GM mosquitoes can kill off dengue fever threat
by Hadyn Parry
Mosquito-borne diseases represent a continuing and, in some cases, a growing threat to human health. Relatively unknown in Europe, except to travellers, Dengue fever is the most rapidly spreading mosquito-borne viral disease with up to 100 million cases per year. The speed of growth of the disease is alarming. Despite the existence of pesticides and other interventions, dengue cases have gone up 30-fold in the last 50 years. Director General of the World Health Organisation Dr Margaret Chan sums it up neatly: "Today, dengue ranks as the most important mosquito-borne viral disease in the world."
Everywhere, the human and economic costs are staggering." Within Oxitec, we are developing a new approach to control the mosquitoes that spread dengue. Recently, the results of the first outdoor trials were published in the Nature Biotechnology journal. The outcome of the trials conducted by the Cayman mosquito research and control unit was that we were able to demonstrate an 80 per cent reduction in the target mosquito population. Similar results have subsequently been achieved in Brazilian trials. So how can we summarise the challenge and our approach?
Currently, there is no vaccine or medication specifically for dengue fever. Development of an effective vaccine for this disease represents a particularly difficult challenge and experts say mosquito control will still be needed even if a vaccine were available. Controlling the disease-carrying mosquito is, therefore, critical in reducing the incidence of the disease. The dramatic increase in the number of new dengue cases is largely due to the biology of the mosquito Aedes aegypti, the insect that transmits this disease. Originating from Africa, this mosquito has spread around the world in recent years; globalisation and urbanisation allowing it to spread and establish in tropical and sub-tropical areas.
It can now be found in cities throughout the United States such as Houston, New Orleans and Miami - and, in the southern hemisphere, as far south as Buenos Aires. A warming global climate creates ever more geographic spread. This mosquito lives in and around the home, and has such a multitude of breeding sites that finding and treating the majority of these in a town or city becomes an impossible task. Rich countries and poor countries suffer the same challenge. High living standards and big budgets are no defence.
Giovanini Coelho, coordinator for the Brazilian national dengue programme says "people are dying here and this mosquito is resistant to many insecticides - we really do need something better than what we have". The WHO agrees and while promoting best practice with existing methods, states that "innovative vector control tools are badly needed". One of the new tools identified by WHO as having potential in this area is the use of genetically modified mosquitoes.
Oxitec is a leading exponent of this approach and is working with academics, regulatory bodies and vector control teams around the world in a careful step by step process. We use a strategy that is based on the well proven sterile insect technique or SIT. However, instead of using radiation to cause sufficient mutations to induce a sterility effect in an insect, we use a more targeted approach through a gene that causes the death of the offspring. With our approach male insects are released, - males do not bite or transmit disease - which mate with wild females and pass on the gene to the offspring which subsequently die.
In effect, this is birth control for insects. If enough of these 'sterile' insects are released over a sufficient period, then the mosquito population declines. Unlike a chemical pesticide that kills most insects it touches regardless of whether they are harmful or beneficial, our approach specifically targets the mosquito that spreads disease. The objective is to dramatically reduce the dengue mosquito population in an area while leaving other species untouched. Interestingly, the outcome of this use of genetic engineering in insects is very different to that practiced in crops.
Within a GM crop, a gene will be incorporated to provide an inherent competitive advantage - say resistance to a particular herbicide - the gene will pass from one generation to another and plants will hybridise; or cross with other plant species. But with a mosquito the genetic effect is a 'dead end'. There is a huge competitive disadvantage – death - while carrying the benefit of controlling the population of mosquitoes that transmit disease to humans. Over many years, we and independent groups have conducted laboratory tests on our lead mosquito strain 'OX513A'.
In 2009, following regulatory approval, open field trials were performed for the first time in the Cayman Islands. This trial proved the capability of the males to compete with their wild counterparts and mate with wild females. The following year, a further trial was conducted but this time the objective was to significantly reduce the Aedes aegypti population compared to a neighbouring untreated area. Releases took place on a 16-hectare site when mosquito numbers were at their seasonal high. About 3.3 million males were released over a 23 week period.
The results showed that the target insect population - Aedes aegypti - was reduced by more than 80 per cent compared to the untreated control site. In 2011 and 2012, further trials have been conducted in Brazil - in suburbs close to the city of Juazeiro with close involvement of the local community and other stakeholders. These trials have confirmed the Cayman results with similar reductions in the dengue mosquito population. We are working with governments around the world on further evaluation of this approach but from these results we potentially have a new way to help control mosquitoes that spread disease.
Hadyn Parry is chief executive of science firm Oxitec, in the United Kingdom
We know enough to distinguish between high-risk and low-risk genetic modifications, and it is now time to apply that knowledge in practice, write Sven Ove Hansson and Martin Weih
Which experts say mosquito control will still be needed even if a vaccine were available and on what basis, and why would your 'technique' still be needed if there was a vaccine? How will you test to see if your idea actually reduces the incidence of dengue fever.
Paul Latham - Walsall
I see Oxitec cannot/will not answer my questions. I wonder why?
Paul Latham - Walsall
Paul - sorry not to respond earlier. To take your points in order:
Experts that would argue that mosquito control will still be needed even if a dengue vaccine were available would include people such as Dr Raman Velayudhan of WHO and Dr Reiter of Institut Pasteur. Sanofi, the company that are in the lead in developing a dengue vaccine also argue for ''stable vector control and treatment programs' as a critical element of any future vaccine introduction. The reason why this view is widely held is for various reasons. Firstly, Aedes aegypti transmit dengue but also transmit other diseases such as yellow fever and chikungunya. Secondly even the best vaccines rarely provide complete protection. For example, the Sanofi vaccine candidate in Phase II trials in Thailand provided reasonably good (but not total) protection against 3 of the 4 forms of dengue virus but did not protect against type 2 which was the main circulating form in the area. So results are quite encouraging but the data is not there yet to suggest that the vaccine is a complete answer. Further, a vaccine is a personal form of protection - whereas mosquito control is an area wide one. Big vaccination programmes funded by government in areas where dengue is prevalent are actually not that common (due to the expense) - so some governments may indeed vaccinate everyone, but I fear that in reality there will be many situations where those that can afford the vaccine will buy it so less expensive mosquito control is the main element of whole population protection. Another point here is that where huge vaccination campaigns are carried out this is often done by cohort. This means that for example children between the age of x-y are vaccinated in year one, next year a new cohort is vaccinated so one gradually covers a large proportion of the population. While this is going on background protection from mosquito control is helpful for those that have not yet received the vaccine - and indeed for those too young or too old to receive it.
Coming back to our approach - dengue in many countries is a reportable illness and monitoring is possible through health centres. Such monitoring would always be carried out by health officials as all parties have an interest in seeing a real decline in dengue cases. In some countries the budget for mosquito control is within Health and in others Environment. But despite the budget holder its generally the case for whatever approach used, ministers will want to see the effect on health to make sure their budget is being spent in the most cost effective manner.
Apologies for the long answer but I hope that is helpful
Hadyn Parry - Oxitec
Dear Hadyn,
Please do not apologise for the length of your answer, in fact I wish it were longer and that you had properly answered the last 2 of my answers.
I will come back to you, if I may, on the answer that you have given so far, but please:
1. Why would your 'technique' still be needed if there was a vaccine, there are many other forms of vector control.
2. How will you (Oxitec) test to see if your idea actually reduces the incidence of dengue fever?
Dear Paul
The reason why we believe our approach merits consideration is because other forms of vector control are not proving sufficient (as recognised by WHO). Even though we have had these other forms of vector control for many years the incidence of dengue and geography of spread are increasing at an alarming rate. Even countries like Singapore, Malaysia, Brazil etc who employ many people and very intense vector control programmes continue to have a high level of dengue incidence. The issue here largely relates to the biology of the insect itself. Aedes aegypti is highly adapted to the human urban environment. It lays eggs around clear water so any tree trunk flowerpot, birdbath, used tyre, blocked drainpipe etc all become ideal breeding sites and treating each and every one of these with chemicals in an urban environment becomes an impossible task. Fogging or space spraying with chemicals can kill flying insects but not eggs or larvae and getting access to properties can be an issue. Also insecticide resistance is a major issue. Possibly the best form of vector control is removal of breeding sites and hence community engagement and education are critical. A good example of this is Malaysia where the governement launched the '10 minute' campaign which asked people to spend 10 minutes a day to go round their homes every day and remove any standing water. This is in addition to government fogging/larviciding programmes. So you are right there are many forms of vector control - but they are not working well with this particular mosquito. How will we test whether our approach reduces dengue fever? - actually our approach is targetting a dramatic reduction in the mosquito that spreads dengue. This virus is only spread by mosquito vectors - overwhelmingly aedes aegytpi but albopictus can spread it too (and we have an Oxitec version here as well if needed). Dengue is not passed from human to human and there are no other vectors - just the mosquito. So if you eliminate the vector or drive it down to minimal levels then you reduce the transmission. The title of the article 'GM mosquitoes can kill off dengue fever threat' is a piece of journalistic license by the website - I actually entitled the article 'using GM mosquitoes in the battle against dengue fever'. But the point remains that the objective is to take the aedes aegypti population number in an area to below the level required for transmission. So our first focus, and indeed that of any vector control approach whether chemical, biologcal or other, is controlling the vector population. We can monitor that quite easily using devices called ovitraps (for larvae) and we also use BG sentinels for adults. Dengue incidence should then fall as a consequence and this can be established by disease surveillance in the area. But good epidemiological data will require scale and time in order to get good statistics. So to be clear, at the scale of current trials (towns of a few thousand people) the output measure is the fall in the number of the vector population. As we go up in scale then epidemiological data becomes more and more possible and the data more robust - but that is a step on from where we are now. I hope that answers your query.
Hadyn Parry - Oxitec
