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      A “reverse pharmacology” approach for developing an anti-malarial phytomedicine

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          Abstract

          A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.

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          Most cited references17

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          Innovative lead discovery strategies for tropical diseases.

          Lead discovery is currently a key bottleneck in the pipeline for much-needed novel drugs for tropical diseases such as malaria, tuberculosis, African sleeping sickness, leishmaniasis and Chagas disease. Here, we discuss the different approaches to lead discovery for tropical diseases and emphasize a coordination strategy that involves highly integrated partnerships and networks between scientists in academic institutions and industry in both wealthy industrialized countries and disease-endemic countries. This strategy offers the promise of reducing the inherently high attrition rate of the early stages of discovery research, thereby increasing the chances of success and enhancing cost-effectiveness.
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            Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?

            Drug discovery strategies based on natural products and traditional medicines are re-emerging as attractive options. We suggest that drug discovery and development need not always be confined to new molecular entities. Rationally designed, carefully standardized, synergistic traditional herbal formulations and botanical drug products with robust scientific evidence can also be alternatives. A reverse pharmacology approach, inspired by traditional medicine and Ayurveda, can offer a smart strategy for new drug candidates to facilitate discovery process and also for the development of rational synergistic botanical formulations.
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              Early treatment of childhood fevers with pre-packaged antimalarial drugs in the home reduces severe malaria morbidity in Burkina Faso.

              In rural, malaria-endemic Burkina Faso, we evaluated the impact of the use of pre-packaged antimalarial drugs (PPAM), by mothers in the home, on the progression of disease in children from uncomplicated fever to severe malaria. In each village of one province, a core group of opinion leaders (mainly older mothers) was trained in the management of uncomplicated malaria, including the administration of PPAM. Full courses of antimalarial (chloroquine) and antipyretic (aspirin) drugs were packaged in age-specific bags and made widely available through community health workers who were supplied through the existing drug distribution system. Drugs were sold under a cost-recovery scheme. Local schoolteachers conducted surveys in a random sample of 32 villages at the end of the high transmission seasons in 1998 and 1999. Disease history and the treatment received were investigated for all children under the age of 6 years having suffered from a fever episode in the previous 4 weeks. 'Uncomplicated malaria' was defined as every episode of fever and 'severe malaria' as every episode of fever followed by convulsions or loss of consciousness. During the study period, 56%[95% confidence interval (CI) 50-62%] of 3202 fever episodes in children under 6 years of age were treated promptly by mothers with the pre-packaged drugs made available by the study. A total of 59% of children receiving PPAM were reported to have received the drugs over the prescribed 3-day period, while 52% received the correct age-specific dose. PPAM use was similar among literate (61%) and non-literate mothers (55%) (P = 0.08). The overall reported risk of developing severe malaria was 8%. This risk was lower in children treated with PPAM (5%) than in children not treated with PPAM (11%) (risk ratio = 0.47; 95% CI 0.37, 0.60; P < 0.0001). This estimate of the impact of PPAM was largely unchanged when account was taken of potential confounding by age, sex, maternal literacy status, year or village. Our findings support the view that, after appropriate training and with adequately packaged drugs made available, mothers can recognize and treat promptly and correctly malarial episodes in their children and, by doing so, reduce the incidence of severe disease.
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                Author and article information

                Conference
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2011
                15 March 2011
                : 10
                : Suppl 1
                : S8
                Affiliations
                [1 ]Department of Primary Health Care, University of Oxford, UK
                [2 ]Research Initiative for Traditional Antimalarial Methods, Oxford, UK
                [3 ]Institut de Médecine Sociale et Préventive, Geneva University, Switzerland
                [4 ]Département de Médecine Traditionnelle, Bamako, Mali
                [5 ]Aidemet NGO, Bamako, Mali
                Article
                1475-2875-10-S1-S8
                10.1186/1475-2875-10-S1-S8
                3059466
                21411019
                299495ab-3225-486a-8258-5ac81323075e
                Copyright ©2011 Willcox et al; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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