Cases of alpha-gal syndrome caused by tick bites on the rise, CDC reports

For many Americans, the warmer spring and summer months bring backyard barbecues and scenic hikes — along with a chorus of cicadas, mosquitoes galore, and hypervigilant self-checks for ticks. Often, insect bites only cause mild discomfort but new reports from the Centers for Disease Control and Prevention warn that a food allergy caused by ticks is on the rise in the U.S. — and a lot of health care providers still don’t even know it exists.

The allergy in question is alpha-gal syndrome (AGS), and those who have it are allergic to the sugar galactose-alpha-1,3-galactose, or alpha-gal for short. Alpha-gal is found in many mammalian food products — like beef, pork, and dairy — but also in the saliva of some ticks. In response to a bite from such a tick, a person’s immune system might produce a specific antibody to recognize alpha-gal called IgE. Long after inflammation from the tick bite subsides however, IgE still floats around, ready to alert the immune system to future alpha-gal intruders, including any alpha-gal from food we eat. Unfortunately, there are no cures or treatments for the condition, and allergies often last for years.

“The alpha-gal story is fascinating,” Scott Commins, associate chief for allergy and immunology in the School of Medicine at the University of North Carolina at Chapel Hill and a leading researcher in AGS, told STAT via email. We have a longstanding “tolerance to eating red meat that somehow the tick bite overcomes…[there’s] lots to unpack from an immunology perspective still,” he wrote.

Two reports published Thursday by the CDC attempt to measure the prevalence and geographical distribution of AGS, as well as the knowledge that health care providers have about the condition. One report analyzed the number of positive alpha-gal-specific IgE blood tests at one of the only commercial alpha-gal testing laboratories in the nation over the past five years. The laboratory processed an estimated 13,371 suspected AGS cases in the U.S. in 2017, compared to 18,885 cases in 2021 — a 41% increase in four years. Another report that surveyed 1,500 health care providers about AGS found that 42% did not know about the syndrome, and that another 35% were “not too confident” about AGS diagnosis and treatment.

Together, the reports establish AGS as an emerging concern in the U.S., and highlight the importance of raising awareness about the condition. People with AGS may not only be allergic to red meat and dairy, but also cosmetics, medicines, and certain surgical devices that contain mammalian products. According to CDC’s Johanna Salzer, the lead author of both reports, “the big take home here for the public is that preventing tick bites not only protects them against infectious diseases…but also against alpha-gal syndrome, which actually can have a more lifelong impact.”

Alpha-gal was definitively implicated in food allergy in just 2008, making AGS relatively new. “Raising awareness of a completely new diagnosis is a difficult task, and there hasn’t been significant educational opportunities beyond the allergy specialist,” Commins wrote. Additionally, AGS presents itself in a multitude of ways, further complicating accurate diagnosis. Allergic reactions to alpha-gal can vary drastically in both severity and symptom type.

“We often say that [people with AGS] are consistently inconsistent in the way that they present,” said Salzer, an epidemiology team lead in the Rickettsial Zoonoses Branch at the CDC. Symptoms include hives, nausea and vomiting, upset stomach and diarrhea, and in extreme cases, anaphylaxis.

Like other food allergies, symptoms can worsen with alcohol, exercise, non-steroidal anti-inflammatory painkillers like aspirin, or existing infections. If symptoms only present in the presence of one of these factors, pinpointing alpha-gal as a culprit can be exceedingly tricky.

Unlike other food allergies, adverse reactions from alpha-gal are delayed, typically occurring two to six hours after exposure. Onyinye Iweala, an assistant professor in the Division of Rheumatology, Allergy, and Immunology at the University of North Carolina at Chapel Hill who studies AGS with Commins, said that this delay “may be due to the amount of time it takes for us to absorb molecules that have the alpha-gal sugar on them, process them, package them, and then distribute them to the parts of the body where the allergic immune cells are located.” Because of the delay, “it takes a really long time to even associate the ingestion of the mammal meat with the development of the allergic symptoms,” Iweala said.

Furthermore, the time and cost of seeking a diagnosis may be prohibitive to certain populations. “Previous reports have found that patients…have to seek multiple health care providers and often an allergist in the highest level health care in the country in order to be diagnosed,” Salzer said. As a result, Commins believes that “there is very likely a [health] equity gap. Allergists don’t exist in every county, and some patients would have to travel quite far to see a specialist. This probably contributes to a fair amount of undiagnosed cases,” he wrote.

Yet, despite all these challenges, reported cases of AGS are still on the rise. Salzer’s report recorded over 90,000 suspected AGS cases from 2017 to 2022; nearly three times the 34,000 suspected cases documented between 2010 and 2018. Commins himself sees “8-10 new patients with AGS every week” at the UNC allergy clinic, “and other providers report [a] similar experience,” he wrote.

Iweala warns that the impact of AGS could extend far beyond diet. For instance, many cosmetic products contain mammalian ingredients, such as collagen and elastin, and could therefore contain alpha-gal. More importantly, AGS could limit a person’s ability to receive certain medicines and procedures — from the gelatin in gel capsules or vaccines, antibody therapies that are manufactured in mammalian cells, surgical mesh, or heart valves that are taken from cows or pigs. Additionally, some studies have shown a correlation between AGS and coronary artery disease, a significant risk factor for heart attack and stroke.

Rising cases may in part be due to gradual increases in awareness of the syndrome, or from the establishment of a commercial blood test for AGS in the last few years. But another contributor may very well be an increase in both the distribution and number of the alpha-gal ticks themselves.

In the U.S., the main tick species responsible for AGS transmission is the lone star tick. According to Salzer, other lone star tick diseases, such as ehrlichiosis, have been increasing as well, suggesting lone star tick numbers could be increasing in the U.S. On top of this, lone star ticks appear to be expanding beyond their known geographic regions.

Rick Ostfeld, a distinguished senior scientist at the Cary Institute of Ecosystem Studies, says that “the expansion [of lone star ticks] has been well documented…it’s pretty unassailable.” Several tools that use climate factors to predict tick habitats “pretty much all predict a range expansion further up into New England, the Midwest, and into Canada,” he said.

Ostfeld, who studies black-legged ticks, offered several potential reasons as to why tick populations could be spreading. First, climate warming may lengthen the tick active season within a given year, increasing their numbers, and also make additional environments hospitable. Second, man-made developments — like agricultural fields and human settlements — interspersed with forests actually provide an optimal habitat for the lone star tick’s main host, the white-tailed deer. Our agriculture gives the deer high quality food while our settlements provide refuge from the deer’s natural predators. Further still, by living in these settlements, we inherently increase our risk of tick exposure. “Our backyards are plunked right down in the danger zone that we’re creating by virtue of habitat modification,” Ostfeld said.

In their report, Salzer and colleagues localized suspected AGS cases to mostly the southern, midwestern, and mid-Atlantic U.S., roughly overlapping with the known habitat of the lone star tick. Unexpectedly however, two AGS hotspots were identified outside the lone star tick geographic range, in Wisconsin and Minnesota. Other ticks beside the lone star have been known to cause AGS in other parts of the world, and it’s possible that could be happening here. Salzer however believes that “if it was other tick species, we would see a different geographic pattern.”

While we can’t rule out that lone star ticks have made their way into these states, Salzer reasoned that a more likely explanation could be that the tick bites occurred in other states and were simply diagnosed in these regions due to specific knowledgeable health care providers in these hotspots.

Could tick population management be a viable way to reduce AGS cases? According to Ostfeld, the preliminary data unexpectedly says, no. Ostfeld and Felicia Keesing, a biologist from Bard College, ran a five-year study to see if reducing neighborhood tick populations would reduce incidences of tick-borne diseases, but found no effect — even when reducing tick populations by half.

Ostfeld believes that they may have failed to reach a critical tick population threshold, or that people could have encountered ticks outside their neighborhood. But for now, the best strategy to prevent tick-borne illnesses — including AGS — is to cover up, use tick repellent, and continue those hypervigilant self-checks.