Oxitec and the Mosquito Research and Control Unit (MRCU) are collaborating on a project with the Friendly Aedes aegypti mosquito.
Wild Mosquito Problem
Aedes aegypti is a non-native species in the Cayman Islands. These mosquitoes are more than just a nuisance as they can spread serious diseases such as dengue fever, Zika and chikungunya. Aedes aegypti is particularly difficult to control as it lives around humans, and the MRCU is looking for new technologies to suppress the population of these disease carriers.
Oxitec has developed an innovative solution for controlling Aedes aegypti mosquitoes. Oxitec mosquitoes have been engineered to contain a self-liming gene. Male mosquitoes are released to mate with wild females, passing on this gene to their offspring. Their offspring die before reaching adulthood, so the mosquito population declines.
Oxitec’s mosquitoes do not stay in the environment, as both the released mosquitoes and their offspring will die. The approach is very targeted: it only affects the Aedes aegypti mosquitoes – the carriers of diseases – because the Oxitec males only produce offspring with their own species. It may also reduce the need for insecticides, allowing more beneficial predators and insects to flourish.
Previous trials in the Cayman Islands, Brazil and Panama, have all shown that the release of Oxitec’s Friendly mosquitoes reduces the wild population by more than 90%.
Following the projects conducted in Cayman Islands in 2009 and 2010, Oxitec is working again with the MRCU to begin a pilot project in West Bay, an area of Grand Cayman that is a hot spot for the Aedes aegypti mosquito. The treatment area will encompass about 1,800 residents, and standard mosquito control measures will continue during the project. This project will include 9 months of mosquito releases that will begin after a period of community engagement. The project has been approved by local regulatory authorities.
View the Spotlight video on the project:
What is dengue?
Dengue fever is a severe, flu-like illness that affects infants, young children and adults. Dengue fever is transmitted by the bite of an Aedes aegypti mosquito infected with any one of the four versions of the dengue virus (and a fifth serotype of dengue has now been discovered in Malaysia). Symptoms appear in 3–14 days (average 4–7 days) after the infective bite. Dengue hemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS) are potentially lethal complications, particularly in children, and early clinical diagnosis and careful clinical management by experienced physicians and nurses is necessary to reduce the number of fatalities.
Dengue can only be transmitted by the bite of an infected mosquito and only female mosquitoes bite. The main vector is the mosquito Aedes aegypti, which originated from Africa and has spread around the world, largely in the last 50 years and, as it has done so, dengue fever has followed and increased dramatically.
The global numbers of dengue cases have grown 30 fold in only 50 years because current control methods, relying mostly on insecticides are not adequate to control this mosquito.
Each year there are an estimated 400 million dengue infections, with 500,000 cases so severe they require hospitalisation and 22,000 deaths, many of them children. New approaches are needed.
What is Zika?
Zika is a flavivirus, transmitted primarily by Aedes mosquitoes. The virus was originally identified in Uganda in 1947, and the first major outbreaks occurred in the Pacific, on Yap Island in 2007 and French Polynesia in 2013. In 2015 an outbreak was reported in Brazil, which has since spread to a large number of countries in the Americas, as well as some Pacific Islands.
Some areas with Zika outbreaks have reported an increase in babies born with microcephaly as well as an increase in Guillain-Barré syndrome, a disorder in which the body’s immune system attacks its nerve cells. According to the WHO, there is growing evidence that Zika virus may be the cause of these disorders. Because of the increased incidence of these disorders in areas of a Zika outbreak, the WHO declared a Public Health Emergency of International Concern on February 1 2016.
According to the CDC, many people infected with Zika do not show symptoms so they may not know that they have the virus. When symptoms do occur, they are usually mild and last for a few days to a week. Symptoms include fever, skin rashes, conjunctivitis, muscle and joint pain, and headache.
In addition to transmission via the Aedes mosquito vector, sexual transmission of the Zika virus has been described in certain cases, and the presence of the Zika virus in semen has also been found.
There is currently no vaccine for Zika, so control of the mosquito and avoidance of bites are the best ways to combat the disease.
What is chikungunya?
Chikungunya (CHIKV) is a viral disease transmitted to humans by infected mosquitoes. The disease shares some clinical signs with dengue such as fever, severe joint pain, muscle pain, headache, nausea, fatigue as well as rash, and can be misdiagnosed in areas where dengue is common.
Chikungunya, like Zika and dengue, has resulted in a number of neurologic diseases such as Guillain-Barré syndrome, meningoencephalitis, and cranial nerve palsies. Additionally CHIKV has been associated with rheumatic disorders including rheumatoid arthritis, spondyloarthritis, and undifferentiated polyarthritis. Other serious complications of CHIKV that are rare include myocarditis, ocular disease (uveitis, retinitis), acute renal disease, and severe bulbous lesions. Additionally intrapartum transmission of CHIKV can result in complications for the baby, including neurologic disease, hemorrhagic symptoms, and myocardial disease. Furthermore after maternal CHIKV infection, there have been rare reports of spontaneous abortions.
There is no available vaccine or specific medication for the virus.
Until recently the disease occurred mainly in Africa, Asia and the Indian subcontinent. In recent decades, mosquito vectors of chikungunya have spread to Europe and the Americas. In 2007, disease transmission was reported for the first time in a localized outbreak in north-eastern Italy. In December 2013 the first case was reported in the Caribbean and within 12 months there was an estimated 1 million cases in the region according to the CDC.
Do all mosquitoes spread dengue, Zika and chikungunya?
No. Aedes aegypti is the species of mosquito which is primarily responsible for spreading these diseases. Only female mosquitoes can bite and spread disease – males do not bite. Other Aedes species, such as Aedes albopictus, can also spread disease, but are not very efficient: Aedes aegypti is overwhelmingly the main vector, and it is this species that is responsible for almost all of the dengue, Zika and chikungunya epidemics around the world. Other mosquito species bite humans but do not spread these diseases.
How does the Oxitec mosquito work?
The Oxitec mosquito (also known as OX513A or the Friendly Aedes aegypti) has been engineered to express two genes, a colour marker and the ‘self-limiting’ pest control gene which causes offspring to die. The modified male insects are released to mate with wild pest females, they pass on these two genes, and over 95% of the offspring die before reaching adulthood. The pest population is brought under control with successive releases.
The colour marker
All Oxitec insects and their offspring express a fluorescent protein that can be seen using a special light. In the Oxitec mosquito this can be seen at the larval and pupal stage. The colour marker is an important part of our approach. We can collect larvae from the area of release and use the colour marker to see how many are Oxitec mosquitoes and how many are wild pest mosquitoes. Using this colour marker we can adjust the number of Oxitec mosquitoes we need to release and we can monitor their mating success. We can then increase or decrease the number of mosquitoes released to optimise release efficiency and control of pest Aedes aegypti. The ability to monitor the insects we release and the effect on the target population in real-time is a key feature of this approach.
With the colour marker we can detect our product in the field and monitor its effect closely to offer mosquito control agencies the most targeted release program to control pests.
The ‘self-limiting’ gene
We have introduced a gene into the mosquitoes so that their cells do not function as they should (also known as a ‘self-limiting’ gene because it makes mosquito reproduction a dead end – the offspring do not survive to adulthood). As a result over 95% of the Oxitec mosquitoes die before they become adults and do not live to breed further and the population is reduced. Aedes aegypti do not produce live offspring with other species so the control is species-specific and the genes don’t spread. The released mosquitoes and their offspring die and so the genes also do not persist in the environment. The colour marker and self-limiting genes are non-toxic and non-allergenic, so if animals were bitten by Oxitec mosquitoes, or predators ate Oxitec mosquitoes, it would be the same as getting bitten by or eating wild ones.
For releases, we need to rear mosquitoes effectively and therefore need to turn off the self-limiting system. If the mosquito larvae in the production unit are given small quantities of tetracycline, this acts as an antidote inactivating the self-limiting gene. The antidote is not present in sufficient quantities in the environment to allow inactivation of the self-limiting gene, so offspring of the Oxitec mosquito will not reach adulthood.
Have Oxitec mosquitoes been tested outdoors?
Yes. From 2009, Oxitec and independent collaborators (below) have performed open release tests of Oxitec’s Aedes aegypti (under permit from the appropriate regulators) in several countries, including the Cayman Islands, Malaysia, Panama and Brazil. In each trial Oxitec mosquitoes reduced the local Aedes aegypti population by over 90%. There have been no noted adverse events or effects.
This is a level of control significantly greater than can be achieved with insecticides (typically 30%; Ballenger-Browning & Elder 2009) and one where we consider the environmental impact to be much lighter. Use of Oxitec’s Friendly Aedes aegypti could significantly reduce the volume and incidence of insecticide spraying.
In every case to date, these mosquito trials have been carried out by external institutes or agencies. Oxitec have provided the OX513A strain and technical support. These external evaluators are:
- The Mosquito Research Control Unit (MRCU) in Cayman
- The Institute of Medical Research (IMR) in Malaysia
- Moscamed and University of Sao Paulo in Brazil
- The Gorgas Memorial Institute in PanamaIn each case the institutes above are able to publish or publicise their results which they have done through a combination of publications, conference presentations, or other media.
The WHO Vector Control Advisory Group (VCAG) has specifically recommended planned pilot deployment of Oxitec’s self-limiting mosquitoes under operational conditions.
Why not just use insecticides?
Insecticides are designed to kill insects and they can be very effective, although the development of insecticide resistance can affect their level of control. In the Cayman Islands, Aedes aegypti are resistant to many of the available insecticides, and so new tools are needed to control the mosquitoes.
Another challenge of insecticide control comes from the fact that Aedes aegypti generally only fly short distances (about 200 yards in their lifetime), so they tend to stay in and around human dwellings. Breeding sites around homes can be difficult to find, and even if a public health authority has access to everyone’s homes to spray and treat standing water and containers on a very regular basis, it is still difficult to find and spray every area, and current methods of control are only 30-50% effective at best. This is why there is a pressing need to develop new tools to control this mosquito species. Oxitec’s technology can be used alongside other methods such as insecticide as part of an integrated pest management strategy.
Are Oxitec’s mosquitoes compatible with mosquitoes found in the Cayman Islands?
Yes. Aedes aegypti is a species that originated in North Africa and has been spread around the world by human activities over time. The spread has occurred mainly passively though the movement of freight and goods from one country to another. Consequently it is thought that there are only two groups of Aedes aegypti – one in North Africa and one in the rest of the world. In the Cayman Islands, Aedes aegypti is a non-native species, just as it is in all the Americas. Oxitec mosquitoes are a strain of this same species so they mate successfully. Mating studies of Oxitec’s OX513A strain have been carried out with local Aedes aegypti in many countries, showing they’re able to compete and mate as effectively as local males.
If Aedes aegypti is controlled, could another species like Aedes albopictus move in?
Aedes aegypti is overwhelmingly the major threat in terms of its ability to efficiently spread dengue, Zika and chikungunya, and is the main target of mosquito control programmes aiming to reduce disease risk. Aedes albopictus has the capacity to spread diseases but is relatively inefficient at disease transmission. Aedes aegypti feeds almost exclusively on humans. It lives in and around the home and can take multiple bites to get a blood meal. These features make it highly effective at spreading disease once a person has entered an area carrying the virus. Aedes albopictus, by contrast, is an aggressive biter and will tend to secure its blood meal more easily from a variety of sources. It is less selective about what it bites – so it will bite dogs, birds, etc. which are unaffected and do not act as a source for onward transmission to people. The two species can occupy the same habitat but Aedes aegypti is predominately restricted to areas of human habitation whereas Aedes albopictus is not, and tends to live more in forested areas and underbrush, etc.
In areas of overlap, it is likely there will be an element of competition for breeding sites, but there is no ‘general rule’ as to whether reduction in the number of one species will have an effect on the other. A year-long trial of Oxitec’s Friendly Aedes aegypti in Panama found no evidence that suppressing Aedes aegypti increased numbers of Aedes albopictus. However, as Aedes aegypti is the major threat in terms of disease, even if the numbers of Aedes aegypti fell and Aedes albopictus were seen to rise, the disease threat would still be significantly reduced. Oxitec monitors both species in our field trials and projects, and will do so in this project.
Could you eradicate Aedes aegypti?
A goal of this project is to demonstrate the ability to control the local non-native Aedes aegypti population. Worldwide eradication of a species using this technique, we believe, is not possible or practical, because the mosquito lives around people and has managed to spread around the world by travelling with people as they move around. However, it may be possible to completely eradicate Aedes aegypti from certain limited localities such as an island. This would require strict monitoring at points of entry, to ensure it is not reintroduced.
Is the Oxitec mosquito harmful to humans or animals?
No. The proteins of the introduced genes (colour marker and self-limiting gene) are non-toxic and non-allergenic. The gene that prevents the offspring from surviving to adulthood affects only those mosquitoes that inherit it, and works by causing subtle adjustments to the insect cells, rather than being toxic.
Animals that eat the Friendly Aedes aegypti mosquito will ingest nutritional elements – protein, fat, carbohydrate and others – just as they would from eating any mosquito.
Independent studies as part of the regulatory approval process showed that OX513A had no effect on arthropods/fish in feeding studies compared to non-GM Aedes aegypti, even when they were fed artificially high levels of the GM mosquitoes in their diet – much higher than they would ever eat in the wild.
To date more than 150 million Oxitec mosquitoes have been released worldwide in different countries and there have been no reports of adverse impacts.
Aedes aegypti mosquitoes only mate successfully with their own species. They cannot produce viable offspring with other insects in the wild, not even with another species of mosquito, so they cannot pass the genes on to other species through reproduction.
It is important to note that the Oxitec mosquitoes can only fly about 200 yards and their offspring die, so the effect is extremely localised. Potential effects of Oxitec Friendly mosquitoes only affect the area in which they are released.
We have been asked whether the food chain could be affected if this approach was adopted widely. There are no predators that are reliant on a single mosquito species as their food source, as they will eat a range of insects. Aedes aegypti is a non-native species and there is nothing that depends on it as a food source.
By contrast, the use of insecticides is less discriminating. Insecticide sprays can kill many species and will impact the diversity of insect life and dependent species. By targeting only the key insect species capable of disease transmission we believe that insecticide spraying can be reduced, to help protect biodiversity in the area.
Do you release male and female mosquitoes?
Oxitec releases virtually all males. We sort the males from the females as pupae and have a greater than 99.9% sorting efficiency. Inevitably we will release some females but this is negligible compared to the number of wild females that are already in the environment and could transmit disease. Any Oxitec females released are disease-free as they have been reared in the lab, and it is highly unlikely that they would live long enough to transmit any disease. During the trial in Panama, the number of female Oxitec mosquitoes released was equivalent to less than one per person per year.
What would happen if a person or animal got bitten by an Oxitec mosquito?
The bite of an Oxitec female mosquito is the same as a wild one because the proteins of the two introduced genes (self-limiting gene and colour marker) are not expressed in the mosquito saliva, and so a person bitten by a female mosquito would not be exposed to the introduced proteins. In addition, these proteins are non-toxic and non-allergenic. This information is based on studies by the National Institute of Health, USA, and by Oxitec.
How many mosquitoes will be released?
The number is determined during the project. There are about 1000 mosquitoes released per pot, and the number of pots and release sites is adjusted during the project based on local conditions which change. There would be about 3 releases per week, and the males disperse quickly.
In a previous 6-month long trial in Cayman in 2010, 3.3 million mosquitoes were released, which resulted in more than 90% suppression of the target Aedes aegypti population. In Panama, a similar sized trial worked out to a release of less than 5,000 mosquitoes per person across the entire 6 month trial to achieve suppression of the local Aedes aegypti population by over 90%.
What is the lifespan of Oxitec mosquitoes?
Oxitec mosquitoes tend to live less than one week. Females that have mated an Oxitec male lay eggs which hatch into larvae, but do not develop into adults.
How do you rear mosquitoes if the offspring die?
In a production facility, the larvae are given an antidote in their rearing water from the tetracycline family which inactivates the self-limiting gene. This enables us to rear large numbers of mosquitoes. Those that are released cannot access this antidote in the right quantities and/or at the right time and so the self-limiting gene works effectively, as demonstrated by field trials in different countries.
Has the Oxitec mosquito been independently evaluated?
Yes. Independent collaborators around the world have conducted extensive testing on Oxitec’s OX513A mosquitoes since the strain was first developed in 2002. The WHO Vector Control Advisory Group (VCAG) has also recommended planned pilot deployment of Oxitec’s self-limiting mosquitoes under operational conditions.
Oxitec insects (mosquitoes and other species) have been tested by independent laboratories including the Institute Pasteur in Paris, the Gorgas Memorial Institute in Panama, the Institute for Medical Research in Malaysia, the University of Colorado (USA) and the United States University of Health Sciences (USUHS). The Centre for Medical and Veterinary Entomology (CMAVE) at Gainesville, FL has also tested our mosquitoes in contained outdoor cage trials.
Outdoor trials, have been carried out by the Mosquito Research and Control Unit Cayman, the Gorgas Memorial Institute in Panama, the Institute for Medical Research in Malaysia, and Moscamed and the University of São Paulo in Brazil. In each of the outdoor suppression trials, the wild population of Aedes aegypti in the areas has been reduced by over 90%.
Who is regulating the project in the Cayman Islands?
Two parties are regulating the project: the Department of Agriculture for the importation of the Friendly Aedes aegypti, and the National Conservation Council for the releases of the mosquitoes.
Where can I get more information?
Oxitec scientists publish data in peer reviewed journals. Information pertaining to our products, and regulatory reviews of their safety is available on public websites. Here’s a link to our publications: /category/publications/.