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      Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for elimination

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          Abstract

          Background

          The heterogeneity of malaria transmission makes widespread elimination a difficult goal to achieve. Most of the current vector control measures insufficiently target outdoor transmission. Also, insecticide resistance threatens to diminish the efficacy of the most prevalent measures, indoor residual spray and insecticide treated nets. Innovative approaches are needed. The use of endectocides, such as ivermectin, could be an important new addition to the toolbox of anti-malarial measures. Ivermectin effectively targets outdoor transmission, has a novel mechanism of action that could circumvent resistance and might be distributed over the channels already in place for the control of onchocerciasis and lymphatic filariasis.

          Methods

          The previous works involving ivermectin and Anopheles vectors are reviewed and summarized. A review of ivermectin’s safety profile is also provided. Finally three definitive clinical trials are described in detail and proposed as the evidence needed for implementation. Several smaller and specific supportive studies are also proposed.

          Conclusions

          The use of ivermectin solves many challenges identified for future vector control strategies. It is an effective and safe endectocide that was approved for human use more than 25 years ago. Recent studies suggest it might become an effective and complementary strategy in malaria elimination and eradication efforts; however, intensive research will be needed to make this a reality.

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          Most cited references50

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          Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?

          The use of pyrethroid insecticides in malaria vector control has increased dramatically in the past decade through the scale up of insecticide treated net distribution programmes and indoor residual spraying campaigns. Inevitably, the major malaria vectors have developed resistance to these insecticides and the resistance alleles are spreading at an exceptionally rapid rate throughout Africa. Although substantial progress has been made on understanding the causes of pyrethroid resistance, remarkably few studies have focused on the epidemiological impact of resistance on current malaria control activities. As we move into the malaria eradication era, it is vital that the implications of insecticide resistance are understood and strategies to mitigate these effects are implemented. Copyright © 2010 Elsevier Ltd. All rights reserved.
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            Malaria: progress, perils, and prospects for eradication.

            There are still approximately 500 million cases of malaria and 1 million deaths from malaria each year. Yet recently, malaria incidence has been dramatically reduced in some parts of Africa by increasing deployment of anti-mosquito measures and new artemisinin-containing treatments, prompting renewed calls for global eradication. However, treatment and mosquito control currently depend on too few compounds and thus are vulnerable to the emergence of compound-resistant parasites and mosquitoes. As discussed in this Review, new drugs, vaccines, and insecticides, as well as improved surveillance methods, are research priorities. Insights into parasite biology, human immunity, and vector behavior will guide efforts to translate parasite and mosquito genome sequences into novel interventions.
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              Artemisinin resistance: current status and scenarios for containment.

              Artemisinin combination therapies are the first-line treatments for uncomplicated Plasmodium falciparum malaria in most malaria-endemic countries. Recently, partial artemisinin-resistant P. falciparum malaria has emerged on the Cambodia-Thailand border. Exposure of the parasite population to artemisinin monotherapies in subtherapeutic doses for over 30 years, and the availability of substandard artemisinins, have probably been the main driving force in the selection of the resistant phenotype in the region. A multifaceted containment programme has recently been launched, including early diagnosis and appropriate treatment, decreasing drug pressure, optimising vector control, targeting the mobile population, strengthening management and surveillance systems, and operational research. Mathematical modelling can be a useful tool to evaluate possible strategies for containment.
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                Author and article information

                Contributors
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central
                1475-2875
                2013
                7 May 2013
                : 12
                : 153
                Affiliations
                [1 ]Internal Medicine Department, Clínica Universidad de Navarra, Av. Pio XII 36, Pamplona 31008, Spain
                [2 ]Instituto de Salud Tropical, Universidad de Navarra, Pamplona, Spain
                [3 ]Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
                [4 ]Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain
                [5 ]Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
                [6 ]Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK
                [7 ]Department of Medical Microbiology, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands
                [8 ]Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, 1692 Campus Delivery, Fort Collins, Colorado 80523-1692, USA
                Article
                1475-2875-12-153
                10.1186/1475-2875-12-153
                3658945
                23647969
                fb413e22-6de8-4967-aee8-a1ab9d7a1545
                Copyright © 2013 Chaccour 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.

                History
                : 1 March 2013
                : 1 May 2013
                Categories
                Case Study

                Infectious disease & Microbiology
                malaria elimination,ivermectin,endectocides,vector control
                Infectious disease & Microbiology
                malaria elimination, ivermectin, endectocides, vector control

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