When it comes to keeping mosquitos from biting, DEET has long been considered the gold standard. Sprayed on before hikes and picnics and while traveling to mosquito-dense corners of the globe, the world’s most widely used insect repellent comes with the expectation that its smell will send mosquitoes zipping off in the opposite direction. 

But research published yesterday in the Journal of Experimental Biology suggests that mosquitoes may learn to associate the smell of DEET with dinner—and start gravitating toward it instead of away from it. The findings challenge long-held assumptions about how DEET works and what mosquitoes may be capable of learning.

Training changed how mosquitoes react to DEET

For the study, researchers from the University of Tours in France and Virginia Tech examined whether female Aedes aegypti mosquitoes, the species that spreads dengue, Zika, yellow fever, and chikungunya, could learn to associate DEET with a food reward. 

The team used a form of Pavlovian conditioning in which mosquitoes feed on warm blood through an artificial membrane. Twenty seconds into their meal, the researchers released DEET into the feeding enclosure—a process they repeated three more times before exposing the mosquitos to DEET but no food reward. 

When the trained mosquitos caught a whiff of DEET alone, more than 60% of them tried to feed again, displaying what researchers termed a “biting attempt response” (BAR). That’s compared with roughly 20% of untrained mosquitoes who performed BAR when exposed to DEET alone.

The mosquito could learn that DEET isn’t so bad after all.

In another experiment, mosquitoes were given a choice between two human hands. One hand was treated with DEET, and one was untreated. All of the untrained mosquitoes avoided the DEET-treated hand. Trained mosquitoes, however, were significantly more likely to orient toward the treated hand.

Reward learning not limited to blood

In a final experiment, the researchers exposed mosquitos to DEET while the insects fed on sugar. Later, when the trained mosquitos were exposed to DEET alone (no sugar), most of them performed a BAR. The findings suggest that the mosquitoes’ learned behavior was not limited to blood alone. 

“What this result suggests is that the neural circuits that are processing the detection and interpretation of a ‘reward,’ or positive reinforcement, are not specific to a given type of reward,” senior author Clement Vinauger, PhD, Virginia Tech associate professor of biochemistry, tells CIDRAP News. 

 Clément Vinauger 

“Practically, this implies that mosquitoes could learn the association between smells and sugary rewards beyond the time window during which they feed on our blood,” he says. “In other words, mosquitoes’ learning abilities could influence many more aspects of their daily lives than we currently think.”

DEET is dose-dependent

At commercial concentrations, DEET is highly effective at repelling mosquitoes. “This is why, in our experiments, we had to give mosquitoes the opportunity to start feeding before introducing the smell of DEET,” says Vinauger. “The other way around, mosquitoes would simply refuse to feed.” 

“However, that repellency is dose-dependent,” he adds. “And there is a risk that lower doses might still be detected by the mosquito’s olfactory system, without effectively repelling it. In this case, one could imagine that the mosquito experiencing this could learn that DEET isn’t so bad after all.”

What the insect has learned matters just as much as what the chemical does. That, I think, is a paradigm shift.

A common assumption about DEET is that it works because of its chemistry—either it blocks mosquitos from smelling us or it simply smells terrible to mosquitoes, sending them scurrying away. “But what we are showing is that the mosquito’s brain can rewrite that response based on experience,” Vinauger says in a Virginia Tech news release. “What the insect has learned matters just as much as what the chemical does. That, I think, is a paradigm shift.”

Proper use key to maintaining effectiveness

DEET was first developed by the US Department of Agriculture in the 1940s and was originally used by the US Army during jungle combat. Today it is the cheapest and most effective insect repellent in the world. 

People should not stop using DEET, says Vinauger, particularly in parts of the world where mosquito-borne illnesses are common. But the findings suggest that, as concentrations of DEET on skin or clothing decline over time, the repellent may become less effective—and concentration may matter more than expected.

“If a mosquito bites someone who applied DEET to their skin several hours earlier and the concentration of the repellent is too low to repel the mosquito, but still strong enough for the insect to smell it, the mosquito may be more likely to bite people who smell of DEET,” lead author Claudio Lazzari, PhD, a professor at the University of Tours, says in a Company of Biologists news release. 

Our study highlights the importance of following the manufacturer’s recommendations for dosage and reapplication frequency.

The authors say more research is needed to determine if, in the real world, mosquitoes could learn that DEET means dinner. “The laboratory experiments we conducted represent a very particular scenario,” says Vinauger. “They don’t translate directly into a real-world situation that we expect to occur.” 

At the same time, the data offer guidance on the most effective way to use insect repellents. “Our study highlights the importance of following the manufacturer’s recommendations for dosage and reapplication frequency with the specific repellents you use to reduce the risk of mosquitoes learning to outsmart our control tools,” he adds. 



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