Brazil will release hundreds of millions of GM mosquitoes

Brazil will release hundreds of millions of GM mosquitoes

November 01, 2016 Source: Science Network

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Every Saturday morning, Maria do Carmo Tunussi will go door-to-door to let neighbors search houses and yards to find anything that can store water and provide a place for mosquito breeding, such as pots, buckets and blocked sinks. For 17 years, Tunussi has become a community health agent for CECAP/Eldorado local clinics. CECAP/Eldorado is an area of ​​approximately 5,000 people in the small town of Piracicaba, Brazil, 2 hours drive northwest of São Paulo. Tunussi witnessed the repeated engulfing of mosquito-borne dengue viruses that caused fever, nausea and afflicted joint pain. Therefore, her work sometimes seems futile. "You cleaned up the breeding ground the first day, and it came back the next day." Tunussi said, "This seems to never end."

In April of this year, CECAP became the first community in Piracicaba to try new things, a mosquito control tool that Tunussi believes can not only eradicate dengue fever, but also prevent Zika virus from "holding a foothold" - OX513A. This is a genetically modified Aedes aegypti that aims to reduce the number of Aedes aegypti by passing a lethal gene to future generations.

In Florida, Oxitec, which cultivates these insects, plans to release them but is blocked by the public. However, at CECAP, residents seem to be calm and self-sufficient in a cloud of mosquitoes that emerge from the window of the caravan that the company is slowly driving in the early morning.

This may be because dengue fever is so common there. Last year, the virus caused about 1.5 million Brazilians to suffer from the disease. From July 2015 to July this year, more than 1,600 people in Piracicaba were sick. The panic caused by the spread of Zika virus has magnified the local interest in pesticides and solutions to clean up breeding grounds. The former is not always effective against Aedes aegypti, and the latter is difficult to year after year. The ground is maintained, although Tunussi has been working hard. So, seven years after the release of the world's first GM mosquitoes, it is not surprising that Oxitec chose to expand its trials in Brazil. It is shifting from small pilot projects such as those at CECAP to planned releases covering thousands of people.

Cultivate mosquitoes carrying lethal genes

Oxitec's headquarters in Brazil is located in the industrial city of Campinas. There, the smell of fish feed for feeding mosquito larvae is everywhere. The company can allow about 4 million mosquitoes to go through the entire life cycle in a week: from gray-white powdered mosquito eggs to twisted gray larvae, followed by dense, black enamels similar in size to rice grains, and finally in fast food boxes. Adult mosquitoes flying around in almost large plastic buckets.

They are about the 200th generation of "children" of a mosquito that was nurtured in a laboratory at the University of Oxford in England 14 years ago. At the time, geneticist Luke Alphey and his team inserted a new gene into the mosquito embryo. This gene encodes a protein called a transcriptional activator that drives the expression of other genes by binding to DNA involved in transcription and specific proteins. However, the gene called Oxitec that inhibits the tetracycline transcriptional activator variant (tTAV) is designed to drive more tTAV expression and turn the process into a fatal feedback loop.

How this process kills mosquitoes is not yet fully understood. Excessive tTAV protein may block the protein synthesis system of cells. "Probably, it caused genetic disruption and mosquitoes died," said Al Handler, an insect geneticist at the US Department of Agriculture.

Oxitec's mosquitoes carrying lethal genes grow by feeding antibiotics that block tTAV activity but keep mosquitoes alive. Male mosquitoes that do not bite are released into towns and cities. There, they mate with wild female mosquitoes. The resulting offspring will quickly accumulate this lethal protein, most of which died before the age of one year.

"Removal of dengue fever" project

If Oxitec's mosquitoes perform suicide missions, then the mosquitoes in the “Dengue Elimination” project are “missionaries”. The purpose of the latter is not to destroy the wild mosquito population, but to transform them. In the slum of the Rulujuba in Niteroi, in the early morning of a drizzle, the researchers spread out on the slopes where the concrete had already peeled off to make up the “source” of the eggs in the container. In the local area, about 130 households agreed to place these containers. White plastic buckets like oversized Easter eggs are hidden under the stairwell, next to the steps, and in the niches behind a pile of plywood and old bicycle parts.

Adult mosquitoes that escape from the bucket carry Wolbachia bacteria. This is a parasite that is thought to occur naturally in about 60% of insect species. However, it was not until 2005 that researchers “deceived” the bacteria to “settle” in Aedes aegypti. At the time, Scott ONeill, a co-founder of the “Dengue Elimination” project and a medical entomologist at Monash University in Australia, found that he was infected with Wolbachia and smoked with dengue or chikungunya virus compared to the control group. Mosquitoes are more likely to be positive in the dengue virus test and to spread the virus. Earlier this year, researchers from the Osvaldo Cruz Group, a Brazilian national public health agency working with the “Denergy Elimination” project, reported similar results in the Zika virus test.

They suspect that the parasite will compete with the virus for limited resources in the mosquito cells. At the same time, Wolbachia may activate the immune system of its host to help it fight subsequent infections. Since Wolbachia is transmitted to the offspring only through the eggs, it requires the release of female mosquitoes that can bite. However, ONeill said that it is because of this bacterium that female mosquitoes do not pose a risk of spreading the disease.

The “Detoxification” project has released the mosquitoes in more than 40 regions in Australia, Vietnam, Indonesia, Colombia and Brazil, most of which are funded by Bill and Melinda. Gates Foundation. Studies have shown that the parasite can spread to "locating points" within 10 to 20 weeks and remain in the mosquito population for at least 5 years. The project aims to make permanent changes to the mosquito population, which is a key different from Oxitec's solution. The latter has to be carried out year after year, otherwise the number of mosquitoes will rebound. However, both methods can only have an impact locally. Wolbachia is not widely spread in areas where it has not been released.

Can it really reduce the disease?

The imminent problem facing the two projects is simple: Can these mosquitoes that fight disease really reduce the disease? "Our goal is not to kill mosquitoes, but to prevent people from getting infected, sick and dying," said Thomas Scott, an epidemiologist and entomologist at the University of California, Davis. So far, there is no evidence that any method has done this. According to Scott, intuition may suggest that fewer mosquitoes that transmit disease mean less infectious lesions, but only a few Aedes aegypti may be enough to spread the disease to susceptible populations.

In July of this year, data released by Oxitec showed that the number of dengue cases in CECAP decreased by 91% in the previous year, from 133 to 22. However, the number of cases in other parts of Piracicaba has only decreased by 52%. However, Scott said that the outbreak of dengue fever is irregular. “There may be an outbreak in a small town, but there are no neighboring towns. In the second year, the situation may be completely reversed.”

The final statement about the effect comes from trials that monitor the disease in community residents who randomly receive mosquitoes or as a control group. However, data from both groups is inherently flawed because people are mobile. This means that such research has to be meaningful, must be large-scale, and costly. In March of this year, a World Health Organization working group led by Scott said that Oxitec and the strategy of “eliminating dengue fever” projects are worthy of “careful planning pilot trials”, but also called for large-scale epidemiological studies.

The “Detoxification Elimination” project has carried out an effect study in Yogyakarta, Indonesia. The study tracked the incidence of 24 regions (about 14.5 million in each region), half of which received Wolbachia mosquitoes. A network of clinics throughout Yogyakarta will continue to test dengue virus for two years. A larger study is being planned in Vietnam. At the same time, Oxitec recruited independent experts to design experiments that were tentatively scheduled for 2018.

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