Karen Sokoloff finds a certain satisfaction in picking lice off a person's scalp, smoothing olive oil into the hair strands and carefully pulling a metal comb through them to catch the stragglers. It's a good thing she enjoys it: Sokoloff co-founded LiceDoctors, one of a handful of national chains of lice pickers, and business is booming, in part because conventional treatments have become largely ineffective.

For decades people have turned to special over-the-counter shampoos containing plant-derived insecticides known as pyrethrins or their synthetic counterparts, called pyrethroids, to treat cases of head lice. When they first came to market, these products worked well. But sustained use of these same few chemicals has allowed the blood-sucking parasites to evolve widespread resistance to them. Indeed, a recent study of lice in the U.S. carried out by pesticide toxicologist John Marshall Clark of the University of Massachusetts Amherst and his colleagues found that two thirds to three quarters of them are immune to the effects of these insecticides. They have become “super lice.”

This high prevalence of resistance means that most people are wasting their money when they turn to over-the-counter lice shampoos, which range in price from about $6 to more than $30 a bottle and remain the weapon of choice for those doing battle with lice. Use of these shampoos may also prolong the misery of the patients, given that it can take a week or more to determine that the treatment has failed. The problem is particularly disruptive for children, the most common victims of lice, because some schools require students to stay home until their scalps are totally clear of both lice and their eggs, called nits.

This resistance problem has spurred scientists to look for new methods of controlling lice. In Europe, nonpesticide treatments have met with success. In the U.S., doctors have recently added new prescription medications to their arsenal. But scientists warn that those drugs need to be used wisely to keep lice from developing resistance to them, too.

A Pervasive Parasite

Lice are far more common than people want to believe—or may perceive at first glance. In a 2001 study Kosta Mumcuoglu of the Hebrew University of Jerusalem and his colleagues examined the scalps of 280 Israeli children. One group of researchers looked for any lice they could spot with a simple visual inspection. They found that upward of 5 percent were infested. Another group reexamined the same children using lice combs. This more rigorous check turned up insects on the heads of more than four times as many children. Researchers have also reported high rates of infestation in Turkey and England, among other places. The findings suggest that an average of one in five children in developed countries has lice, Mumcuoglu says.

Lice mostly spread when people touch heads; children are particularly susceptible because they come into closer physical contact than adults. Sokoloff, whose LiceDoctors chain has technicians in 40 states, says her business always sees a spike when kids come home from summer camp, as well as after the winter holidays, when they have shared beds with friends and relatives. Personal hygiene does not seem to be a determining factor in who gets lice, but long hair hides the parasites more readily than short hair does and makes it harder to comb out nits.

Head lice technically belong to the same species as body lice, Pediculus humanus. But whereas body lice can spread diseases, including epidemic typhus, trench fever and even the plague, head lice have never been blamed for any such outbreak. The distinction may have to do with differences in immune response between the two types of lice. Clark and his colleagues found that when they infected both kinds of lice with the bacterium that causes trench fever, the head lice fought off the infection far more aggressively than the body lice did. Perhaps head lice do not transmit disease partly because their immune system eradicates the infection before they can pass it along to humans.

Still, head lice cause plenty of discomfort and distress. And in a really bad infestation, as can happen with homeless people living in crowded shelters, severe scalp itching can open up wounds in the head, allowing bacteria to enter the person's bloodstream and cause systemic infections.

Growing Resistance

The roots of pesticide resistance in head lice reach back over decades to World War II, when millions of people in Europe and Asia were doused with the insecticide DDT to prevent body lice. Use of DDT to combat lice and other insects continued until the 1980s in Europe and Asia; in the U.S., the insecticide was phased out a decade earlier amid safety concerns. But it left a lasting legacy in the insects.

When pyrethroids were introduced into Israel in the early 1990s, just one treatment would destroy all the adult lice on an individual within a few weeks. The chemicals also lingered on the scalp long enough to kill the eggs, which normally hatch up to 10 days later. Within two to three years, however, these pyrethroid-based treatments ceased to kill the majority of the parasites.

The earlier use of DDT had primed lice to develop this resistance. DDT works by disrupting the nervous system. Nerve cells have tiny pores in their cell membranes that regulate the flow of sodium ions into the cell, which in turn modulates the firing of the cell. DDT holds open the tiny sodium pores, allowing sodium to flow into the cell unabated. The influx causes the nerve cells to fire constantly, leading to convulsion of the insect, paralysis and eventually death. Decades of DDT exposure allowed lice to evolve mutations that block its effects on the sodium pores. These mutations persisted in the lice population. Pyrethrins and pyrethroids also work by interfering with sodium pores. Lice have thus been able to readily evolve resistance to them, by co-opting mutations that fortified them against DDT.

Mutations that confer protection to head lice have spread to high frequency. From 2013 to 2015 Kyong Sup Yoon, an entomologist at Southern Illinois University Edwardsville, gathered lice from 48 U.S. states. He and his colleagues, including Clark, found that 132 out of the 138 populations they tested carry so-called knockdown resistance–type mutations, which desensitize the louse nervous system to pyrethroids.

New Tactics

Humans have given head lice an advantage by subjecting them to the same treatments again and again. Such repeated exposure builds resistance not only to that treatment but to virtually all others that work according to the same or similar mechanisms, Clark says. At that point, the only way to defeat the lice is to find a completely novel approach, one that the parasites are not preadapted to fending off. To that end, in recent years researchers have developed a few treatments that are based on entirely different mechanisms of action than the pyrethroids are. In the U.S., the Food and Drug Administration has approved three prescription treatments since 2009: Ulesfia, which contains high levels of alcohol and kills the lice essentially by suffocating them; Natroba, which overexcites nerve cells by activating their nicotinic acetylcholine receptors; and Sklice, which inhibits nerve impulses by activating their glutamate chloride channels.

For these treatments to work over the long term, health care providers need to rotate them among patients to avoid overexposing lice to any single drug and thus lessen the chances of the lice developing resistance to it. There are no official medical guidelines requiring such a rotation, however. Doctors can prescribe whichever drug they want, and they are usually unaware of the benefits of alternating treatments.

Further confounding matters, the co-pay for visiting a doctor, plus the cost of prescriptions, which may or may not be covered by insurance, can impede patient access to these newer medications. And despite their diminishing efficacy, over-the-counter lice shampoos remain the first response recommended by most doctors, health plans and even the American Academy of Pediatrics. For its part, the combing method used by many parents and professional lice pickers such as LiceDoctors is theoretically effective, Clark and Yoon note, but hard to do well.

The situation is totally different in Europe, where treatment moved on from pyrethroids and virtually all insecticides about a decade ago, says Ian Burgess, president of the International Society of Phthirapterists (people who study lice). Instead most Europeans now rely on silicone and other synthetic oils to eliminate head lice. The oils envelop the lice, preventing them from excreting water. As liquid builds up inside the louse, its internal organs start to shut down from the exhaustion of trying to pump out the water. Either it dies of this exhaustion, Burgess says, or its guts rupture from the liquid.

In Europe, such synthetic oil treatments are considered medical devices rather than drugs and so are subject to fewer regulations; in the U.S., they are viewed as medications and have not passed regulatory hurdles, observes Burgess, who also works for a contract research company that helps to develop anti-lice devices. Overall, Burgess says he thinks Europe's approach to lice is working. When he tests schoolchildren today, he finds the same percentage infested as he did two decades ago, but each child has fewer lice.

Still, despite this progress, lice seem poised to keep researchers—and the rest of us—scratching our heads for quite some time to come.