Oxitec Newsletter November 2012

October 31, 2012

NEWSLETTER November 2012

Brazil update: Community support

Following success in two settlements in the Brazilian state of Juazeiro, control of the dengue mosquito Aedes aegypti, by Oxitec in partnership with Brazil’s Moscamed, is expanding to new areas. Step-by-step trials in a neighbourhood of Itaberaba have resulted in effective reduction of the dengue mosquito population. Oxitec’s technical manager, biologist Daniel Carvalho, stated that, in the communities that received Oxitec ‘sterile’ male mosquitoes, the wild populations was reduced by an estimated 84%. Similar success has followed in the nearby village of Mandaracu, and these data are currently being prepared for peer-review publication.

Following this success, the state government has approved the expansion of the technology to the city of Jacobina, northwest of Bahia, which has suffered a high number of dengue cases so far this year. According to Danilo Carvalho, “In the case of the city of Jacobina, the project faces a big challenge because the objective is to perform releases throughout the urban area to reduce the mosquito population in a large area that suffers from dengue “. To inform local students about this work, seven technicians from Moscamed undertook a lecture circuit in municipal schools in August.

Between the 20th and 24th of August, health officials in Jacobina accompanied the team on home visits to explaining the project and to encourage community participation. “We developed a plan for publicising the project with home visits, lectures in city schools and communication through local media outlets, so that the population is aware of the stages of the project and will be happy to open their homes to the installation of monitoring traps,” explained technical director Rodrigo Viana.

With the slogan, “It makes a difference,” project staff taught Jacobina school children and teenagers the goals of the production and release of the sterile mosquitoes. “We talked about the potential of the mosquito in reducing dengue cases. We also reported that the mosquitoes released in communities by our staff do not bite because they are only males.” recalls Carvalho. Altogether, 11 schools and around 10,000 students heard lectures about the project.

Hand-in-hand with the ongoing success of Oxitec mosquitoes in controlling urban populations of dengue-transmitting mosquitoes, this project is breaking new ground in conducting such extensive engagement with local people. We see both of these aspects of our work as equally important for the long-term success of our work in Brazil.

Programme staff releasing Oxitec male mosquitoes in Juazeiro State


Oxitec olive fly and Mediterranean fruit fly strains ready for national evaluation

Mating Medfly

Two of Oxitec’s agricultural product strains have now completed the first phase of developmental testing and the company is now seeking to work with third parties to evaluate the strains in different countries under appropriate regulatory oversight.

The olive fly (Bactrocera oleae) is the single major pest of olives, causing major crop damage and economic loss and is not well controlled by current methods. Insecticide resistance and the withdrawal of older, more environmentally unacceptable, insecticides are currently exacerbating the problem, increasing both crop losses and the cost of control.

The Mediterranean fruit fly (‘medfly’, Ceratitis capitata) is a global pest and attacks over 300 types of fruits, vegetables and nuts worldwide. Current control measures include insecticides, mass trapping and lures. In some countries, such as the USA, the radiation-based sterile insect technique (SIT) has been used successfully to reduce infestations to near zero levels. Oxitec’s RIDL® technology has been designed to improve upon the scope, cost efficiency and flexibility of SIT across a wide range of insect species.

In many insect species, including olive fly and medfly, the female causes damage to the crop through depositing their eggs into the fruit. Oxitec’s solution harnesses advanced genetics to be able to release ‘sterile’ male insects that mate with wild females of the same species. The genetic modification prevents females in the next generation from surviving to adulthood and hence reproducing. Successive releases of these ‘sterile’ males, depending on the control strategy adopted, would result in either the prevention of a seasonal build-up of the insect pest or an area-wide target pest population decline.

Oxitec have now completed a suite of laboratory based tests of its RIDL medfly OX3864A and olive fly OX3097D product strains. Both strains successfully met internal target profiles including genetic sex specificity, bright dominant fluorescent marking and genetic sterility from the female-specific transgene. Laboratory testing under simulated mass-rearing conditions shows that the transgenes have no significant negative effects on productivity which should indicate an efficient cost of production. Furthermore, from greenhouse-based sexual competition tests Oxitec males are equally as competitive as wild-type males. Studies also indicate similar behaviours of the Oxitec males compared to the wild-type males. Both of the product strains have been shown in contained trials to be able to eliminate an established pest target population.

The next stage of development for these strains will depend upon potential use within a country, the collaborating partner, stakeholder engagement and appropriate regulatory processes but would include a series of step-by-step trials to establish efficacy, safety and environmental impact.


Female olive fly ovipositing – laying an egg – into an olive

Mosquito-borne diseases in Europe

Temperature and rainfall patterns in Europe are expected to change significantly over the next century. Parts of the warm and dry Mediterranean are expected to become more so, and northern European areas also expected to warm, but become wetter (Ciscar et al. 2009, PESETA Research Project). These changes in climate will result in changing habitats for all flora and fauna, including disease-vectoring mosquitoes, such as the main vectors for dengue virus and chikungunya, Aedes aegypti and Aedes albopictus.

The ranges of Ae. aegypti and Ae. albopictus, which are invasive in Europe, are most often limited here by temperature as much of the region is suitably wet to support numerous mosquito species. Ae. albopictus already has a strong foothold in the Mediterranean, having colonised Albania as early as the 1970s, and since then spread into Spain, Greece, southern France, Italy and the Baltic States. Given the already mild climates of these areas, the mosquito’s presence does not come as a great surprise, but its more recent migration into Switzerland is a warning sign that the northward march of Ae. albopictus has already begun. The species is known for its adaptability, and has been able to occupy many areas previously thought unsuitable.

Current range of Aedes albopictus in Europe shown in red. ECDC 2012/VBORNET

Ae. aegypti seems more dependent on certain environmental conditions to assist its spread, but having already established populations around the Black Sea, climate change may soon mean more suitable habitats are available in the Mediterranean. Moreover, urban areas generally provide sufficient breeding sites for this mosquito (small bodies of water) to support a population, even in very hot, arid environments.

Scientists have already started to explore mosquito migrations and range expansion. Models are used to extrapolate future range expansion of Ae. albopictus, based on climate predictions. The data show that the habitable range of Ae. albopictus in Europe is likely to expand in the coming decades (Fischer et al. 2011 Global & Planetary Change). Most models agree that Ae. albopictus could be making its home as far north as southern England by the end of the 21st century!

Increasing globalisation and ease of travel, combined with the expanding ranges of the invasive Aedes species will mean that travellers contracting diseases abroad will find vectors ready to transmit the diseases on the ground in Europe. Already, an imported case of chikungunya in Italy in 2007 turned into a localised epidemic affecting over 200 people in the Emiglia-Romania region. Outbreaks of dengue and chikungunya are likely to become more frequent, and ways to manage the mosquito vectors of these diseases are currently our most potent tools in the fight against them.

Aedes albopictus resting on water. Jake Galson 2012


Mosquitoes on the move

Adult mosquitoes are not able to fly great distances. They tend to remain in a location with favourable conditions and hosts on which to feed.  Without humans to transport them to new locations mosquito species would be highly localised. In fact this was largely the case until the advent of long-distance human travel. In the Hawaiian Islands, for example, mosquitoes were reportedly not present until the arrival of Captain Cook’s ships in 1778-1779 (Kirkaldy 1907 Proc Hawaiian Ent Soc). As human travel has increased, so has the spread of disease vector mosquitoes and their respective maladies. So it’s an unpleasant fact that whilst diseases spread by mosquitoes are on the increase globally, we only have ourselves to blame.

The tiger mosquito, Aedes albopictus, which is a vector for dengue and chikungunya viruses, is perhaps best-known for adaptive travel by piggy-backing on used tyres shipped around the world. The eggs of Aedes mosquitoes are able to survive and lay dormant in a dessicated state, so are able to survive and travel even in the absence of water. Goods and freight awaiting shipment at a dock will provide plenty of breeding site opportunities. When such eggs arrive in a new location, all it takes is a rain shower to spark the eggs’ development into larvae, pupae and then adults.

The past few decades have seen a massive increase in the number of people travelling to tropical regions, raising the risk of regular influx of vector species with frequent long-haul flights. In 1994, for example, 2000-5000 Anopheline mosquitoes (the type that transmits malaria) were introduced into Roissy airport in France over 3 weeks (Gratz et al. 2000 Bull World Health Organ), leading to 6 cases of so-called ‘airport malaria’ in Roissy. Repeated such cases of airport malaria have driven the use of insecticide spraying in aeroplanes prior to flights from malaria-endemic countries, although this is by no means universally implemented or completely effective.

With disease vectors travelling the globe, the associated nightmare for public health authorities is the arrival of the disease agent. The accompanying article, ‘RIDL®: potential to help combat Malaria and West Nile virus‘,discusses the relatively recent arrival of West Nile virus – originally from North-Eastern Africa, in the Americas and its subsequent impact on human health. Similarly, dengue has followed Aedes mosquitoes as they have expanded their ranges, and according to the World Health Organisation this virus now poses a risk for around half of the world’s population.

Unlike cases of airport malaria, dengue vector mosquitoes have tended to quickly establish upon arrival, and they can then be very difficult to remove. Once the insect vector is established then the conditions exist for an outbreak once the virus is introduced. It is largely a matter of time before disease follows; the greater the number and frequency of visitors from dengue endemic countries, the greater the likelihood of an epidemic. For example the dengue vector Aedes aegypti was first found on the Atlantic Island of Madeira in 2005, and has since become well-established. With the vector mosquito present, a recent outbreak of dengue fever has confirmed the fears of Portuguese public health authorities. As of 10th October, 18 confirmed cases and 191 probable cases have been reported on the island. Worse happened in the Indian Ocean island of La Réunion in 2005-2006, where a third of the population were affected by chikungunya. Such outbreaks indicate the threat that the presence of the vector poses, and it justifies efforts to control these mosquito species even when the disease agent is not yet present.

Larvae of Aedes albopictus, which spreads dengue and chikungunya (Photo, Jake Galson 2012)


RIDL®: potential to help combat Malaria and West Nile virus

For public health, we have developed product strains for control of the principal dengue vector mosquito, Aedes aegypti, and for Aedes albopictus, which also transmits dengue and another viral disease, chikungunya. With malaria and other mosquito-borne diseases causing fatalities across the world, could RIDL provide a solution by targeting the mosquito vectors?

Malaria is the world’s most significant vector-borne disease: around half of the world’s population are at risk of infection. Despite the huge focus of philanthropic funding over the last decades malaria still remains a major killer. According to the World Health Organisation, there were around 216 million malaria cases in 2010, and an estimated 655,000 deaths. Malaria is transmitted by mosquitoes in the genus Anopheles. The picture for disease transmission is somewhat complicated because malaria can be transmitted by several Anopheles species, many with overlapping geographic ranges. RIDL is species-specific, which is attractive from an environmental perspective, but makes control of multiple pest species in one area more challenging. However, a one-strain or two strain approach would work well in locations with one or two main vector species. While a potential requirement for additional strains for multiple species may add to the required malaria vector control activities, it may still represent a much-needed effective control tool where none exists. Even though a multi-strain approach may be more challenging to implement, RIDL could make a huge impact with the added benefit that the environmental impact is still likely to be very low Oxitec staff have experience in working with Anopheles species and hope to commence a RIDL programme in the future.

The potential of mosquitoes to bring new diseases to an area is highlighted by the recent outbreak of West Nile Virus (WNV) in the USA. So far this year there has been 219 deaths from a virus that was unknown in the USA until 1999.WNV was first described in Uganda in 1937 but has since spread much further. WNV’s natural range is Africa, Europe and the Middle East, but is now prevalent in the USA, Canada and other countries in the Americas. In 2012, there have been reports in 47 US states, with 75% coming from just five: Texas, Mississippi, Louisiana, South Dakota and Oklahoma. In most cases humans infected with the virus are not aware they have it. About 20% infected develop symptoms similar to a cold or flu but about 1 in 150 develop severe symptoms that can include high fever stupor, disorientation and paralysis. The Centre for Disease Control has confirmed 4725 cases nationwide in the USA this year (to October 25th). Like malaria, it is spread by multiple species, this time mosquitoes of the genus Culex. The natural hosts for the virus are wild birds and the disease kills thousands every year but humans are also affected.  The challenge of tackling a multiple-species problem is similar to that described in malaria, but control would have the added benefit of preventing the deaths of thousands of birds. Because Culex mosquitoes don’t tend to travel far in their lifetime – on average, around 0.2-2 km (Ciota & Drummond 2012 J Med Entomology; Lapointe 2008 J Med Entomology;  – focussed efforts against the chief vector species in hotspots for WNV may provide effective seasonal protection in urban or semi-urban areas.

The mosquitoes that spread Malaria and West Nile Virus are two potential targets for RIDL technology. Clearly, each problem presents its own challenges, but with vector control agencies still struggling to control mosquitoes with conventional chemical approaches, RIDL merit serious consideration.

Public information image for West Nile virus, Utah State, USA

In the news…

For those who would like to follow Oxitec on a more frequent basis we have both Facebook and Twitter accounts. You can follow us on Twitter, on @Oxitec, and just look for us as Oxitec on Facebook. Even if you are not a regular Twitter or Facebook user please direct others to our streams.

We have also added a new section to our website recently; Technical Releases. In common with many, we find that often it takes a long time to publish the results of specific studies but pre-publication releases of a study result can often compromise the publication itself. So we have included this section which provides a short snapshot of some of the studies performed or waiting for publication so that you can keep up to date with the direction of our work. For publication themselves please look at /category/publications/

Last month, Oxitec’s project in Brazil received recognition as Oxitec were one of a few companies to accompany the UK Prime Minister, David Cameron, on a commercial mission to Brazil. /press-release-oxitec-joins-prime-minister-david-cameron-on-brazil-trade-mission-as-exemplar-uk-export-business-2/ Dengue is a prime health concern in Brazil and the Government is determined to reduce disease incidence. Brazil’s President, Dilma Rousseff, highlighted biotechnology as a key area of cooperation between the UK and Brazil.

Oxitec was also invited by the Gates Foundation to attend and present at a dengue meeting within the broader framework of the Asia Pacific Development Summit in Jakarta in September. Much of the focus of discussion was bringing the private and public sectors together to help meet the Millennium Development Goals. The three-day high-level event was hosted by the Government of Indonesia, the Bill & Melinda Gates Foundation and the ASEAN (Association of Southeast Asian Nations) Foundation, and brought together over 300 health officials, private sector leaders, international organisations, non-government organisations, and academic experts to collectively advance health priorities across the region.

Amongst the more recent articles on Oxitec, Clive Cookson in the Financial Times highlighted the potential of our approach in combating dengue ‘Genetic modification could be a powerful weapon against the mosquitoes that transmit dengue’. http://www.ft.com/cms/s/0/b46f5f06-0bdc-11e2-8e06-00144feabdc0.html#axzz2AO0xPyXO Free registration is required to view the article. Finally, and on a broader front, John Marshall considers the remarkable potential of genetic engineering and using it for the public good in his article ‘If Mother Teresa was a Genetic Engineer’ http://www.its.caltech.edu/~johnmm/MotherTeresaGeneticEngineerTEDx.pdf

Model of the dengue mosquito, Aedes aegypti, built by Oxitec’s head of mosquito research, Derric Nimmo