A little over a decade ago, researchers discovered that bites from lone star ticks could cause some people to develop a food allergy to meat and meat products—an allergic condition called alpha-gal syndrome (AGS), which can vary from mild to life-threatening.
The condition is named after a carbohydrate called galactose-α-1,3-galactose (aka alpha-gal), which is commonly found on proteins in most mammals—with the important exception of primates, like humans. Alpha-gal shows up on all sorts of non-primate mammalian tissue, which means it's also in meat—such as pork, beef, rabbit, and lamb—and animal products, like milk and gelatin. Its presence on animal tissue is one of the big, long-recognized barriers to xenotransplantation—that is, transplanting pig hearts into people, for example. Human immune systems will, in part, reject the organ because of the presence of the foreign alpha-gal.
But, in recent years, researchers have also discovered that alpha-gal is in tick saliva. And, for reasons researchers still haven't worked out, some people bitten by ticks develop a type of antibody called anti-alpha-gal IgE. This antibody may help protect people from tick bites, but it also renders them allergic to anything with alpha-gal—i.e., mammalian meat and animal products. It's a double-edged sword that has been hypothesized to be an "allergic klendusity."
If this is all news to you, you're far from alone. Although tens of thousands of people in the US have been diagnosed with AGS in recent years, awareness of the condition has remained low—and this is leading to a critical public health problem, researchers say in a pair of complementary studies published Thursday.
The studies indicate that while the actual number of Americans with AGS may be as high as 450,000, few primary health care providers know the condition. In a survey of 1,500 primary care doctors, pediatricians, physician assistants, and nurse practitioners, a concerning 78 percent (1,165) had little to no knowledge of AGS.
Specifically, 635 (42 percent) of the survey takers said they had not heard of AGS at all. Another 530 said they were "not too confident" in their ability to diagnose it. Of the 865 medical professionals who had at least heard of the condition, only 42 of them were able to correctly answer three basic questions related to the condition's cause, diagnosis, and counseling.
"Alpha-gal syndrome is an important emerging public health problem, with potentially severe health impacts that can last a lifetime for some patients," Dr. Ann Carpenter, an epidemiologist at the Centers for Disease Control and Prevention and the lead author of the newly published survey study, said in a statement. "It’s critical for clinicians to be aware of AGS so they can properly evaluate, diagnose, and manage their patients and also educate them on tick-bite prevention to protect patients from developing this allergic condition."
A growing problem
The urgency to raise awareness of the condition was underscored in the second study, which looked at the prevalence and distribution of AGS cases in the US. Researchers collected alpha-gal–specific IgE (sIgE) antibody testing results between 2017 and 2022. They got the test results from the commercial lab testing company Eurofins Viracor, which, until 2022, conducted nearly all alpha-gal–specific IgE tests in the country. As such, they had testing results on over 295,000 people from all over the US.
Overall, 90,018 (30.5 percent) were positive for the antibody, meaning they likely had AGS. Throughout the studied time period, the percentage of people getting positive tests stayed around 30 percent. But each year, the number of people getting tested increased. This resulted in the number of new suspected cases increasing by about 15,000 each year between 2017 and 2022.
When the researchers combined the 90,018 suspected cases from 2017 to 2022 with suspected cases between 2010 and 2018, they came to a total of 110,229 suspected cases in the 2010 to 2022 period after AGS's discovery. Then they did some simple math to estimate the true number of cases that may be out there:
Assuming 70 percent–90 percent of these suspected cases (77,161–99,207) are clinically compatible AGS cases, and assuming that 22 percent–80 percent of all persons with AGS have access to knowledgeable [health care providers] who submit a specimen for alpha-gal sIgE testing, 96,000–450,000 persons in the United States might have been affected by AGS since 2010.
The researchers also used geographic data linked to test results to determine where the cases were occurring. Unsurprisingly, the cases clustered in areas where the lone star tick is known to be established—though other ticks and potentially chiggers have also been linked to AGS. For now, the high-prevalence regions included parts of Oklahoma, Kansas, Arkansas, Missouri, Mississippi, Tennessee, Kentucky, Illinois, Indiana, North Carolina, Virginia, Maryland, and Delaware.
"The burden of alpha-gal syndrome in the United States could be substantial given the large percentage of cases suspected to be going undiagnosed due to non-specific and inconsistent symptoms, challenges seeking healthcare, and lack of clinician awareness," Dr. Johanna Salzer, a CDC researcher and senior author on both papers released today, said in a statement. "It’s important that people who think they may suffer from AGS see their healthcare provider or an allergist, provide a detailed history of symptoms, get a physical examination, and a blood test that looks for specific antibodies (proteins made by your immune system) to alpha-gal."
The CDC notes that people who have AGS can have wide-ranging experiences, including hives or itchy rash; nausea or vomiting; heartburn or indigestion; diarrhea; cough; shortness of breath or difficulty breathing; drop in blood pressure; swelling of the lips, throat, tongue, or eyelids; dizziness or faintness; or severe stomach pain.
Symptoms often appear two to six hours after eating alpha-gal-containing food or having another type of exposure to the carbohydrate (e.g., gelatin-coated medications). The several-hour delay in an allergic reaction after exposure is unique to AGE among food allergies, which usually occur within minutes to two hours. This can make it harder for people with AGS to identify foods as the trigger of their symptoms. It's unclear what's behind the delay, but it's thought that alpha-gal may have slower digestion and absorption than other allergens.
There is no cure or treatment for AGS other than avoiding alpha-gal. For those with severe allergic reactions, common medications like epinephrine are used for treatment.