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Promising new tools to fight Aedes mosquitoes Two new tools for suppressing populations have been recommended for pilot testing. Carefully designed trials will be needed to see whether they actually reduce disease as well. Andréia Azevedo Soares reports.

“When we heard that scientists were going goes to plan, most mosquitoes in Tubia- ect leader at Oswaldo Cruz Foundation to release mosquitoes in Tubiacanga a few canga and Jurujuba, another neighbour- who coordinates the Brazilian part of years ago, we were afraid. ‘Why here?’ we hood involved in the study, will carry the international, non-profit Eliminate wondered,” says Toni Salgado, a 52-year- and be unable to transmit the Dengue research programme. old hairdresser who lives and works in the three viruses to humans. “Now we’re ready to scale-up the suburb of Rio de Janeiro in Brazil. As Salgado recalls: “There was some project. If we begin today, in three years It is easy to understand Salgado’s hesitation in the beginning, in 2012, when we would have the capacity to cover a city fear: Aedes aegypti is the main mosquito the scientists first came here. But then we like Rio de Janeiro.” that transmits the Zika, dengue, had meetings in which they explained Once the experiment is done on a and viruses to the community why this release was large-scale – for example in Rio de Ja- when it bites humans. needed and residents agreed to participate. neiro, a metropolitan area of more than Communities affected by these dis- I am now proud to be part of it.” 6 million people – scientists will be able eases don’t want more mosquitoes and for to measure more accurately how much years they have tried in vain to get rid of mass release of Aedes with Wolbachia them by covering containers or removing actually reduces the incidence of dengue, other objects that collect water – such as Now we’re ready Zika and chikungunya. discarded bottles and used car tyres – to to“ scale-up the project. There are an estimated 390 mil- reduce mosquito-breeding grounds. If we begin today, in lion dengue infections globally every But the mosquitoes released in Rio three years we would year, including 96 million with clinical de Janeiro, where the Olympic Games have the capacity to symptoms. start on the 5th of this month, were not cover a city like Rio de Now a Zika epidemic across Latin ordinary Aedes mosquitoes but ones Janeiro. America is raising international concerns that had been artificially infected with about the virus’s association with birth Wolbachia – a bacterium that stops den- Luciano Moreira ” defects such as microcephaly and neuro- gue, chikungunya and Zika viruses from logical conditions, while chikungunya is replicating inside their mosquito vectors. on the rise too. Scientists released 12 000 to 15 000 “It’s a bone-breaker of a disease,” Wolbachia is naturally present in Wolbachia-infected mosquitoes every Salgado says, recalling how he suffered a more than 60% of species, but week for 20 weeks in this suburb of Rio bout of dengue before the study. Aedes is not one of them. de Janeiro from September 2014 and “We have gone through all the Scott O’Neill, a professor at the repeated this a year later. required small-scale field trials and the Monash University in Melbourne, Aus- When Wolbachia-infected mosqui- results are very promising in terms of tralia, leads the Eliminate Dengue re- toes mate with wild mosquitoes, they pass the proliferation of Aedes infected with search programme. Wolbachia on to the next generation. If all Wolbachia,” says Luciano Moreira, proj- He and his team used microscopic needles to collect Wolbachia from fruit flies and inject the into the Aedes mosquito eggs. After “many thousands” of attempts, they succeeded. “Imagine taking a knitting needle and poking it into a balloon. Next, you have to remove the needle without pop- ping the balloon. That pretty well sums up the process of infecting mosquito eggs with Wolbachia,” O’Neill wrote in Scientific American last year. After almost a decade of research, O’Neill’s team managed to rear mosqui- toes carrying Wolbachia in the laboratory. The first Wolbachia-infected Aedes were released in 2011 in Cairns, a small coastal city in Queensland, Australia. O’Neill’s team did a similar experiment

Eliminate Dengue Brazil Eliminate in Townsville, 346 km to the south, in Octo- ber 2014 and other members of the research Luciano Moreira (left) and Scott O’Neill in the Fiocruz laboratory with a vat for breeding Wolbachia-infected consortium have done similar field trials in mosquitoes Colombia, Indonesia and Viet Nam.

562 Bull World Health Organ 2016;94:562–563 | doi: http://dx.doi.org/10.2471/BLT.16.020816 News

Wolbachia-infected Aedes aegypti was led to a reduction of more than succeed or might work best” in terms of one of five promising new tools to reduce 90% in mosquito populations. reducing dengue. mosquito populations discussed at an Oxitec is awaiting approval from the “It is important to stress that lack emergency meeting of the World Health United States Food and Drug Adminis- of evidence does not mean lack of effec- Organization (WHO) tration to do a large-scale trial near Key tiveness,” says co-author Philip McCall, Advisory Group in March in Geneva. West in the southern state of Florida. professor of medical entomology at the The meeting was held a month after The company has been deploying ge- Liverpool School of Tropical Medicine WHO declared the Zika epidemic an netically modified mosquitoes in Piraci- in England. international public health emergency. caba in the Brazilian state of São Paulo “We need more randomized con- At that meeting, experts from the in collaboration with the city authorities trolled trials to evaluate the most promis- Vector Control Advisory Group reviewed since April last year. ing approaches to help affected countries four other new tools: transgenic mos- “In January, we reported interim design better evidence-based vector quitoes called Oxitec OX513A, vector results already showing an 82% reduc- control strategies for reducing the disease traps, the and the tion in wild mosquito larvae,” says Simon burden,” McCall says. attractive toxic sugar bait. Warner, chief scientific officer at Oxitec. To support these countries members They recommended the pilot de- There are plans to increase the pro- of the WHO Vector Control Advisory ployment of two contrasting approaches: duction of Oxitec . “We are Group are preparing a manual on how Wolbachia-infected Aedes aegypti mos- building a facility in Piracicaba that will best to design such studies. The manual quitoes and Oxitec transgenic mosqui- be ready by the third quarter this year will be released later this year. toes to see whether the latter reduces … to protect a population of 300 000 At their meeting in March, the mosquito populations when released on people,” Warner says. group stressed that some measures to a large scale. While both Wolbachia-infected and protect humans from mosquitoes work While the Wolbachia approach aims Oxitec mosquitoes have shown promise if implemented well. to make Aedes mosquito populations less in terms of reducing or suppressing Aedes “The large-scale use of insecticide- harmful to human health, the Oxitec ap- aegypti mosquito populations, it has yet treated bednets (ITNs) and indoor proach seeks to reduce the size of these to be proven that these interventions residual spraying have contributed populations. result in a reduction of the associated significantly to the decline of , Scientists at Oxitec, a subsidiary of vector-borne diseases in humans. for example,” says Dr Abraham Mnzava, the company Intrexon Without this evidence, it is im- coordinator of entomology and vector based in England, developed the ge- possible to fight epidemics of dengue, control in the Global Malaria Programme netically modified mosquitoes back in Zika and chikungunya effectively. Such department. 2002. These mosquitoes have a gene that evidence is now needed for these two However, ITNs are of limited use prevents their offspring from surviving promising new tools, but is also lacking against Aedes because these mosquitoes to maturity. when it comes to traditional methods of bite during the day. Traditional ap- Only males are released, so there controlling mosquito populations. proaches to tackling Aedes mosquitoes, is no effect on disease transmission A systematic review published in such as fogging and space-spraying with because only females bite humans. Once March in PLOS Neglected Tropical Dis- insecticides and larvicides in household free, they mate with wild females and eases entitled: “Is dengue vector control water storage containers, have been pass this self-limiting gene on to future deficient in effectiveness or evidence?” deployed for decades while dengue epi- generations. concluded that “we do not have a clear demics and resistance to insecticides have According to Oxitec, five small-scale understanding of which of the available continued to grow. trials in Brazil, the Cayman Islands and interventions actually work, when they “New tools to reduce mosquito populations are needed, but these tra- ditional methods are currently the only ones available and should, therefore, be promoted,” says Dr Raman Velayudhan, coordinator of vector ecology and man- agement in the Department of Neglected Tropical Diseases at WHO headquarters. “The lack of evidence that traditional approaches to vector control actually re- duce human disease is one of the reasons why we say dengue is a neglected disease,” Velayudhan says, adding: “This may change in the next few years with the pilot deployment of these two promising new tools against the Aedes aegypti mosquito and carefully designed studies. This way we can rigorously monitor and evaluate Oxitec not only whether these tools suppress mosquito populations – but also stop the Oxitec (OX513A) mosquito larvae and pupae spread of disease as well.” ■

Bull World Health Organ 2016;94:562–563| doi: http://dx.doi.org/10.2471/BLT.16.020816 563