Mosquitoes with lethal genes to help Brazil fight dengue

Bloomberg

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Infant mosquitos are seen through a microscope in a laboratory at the Oxitec Ltd. company headquarters in Abingdon. Infant mosquitos are seen through a microscope in a laboratory at the Oxitec Ltd. company headquarters in Abingdon.
When he announced he was going to Brazil for the World Cup, Andy Quinn was warned by friends and a travel agent to lather on mosquito repellent to avoid potentially fatal dengue fever.
Some of the mosquitoes he saw “were like aliens -- I’ve never seen them that big before,” said the 32-year-old Londoner, who attended three games in Brazil before his England team was sent packing. Brazil’s stepped up spraying of insecticides didn’t seem to help matters.
The country may soon have a more powerful weapon to use before it hosts the 2016 Summer Olympics: genetically modified mosquitoes that self-destruct before doing any damage.
Brazil will probably be the first nation to approve large-scale releases of male mosquitoes with a lethal gene that causes their offspring to die before reaching adulthood, according to Hadyn Parry, chief executive officer of Oxitec Ltd., a U.K. biotechnology company that has developed the technology.
“I’m hopeful it comes through this year,” Parry said in an interview. “It would be an opportunity to use the occasion of the Olympics to say, ‘Why don’t we actually solve this problem?’”
The soccer World Cup, which runs through July 13, has brought thousands of visitors to a country with the world’s largest incidence of dengue. A heatwave has extended the mosquito season and fans have been urged to use repellent and wear long-sleeved clothing in the early morning and late afternoon.
‘Pretty thick’
“They were pretty thick in open spaces,” particularly near the Manaus stadium in the Amazon rainforest region, Quinn said.
Dengue, for which there is no vaccine or treatment, causes flu-like illness that can develop into potentially fatal complications. Warning signs include bleeding gums, vomiting, rapid breathing and severe abdominal pain. More than 50 million people are infected a year, with about 500,000 requiring hospitalization, the World Health Organization estimates.

 

The incidence of dengue has grown “dramatically” in recent years, and more than 40 percent of the global population is at risk, according to the WHO. The disease appeared in Florida in 2009 for the first time since 1934, and cases among travelers returning to the U.K. tripled in 2013 from a year earlier.
Eradication success
Oxitec’s technique eradicated almost all wild mosquitoes in a test in one small area in Brazil. The company is awaiting final regulatory approval to start selling the insects in Brazil, meaning relief is in sight for the Olympics, Parry said.
New tools to fight dengue are emerging elsewhere. Drugmakers including Sanofi (SAN), Takeda Pharmaceutical Co. and Merck & Co. are racing to develop the first vaccine.
Our approach is almost like a vaccine for the mosquito rather than for the human” -- Scott O’Neill, Eliminate Dengue project
Another preventative technique, developed at Monash University in Melbourne and backed by the Bill & Melinda Gates Foundation, will soon be tested in Australia and Indonesia. It blocks transmission to humans by injecting the Wolbachia bacteria in mosquitoes. When the insects mate, they spread the bacteria, making more mosquitoes unable to transmit dengue.
“Our approach is almost like a vaccine for the mosquito rather than for the human,” Scott O’Neill, the Monash professor leading the non-profit Eliminate Dengue project, said in a telephone interview.
The researchers will deploy mosquitoes in Townsville, Australia, in October and in Yogyakarta, Indonesia, next year, O’Neill said. Regulatory approval has also been secured in Vietnam, China, Brazil and Colombia, he said. Smaller-scale trials have already been conducted in Australia since January 2011, said Helen Cook, the organization’s external relations adviser.
Bill Gates
“Many more of these amazing mosquitoes will need to be released into the wild in the months ahead before we can assess the impact,” Microsoft founder Bill Gates wrote in an April blog post in which he described offering up his arm to a cage of Wolbachia mosquitoes for them to feast on human blood to develop eggs. “It was a small price to pay for an amazing project that has the potential to turn the tide against a terrible disease.”
The new approaches contrast with spraying insecticides and other methods that have proven ineffective in thwarting the Aedes aegypti mosquito that carries dengue.
Oxitec’s method is similar to some techniques that have successfully controlled other types of insects, said Duane Gubler, a professor of emerging infectious diseases at the Duke-NUS Graduate Medical School in Singapore.
“I am enthusiastic” about Oxitec’s solution, said Gubler, author of a textbook on dengue. “For the past 40 years, we have failed to control dengue. We simply haven’t had the tools.”
Last step
Oxitec won approval for its mosquito in April from Brazil’s biosecurity commission, which regulates transgenic organisms, and has built a factory in Campinas, near Sao Paulo, Parry said. Final clearance will specify who the company can sell to, such as local authorities or private operators.
The mosquitoes would be released two or three times a week to outnumber the local wild population. In a trial in Mandacaru in eastern Brazil, releases resulted in a 96 percent reduction of the wild population after six months. That level of suppression was maintained for a further seven months with smaller releases, according to Oxitec.
A trial began in Panama last month, and others may begin in India and in the Florida Keys later this year, Parry said.
While Oxitec has sufficient funds for testing, the company, based near Oxford, England, is considering an initial public offering to help it expand in Asia and commercialize the product. Closely held Oxitec was spun out from Oxford University in 2002.
Modification critics
To be sure, Oxitec’s proposal has drawn criticism in the U.S. and Britain, where campaigners have said the potential adverse effects of genetically modified mosquitoes and their interactions with other mosquitoes and humans aren’t fully understood.
Oxitec’s mosquito and the Wolbachia bacteria project may be most effective when used in combination with other methods, Gubler said.
“I do not believe we can or will ever eradicate dengue or Aedes aegypti mosquitoes, but we can control them to the point where the disease isn’t a public health problem,” he said. About 12,500 people die from the disease each year, according to the WHO.
While peak transmission in Brazil is usually during the rainy season from December to April, dengue risk is always present. The heatwave means the threat is greater at the World Cup than expected.
Until the modified mosquitoes arrive, Gubler recommends prevention. His best advice? Insect repellent.

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