Dengue fever, Zika, chikungunya, yellow fever and other diseases are spread by the Aedes aegypti mosquito. Image courtesy of Oxitec

Releasing genetically modified Aedes aegypti sterile ‘dengue mosquitoes’ has caused the species’ population to fall by 90% in local trial sites. These results have raised expectations that this novel approach could be used to defeat dengue in combination with traditional vector control methods and vaccination in global efforts to monitor the spread of dengue and other viruses borne by this mosquito species.

The dramatic results were seen in several field trials in small Latin America towns conducted by Oxitec. The UK-based biotech company breeds male mosquitoes whose offspring are incapable of reaching maturity.

Dr. Andy McKemey, Head of Field Operations at Oxitec, told Break Dengue that the company is now set to expand into much larger towns and is planning a new facility capable of producing the necessarily large volumes of modified mosquitoes.

The production facility located in Piracicaba, Brazil, and will have the capacity to provide enough genetically modified mosquitos to protect over 300,000 people from disease-spreading mosquito bites.

Piracicaba is a natural choice for the plant. The municipality became the first public sector partner for Oxitec’s field trials which saw thousands of self-limiting mosquitoes released into the Eldorado district – home to 5,000.

During the early developmental pupal stage, Oxitec scientists separate the female mosquitoes from the males. Image courtesy of Oxitec.

“The city of Piracicaba has always sought innovative solutions to serious problems,” says Mayor Gabriel Ferrato. “In the case of Aedes aegypti, we looked for the tool that seemed most appropriate to help in the desperate battle against this mosquito that transmits dengue, Zika and chikungunya. This will bring to the city a new Oxitec factory to meet the demand for years to come and help protect the public’s health with this clean and innovative technology.”

Following approval by Brazil’s National Biosafety Committee, the trial was extended for a year and authorities have agreed to extend it to a wider area, which will cover between 35,000 and 60,000 people.

This geographic region included the city center, chosen due to the large flow of people commuting between it and surrounding neighborhoods, which may contribute to the spread of infestations and infections.

Measuring the impact on dengue transmission – a challenging task

The success of the Piracicaba trial fits with results of a series of field trials of the GM mosquito. Research published last year in the journal PLOS Neglected Tropical Diseases showed mosquito suppression of between 80%-95%, depending on how the population is estimated.

Image of Dr McKemey working in lab courtesy of Oxitec.

Previous trials in the Cayman Islands showed that the presence of the mosquito in the wild was down 96% while a small study in Mandacaru saw mosquito numbers down around 99%. In a Panama trial, suppression was 93%.

These successes have reassured local populations – some of whom had been skeptical about the idea of releasing GM-mosquitoes into their environment. “The results we have had, along with the regulatory approval for the commercial release of our mosquito strain, are huge milestones for us,” says Dr. McKemey.

The big question is how the drop in mosquito numbers will affect the spread of dengue fever and other mosquito-borne illnesses.

“We have achieved greater than 90% suppression of the Aedes population in these trials, bringing the numbers well below the level which mathematical models suggest is the dengue transmission threshold,” says Dr McKemey. However, it remains difficult to prove empirically that the trials have had an impact on dengue fever rates. “It’s hard to demonstrate a causal link in trials covering a population of a few thousand people. You cannot monitor dengue cases in a statistically significant way that accounts for seasonal variation and how people move around.”

It would, he suggests, require a study of 200,000 to 300,000 people over several years. “The best we can do at the moment is look at whether we have reduced the mosquito population and then use mathematical modeling to determine whether this is likely to be of value.”

An additional tool to control the spread of dengue and vector-borne diseases

Interest in the modified Aedes aegypti has increased with local and regional authorities from across Brazil. Faced with two pressing concerns: the 2016 Olympic Games and the rise of Zika fever, they are intensifying their efforts to control the virus-carrying mosquito population.

“It is essentially very similar to dengue regarding transmission, so the approach we have taken to control dengue can also apply to Zika…”

“Zika virus has exploded onto the scene,” says Dr McKemey. “It is essentially very similar to dengue regarding transmission, so the approach we have taken to control dengue can also apply to Zika. Cities all over Brazil are interested in this and how we can work with them.”

Public engagement campaign in Brazil to educate the public on the GM mosquitoes fighting dengue outbreaks. Image courtesy of Oxitec

While the GM mosquito holds real promise as a breakthrough, Oxitec doesn’t expect it to solve the dengue fever problem on its own. “There is no silver bullet. We can achieve phenomenal suppression of the mosquito population, but it still needs to be managed with conventional tools – insecticide and clearing breeding grounds, in addition to vaccines.”

Oxitec may be adding a new weapon to the arsenal, but it is likely that a range of tools, addressing surveillance, disease management, long-term vector control and vaccination, will need to be used in synergy – meaning collaboration between various players is more important than ever.