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      Treatment of pigs with endectocides as a complementary tool for combating malaria transmission by Anopheles farauti ( s.s.) in Papua New Guinea

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          Abstract

          Background

          Outdoor, early-biting, zoophagic behaviours by Anopheles farauti ( s.s.) can compromise the effectiveness of bed nets for malaria control. In the Western Pacific region, pigs and dogs represent significant alternative blood sources for mosquitoes. Treating these animals with endectocides may impact mosquito survival and complement control measures. This hypothesis was explored using membrane feeding assays (MFAs), direct feeds on treated pigs, pharmacokinetic analyses and a transmission model.

          Results

          Ivermectin was 375-fold more mosquitocidal than moxidectin (24 h LC 50 = 17.8 ng/ml vs 6.7 µg/ml) in MFAs, and reduced mosquito fecundity by > 50% at ≥ 5 ng/ml. Treatment of pigs with subcutaneous doses of 0.6 mg/kg ivermectin caused 100% mosquito mortality 8 days after administration. Lethal effects persisted for up to 15 days after administration (75% death within 10 days).

          Conclusion

          The application of these empirical data to a unique malaria transmission model that used a three-host system (humans, pigs and dogs) predicts that the application of ivermectin will cause a significant reduction in the entomological inoculation rate (EIR = 100 to 0.35). However, this is contingent on local malaria vectors sourcing a significant proportion of their blood meals from pigs. This provides significant insights on the benefits of deploying endectocides alongside long-lasting insecticide-treated nets (LLINs) to address residual malaria transmission.

          Electronic supplementary material

          The online version of this article (10.1186/s13071-019-3392-0) contains supplementary material, which is available to authorized users.

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          Most cited references50

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          The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

          Background The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed. Results Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented. Conclusions This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.
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            Primaquine therapy for malaria.

            Primaquine is the only available drug for preventing relapse of malaria, and confusion surrounds its use. This review examines the wide range of clinical applications of primaquine described in the medical literature between 1946 and 2004. The risk of relapse of Plasmodium vivax malaria without primaquine therapy ranged from 5% to 80% or more, depending largely upon geographic location. Supervision of therapy profoundly impacts the risk of relapse, and almost all reports of malaria resistant to primaquine are associated with lack of such supervision. We nonetheless suspect that there is widespread resistance to the standard course of primaquine therapy, which is 15 mg primaquine base daily for 14 days. Clinical evidence confirms that a course of 15 mg daily for just 5 days, a regimen widely used in areas where malaria is endemic, has no discernible efficacy. This review supports a recommendation for a regimen of 0.5 mg/kg primaquine daily for 14 days, on the basis of superior efficacy and good tolerability and safety in nonpregnant persons without glucose-6-phosphate dehydrogenase deficiency.
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              Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for elimination

              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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                Author and article information

                Contributors
                Cielo.Pasay@qimrberghofer.edu.au
                Laith.Yakob@lshtm.ac.uk
                Hannah.Meredith@lshtm.ac.uk
                Romal.Stewart@qimrberghofer.edu.au
                p.mills@uq.edu.au
                m.dekkers@uq.edu.au
                Oselyne.Ong@qimrberghofer.edu.au
                Stacey.Llewellyn@qimrberghofer.edu.au
                Leon.Hugo@qimrberghofer.edu.au
                James.McCarthy@qimrberghofer.edu.au
                Greg.Devine@qimrberghofer.edu.au
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                19 March 2019
                19 March 2019
                2019
                : 12
                : 124
                Affiliations
                [1 ]ISNI 0000 0001 2294 1395, GRID grid.1049.c, Clinical Tropical Medicine, , QIMR Berghofer Medical Research Institute, ; Herston, QLD Australia
                [2 ]Department of Disease Control, School of Hygiene and Tropical Medicine, London, London, UK
                [3 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, School of Veterinary Science, , University of Queensland, ; Gatton, QLD Australia
                [4 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, Queensland Animal Science Precinct, University of Queensland, ; Gatton, QLD Australia
                [5 ]ISNI 0000 0001 2294 1395, GRID grid.1049.c, Mosquito Control Laboratory, , QIMR Berghofer Medical Research Institute, ; Herston, QLD Australia
                Article
                3392
                10.1186/s13071-019-3392-0
                6423892
                30890165
                97584c02-928a-4a1b-91a9-02bbf8aa6d27
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 October 2018
                : 8 March 2019
                Funding
                Funded by: NHMRC Program Grant
                Award ID: 1037304
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Parasitology
                endectocides,ivermectin,malaria control,anopheles farauti
                Parasitology
                endectocides, ivermectin, malaria control, anopheles farauti

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