Research Priorities
Current interventions to combat malaria remain inadequate for achieving the increased levels of successful patient management and prevention to which all malarious countries aspire and for which ambitious targets have been set (box 21.1). Greatly increased support for malaria research and for developing institutional capacity must occur to make advances and to bring them to populations in need. The WHO Scientific Working Group on Malaria and others have identified four major areas of research as follows (Remme and others 2002; WHO 1996; WHO 2003c).
Patient Management
Patient management, including treatment, should address the following:
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evaluation of treatment effectiveness and of access to treatment for uncomplicated malaria in children and during pregnancy, with an emphasis on home management and evaluation of alternative delivery systems
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investigation of the pathogenesis of malaria, in particular anemia and immune response mechanisms
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evaluation of new approaches, for example, rectal drug administration, for managing severe illness
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evaluation of ACT, including delivery approaches via the public and private sectors
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development of new drugs with novel targets; the Medicines for Malaria Ventura (MMV) is spearheading this activity.
Prevention Research
Prevention research should focus on the following:
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new approaches to drug-based malaria prevention, including IPT in children and during pregnancy
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strategies for scaling up the use of ITNs.
Innovative Approaches
Innovative approaches should use new technologies, including recent advances in sequencing the DNA of P. falciparum and A. gambiae, to achieve the following:
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discover and develop drugs, diagnostics, vaccines, insecticides, and antiparasite effector molecules using genomics
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carry out strategic and basic research on vector-parasite-host interactions
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assess mechanisms for addressing drug and insecticide resistance
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develop and carry out field evaluations of transgenic methods for interrupting malaria transmission.
Policy Research
Social, economic, and policy research should focus on the following:
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developing and applying a common methodology for measuring socioeconomic status
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carrying out policy and operational research on the impact, viability, sustainability, and optimal balance of public-private partnerships
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investigating ethical, legal, and social issues pertaining to new malaria-related tools.
Capacity strengthening for research and operations (including clinical trials) is urgently needed. This strengthening will result in the ability to better evaluate new drugs and vaccines and existing malaria control tools (ITNs, IPT) and to tackle the scaling up of malaria strategies.
A classification of research priorities by time frame includes the three-year, five-year, and ten-year targeting.
Three-year completion targeting includes the following:
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apply to the U.S. Food and Drug Administration (FDA) with evidence for two separate fixed-dose artemisinin combinations at a target adult treatment price of US$1.00, or US$0.60 or less for children; two combinations are necessary, as one may fail in testing or have other unforeseen problems
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evaluate the two best candidate ACT drugs for IPT in pregnant women and in infancy and early childhood (IPTi)
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launch studies to reach an evidence-based conclusion on the costs and benefits of long-lasting ITNs versus IRS in Sub-Saharan Africa and other endemic areas
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carry out operational studies to determine the best methods of deploying ACT through the public and private sectors so that first-level patient management can occur at the home and at the village levels; this involves studying packaging and distribution networks, assessing adherence, and addressing how to deploy and supervise use of artesunate rectal suppositories
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conduct economic reviews and predictive modeling to make an economic case for increased international investment in malaria control, including collecting detailed data from several scaled-up, national, fully supported control programs employing the best available strategies and interventions
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conduct in Africa and other endemic continents a maximum number of FDA-compliant phase I and phase II malaria vaccine trials to select candidates for clinical trials.
The five-year completion target is as follows:
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develop and deploy more sensitive, specific, and predictive diagnostic tests that are inexpensive and practical
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carry out operational studies on how to deploy diagnostics in areas of low, intermediate, and high transmission.
The ten-year completion target has these focuses:
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develop an inexpensive, safe, and synthetic trioxane anti-malarial drug
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develop another new drug with a target and resistance mechanism that is unrelated to existing drugs
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carry out basic insecticide research to develop new approaches to both personal protection and residual house spraying
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launch successful phase III and phase IV field testing of malaria vaccines to prevent clinical illness and transmission with licensure by regulatory bodies
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use genomic, proteomic, and bioinformatic tools to better understand the pathogenesis of malaria, to design new drugs and vaccine candidates for training scientists, and to transfer technologies
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train a critical mass of leaders in science and operations to carry out the required research in support of control.
