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Delivering sugars

The lone star tick, the most prevalent species in Georgia, is a primary transmitter of alpha-gal sugars to humans. It’s an aggressive tick distinguished by a white dot—or “lone star”—on the back of the female. When a lone star tick bites a mammal such as a white-tailed deer or raccoon, its saliva picks up alpha-gal molecules from the host. If that tick then bites a person, its saliva can introduce alpha-gal into the human bloodstream.

In some people, the immune system mistakenly treats alpha-gal sugars in certain foods they eat as a threat, leading to allergic reactions hours later that range from hives and gastrointestinal distress to life-threatening anaphylaxis. Foods that set off an alpha-gal immune reaction include red meat (beef, pork, lamb, and venison) and, less commonly, dairy. Tragically, in 2024 a New Jersey man became the first known U.S. fatality from an anaphylaxis reaction associated with alpha-gal syndrome after consuming red meat. Still, many people bitten by implicated ticks never develop the allergy, and careful prevention of tick bites greatly reduce risk.

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But reported cases are rising sharply. The Centers for Disease Control and Prevention (CDC) has identified over 110,000 suspected U.S. cases between 2010 and 2022 and estimates that up to 450,000 may have been affected. While the core area of the lone star tick is in the Southeast, they are spreading to the Upper Midwest and Northeast, as are alpha-gal diagnoses. Tick-borne meat allergies, such as alpha-gal syndrome, have been reported in 17 countries across all six continents.

Parastoo Azadi is one of the UGA researchers studying the biology behind alpha-gal syndrome. In 2019, she led a team to characterize carbohydrates in the tick saliva and showed that some tick species—lone star and blacklegged—are more prone to having alpha-gal sugars than others.

“We are still in the early stages of understanding the syndrome, but our basic research is essential for developing future treatments,” says Azadi, director of CCRC Service and Training.

Azadi and Gudenrath were part of a coalition of Georgia leaders that organized the 2024 Alpha-Gal Symposium hosted by CCRC. The symposium was crucial, according to Gudenrath, to bring researchers across Georgia’s universities together with agriculture, forestry, and wildlife communities.

“Georgians need protecting from alpha-gal disease,” says Gudenrath. “It’s a life-altering syndrome with negative consequences. We wanted to make the case that addressing it is a worthy state investment.”

Surveys have found that about three-quarters of providers know little or nothing about the syndrome and that only a small minority feel confident diagnosing it. A single lab test can often identify the condition, yet some people—like Matthis—do not show a positive reaction, and diagnosis can require thorough clinical evaluation and food challenges. Symptoms can vary widely from patient to patient. Allergic reactions to mammalian food don’t occur every single time for everyone. But reactions can intensify with additional tick bites.

Gudenrath has a folksy way of describing how he’s adapted his diet. He only eats things that “float, swim, or fly.” He is cautious about potentially hidden beef ingredients, even in something as common as gravy on mashed potatoes, but he does not have to be rigorous about diet choices as he used to. “My symptoms are not as severe now, 13 years later.”

Meanwhile, Nichols and Matthis continue to have very high sensitivities to mammalian products, even reacting to fumes from cooking meat. They scope out mammalian derived ingredients, which can include “natural flavors” in packaged foods. Some allergenic ingredients are in medications or other products such as gelatin, glycerin, or magnesium stearate. With alpha-gal cases expanding, the Two Alpha Gals argue, clearer labels on foods and eventually medications are essential for people who can become sick or anaphylactic from even trace exposures. They always carry epinephrine pens to treat attacks.

Even so, both report feeling much healthier than before. For now, adaptation—not treatment—is the reality for patients.

“We emphasize the lifestyle piece of this, because there is no cure,” says Nichols. “Some people think it is the end of their lives. They won’t be able to eat this or that forever. But the truth is that when I was eating red meat, I felt so sick. And even though I got this diagnosis and had to give up these things, it was worth it to feel as good as I do [now].”

Champagne and his colleagues are exploring tick saliva, which is a blend of proteins, peptides, and other compounds. The team, supported by a grant from the National Institutes of Health, is looking for a potential missing factor.

Tick saliva itself is a highly evolved survival tool. It contains molecules that reduce inflammation, prevent blood clotting, and numb the skin, allowing ticks to feed for days without being detected. These same adaptations could also shape how the human immune system responds.

“The immune system is extraordinarily complex, and so is tick saliva,” Champagne says. “With so many interacting components, it’s difficult to pinpoint which ones drive alpha-gal sensitization.”

Progress was slowed for years by the lack of suitable animal models. Most mammals naturally produce alpha-gal, meaning their immune systems do not see it as foreign. “They recognize alpha-gal sugar as part of themselves,” Champagne explains. “So, they don’t develop an allergy.”

That barrier is beginning to fall. Australian researchers have designed genetically altered mice that do not produce alpha-gal and react to it as an invader, much like humans do, and one of Champagne’s collaborators has obtained some of these mice for research.

“This model allows us to separate saliva into its components,” Champagne says. “We can combine individual salivary factors with alpha-gal and observe which mixtures trigger the allergy.”

For scientists, the goal is clear: understand the biology well enough to move from explanation toward prevention and, eventually, treatment.