The earliest signs of summer herald my annual metamorphosis – from woman to lifesize pincushion. Whether at home or abroad, when mosquitoes begin their hunt for blood I am reminded, via a blanket of red blotches that have more than once swelled to the size of a golf ball, that mine is a godlike nectar. On a single day last December, a tropical Christmas trip quickly became a less-than-festive scratchathon after a glut of bites arrived, following which I was stung by jellyfish, then wasps. At this point, I can only assume the mosquitoes are giving other species ideas.
But there are signs that a solution for the 20% of the population who receive above-average numbers of bites may soon be at hand. Earlier this month, researchers at the Hebrew University of Jerusalem (HUJI) developed a new repellant capable of reducing the number of mosquitoes feeding by 80%. Applying a thin coating made from naturally occurring cellulose nanocrystals (CNC), a renewable raw material found in the likes of cotton and wood, and indole, an organic compound with an unpleasant odour, to skin served as “chemical camouflage”, said the study published in PNAS Nexus. This combination – which derails the cues that mosquitoes use to select their victims – is “unprecedented”, according to Jonathan Bohbot, a senior lecturer at HUJI and one of the paper’s co-authors. Indeed, the results are considered so promising that further human studies are planned, with a view to having the coating approved by regulators ahead of commercial use. “The CNC-repellant combination will have a longer efficacy and range of action than other products currently available on the market,” says Bohbot, adding that they expect “high levels of product adoption” if and when it does hit shelves.
Whether you get bitten or not is, in large part, a foregone conclusion: by some estimates, genes account for 85% of a person’s propensity to be stung, while DNA testing company 23andMe says it has identified 285 heritable genetic markers responsible for their frequency, itchiness and size.
Mosquitoes are attracted to humans by volatiles (organic compounds) we emit in our breath. But it is those we release through our skin that serve as signposts to where they should feed from; chemicals we naturally produce, such as lactic acid and ammonia. The more lactic acid your body produces, the worse the feeding frenzy is likely to be. Given the limitations in changing our physiology, repellants are, for now, really the only defence we have – bought across the globe in such numbers that the market is predicted to reach $9bn (£7.2bn) by 2026.
HUJI’s researchers aren’t the only ones looking to solve the bite problem. Earlier this year, a group of Italian scientists developed a repellant combining cyclic acetals and carbonyl compounds, creating a formula they say is four times as effective as DEET (diethyltoluamide, the chemical compound that makes up a large tranche of sprays and creams). Tested against the tiger mosquito, Aedes albopictus, it was found to protect 95% of people for eight hours at a time (DEET lasts for about two) and is a less toxic and odorous blend than those currently available. The results, published in the Journal of Agricultural and Food Chemistry, could make it another welcome addition to the market. “We didn’t think it was that easy to find new repellant,” says Francesca Dani, associate professor of zoology at the University of Florence, adding: “We were pretty satisfied.”
The team’s next goal is to see whether their repellant can ward off other pests, too. Those currently in their sights are ticks (health officials warned last month that tick-borne encephalitis, a virus that can be fatal, had been found in the UK) and Anopheles gambiae, the mosquito species responsible for spreading malaria. Repellants are “the only way you can keep vectors [of disease] away”, says Dani. “It’s a very simple way to protect people.”
While ancient civilisations relied on the likes of vinegar or burnt snakeskin to deter mosquitoes, chemical remedies only became an option in 1957, when DEET first hit shelves. Initially developed for the US military more than a decade earlier, the synthetic repellant cannot be sold in concentrations higher than 50% in the UK or Europe, such is its toxicity. Icaridin has become a popular alternative, along with IR3535 (ethyl butylacetylaminopropionate) and citriodiol (menthoglycol, a natural blend), though none are yet considered to have achieved the perfect nexus of being highly effective in small doses, odour-free, nontoxic to humans, animals and the planet, water-resistant, and non-greasy.
The Defense Advanced Research Projects Agency (Darpa), the research and development agency of the United States Department of Defense, is looking to overcome that hurdle. Given that current repellants are impractical for those in need of longer-term protection, such as soldiers, they are investigating a new possibility: altering the skin’s microbiome (the bacteria and fungi that live there). Their ReVector programme is seeking to create a product that can be applied just hours before entering an area with a large mosquito population, produces no detectable scent, and can offer protection of up to two weeks at a time with a single application.
This involves “taking natural human skin microbes and engineering them to, for example, knock out an enzymatic pathway that produces a known mosquito attractant, like lactic acid, and then reapplying that same human skin microbe [to the skin as a repellant],” says Dr Linda Chrisey, a programme manager at Darpa’s Biological Technologies Office. Should their hunch prove correct, a repellant of this kind “could be really gamechanging”. Studies have thus far only been carried out on animals, but have shown that “applying a human skin microbe engineered to reduce production of an attractive molecule appears to have some level of efficacy”, Chrisey says.
Proof of concept is the ReVector team’s chief aim: after that, says Chrisey: “We will then be looking for the right partners in industry, or within the Department of Defense, to either expand the human studies, or to try to commercialise the product.” Like the Italian researchers, they also have ambitions of expanding the species targeted, hoping to extend ReVector’s reach to sandflies (which can cause leishmaniasis, a parasitic disease).
The discomfort of being bitten is, of course, among the more minor issues caused by mosquitoes – the deadliest animal to humans in the world, responsible for 725,000 deaths each year. Repellants can do little to combat the likes of malaria, says Dr Jan Kolaczinski, global malaria lead at the World Health Organization (WHO), with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) considered the most effective options for disease control. (A 2015 Nature study found that ITNs were responsible for 68% of averted cases of Plasmodium falciparum, the most dangerous strain of malaria, between 2000 and 2015.) Caused in part by the climate crisis (warmer, wetter temperatures are optimal for the insects) and globalisation, in which the frequency of travel has boosted viral species’ abilities to cross borders, cases of mosquito-borne diseases such as malaria and dengue fever are rising sharply around the world – a trajectory the WHO has warned will only worsen. Effective control has never been more pressing, Kolaczinski says, “but we are faced with the challenge of insecticide resistance, which in turn requires new and more expensive ITNs and IRS products, while the funding to purchase these has flatlined or, in some countries, is even decreasing”. A new malaria vaccine approved in Ghana and Nigeria earlier this month may go some way to changing the course of the rise in cases, it is hoped, although the WHO has yet to recommend it for use.
There is more optimism, perhaps, for the holidaymaking cohort keen for an itch-free break. But further testing, regulatory approvals and commercial tie-ups are required before any of the latest research becomes a reality (Dani says her team is currently discussing one such partnership, but nothing has yet been formalised).
Meanwhile, as we wait for these remedies to arrive on the shelves, some scientists are hoping to galvanise the public to help track and thwart the blood-sucking insects. April saw the release of Mosquito Alert St Louis – an app using citizen science to combat the spread of the insects in Missouri. First developed in Catalonia in response to the arrival of the tiger mosquito, this American iteration is seeking to target both “nuisance and public health”, explains John Palmer, associate professor at Universitat Pompeu Fabra and the app’s co-director.
Users are charged with taking photos of adult mosquitoes and submitting them, along with information about their size and location, with volunteer experts on hand to help label each species. Creating a database will identify mosquito hotbeds and determine their disease-carrying potential, allowing locals to better protect themselves.
“You can get really good data from citizen scientists,” enthuses Palmer; information about the times of day a mosquito is biting people “tells you a lot also about the species, because different species tend to bite at different times”. The number of bites each user gets “is really important from an epidemiological modelling perspective”; ditto data on where on the body an individual has been bitten. While larger-scale prevention is typically reliant on government data, or costly installation and monitoring of treated nets, this rapid information provides a “much more high-resolution or fine-grained picture of where disease-vector mosquitoes are present”.
There is another key benefit, he notes: that it leaves no environmental trace. This means of mosquito control is “less damaging than what happens when you are at a crisis moment, and [countries] have a major disease problem and authorities simply do things like major spraying of adults … it’s much, much better to control at the stage of the larvae … and eliminate breeding sites, and you can often do that in ways that don’t cause any environmental harm.” This change in tactics, as well as being less of an eco-hazard, can be much more effective, he says, in staving off bites. “If you really know where the breeding sites are, you’re going to the heart of the problem.”
The race for the first bite-free summer may not yet have been won. But for the perma-bitten, there is finally hope that it has at least begun.
