The small, itchy raised bumps that signal bedbugs’ presence in a home are just the start of aggravations to come. Laundering every piece of clothing and bedding, sealing up mattresses, steam-cleaning floors, and spraying insecticides are all part of the tedious process of eradicating the pests.

But a study published Thursday finds the bloodsucking bugs are fighting back.

Bedbugs from Michigan and Cincinnati are up to 33,000 times more resistant to neonicotinoids (or neonics), insecticides used to combat the insects, compared with bug populations never exposed to the chemical, researchers from Virginia Tech and New Mexico State University have found.

“In the past couple of years, neonics in combination with other pesticides have become the industry standard for killing bedbugs chemically,” said Alvaro Romero, the study’s lead author and an urban entomologist at New Mexico State. “This study shows how quickly these bugs are adapting and that non-chemical use could be a more effective approach.”

Neonics, a systemic class of insecticide widely used on corn, soybeans, and other crops, have been linked to the mass die-offs of bees that pollinate a third of the world’s food supply. Neonics are just the latest pesticide deployed against bedbugs. In the 1940s and ’50s, prevalent use of DDT and other toxic insecticides limited the bugs’ populations; in the 1960s, they developed a resistance. DDT’s devastating impact on birds and other wildlife led the U.S. government to ban its use in 1972.

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Pyrethroid-based insecticides then were used to fight bedbugs and kept populations down. In 2007, Romero discovered the bugs had developed a resistance to pyrethroids, and outbreaks subsequently occurred in New York and other cities. The response from chemical companies such as Bayer, BASF, and Syngenta has been to lace their bedbug sprays and fogs with more potent chemicals such as neonics.

The study, published Thursday in the Journal of Medical Entomology, tested four neonics (acetamiprid, imidacloprid, dinotefuran, and thiomethoxam) on four populations of bedbugs.

One strain, called the Harlan bedbug population, has been in a controlled environment since 1978, with little to no chemical exposure. The bugs belong to Harold Harlan, a retired military medical entomologist who became fascinated with bedbugs. He told ABC News in 2010 that he lets the bugs feed on his leg every few days.

“That population is key to our studies,” Romero said. “Without it, we wouldn’t have a baseline to test how environmental changes like chemical exposure are affecting bedbugs in cities today.”

The researchers also tested bugs collected from Jersey City, New Jersey, in 2007—before the rise of neonics in pest control—and bedbug specimens taken from homes in Cincinnati and Michigan in 2015.

Not surprisingly, the Harlan bedbugs were highly susceptible to neonics, with a small dose of 0.3 nanograms of acetamiprid killing half of the bugs exposed. In comparison, it took more than 10,000 nanograms to have the same impact on the Michigan and Cincinnati bedbugs.

Romero noted that the Jersey City bugs, which hadn’t been exposed to neonic use, still fared better than the Harlan group. That could be because the Jersey City bugs have adapted to resist other chemicals.

The Michigan bugs were 462 times more resistant to imadacloprid, 198 times more resistant to dinotefuran, 546 times more resistant to thiamethoxam, and 33,333 times more resistant to acetamiprid. The Cincinnati bugs fared similarly.

Indoors or outdoors, pests have been shown to adapt to and resist chemical use over time. Humans have often responded with stronger, more systematic forms of pesticides to protect homes and crops. But there is an increasing level of evidence that suggests those poisons are doing more harm than good and contributing to the worldwide decline in pollinator populations.

“When you have an insect, particularly one that rapidly reproduces, you have increasing opportunities for mutations that can lead to a population becoming resistant,” said Thomas Green, an integrated pest management expert at the nonprofit IPM Institute of North America, which was not involved with the study. “But when you ban neonics, that brings in another range of issues, because that can mean other chemicals could be brought in, and those alternatives could be just as risky.”

Romero said more research needs to be conducted on a larger and more geographically diverse population of bedbugs to determine the scope of the problem.

“If these chemicals lose their potency, people need to be aware of that,” Romero said. “And more non-chemical methods, such as vapor, heat, diatomaceous earth, and others, can be used as alternatives.”