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      Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes

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          Abstract

          The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5%) based on adult trap data and 81% (95% CI: 74.9-85.2%) based on ovitrap indices compared to the adjacent no-release control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036) was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011 – 0.210), indicating that environmental and target-strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission.

          Author Summary

          Dengue is a major mosquito-borne disease, increasing in prevalence and severity; there are no specific drugs or licensed vaccine. It is primarily transmitted by one mosquito species, Aedes aegypti. We released transgenic ‘sterile’ male mosquitoes in Itaberaba, a suburb of Juazeiro, a Brazilian city. Sustained release of these males, whose offspring typically die before adulthood as a consequence of the transgenic modification, strongly suppressed the target wild population—by 80–95% according to different measures. These data are consistent with previous releases in the Cayman Islands, suggesting that differences between the two locations, including the environment or wild mosquito strain, made little difference. Mathematical models suggest that this degree of suppression would be highly effective in preventing epidemic dengue.

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          Economic Impact of Dengue Illness in the Americas

          The growing burden of dengue in endemic countries and outbreaks in previously unaffected countries stress the need to assess the economic impact of this disease. This paper synthesizes existing studies to calculate the economic burden of dengue illness in the Americas from a societal perspective. Major data sources include national case reporting data from 2000 to 2007, prospective cost of illness studies, and analyses quantifying underreporting in national routine surveillance systems. Dengue illness in the Americas was estimated to cost $2.1 billion per year on average (in 2010 US dollars), with a range of $1–4 billion in sensitivity analyses and substantial year to year variation. The results highlight the substantial economic burden from dengue in the Americas. The burden for dengue exceeds that from other viral illnesses, such as human papillomavirus (HPV) or rotavirus. Because this study does not include some components (e.g., vector control), it may still underestimate total economic consequences of dengue.
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            Insect population control using a dominant, repressible, lethal genetic system.

            A major modification to the sterile insect technique is described, in which transgenic insects homozygous for a dominant, repressible, female-specific lethal gene system are used. We demonstrate two methods that give the required genetic characteristics in an otherwise wild-type genetic background. The first system uses a sex-specific promoter or enhancer to drive the expression of a repressible transcription factor, which in turn controls the expression of a toxic gene product. The second system uses non-sex-specific expression of the repressible transcription factor to regulate a selectively lethal gene product. Both methods work efficiently in Drosophila melanogaster, and we expect these principles to be widely applicable to more economically important organisms.
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              The first releases of transgenic mosquitoes: an argument for the sterile insect technique

              Potential applications for reducing transmission of mosquito-borne diseases by releasing genetically modified mosquitoes have been proposed, and mosquitoes are being created with such an application in mind in several laboratories. The use of the sterile insect technique (SIT) provides a safe programme in which production, release and mating competitiveness questions related to mass-reared genetically modified mosquitoes could be answered. It also provides a reversible effect that would be difficult to accomplish with gene introgression approaches. Could new technologies, including recombinant DNA techniques, have improved the success of previous mosquito releases? Criteria for an acceptable transgenic sterile mosquito are described, and the characteristics of radiation-induced sterility are compared with that of current transgenic approaches. We argue that SIT using transgenic material would provide an essentially safe and efficacious foundation for other possible approaches that are more ambitious.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                2 July 2015
                July 2015
                : 9
                : 7
                : e0003864
                Affiliations
                [1 ]Oxitec Ltd, Abingdon, Oxfordshire, United Kingdom
                [2 ]Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil
                [3 ]Moscamed Brasil, Juazeiro, Bahia, Brasil
                [4 ]Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, St Mary's Campus, London, United Kingdom
                [5 ]Department of Zoology, University of Oxford, Oxford, United Kindgom
                [6 ]The Pirbright Institute, Pirbright, Woking, Surrey, United Kingdom
                [7 ]Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, Brasil
                Colorado State University, UNITED STATES
                Author notes

                I have read the journal's policy and the authors of this manuscript have the following competing interests: Those authors affiliated to Oxitec Ltd. (ARM, DOC, RL and LA) are/or were employees of this company, which therefore provided salary and other support for the research program. Also, such employees may have shares or share options in Oxitec Ltd. Both Oxitec Ltd. and Oxford University have one or more patents or patent applications related to the subject of this paper. LG, CAD, MLC, AM have no patent interests, shares, or share options in Oxitec or any other entity for this technology. This does not alter our adherence to all PLOS policies on sharing data and materials.

                Conceived and designed the experiments: ARM DOC MLC LA AM. Performed the experiments: ARM DOC LG RL. Analyzed the data: ARM RL DOC CAD. Wrote the paper: ARM RL LA DOC MLC. Supervised research: ARM MLC LA AM.

                Article
                PNTD-D-14-00786
                10.1371/journal.pntd.0003864
                4489809
                26135160
                de8b0437-faa9-4ca3-82f4-9b273323691b
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 9 May 2014
                : 1 June 2015
                Page count
                Figures: 3, Tables: 0, Pages: 15
                Funding
                AM and LG received support from Biofábrica Moscamed Brasil ( www.moscamed.org.br. MLC and DOC received support form Fundação de Amparo a Pesquisa do Estado de São Paulo ( www.fapesp.b) and Conselho Nacional de Desenvolvimento Científico e Tecnologia ( www.cnpq.br). CAD received support from Medical Research Council ( www.mrc.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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