tag:theconversation.com,2011:/fr/topics/wolbachia-17812/articlesWolbachia – The Conversation2018-12-04T11:33:13Ztag:theconversation.com,2011:article/1055502018-12-04T11:33:13Z2018-12-04T11:33:13ZOpening up research labs with modified mosquitoes to the community<figure><img src="https://images.theconversation.com/files/244375/original/file-20181107-74757-1b7ob0j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">View of Taichung City, Taiwan, behind a mosquito net. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/view-mosquito-net-taichung-city-taiwan-662487235?src=eoF5QMrNkj4UaA26ScSy2A-4-8">Alan Picard / Shutterstock.com</a></span></figcaption></figure><p>By bringing people close to disease-spreading insects, might we improve public health?</p>
<p>Because they spread malaria, Zika, West Nile, dengue, yellow fever and other diseases, mosquitoes are <a href="https://www.smithsonianmag.com/innovation/kill-all-mosquitos-180959069/">responsible for more human deaths than any other organism</a>. Some of these diseases flourish in tropical regions like sub-Saharan Africa that are urbanizing rapidly and feeling the effects of climate change. Research indicates that <a href="https://doi.org/10.1016/j.jclepro.2017.12.144">temperature increases</a> lead to mosquitoes breeding more frequently, living longer and biting more often. </p>
<p>Meanwhile, advances in scientific research are leading to new approaches to mosquito control. These include <a href="https://www.newyorker.com/magazine/2012/07/09/the-mosquito-solution">genetic</a> <a href="https://www.scientificamerican.com/article/the-wipeout-gene/">modification</a> of male mosquitoes, leading to sterile offspring. Scientists are also exploring the <a href="http://doi.org/10.1016/j.pt.2015.10.011">use of bacteria such as <em>Wolbachia</em></a> to limit the ability of mosquitoes to spread disease. </p>
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<a href="https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/244382/original/file-20181107-74766-n4vd3g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Mosquito research facilities are often cloaked in secrecy which breeds distrust among the public.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mosquito-testing-center-infected-germs-628430486">Aomboon / Shutterstock.com</a></span>
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<p>But mosquito research faces one enormous challenge: a lack of community engagement around this science leads to the <a href="https://theconversation.com/gene-drives-may-cause-a-revolution-but-safeguards-and-public-engagement-are-needed-77012">public feeling anxiety and mistrust</a>. Negative public opinion has the potential to derail this research and associated efforts, such as release of genetically modified mosquitoes in cities. My colleague John Bauer, assistant dean for the UC San Diego Division of Biological Sciences, noted to me that scientists work in high security buildings that the public are banned from entering and then wonder why they are so misunderstood. </p>
<p>I am a professor of architecture at the University of Oregon and am involved in an effort to re-imagine these mosquito research facilities and make them accessible to the public. In an effort to do so we have convened teams of designers, artists and scientists to rethink the design of mosquito research sites so that they include spaces of community engagement. </p>
<h2>Making genetic research transparent</h2>
<p>I have long worked at the <a href="http://www.worldcat.org/title/ecology-and-the-architectural-imagination/oclc/854611173">intersection of people and the environment</a>. I am now working together with <a href="http://www.michaelsinger.com">artist Michael Singer</a>, <a href="https://www.researchgate.net/profile/Mark_Benedict2">Mark Benedict</a> of the Centers for Disease Control and Prevention’s Entomology Branch, <a href="https://ihi.or.tz/staff/dr-fredros-okumu">Fredros Okumu</a> from Tanzania-based <a href="https://ihi.or.tz">Ifakara Health Institute</a> (IHI), and scholars and scientists from the U.K. and U.S., on the “Protective Atmospheres” project to redesign these facilities. </p>
<p>This has the potential to be a game-changing effort. Our hope is that opening up the facility will lead to greater acceptance of this work and lead to better health outcomes. My collaborators and I are not aware of any similar effort meant to integrate research facilities and the community in order to make science approachable.</p>
<p>This is where effective design comes in. </p>
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<a href="https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=285&fit=crop&dpr=1 600w, https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=285&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=285&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=358&fit=crop&dpr=1 754w, https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=358&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/245814/original/file-20181115-194513-1vieixh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=358&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">An artist rendition of a research facility integrated with the community.</span>
<span class="attribution"><span class="source">Brook Muller</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<a href="https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=160&fit=crop&dpr=1 600w, https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=160&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=160&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=201&fit=crop&dpr=1 754w, https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=201&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/245815/original/file-20181115-194513-16c7sg0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=201&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Integrating labs with open fields may reduce the fear factor surrounding mosquito research.</span>
<span class="attribution"><span class="source">Brook Muller</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>What if “arthropod containment” labs with strict biosecurity standards where scientists work with pathogen-carrying mosquitoes are not located at the “back of house” as is typical now. While ensuring that these standards are met, could labs be brought out of the darkness and placed alongside spaces where visitors to these facilities are allowed to go? </p>
<p>Could people walk through protective enclosures alongside or within “mosquito cities,” large spaces of experimentation that are open-air yet netted and that include trees and other outdoor elements allowing controlled study of mosquito populations in quasi-natural conditions? </p>
<p>Could spaces be included that help people understand how to modify their homes to decrease chances they will get bitten? What about recreational spaces such as the tennis court that Okumu hopes to build at Ifakara as a way to make IHI’s research a part of everyday community life? These are some of the questions we are addressing as part of the Protective Atmospheres project. </p>
<h2>Integrating scientists and the community</h2>
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<a href="https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=382&fit=crop&dpr=1 600w, https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=382&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=382&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=480&fit=crop&dpr=1 754w, https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=480&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/245849/original/file-20181115-194497-ciunx.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=480&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Mosquito City Vision. The goal is not just to mix communities and lab and research facilities. Muller wants the scientists to engage with the local people over normal recreation and participate in daily life.</span>
<span class="attribution"><span class="source">Brook Muller</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Creating interactive facilities that promote public engagement and understanding while adhering to biosafety regulations requires a two-way conversation. Architects and artists must learn from scientists. As one example, they must understand that keeping mosquitoes alive in captivity is difficult. Or that for <em>Anopheles</em>, a genus of mosquito carrying malaria, the setting sun and low light triggers swarm behavior and mating. For a mosquito city built to study swarming behavior, it’s best to orient it toward the sun, and let the romance begin. </p>
<p>And scientists can learn from architects and artists that buildings can tell stories. A walk through a research facility may also be an educational journey through the scientific process along a continuum from genetic engineering to containment to release. By the time a visitor arrives at a mosquito release site at the journey’s end, it may no longer seems so dangerous. Perhaps at that point, visitors actually participate in the release event.</p>
<p>The Protective Atmospheres project is in its infancy, and yet we are hopeful that it has the potential to transform perceptions. It can make scientific activity transparent and encourage the role of citizenry in biological research. It might also change understandings of mosquitoes themselves – for mosquitoes do not kill, they just host organisms that do. </p>
<p>The end game of course is to build one of these facilities. When we do, we hope that children – and others – line up to visit. Concept shifts to reality when members of the Michael Singer Studio and I travel to the Ifakara Health Institute in early 2019 to begin the development of a master plan for their complex. It will include a tennis court.</p><img src="https://counter.theconversation.com/content/105550/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brook Muller works for the University of Oregon. </span></em></p>Genetically modified mosquitoes breed fear and suspicion, especially since the research happens behind closed doors, away from the public. Now scientists and architects are trying to change that model.Brook Muller, Professor of Architecture and Environment, University of OregonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1007192018-08-20T10:30:22Z2018-08-20T10:30:22ZGenetically modified mosquitoes may be best weapon for curbing disease transmission<figure><img src="https://images.theconversation.com/files/231765/original/file-20180813-2912-10016ka.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">More than 3.9 billion people live in regions where the Aedes aegypti mosquito is present. This species transmits Zika, dengue, chikungunya, and yellow fever.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mosquito-on-human-skin-sunset-200494427?src=hPItT4Sw3Cn291eDH36Amw-1-5">mycteria/Shutterstock.com</a></span></figcaption></figure><p>Mosquitoes are some of the most deadly creatures on the planet. They carry viruses, bacteria and parasites, which they transmit through bites, infecting some <a href="https://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=405">700 million people and killing more than 1 million each year</a>. </p>
<p>With international travel, migration and climate change, these infections are no longer confined to tropical and subtropical developing countries. Pathogens such as West Nile virus and Zika virus have caused significant outbreaks in the United States and its territories that are likely to continue, with new invasive pathogens being discovered all the time. Currently, control of these diseases is mostly limited to broad-spectrum insecticide sprays, <a href="https://extension.psu.edu/potential-health-effects-of-pesticides">which can harm both humans and non-target animals and insects</a>. What if there was a way to control these devastating diseases without the environmental problems of widespread insecticide use?</p>
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<a href="https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=405&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=405&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=405&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=509&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=509&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231774/original/file-20180813-2915-1owb6a2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=509&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption"><em>Aedes aegypti</em> mosquito larvae swim in a container at the Florida Mosquito Control District Office in Marathon, Fla. A study released in May 2017 suggests Zika began spreading in Florida mosquitoes about three months before infections showed up in the Miami area in the summer of 2016, and the virus likely was carried in by travelers from the Caribbean.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Zika-Florida/91cc1668742e45928ef2bc67aef56efe/18/0">Wilfredo Lee / AP Photo</a></span>
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<p>Genetically modifying mosquitoes to prevent disease may sound like science fiction, but the technology has advanced in recent years to the point where this is no longer a scenario relegated to late-night movies. In fact, it’s not even a new idea; scientists were talking about modifying insect populations to control diseases as <a href="http://doi.org/10.3390/ijerph14091006">early as the 1940s</a>. Today, genetically modified (GM) mosquitoes, developed during the past <a href="http://www.pnas.org/content/95/7/3743.long">several</a> <a href="https://www.nature.com/articles/417452a">decades</a> of <a href="http://www.pnas.org/content/104/13/5580.long">research</a> in <a href="http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001003">university</a> <a href="http://www.pnas.org/content/112/49/E6736.long">laboratories</a>, are being used to combat mosquito-borne pathogens – including viruses such as dengue and Zika – in many locations around the globe, including the United States. Progress is also being made to use GM mosquitoes to combat malaria, the most devastating mosquito-borne disease, although field releases for malaria control have not yet taken place. </p>
<p>I have been working on GM mosquitoes, both as a lab tool and to combat disease, for over 20 years. During that time, I have personally witnessed the technology go from theoretical, to seeing it used in the field. I’ve seen <a href="http://doi.org/10.3390/ijerph14091006">older techniques</a> that were inefficient, random and slow pave the way for new methods like <a href="http://doi.org/10.1016/j.celrep.2015.03.009">CRISPR</a>, which enables efficient, rapid and precise editing of mosquito genomes, and <a href="http://www.nature.com/articles/s41467-018-05425-9">ReMOT Control</a> which eliminates the requirement for injecting materials into mosquito embryos. These new technologies make GM mosquitoes for disease control not a question of “if,” but rather a question of “where” and “when.” </p>
<p>Don’t worry, these genetic changes only affect the mosquitoes – they are not transmitted to people when the mosquito bites them. </p>
<h2>Ways to use genetically modified mosquitoes</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/231773/original/file-20180813-2924-1n9iixt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/231773/original/file-20180813-2924-1n9iixt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=421&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231773/original/file-20180813-2924-1n9iixt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=421&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231773/original/file-20180813-2924-1n9iixt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=421&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231773/original/file-20180813-2924-1n9iixt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=530&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231773/original/file-20180813-2924-1n9iixt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=530&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231773/original/file-20180813-2924-1n9iixt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=530&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A worker sprays anti-mosquito fog in an attempt to control dengue fever at a neighborhood in Jakarta, Indonesia. Highly populated areas in the country are often hit with severe outbreaks of the mosquito-borne disease especially during the annual rainy season due to poor health services and unsanitary living conditions.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Indonesia-Daily-Life/85bc77e9a29747c588688c5391bd7159/3/0">Achmad Ibrahim / AP Photo</a></span>
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<p>There are two alternative methods currently used to control mosquito-borne diseases using GM mosquitoes. The first is “population replacement” in which a mosquito population biologically able to transmit pathogens is “replaced” by one that is unable to transmit pathogens. This approach generally relies on a concept known as “gene drive” to spread the anti-pathogen genes. In gene drive, a genetic trait – a gene or group of genes – relies on a quirk on inheritance to spread to more than half of a mosquito’s offspring, boosting the frequency of the trait in the population.</p>
<p>The second approach is called “population suppression.” This strategy reduces mosquito populations so that there are fewer mosquitoes to pass on the <a href="http://doi.org/10.1371/journal.pntd.0000508">pathogen</a>. </p>
<p>While the concept of <a href="http://doi.org/10.1073/pnas.1521077112">gene drive in mosquitoes</a> is <a href="http://www.mdpi.com/1660-4601/14/9/1006">many decades old</a>, the gene-editing technique CRISPR has finally made it possible to easily engineer it in the laboratory. However, CRISPR-based gene drives have not yet been deployed in nature, mostly because they are still a new technology that lacks a firm international regulatory framework, but also due to problems related to the <a href="http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006796">evolution of resistance</a> in mosquito populations that will stop the gene from spreading.</p>
<p>It may not be immediately obvious, but the gene in “gene drive” need not be a gene at all – it can be a microbe. All organisms exist not just with their own genomes, but also with the genomes of all their associated microbes – the “hologenome.” Spread of a microbial genome through a population by inheritance can also be thought of as gene drive. By this definition, the first gene drive that has been deployed in mosquito populations for disease control is a bacterial symbiont known as <em>Wolbachia</em>. <em>Wolbachia</em> is a bacterium that infects up to 70 percent of all known insect species, where it hijacks the insect reproduction to spread itself through the population. </p>
<p>Thus, the <em>Wolbachia</em> itself (with its genome of approximately 1,500 genes) acts as the genetic trait that is driven into the population. When <em>Wolbachia</em> is transferred into a previously uninfected mosquito, it often makes the mosquito more resistant to infection with pathogen that can cause disease in humans, such as multiple viruses (including <a href="https://www.nature.com/articles/nature10355">dengue</a> and <a href="https://www.sciencedirect.com/science/article/pii/S1931312816301573?via%3Dihub">Zika</a> viruses) and <a href="http://doi.org/10.1371/journal.ppat.1002043">malaria parasites</a>.</p>
<h2>A bacterium that fights disease</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/231775/original/file-20180813-2894-1rqbhre.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/231775/original/file-20180813-2894-1rqbhre.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=405&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231775/original/file-20180813-2894-1rqbhre.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=405&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231775/original/file-20180813-2894-1rqbhre.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=405&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231775/original/file-20180813-2894-1rqbhre.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=509&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231775/original/file-20180813-2894-1rqbhre.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=509&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231775/original/file-20180813-2894-1rqbhre.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=509&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Resident Annick Sternberg, left, releases <em>Wolbachia</em>-infected male mosquitoes, as Bill Petrie, director of Miami-Dade County Mosquito Control, center, looks on in South Miami, Fla., Feb. 8, 2018. Thousands of bacteria-infected mosquitoes are flying near Miami to test a new way to suppress insect populations that carry Zika and other viruses. At right is Patrick Kelly, field operations manager for Mosquito Mate.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Modified-Mosquitoes/d689afb66095432f857ac61123442f36/4/0">Lynne Sladky/AP Photo</a></span>
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</figure>
<p>In the last eight years, researchers have taken <em>Wolbachia</em> present in fruit flies and <a href="http://doi.org/10.1038/nature10356">transferred that bacteria into mosquitoes that transmit dengue virus.</a> Those modified insects were then released <a href="https://www.worldmosquitoprogram.org">in a dozen countries to control the disease</a>. Although marketed as a “non-GM strategy,” artificially infecting mosquitoes with <em>Wolbachia</em> clearly falls under the GM umbrella, as over 1,500 genes (the entire bacterial genome) have been transferred from the original fruit fly host into the mosquitoes. </p>
<p><a href="https://gatesopenresearch.org/articles/2-36/v1">Preliminary</a> dengue control results from these releases in Australia have been promising. However, control of the disease in other release areas with higher disease risk, such as South America and Asia, still needs to be determined, particularly as some <a href="http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002965">studies</a> <a href="https://aem.asm.org/content/78/5/1491">have</a> <a href="http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004182">demonstrated</a> <a href="http://rspb.royalsocietypublishing.org/content/281/1779/20132837.long">that</a> <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059619"><em>Wolbachia</em></a> can sometimes increase pathogen infection in mosquitoes rather than suppress it. </p>
<h2>GM mosquitoes that eliminate mosquitoes</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/232490/original/file-20180817-165934-1w65rx4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/232490/original/file-20180817-165934-1w65rx4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/232490/original/file-20180817-165934-1w65rx4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/232490/original/file-20180817-165934-1w65rx4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/232490/original/file-20180817-165934-1w65rx4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/232490/original/file-20180817-165934-1w65rx4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/232490/original/file-20180817-165934-1w65rx4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Estimated range of the dengue and Zika virus carrying mosquito species in the United States, <em>Aedes aegypti</em>, blue, and <em>Aedes albopictus</em>, red. States and territories where both species have been collected are purple. All U.S. states and territories except Alaska are at risk for West Nile virus.</span>
<span class="attribution"><span class="source">Jason Rasgon</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>The best current example of population suppression is the release of genetically modified sterile mosquitoes. This is a modern spin on the decades-old Sterile Insect Technique (SIT), where sterile male insects are released into natural populations to mate with the wild females, reducing the mosquito population. But, rather than crudely sterilizing mosquitoes with radiation or chemicals, clever genetic engineering is now used to sterilize them instead. The <a href="http://doi.org/10.1371/journal.pntd.0003864">company Oxitec has engineered mosquitoes with a gene that is lethal to females but not to males</a>, which do not bite or transmit disease. Thousands of these transgenic males are released into nature, where they mate with the wild females in the population. The genetic modification is inherited by the offspring of these matings; female offspring die, while male offspring, which carry the gene, survive and continue passing the trait to further generations. With fewer and fewer females the mosquito population is drastically suppressed. Oxitec has conducted releases in the <a href="https://www.caymancompass.com/2017/10/24/genetically-modified-mosquitoes-in-cayman-swat-wild-population/">Grand Caymans</a>, <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042771">Malaysia</a>, <a href="http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003864">Brazil</a>, and <a href="https://www.cnn.com/2017/04/20/health/florida-mosquito-wolbachia-trial-zika/index.html">Florida</a>.</p>
<p>There has been some opposition to these sterile mosquito releases, particularly in Florida. For example, in 2016, <a href="https://e360.yale.edu/features/genetically_modified_mosquito_sparks_a_controversy_in_florida">an Oxitec trial in the Florida Keys was met with some local resistance</a>. However, unlike gene drive strategies, release of sterile mosquitoes (genetically modified or not) has about the smallest environmental footprint and highest safety of any disease control strategy; certainly safer than broad-spectrum insecticide sprays. It is highly targeted, and thus if it works, will only result in elimination of the target mosquito species, which in this case (<em>Aedes aegypti</em>) is a highly invasive and non-native mosquito in Florida. </p>
<p>In addition to gene drive, <em>Wolbachia</em> bacteria have also been used for population suppression. Males infected with the bacteria are released into a mosquito population that is either not infected, or infected with a different <em>Wolbachia</em> strain, which leads to “incompatible” or sterile matings. This strategy again has a long history, and was <a href="http://doi.org/10.3390/ijerph14091006">first used to suppress mosquito populations</a> in the 1960s before people even knew that <em>Wolbachia</em> was causing certain populations of mosquitoes to be sterile when mated with one another. In current times, <a href="http://doi.org/10.1038/srep33846"><em>Wolbachia</em>-sterilized males have been released in multiple countries</a> including Australia and the U.S., in California and Florida, to control dengue virus.</p>
<p>In an increasingly interconnected world, and with the added problems of <a href="https://www.sciencedirect.com/science/article/pii/S1471492217302805?via%3Dihub">global climate change</a>, pathogens are not likely to stay confined to the developing world, but will be an increasing issue for the U.S. as well. With the evolution of insecticide resistance in mosquitoes a certainty, GM technology has the potential to reduce the burden of mosquito-borne diseases across the globe, without the environmental and health risks associated with harmful pesticide use. </p>
<p>Don’t be afraid if it sounds like science fiction; it may just save your life.</p><img src="https://counter.theconversation.com/content/100719/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jason Rasgon receives funding from the National Institutes of Health, and the National Science Foundation</span></em></p>For several billion people mosquitoes are more than a nuisance – they transmit deadly diseases. Now genetic modification may prove the most effective defense against the mosquito, preventing disease.Jason Rasgon, Professor of Entomology and Disease Epidemiology, Penn StateLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/775412017-05-23T03:48:21Z2017-05-23T03:48:21ZInfecting mosquitoes with bacteria so they can’t infect us with viruses like Zika and dengue<figure><img src="https://images.theconversation.com/files/170203/original/file-20170519-12250-7w6chd.jpg?ixlib=rb-1.1.0&rect=267%2C0%2C3640%2C2450&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tiny bug, major disease spreader.</span> <span class="attribution"><a class="source" href="https://pixnio.com/science/microscopy-images/insects/anopheles-gambiae-mosquito/of-the-approximately-430-anopheles-species-only-30-40-transmit-malaria-in-nature">Dr. Paul Howell, USCDCP</a></span></figcaption></figure><p>Mosquitoes and their itchy bites are more than just an annoyance. They transmit dangerous viruses with deadly consequences – making them the <a href="https://www.gatesnotes.com/Health/Most-Lethal-Animal-Mosquito-Week">most lethal animal on Earth</a>. It’s the <em>Aedes aegypti</em> and <em>Aedes albopictus</em> mosquito species that are behind outbreaks of <a href="https://www.cdc.gov/dengue/">dengue virus</a>, <a href="https://www.cdc.gov/zika/">Zika virus</a>, <a href="https://www.cdc.gov/yellowfever/">yellow fever virus</a> and <a href="https://www.cdc.gov/chikungunya/index.html">Chikungunya virus</a>, responsible for over <a href="https://www.cdc.gov/ncezid/dvbd/">100 million human cases</a> around the world annually. And they’re <a href="https://dx.doi.org/10.7554/eLife.08347">expanding their habitat</a> around the world as the <a href="https://doi.org/10.1371/journal.pone.0060874">global climate warms</a>, bringing them into contact with more potential victims who have <a href="https://doi.org/10.1128/JVI.00252-16">less immunity and increased susceptibility</a> to these mosquito-transmitted viruses.</p>
<p>A vaccine can provide the recipient with immunity to one or two of these viruses at a time. But there’s another way to tackle these diseases: by going after the insects. Targeting the mosquito population as a whole or their ability to transmit disease takes aim at all these viruses at the same time.</p>
<p>As the U.S. enters another mosquito season, mosquito control districts in <a href="http://keysmosquito.org/2017/03/03/fkmcd-to-test-wolbachia-mosquitoes-in-mid-april/">Florida</a> and <a href="https://cmad.maps.arcgis.com/apps/MapJournal/index.html?appid=f90115bcf15943928fc82a79af89d71e">California</a> are preparing <a href="http://www.cnn.com/2017/04/20/health/florida-mosquito-wolbachia-trial-zika/">new strategies to combat mosquitoes</a> and the viruses they transmit. They’re trying out one of two new mosquito management methods made possible by a bacterium called <em>Wolbachia pipientis</em>. </p>
<h2>A bacterium that’s our enemy’s enemy</h2>
<p><em>Wolbachia</em> are bacteria naturally found in insects throughout the world. They live inside a host organism’s cells. From there, <em>Wolbachia</em> are able to manipulate their host in many ways – things like <a href="https://doi.org/10.1126/science.1209609">increasing the number of eggs</a> a host lays or even <a href="https://doi.org/10.1038/nrmicro1969">changing the host’s sex</a> from male to female by manipulating its hormones.</p>
<p>Researchers discovered in 2008 that <em>Wolbachia</em> in fruit flies <a href="https://dx.doi.org/10.1126/science.1162418">protect their hosts from fruit fly viruses</a>. That realization got them wondering: Could <em>Wolbachia</em> also protect <em>Aedes aegypti</em> mosquitoes from viruses that cause human diseases?</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/170430/original/file-20170522-7361-cycavo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"><em>Wolbachia</em> bacteria, indicated in red, are distributed throughout the infected mosquitoes.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/pennstatelive/12589512185">Penn State</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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</figure>
<p><em>Aedes aegypti</em> mosquitoes don’t naturally carry <em>Wolbachia</em>. But consistent with the fruit fly studies, when researchers infected <em>Aedes aegypti</em> in the lab, the viruses they carry <a href="http://dx.doi.org/10.1016/j.cell.2009.11.042">replicated less</a>. Fewer of the infectious bits of the disease-carrying virus inside the mosquito meant disease transmission was limited – they were less likely to be passed on when mosquitoes fed on their prey.</p>
<p>Researchers in <a href="http://vectorbiologygroup.com/">Australia</a>, the <a href="http://people.bu.edu/hfrydman/">United States</a> and elsewhere are currently investigating the reasons why <em>Wolbachia</em> limit viruses. Some hypothesize <em>Wolbachia</em> improves the <a href="https://doi.org/10.1371/journal.ppat.1002548">mosquitoes’ immunity to the virus</a>, while other research, including my own, suggests <em>Wolbachia</em> <a href="https://doi.org/10.1128/JVI.00339-17">steals key nutrients</a> the virus needs. Both may be true.</p>
<p>The real need to employ this strategy now is motivating field trials to release <em>Wolbachia</em>-infected mosquitoes in several regions of the world. </p>
<h2>Vector competency: The female approach</h2>
<p>Only female mosquitoes bite and transmit viruses. Thus, the most powerful approach to reducing virus spread is limiting viruses in the female mosquito.</p>
<p><em>Wolbachia</em> bacteria are transmitted from mother to offspring. If you introduce <em>Wolbachia</em>-infected female mosquitoes to a population, all offspring will have <em>Wolbachia</em> – and therefore be less likely to transmit disease-causing viruses.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/170427/original/file-20170522-7372-1d6t4ca.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Researchers in Vietnam working with <em>Wolbachia</em>-infected mosquito pupae.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Vietnam-Dengue-Blocking-Mosquito/199b148f9cf54dfa822d6ff0e6ff119f/14/0">AP Photo/Na Son Nguyen</a></span>
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<p>This strategy is used by the <a href="http://www.eliminatedengue.com/program">Eliminate Dengue</a> program, a nonprofit collaboration employing seven research institutes around the world. In test areas, Eliminate Dengue has successfully incorporated <em>Wolbachia</em> into mosquito populations.</p>
<p>In this context, an interesting aspect of <em>Aedes aegypti</em> behavior is their tendency not to travel far. In fact, a highway is a sufficient barrier to <a href="https://doi.org/10.1371/journal.pntd.0000634">prevent mosquito spread</a>. When researchers set up a release site in one city or town, they don’t see their mosquitoes travel to other areas.</p>
<p>This allows for controlled studies, as well as the release of these mosquitoes only where it’s been approved. The limited spread and isolated sites used were important factors in the <a href="https://www.epa.gov/pesticides/epa-grants-extension-experimental-use-permit-wolbachia-mosquito">decision to allow mosquito releases in the United States</a>.</p>
<p>Eliminate Dengue is not yet active in the U.S. Instead, the U.S. is taking a different approach, looking to male rather than female mosquitoes.</p>
<h2>Population control: The male approach</h2>
<p><a href="http://mosquitomate.com/?v=3.0">MosquitoMate</a> is a company developed out of the University of Kentucky in Lexington by medical entomologist Stephen Dobson. Partnering with the <a href="http://keysmosquito.org/">Florida Keys Mosquito Control District</a>, they started the <a href="http://keysmosquito.org/2017/04/18/fkmcd-releases-wolbachia-mosquitoes-on-stock-island/">release of 40,000 <em>Wolbachia</em>-infected</a> <a href="http://fkmcd.maps.arcgis.com/apps/MapJournal/index.html?appid=d8c2b636e93b40b4b940e6042ef286c6">male mosquitoes per week this spring</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/170426/original/file-20170522-7358-lhsm36.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A Florida Keys Mosquito Control District research entomologist releasing <em>Wolbachia</em>-infected male mosquitoes in Key West, Florida, in April.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Modified-Mosquitoes/0ef1eb60fb234e628c7ce2c3fe5a9522/1/0">Beth Ranson/Florida Keys Mosquito Control District via AP</a></span>
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<p>The strategy relies on a phenomenon called <a href="https://doi.org/10.1073/pnas.0403853101">cytoplasmic incompatibility (CI)</a> to reduce mosquito populations. CI occurs when a male mosquito infected with <em>Wolbachia</em> mates with an uninfected female. Because <em>Wolbachia</em> is transmitted through the female egg, the offspring will be <em>Wolbachia</em>-free. But <em>Wolbachia</em> has already altered the father’s sperm DNA in a way that allows offspring to survive only if the fertilized egg has <em>Wolbachia</em>. Since the infected males will come in contact only with the naturally occurring <em>Wolbachia</em>-free population, their offspring will die during embryonic development – the eggs won’t hatch. </p>
<p>And unfortunately for the mosquitoes, females store sperm inside them to continuously fertilize their eggs. This means that the female mosquito’s first mate will be the father of all her offspring. So even if a female just mates again, once she’s partnered with a <em>Wolbachia</em>-infected male, all her offspring will not be viable.</p>
<p>The Florida Keys Mosquito District is not limiting its attack to <a href="http://keysmosquito.org/control-methods/">just one approach</a>. Beyond <em>Wolbachia</em> and more traditional strategies, they’re also partnering with <a href="http://www.oxitec.com">Oxitec</a>, a genetic engineering company. Like MosquitoMate, Oxitec also releases male mosquitoes. But, in place of <em>Wolbachia</em>, Oxitec genetically modifies its mosquito to <a href="http://www.oxitec.com/our-solution/technology/">contain a self-limiting gene that causes offspring to die</a>.</p>
<p>The goal remains the same: Release males into the environment that will mate with females and cause all offspring to die, eventually leading to a mosquito population crash.</p>
<h2>Male and female strategies share one goal</h2>
<p>Each <em>Wolbachia</em> mosquito strategy has its strengths: The female approach is broad-reaching and should directly decrease disease transmission. The male strategy effectively lowers the local mosquito population, without releasing female nuisance mosquitoes.</p>
<p>The male release strategies are an important “right-now” fix, but they’ll require an annual, costly release because male mosquitoes – with either MosquitoMate’s <em>Wolbachia</em> or Oxitec’s self-limiting gene – cannot pass on to the next generation their crucial trait. When these males are not being released, fertile wild males will mate with females and the population will rebound.</p>
<p>Eliminate Dengue’s female release strategy is sustainable long-term, but it takes extensive monitoring to ensure the initial establishment of mosquitoes. While MosquitoMate and Oxitec do not disclose their costs, Eliminate Dengue hopes to make their system affordable at a cost of <a href="https://dx.doi.org/10.1038/533450a">approximately US$1 per person</a>.</p>
<p>Some members of the public have <a href="https://dx.doi.org/10.1126/science.aal0350">advocated against these kinds of mosquito release programs</a>, particularly when the mosquitoes have been genetically modified, as with Oxitec’s transgenic insects. While the United States Department of Agriculture received <a href="https://dx.doi.org/10.1038/533450a">2,600 responses to the Oxitec plan, only one response</a> was filed regarding MosquitoMate’s non-GMO strategy.</p>
<p>In the U.S., mosquito control districts are taking a cautious approach. They’re first trying the two nonpermanent male strategies in small areas. The Florida Keys will be <a href="http://keysmosquito.org/2017/03/03/fkmcd-to-test-wolbachia-mosquitoes-in-mid-april/">evaluating mosquitoes on their Stock Island release site for 12 weeks</a>. We should know how effective male <em>Wolbachia</em>-infected mosquitoes are at reducing populations by late summer.</p><img src="https://counter.theconversation.com/content/77541/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michaela Schultz does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Several sites in the US are releasing bacteria-infected mosquitoes as a way to fight mosquito-borne viruses that threaten people. What’s the science – and how well will it work?Michaela Schultz, Graduate Student in Biology, Boston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/566922016-06-20T20:13:16Z2016-06-20T20:13:16ZHow we convinced people to trust a new innovative approach to eliminate dengue<figure><img src="https://images.theconversation.com/files/126887/original/image-20160616-19916-yyxgu4.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Community members visit our insectary and diagnostic laboratory to gain a better understanding about Aedes mosquitoes and Wolbachia. </span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><p>In recent years, scientists have found an alternative to significantly <a href="http://www.who.int/mediacentre/factsheets/fs117/en/">decrease dengue transmission by the mosquito <em>Aedes aegypti</em></a>. By transferring Wolbachia, a bacteria that stops the dengue virus from surviving in their mosquito hosts, into <em>Aedes aegypti</em> mosquitoes and then releasing them to the general population, scientists dream of <a href="http://www.nature.com/nature/journal/v476/n7361/full/nature10355.html">eliminating dengue</a> worldwide. </p>
<p>But releasing mosquitoes to communities requires a high amount of trust. How do we convince people that spreading mosquitoes can eliminate dengue when they have long came to understand that <em>Aedes</em> mosquitoes transmit dengue? </p>
<p>The answer? Careful preparation and community engagement.</p>
<p>I lead the Eliminate Dengue Project in Yogyakarta (EDP-Yogya), the first project to use Wolbachia to reduce dengue cases in Indonesia, the most dengue-vulnerable country in Asia. Funded by Tahija Foundation, EDP-Yogya works in collaboration with EDP-Global led by Professor Scott O'Neill, based at Monash University. </p>
<p>Two districts in Sleman, Yogyakarta became our release sites. For two years since 2011, while we prepared for the first small-scale release of Wolbachia infected mosquitoes, we carried out intensive community engagement. </p>
<h2>Community engagement</h2>
<p>We worked closely with the smallest community unit, called Rukun Tetangga (RT) to gain trust. An RT consists of about 20 to 30 households. We held face-to-face community meetings to educate the community on dengue-related subjects, both piggybacking on their existing meetings and arranging special meetings. </p>
<p>We formed community referral groups to be able to discuss key issues raised by the community as well as issues to be put to the community. As the project develops, members of this group are often called on as resource persons for other communities. </p>
<p>We also adopted the saying “seeing is believing”. Community members visit our insectary and diagnostic laboratory to gain a better understanding about Aedes mosquitoes and Wolbachia. These visits to our lab create a strong sense of transparency. We hide nothing from our community. </p>
<p>Two years into the preparatory phase, we built a stakeholder inquiry system (SIS) to capture any community concerns, opinions and complaints as the project moves closer to the mosquito release. We use various mediums from direct face-to-face conversation, short text messages, telephone and email. We monitor concerns daily and we develop protocols to address these concerns. </p>
<p>Finally, building trust also involves sharing information back to the community. Every two months, progress and activities in specific hamlets are communicated via newsletters (“Pawartos”), distributed to all households in the community. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/126889/original/image-20160616-19913-1y0q0gk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/126889/original/image-20160616-19913-1y0q0gk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/126889/original/image-20160616-19913-1y0q0gk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/126889/original/image-20160616-19913-1y0q0gk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/126889/original/image-20160616-19913-1y0q0gk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/126889/original/image-20160616-19913-1y0q0gk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/126889/original/image-20160616-19913-1y0q0gk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">EDP staff distributing newsletters to the community.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>Community consent</h2>
<p>Enhancing community understanding in a community-based project like EDP-Yogya is a prerequisite toward acceptance of the project. However, improved community understanding about dengue and Wolbachia intervention does not imply approval from the community. </p>
<p>Consent must be obtained from the research participants. We collaborate with EDP Global at Monash University, and for the first release in Sleman district, the Independent Review Board requests individual consent from each household member. We obtained approval from nearly 4,500 people.</p>
<p>From the Sleman trial, we learnt obtaining individual consent can generate conflicts in the community. Culturally, communities in these areas use collective decision-making process when dealing with community issues. The protocol protects the rights of people who refuse the release over those who approve. </p>
<p>Additionally, obtaining individual consent required tedious work. Although we managed to obtain more than 95% approval, this approach is impractical to do on a larger scale. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/126890/original/image-20160616-19925-1vkh2ye.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/126890/original/image-20160616-19925-1vkh2ye.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/126890/original/image-20160616-19925-1vkh2ye.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/126890/original/image-20160616-19925-1vkh2ye.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/126890/original/image-20160616-19925-1vkh2ye.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/126890/original/image-20160616-19925-1vkh2ye.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/126890/original/image-20160616-19925-1vkh2ye.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Community leaders signing informed consent.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Finally, a low percentage of household members who rejected the intervention turned out to have influenced the release areas. When one household rejects the mosquito release, we do not release the mosquitoes in that household and its surrounding areas within the radius of 25-50 square meters. As a result, 5% of the population that doesn’t approve does not translate to 5% of the area not released, but somewhat larger. </p>
<p>Based on the experience in Sleman, for Bantul release we obtained community consent but still allowed individuals to reject. All RTs in Jomblangan and Singosaren (Bantul district) gave consent and no households refused the release. </p>
<p>We also changed the method to releasing young <em>Aedes</em> eggs instead of adult mosquitoes. We engaged the community to hatch Wolbachia-infected eggs, placed in buckets, in their households. Involving the community to hatch _Aedes _eggs in their own houses creates a higher sense of ownership. </p>
<h2>Result</h2>
<p>Weekly monitoring of the local <em>Aedes</em> mosquito found the bacteria spread through more than 80% of the local population. The mosquitoes have remained infected, showing that the establishment of Wolbachia in the population is sustainable. </p>
<p>Our observation on dengue cases in the community revealed that once most mosquitoes are infected by Wolbachia, there was no evidence of local dengue transmission. This means that those who have had dengue could have been infected from outside the release areas. </p>
<p>Without community involvement and consent, it would have been impossible to achieve this positive result. Our next step is to carry the successes in Sleman and Bantul to a larger population: the city of Yogyakarta with around 450,000 residents. By 2020, we hope Indonesia will adopt the use of Wolbachia in dengue-prevention nationwide.</p><img src="https://counter.theconversation.com/content/56692/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adi Utarini works for the Eliminate Dengue Project in Yogyakarta in Faculty of Medicine Universitas Gadjah Mada, Yogyakarta, Indonesia. She receives funding from Tahija Foundation for this project. </span></em></p>How do we convince people that spreading Wolbachia-infected mosquitoes can eliminate dengue when they have long came to understand that mosquitoes transmit dengue?Adi Utarini, Professor in Public Health and Project Leader of Eliminate Dengue Project Yogyakarta, Faculty of Medicine, Universitas Gadjah Mada Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/422872015-06-12T10:17:49Z2015-06-12T10:17:49ZModifying mosquitoes to stop transmission of dengue fever<figure><img src="https://images.theconversation.com/files/84748/original/image-20150611-11427-71p6ty.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Female _Aedes aegypti_ mosquitoes transmit dengue fever when enjoying blood meals.</span> <span class="attribution"><a class="source" href="http://phil.cdc.gov/phil/details.asp">James Gathany</a></span></figcaption></figure><p><a href="http://www.cdc.gov/dengue/">Dengue</a> is a virus spread via the <em>Aedes aegypti</em> mosquito that infects as many as <a href="http://www.cdc.gov/dengue/fAQFacts/index.html">100 million people</a> annually in more than 100 tropical countries worldwide. It causes fevers, extreme headaches, and muscle and joint pains. In a few extreme cases, leakage of blood plasma through the walls of small blood vessels into the body cavity occurs, resulting in bleeding. This is known as dengue hemorrhagic fever. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/83436/original/image-20150529-15253-16obi8q.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Global Dengue Transmission Risk Map.</span>
<span class="attribution"><a class="source" href="http://caring.ridpest.com/wp-content/uploads/2015/04/Global_DengueTransmission_ITHRiskMap.png">World Health Organization</a></span>
</figcaption>
</figure>
<p>The number and severity of dengue infections has been escalating since the Second World War, culminating in a 30-fold increase between <a href="http://apps.who.int/iris/bitstream/10665/75303/1/9789241504034_eng.pdf">1960 and 2010</a>. It is now 20 times more common than the flu. Because of global warming, decreased heavy pesticide use due to environmental concerns, and the <em>Aedes</em> mosquito’s preference for urban environments, the insect – and the virus it carries – are rapidly spreading around the world.</p>
<p>There is no treatment for dengue fever. At best, doctors can give their patients supportive care, such as painkillers and liquids to keep them hydrated. Untreated dengue fever has a mortality rate of about 5%; fortunately, with treatment that number drops to zero and each year “only” 20,000 dengue deaths <a href="http://apps.who.int/iris/bitstream/10665/75303/1/9789241504034_eng.pdf">are recorded</a>.</p>
<p>As a result of its prevalence all around the world, scientists are looking for new ways to control <em>Aedes</em> mosquitoes – and thus dengue transmission. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84749/original/image-20150611-11427-5o9skt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">I’ll take your blood, you can have some dengue virus.</span>
<span class="attribution"><a class="source" href="http://phil.cdc.gov/phil/details.asp">James Gathany</a></span>
</figcaption>
</figure>
<h2>Helpful host</h2>
<p>The dengue virus does not harm its mosquito host. When an infected female mosquito bites a person, the virus enters the blood stream with the mosquito’s saliva and anticoagulant.</p>
<p><em>Aedes aegypti</em> are smaller and quieter than the mosquitoes typically found in the US. They thrive in urban environments and are more at home in the city than in the jungle. Controlling and limiting <em>Aedes</em> habitats is extremely difficult since they like to live indoors, residing in places such as dim closets and cupboards. They can lay eggs in a single drop of water. The stealthy bloodsuckers enjoy feeding around human beings’ ankles, biting as many as 20 people a day.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=588&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=588&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=588&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=739&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=739&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84747/original/image-20150611-11433-1vcbs20.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=739&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Transmission electron micrograph depicts a number of round, dengue virus particles in a tissue specimen.</span>
<span class="attribution"><a class="source" href="http://phil.cdc.gov/phil/details.asp">Frederick Murphy</a></span>
</figcaption>
</figure>
<p>Somehow, the simple dengue viruses with RNA genetic material coding for just 10 proteins can change the production of 147 different proteins expressed by <em>Aedes</em>. It <a href="http://dx.doi.org/10.1371/journal.ppat.1002631">makes the mosquito</a> hungrier for human blood, its saliva more hospitable to the viruses, and changes the protein mix in the antennae of the mosquitoes making them more sensitive to odors – thereby increasing the mosquito’s ability to find a victim. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=558&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=558&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=558&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=702&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=702&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84750/original/image-20150611-11427-1kvs1c1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=702&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Inside a cross-section of a mosquito, Wolbachia show up as red dots. The blue circles are mosquito DNA.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/pennstatelive/14863946016">Penn State</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>Bombarding them with bacteria</h2>
<p>An Australian group led by <a href="https://www.monash.edu/science/schools/biological-sciences/staff2/oneill">Scott O’Neill</a> at Monash University has infected mosquitoes with bacteria that prevent the dengue viruses from taking up residence in the mosquito. It prevents the dengue’s carrier from hosting the virus.</p>
<p>The Wolbachia-infected mosquitoes are the result of an idea that O’Neill had 20 years ago. He knew that Wolbachia-infected fruit flies would not transmit any RNA virus. So he hoped Wolbachia-infected <em>Aedes aegypi</em> would act in the same way and not transmit dengue, an RNA virus. The trouble was, even though Wolbachia infections are common in many insects, including non-<em>Aedes</em> mosquitoes, he couldn’t infect sufficient numbers of <em>Aedes</em> with the bacteria. He says he persisted because, “I thought <a href="http://www.npr.org/2012/06/07/154322744/a-scientists-20-year-quest-to-defeat-dengue-fever">the idea was a good idea</a>, and I don’t think you get too many ideas in your life, actually. At least I don’t. I’m not smart enough.”</p>
<figure>
<iframe src="https://player.vimeo.com/video/99686346" width="500" height="281" frameborder="0" webkitallowfullscreen="" mozallowfullscreen="" allowfullscreen=""></iframe>
</figure>
<p>It wasn’t easy, but by obsessively trying new and different ways to infect <em>Aedes</em> with a strain of the bacteria obtained from the fruit fly, his group <a href="http://dx.doi.org/10.1038/nature10356">managed to overcome the mosquitoes’ resistance</a> to Wolbachia. Infecting young <em>Aedes</em> eggs worked best, particularly since all female eggs that were infected grew into adult <em>Aedes</em> mosquitoes that passed on the bacteria to all their offspring.</p>
<p>Field trials in Australia, China, Vietnam, Brazil and Thailand have been promising. In Australia, within 10 weeks of releasing the infected mosquitoes, the Wolbachia spread through 100% of the <em>Aedes</em> population of the two towns studied. The mosquitoes have remained infected ever since. O’Neill is now dreaming of world-wide <a href="http://dx.doi.org/10.1038/nature10355">dengue eradication</a> by his Wolbachia-infected <em>Aedes</em>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84754/original/image-20150611-11398-1kwyhy8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Release of genetically modified <em>Aedes aegypti</em> in Brazil.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/agecombahia/5679639329">Fotos GOVBA</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<h2>Transgenic population crashers</h2>
<p>A British biotech company, <a href="http://www.oxitec.com">Oxitec</a>, regularly releases millions of <a href="http://dx.doi.org/10.1038/nbt.2019">genetically modified mosquitoes</a> in trials in Brazil. Its chief scientific officer, Luke Alphey, found a gene that kills off all <em>Aedes</em> offspring in their larval stage. In a neat trick, he also found a way to suppress the deadly gene’s expression using the antibiotic tetracycline. So in the presence of tetracycline, the larvae develop normally, allowing researchers to grow large batches of adult transgenic <em>Aedes</em>. Then they’re released into the wild, where of course the mosquitoes have no contact with the antibiotic antidote. The genetically modified mosquitoes breed with their wild counterparts, yielding offspring that will die as larvae. </p>
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<a href="https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=410&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=410&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=410&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=515&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=515&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84741/original/image-20150611-11433-8t70xm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=515&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Closeup of <em>Aedes aegypti</em> mosquito fourth stage larvae.</span>
<span class="attribution"><a class="source" href="http://phil.cdc.gov/phil/details.asp">CDC/ Dr. Pratt</a></span>
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<p>When enough males are released, their mating with wild females will <a href="http://dx.doi.org/10.1371/journal.pone.0062711">collapse the population</a>. It’s like a form of birth control for the mosquitoes, since no offspring make it past the larval stage. In all field tests no genetically modified females are released. This is critical because Oxitec has to prevent the genetically modified insects from breeding with each other in the wild and to ensure that transgenic mosquitoes do not bite any humans – remember, only female mosquitoes bite.</p>
<p>In July 2012 the Minister of Health of Brazil, Alexandre Padilha, <a href="http://fox2now.com/2012/07/12/genetically-modified-mosquitoes-fight-dengue-fever/">opened a new facility</a> to create enough mosquitoes to protect a town of approximately 50,000 inhabitants from <em>Aedes aegypti</em>. At maximum production, the facility will produce 4 million sterile mosquitoes a week. Key West, Florida is next on the list. The US Food and Drug Administration is currently reviewing an application to release the <a href="http://www.nytimes.com/2015/02/20/us/battle-rises-in-florida-keys-over-fighting-mosquitoes-with-mosquitoes.html?_r=0">Oxitec mosquitoes there</a>. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/-2pO_d4HAmc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
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<h2>Sex skew</h2>
<p>While the Oxitec and Wolbachia mosquitoes are already being released in fairly large field trials, a new player has just entered the arena. Using computational methods, researchers at Virginia Tech have found a <a href="http://dx.doi.org/10.1126/science.aaa2850">gene they call Nix</a> that’s responsible for the male sexual characteristics of <em>Aedes aegypti</em>. More than two thirds of the females produced when the Nix gene is added to female <em>Aedes</em> embryos have male genitals and testicles, making them infertile and perfect vehicles, like the Oxitec mosquitoes, to collapse a local <em>Aedes</em> population.</p>
<p>The researchers acknowledge they’re still years from doing field tests. For example, they haven’t tested whether their masculinized females can bite and transmit disease. But Zach Adelman, one of the paper’s authors, <a href="http://www.theverge.com/2015/5/21/8634813/mosquitoes-disease-sex-dengue-yellow-fever">sees some advantages</a> of using the Nix gene over sterilization-based techniques, such as those used by Oxitec: “They’re throwing away half of the mosquitoes that they rear because they’re females. If we have a strain that doesn’t even make females then you don’t have to spend all the labor costs associating with separating those out, and you don’t have to spend the money rearing them and then throwing them away,” Adelman says.</p>
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<a href="https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=391&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=391&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=391&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=492&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=492&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84758/original/image-20150611-11396-1qffvnp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=492&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Tiny mosquitoes, big problem.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/rooymans/3493630510">Joost Rooijmans</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<h2>Ongoing search for innovation</h2>
<p>As long as there are no cures or vaccines for dengue fever, the only way to control the world’s fastest growing infectious disease is to manage the <em>Aedes</em> population, either by killing them or by making them inhospitable to the dengue viruses. The current techniques of removing all sources of stagnant water and using limited and targeted insecticide applications are insufficient.</p>
<p>These solutions that require scientifically altered mosquito <a href="http://www.theguardian.com/world/2015/may/24/sterile-mosquitoes-released-in-china-to-fight-dengue-fever">releases</a> are <a href="http://e360.yale.edu/feature/genetically_modified_mosquito_sparks_a_controversy_in_florida/2883/">controversial</a>. The most common fears people have are that the genetic modifications could cross over into other species, result in super-mosquitoes, or that the disappearance of <em>Aedes</em> from the ecosystem will affect other organisms that depend on them for survival.</p>
<p>Despite all the concerns about using genetically modified or bacterially infected <em>Aedes</em> mosquitoes, it’s hard to imagine a way to beat dengue that doesn’t involve them. And there are some clear advantages to using Wolbachia infections or genetically modified self-destructing mosquitoes. They are both species-specific and will not affect any other mosquitoes, butterflies or bees – as indiscriminate insecticide applications would – and they can reach places that only male mosquitoes could find.</p><img src="https://counter.theconversation.com/content/42287/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marc Zimmer does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Annihilate the Aedes aegypti mosquito population and you’d stop dengue fever from infecting up to 100 million people worldwide annually. Here are some high-tech methods under development.Marc Zimmer, Professor of Chemistry and author of Illuminating Disease, Connecticut CollegeLicensed as Creative Commons – attribution, no derivatives.