral Initiative on Malaria (MIM) working with the WHO Special Programme for research and Training in Tropical Diseases (TDR), has supported 40 African investigators working in 24 African countries. Most of these investigators continue to work in Africa engaged in malaria research or control programs. Their work is facilitating the formulation, update and implementation of antimalarial drug policies; improve malaria vector control and use of bed nets; provide critical information for the management of severe malaria; provide information on the use of indigenous plant products for malaria control and develop strategies for improved access to health systems at the community level.

2 On behalf of the MIM and the MIM/TDR Task Force, The UNICEF / UNDP/ World Bank / WHO Special Programme for Research and Training in Tropical Diseases (TDR) invites letters of intent which focus on research useful in understanding malaria and reducing the disease burden as well as creating opportunities for developing African scientific and public health leadership in research and management. The letters of intent should propose innovative cross cutting or multidisciplinary "use inspired" research in the areas listed below. A well outlined training and capacity building component must be included in the proposal. In 2005, a total of 11 projects with annual budgets ranging between $35,000 and $72,000 were funded by the Task Force out of 41 letters of intent initially received. A similar level of funding is envisaged for The broad areas of interest are listed here under from 1-6. The examples given for each area of interest should serve only as possible examples and should not inhibit submission of innovative research proposals related to malaria. Well-formulated applications focused on addressing social and behavioural aspects of malaria or integrating biomedical and social science research in malaria are strongly encouraged. 1. Chemotherapy and mechanisms of antimalarial drug resistance Goal of MIM support: To enhance the capacity of African scientists and institutions to generate, analyse and collate new knowledge for case management and use of antimalarial drugs through research on innovative strategies for the reduction of malaria-related morbidity and mortality, the underlying mechanisms and distribution of resistance to new and existing antimalarial drugs including combination therapy, and pharmacogenetic and pharmacokinetic studies. Prompt access and appropriate treatment with effective antimalarial drugs is a principal strategy for malaria control. The emergence and spread of antimalarial drug resistance continue to mitigate this strategy in Africa. Combination therapy has proven effective against drug resistant malaria and has been adopted to replace monotherapy in 33 out of 43 African countries where falciparum malaria is endemic ( For successful large scale implementation of combination therapy, many challenges remain including: providing prompt access to treatment and effective use of the drugs by populations at risk; ensuring that patient have access only to high quality antimalarials in settings where fake and substandard drugs are prevalent; establishing capacity and infrastructure to track and document adverse reactions associated with new drugs / combinations; improving understanding of the risk factors for the development of resistance to combination therapy; assessing drug interactions and factors responsible for variations in patient response; developing or evaluating strategies such as intermittent preventive treatment to prevent malaria related morbidity and mortality in populations at risk, such as children, pregnant women, and other high risk groups; and understanding drug utilization at the community and household levels and its relationship to drug resistance. Optimizing case management and intermittent treatment strategies in special populations - (children under 5 and pregnant women), through improved case detection, referral systems, access and dosing regimen to enhance compliance and effectiveness at the community level; Identifying and assessing markers of resistance to the combination therapies and elucidating the underlying mechanisms of resistance to these drugs; Identifying the socio-economic and health system factors that contribute to the spread of resistance; Elucidating genetic factors modulating patient response to treatment with new drugs;

3 Developing a system for detecting and reporting adverse effects of new antimalarial drug combinations following wide spread deployment in the population at the health facility and community / household. 2. Health systems research to improve malaria control in Africa Goal of MIM support: To increase capacity for malaria related social sciences and health systems research that is needed to establish partnerships with bio-scientists and national stakeholders to assist in revising and formulating malaria control strategies in Africa. Knowledge levels about malaria, human behaviour, economic (macro or micro) factors and the status of health systems have a direct effect on various aspects of malaria control. For example, the prompt and appropriate use of preventive tools and case management medications against malaria require adequate information and involve major changes in behaviour. Further, economic policies or health sector reforms such as the introduction of user fees, privatisation of health services and market liberalisation also impact on malaria management and control. For this reason, existence of an effective treatment, tool or control measure may not necessarily translate into effective and widespread use by the populations at risk or reduction in the burden of the disease. The capacity of the research community to effectively engage with policy makers, health care providers and the community is currently limited in most African countries. Consequently, uptake and application of results from research to form policies and strategies, which may enhance malaria management and control, is not optimal. Social research from a medical sociology / medical anthropology or health economics / health policy research perspective is encouraged to study the bio-social dimensions of treatment outcome, drug and insecticide resistance, and effective use of new tools and simple control measures. A key factor influencing effective use is that of financial access of households to malaria prevention and treatment measures, necessitating research into appropriate financing mechanisms for malaria control interventions. Health communication research on effective communication for behaviour change is also needed and highly relevant to all areas of malaria control especially uptake of intervention tools. Multidisciplinary cross cutting research programs are essential for addressing all the concerns above. Identifying barriers to effective use of malaria control tools (e.g. antimalarial drugs, insecticide treated nets or other control strategies) in specific populations and assess novel strategies to overcome them. Understanding the interaction of biological and social, behavioural and economic factors in the emergence of malaria-related drug resistance and insecticide resistance. Developing pragmatic health communication strategies for effective engagement with policy makers, health care providers and the community. Investigating household, community, and health facility level factors associated with the introduction of combined therapies, in the context of home management of malaria policies. Evaluating the impact of specific health care financing mechanisms on access to malaria control tools (e.g. antimalarial drugs, insecticide treated nets), particularly the impact of removal of user fees at public sector facilities, voucher schemes, community-based pre-payment schemes and other forms of health insurance.

4 3. Vector control Goal of MIM support: To provide, through global and regional partnerships, knowledge needed for understanding vector biology and ecology, with a view to improve the current vector control methods, and to develop new vector control approaches. Vector control is an important strategy for malaria control; however the impact of malaria vector control has been limited mainly due to inadequate implementation of existing interventions, development and spread of vector resistance, and limited knowledge of mosquito biology and ecology. There is a need for research aimed at effective implementation and improvement of existing vector control strategies, development of new strategies as well as undertaking vector resistance monitoring and management. Examples of research areas of interest include but are not limited to: The assessment of vector biology, ecology, behaviour and genetics to improve existing strategies including use of Insecticide Treated Nets and development of an integrated approach to malaria vector management; Using molecular tools and genome data to develop new methods for malaria vector control e.g. genetic control; Understanding the mechanisms of insecticide resistance to enhance resistance management; Elucidating human behaviour that may contribute to the development of insecticide resistance in the vector population. Social and behavioural research on perceived needs and willingness to participate in malaria vector control, including use of personal protection tools. 4. Research and development of novel malaria control tools from natural products. Goal of MIM support: To develop competence beyond descriptive studies on crude extracts to pharmacology, medicinal chemistry and phytochemistry and engage African scientists in a network of institutions involved the research and development of novel malaria control tools from natural products. Two of the most important antimalarial drugs now in use were originally identified from herbal medicines and natural products remain a potential source of new antimalarial drugs. In sub Saharan Africa, a large proportion of the population use indigenous herbal medicines for febrile illness and control of malaria vectors. The isolation of active compounds from such preparations may yield antipyretics, analgesics and other useful compounds as well as antimalarial or insecticides. This is an area where collaboration could transform work that is often primarily descriptive to hypothesis driven biochemical research, identification of lead compound active against drug resistant P. falciparum (or insecticide resistant anopheline vectors) and studies on structure activity relationships. Isolating and characterizing chemical entities in indigenous African herbal medicines active against P. falciparum in vitro and malaria in animal models. Optimizing the activity of active agents in whole cell cultures and animal models. Elucidating the possible mechanism of action / targets of compounds isolated from indigenous herbal medicines; Elucidating the interactions of compounds isolated from indigenous herbal medicines with mammalian homeostasis.

5 5. Research to facilitate malaria control interventions including introduction and evaluation of new strategies and policies. Goal of MIM support: To establish partnerships between public health and research institutions to facilitate introduction of new and improved interventions, strategies, policies and surveillance systems with potential impact on malaria control. Rational deployment and use of existing, new or improved interventions, strategies and policies is necessary for effective malaria control. This involves changes in policy and behaviour, and good surveillance / follow up systems at the household, community and health facility. There are few reliable malaria surveillance systems in Africa and even fewer that are used to guide control programmes. This results from the lack of motivation or low-quality of the health services, poor diagnosis (clinical and parasitological) as well the poor documentation and use of data. Moreover, the most relevant indicators and the follow-up methods adapted to each epidemiological situation remain poorly identified. Research on delivery strategies of tools for malaria control with a focus on effectiveness, efficiency and equity issues; Evaluating the role of parasitological diagnosis in case management of high risk groups in areas of high endemicity; Developing strategies for cost effective implementation and scaling up of new methods to treat and prevent malaria; Developing a frame work to evaluate the impact of combined control strategies; Developing a frame work for providing evidence for policies on drug treatment and prevention of malaria complications; Developing and operationally implementing appropriate surveillance systems for malaria and its resulting morbidity and mortality in Africa. 6. Pathogenesis and immunology of malaria Goals of MIM support: To provide new knowledge for understanding predisposition to severe forms of the disease (severe anaemia, cerebral malaria), to elucidate mechanisms involved in the susceptibility to malaria during pregnancy, to elucidate the mechanisms involved in the development of severe disease and protection against malaria, to increase regional capacity for training in malaria immunopathology and to evaluate the effects of new interventions on malaria specific immunity and predisposition to severe disease. Severe malaria including anaemia and cerebral complications account for the majority of malaria mortality in Africa. In most settings, co infections with HIV and (or) mycobacterium tuberculosis exist and ipact on clinical management of the patient. Better understanding of the pathogenesis and mechanisms of immune response to malaria may accelerate the development of better tools and strategies for case management including early diagnosis and follow up of recovery parameters. Novel cross cutting approaches involving clinical, biomedical, or in silico research methods (or) genome data and bioinformatics to address critical questions and aspects of host, parasite and disease interaction are needed. Elucidating the immune mechanisms involved in the development and progression of severe disease; Elucidating the immune mechanisms involved in protection against clinical malaria and / or severity of disease; Elucidating the social and health system factors that predispose to severe disease.

6 Elucidating the host genetic factors underlying predisposition to severe malarial anaemia and cerebral malaria; Elucidating the immune mechanisms involved in the susceptibility of pregnant women to malaria; Identifying new targets of protective immune responses and immune correlates of protection against clinical malaria; Establishing functional immune assays for evaluating protection against clinical malaria; Interactions between malaria, HIV - AIDS and tuberculosis - Elucidating the interactions between HIV and (or) mycobacterium tuberculosis and human polymorphisms associated with natural protection against malaria, HOW TO APPLY Letters of intent that build on existing multidisciplinary platforms / networks are strongly encouraged. Scientists who have previously benefited from MIM support as trainees are strongly encouraged to submit letters of intent. For each application, the principal investigator must be an African scientist working in Africa. In conformity with the principles of MIM for promoting collaborative research and training, each letter of intent must reflect partnership between, at the minimum, two African research institutions. One of these two must be an established institution and the other one an emerging institution. In addition, at least one non-african research group / institution must be involved. Interested groups are invited to submit a letter of intent of no more than 3 pages - size A4 and a minimum font size equivalent to 12pt Times New Roman (excluding CVs). Each letter should outline the following: 1. Project title 2. Proposed principal investigator, research institution and study team 3. Background and statement of the research question to be addressed indicating relevance to the overall objectives of the Task Force as described in the call. 4. Overall and specific objectives of the proposed research 5. Methods 6. Estimated budget 7. Relationship with any ongoing programme, research project, network, external funding Research team / institutions involved and collaborators - clear outline of links with established research institutions. Contribution and benefit of each collaborating institution to the program. Letters of intent can be submitted in English or French (submissions in French should include a summary in English). The curriculum vitae of the principal investigator should be no more than one page. Each letter of intent should be prepared and sent as an document file (*.doc) attachment to mimtdr@who.int no later than 15 September The MIM/TDR Task Force will select a short list of letters of intent for further development into full proposals. Authors of short listed letters of intent will be notified by 30th September Full proposals will be submitted by January 15th 2006 and reviewed in March Dr Olumide Ogundahunsi, MIM / TDR Task Force on Malaria Research Capability Strengthening in Africa TDR, World Health Organization 1211 Geneva 27 Switzerland ogundahunsio@who.int Tel: Fax:

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