Breakthrough in dengue battle brings new hope

By Fathima Riznaz Hafi

A ground-breaking discovery enabling the elimination of the dengue-causing vector by means of releasing ‘self-limiting mosquitoes’ brings new hope to the global dengue dilemma. 

The technique involves releasing genetically sterile male mosquitoes to mate with wild female ‘Aedes aegypti’ mosquitoes, after which she lays eggs which do not pass the pupa stage, thereby suppressing the production of dengue-carrying mosquitoes.

This was revealed by Oxitec Ltd. Field Manager Dr. Kevin Gorman in an exclusive interview with the Daily FT. 

“Only female mosquitoes bite; we’ve developed a technology where we can modify a strain of mosquitoes, to carry two additional genes. One gene is a self-limiting gene – this means that the progeny won’t survive. The other is a fluorescent marker which allows us to track each individual. Then we mechanically sex mosquitoes before we release them – and release only the males; the males are sterile and then they seek out females.

“We release them regularly at pre-determined points to make sure we have very good coverage of the area and they seek out the females in all those little nooks and crannies that you can’t get to with an insecticide – right into people’s houses, into their water tanks; everywhere a female mosquito goes a male can find them and mate with them. Mosquitoes generally only mate once and once they’re mated without males they don’t produce any progeny and quite quickly if we release often enough we get a suppression of the population. 

“We tend to get suppression in about six to nine months so over a given area where we’re releasing we get around 80 to 100% efficacy over that period. So it works really well; in all the completed field trials we’ve had over 90% efficacy so far,” Dr. Gorman said. 

“This is a switchable gene; in the presence of an antibiotic the gene is switched off and so we rear them in a laboratory in the presence of an antibiotic – that just means we put an antibiotic in the water that we put the mosquitoes in – that way we can rear them in mass numbers and when we release them they’re not exposed to the antibiotic anymore and all the progeny die; the gene becomes switched on in that sense. 

“As with all sterile males when we release them for sterile insect pest control – the males mate with the females and in this case they produce eggs but the eggs are inviable and they die before adulthood.”

Eco-friendly

This technique is environmentally benign since anything other than the target pest is not directly affected because these mosquitoes only breed with their own species which means they are exquisitely species-specific – it only affects directly Aedes aegypti. So it doesn’t affect birds, butterflies or even other mosquito species directly. 

Only non-biting male mosquitoes are released, eliminating disease risk. Released mosquitoes will not establish in the environment due to lack of ‘tetracycline’ in the environment. 

“Clearly there’s an ecological niche which can develop when you take away a pest as is the case when you try and control any pest, such as rats but that ecological hole behind this technology is the smallest it could be because it’s just a single species.” 

The ecological bonus is that it doesn’t leave a footprint because all the mosquitoes are destined to die within just a couple of weeks of us releasing the mosquitoes – they’re all gone. They are specially engineered so their offspring die before they can reproduce.This keeps the pest population under control.

This method alsocuts the use of insecticides. Insecticides are currently used to reduce Aedes aegypti numbers, but can affect other vulnerable species. Controlling the non-native Aedes aegypti with chemicals is difficult because they are developing resistance to many insecticides. The use of new additional approaches may help control the mosquitoes and reduce reliance on insecticide.

“So if in the future a better, newer technology comes along there will be no footprint left from this technology in the meantime; so we’re not changing the population or replacing it; we’re simply suppressing it with a very benign tool.”

International Conference on Dengue and Dengue Haemorrhagic Fever 2016

Dr. Gorman, representing Oxitec Ltd., was in Sri Lanka recently to join fellow researchers, scholars, scientists and clinicians from around the world, who had gathered here to attend an international conference where they shared latest findings in dengue-related research and discussed its prevention and control strategies. The conference is an annual event that takes place in a different country each year, this time being Sri Lanka. 

The ‘International Conference on Dengue and Dengue Haemorrhagic Fever 2016’, held in BMICH under the theme ‘Dengue: To Stem the Tide’, was organised by the Epidemiology Unit, Ministry of Health, Sri Lanka in collaboration with the Centre for Global Health Research at the University of Umeå, Sweden with its14 partners from Europe, Asia and South America and the Partnership for Dengue Control (PDC) of the Fondation Mérieux (FMx), France.

Plans for Sri Lanka

Local company Omega Global is a partner for Oxitec (technology owner) and GBIT (technology developer for region), aiming to introduce the Oxitec sterile mosquitoes technology to Sri Lanka. Omega Global Managing Director Manik Suriyaaratchi has taken up the initiative on CSR grounds to facilitate the proposed regulatory process among the Ministry of Health (Epidemiology Unit – National Dengue Control Unit), Ministry of Environment – Bio diversity/safety along with proposed joint research collaboration with University of Sri Jayewardenepura (Centre of Dengue Research – Dr. Neelika Malavige) under the guidance and audit supervision of the Ministry of Health.

The proposed project leads would jointly be the National Dengue Control Unit (NDCU) of the Sri Lankan Ministry of Health (MoH) and the University of Sri Jayewardenepura. The technical expertise and sponsorship will be provided jointly by Oxitec, GBIT and local partner Omega Global. Omega Global will play a key role in community engagement and awareness of 21st century environment friendly vector control – Oxitec self-limiting mosquito technique to be introduced to Sri Lanka.

Oxitec Ltd.’s solution is important to Sri Lanka because of its potential to prevent dengue and chikungunya cases in the country, via unprecedented levels of control of the principal mosquito vector Aedes aegypti. 

“Sri Lanka has suffered from dengue quite heavily so we’re working with the Ministry of Health primarily to try and bring this technology to Sri Lanka. The overall intention would be to try and mitigate against dengue, chikungunya and also for zika and other viruses should they appear in the future. There’s a process to go through – a regulatory process, an evaluation process on the scientific side. So we would start with some laboratory studies, we would then go for small scale open release study and then providing the ministry was happy and wanted to proceed, then that would hopefully progress to widen the implementation where we can actually make some real headway into combating the disease,” said Dr. Gorman. 

Oxitec’s decade of research

Oxitec Ltd. is a British company, founded in 2002 as a spin-off from the University of Oxford, to develop and deploy self-limiting gene technology in the Aedes aegypti mosquito and other insect species. Oxford University remains a part-owner of Oxitec and deploys self-limiting gene technology in the Aedes aegyptimosquito and other insect species. 

Oxitec Ltd. is a pioneer in controlling insects that spread disease and damage crops. Through world class science it has developed this innovative new solution to controlling harmful insect pests. Its solution can help governments and communities around the world keep people healthy and increase food production, and to do so in a way which is sustainable, environmentally friendly and cost effective.

“Oxitec Ltd. has been carrying out research on the ‘self limiting mosquitoes’ since 2002, for well over 10 years nowand it was 2002 when this strain was first developed; it’s been 13 years in the making,” said Dr. Gorman.

“Five different field trials have been completed in four different countries: Kenya, Malaysia, Brazil and Panama where we’ve released into the environment but we’ve been doing laboratory studies in many countries over many more years and we’ve been releasing in the field since 2010 for actual suppression of pest population; we’ve now released over 150 million mosquitoes into the environment with not one effect on either humans or the environment.”

He added that the sterile insect technique has been around for decades, since the 1950s and has proved effective on a continental scale and this is just a very convenient way of improving the sterile insect technique to the point where you can apply it to the mosquito; previously they were rather too delicate to take the amount of radiation required to make them sterile. 

The Oxitec solution improves upon the ‘Sterile Insect Technique’ (SIT) that for over 50 years has been using radiation to sterilise male insects to control pests. Oxitec uses genetic modification rather than radiation so the insects are more effective at finding and mating with wild females. 

“Now with this technology we can actually apply sterile insect technique to mosquitoes. There’s no toxin involved, it’s a benign protein which prevents the cells from functioning.There’s no toxin and yet it performs a very valuable function of making them self-limiting.The agricultural pest management has been benefitting for many years. So it’s bringing public health pest control into the modern age.”

Costs involved

This method is cost-effective compared to current control approaches. “The costs vary a lot depending on where you are in the world. It’s different to a bottle of insecticide which costs a certain amount to produce. In this case it’s more of a solution because pest levels vary remarkably in different places – not only pest levels, its service levels too because it requires a lot of employment. 

“It’s not just about the mosquitoes that we produce – it’s about actually deploying these mosquitoes and monitoring the effects. So it’s more of a complete solution and it’s more affected by costs of the local staff and factories producing the insects. But to put a long story short on a commercial basis we are aiming to bring this solution somewhere in the region of $5-8 per person per year.”

‘Dengue Tool’ project

Joining Dr. Gorman at the interview was Institute Pasteur, France Professor of Medical Entomology Professor Paul Reiter, who was also one of the speakers at the conference,sharing his expertise with the Epidemiology Unit – Ministry of Health in Sri Lanka based onthe ‘Dengue Tool’ project.

Prof. Reiter is a member of the World Health Organization Expert Advisory Committee on Vector Biology and Control and was an employee of the Centre for Disease Control (Dengue Branch) for 22 years. He is a specialist in the natural history, epidemiology and control of mosquito-borne diseasesuch as dengue fever, West Nile Virus and malaria. 

Sharing his views at the interview, the professor said, “I’ve been openly enthusiastic about this new concept because it’s non-polluting and because I can see it as something that is highly specific.” He frowns upon the use of insecticides. “One of the methods that everyone knows about is to use insecticides. I don’t like insecticides. I don’t like them because I don’t like to think of my grandchildren as living in a house full of insecticides. In any case insecticides have a very limited life in terms of how long you can use them before they become resistant to insecticide.”

No need of red flag

“Dengue is a horrible problem in many tropical countries; I’ve had it so I know it’s not very pleasant and now we’ve got Zika – a very horrific, science-fiction type of thing. So we’ve got to get our act together and do something. 

“I don’t know enough about Sri Lanka but this is in some ways very frustrating;when many people hear ‘genetically modified’ it raises a red flag! People get scared. I wish there was a way of saying something other than genetically modified but it is not a scary thing – on the contrary, not to use insecticide is a very great plus and this is something so incredibly specific; not only do the males mate with females and make them monogamous but it’s almost impossible for a male to mate with a female of different species. They are incompatible with any other species and are highly specific. It’s like holding a gun that only points at one target. It’s reassuring. 

“The trouble is people don’t understand enough about what it means to do genetic modification. So they’re scared – understandably scared; and then of course there are people who would like to undermine the whole concept by making people scared. 

“I’ve been working in the States a lot and for years they have been making genetically modified soya bean, corn and other crops and so far there’s no evidence that the American people are being poisoned by these things. 

“Once people get over the fear of modified organisms and once they discover the advantageous aspects, then I think we’re going to see some impact on diseases like zika, dengue and yellow fever. And zika has literally come out of the woodworks – God knows where we’re going to be in a year’s time with zika. So we’ve got to step up.”

Omega Global Managing Director Manik Suriyaaratchi has sought Professor Reiter’s independent expertise/opinion and guidance over the proposed Oxitec self-limiting male mosquito project for Sri Lanka.

With Oxitec providing the technological expertise and Prof. Reiter providing his independent guidance, Omega Global as the facilitator, is optimistic that we are approaching a solution to the country’s long-standing terror – the dengue-causing vector.