The highest seroprevalence levels of alpha-gal syndrome (AGS) in the US align with states with the highest suspected case counts, according to a study published in the CDC’s Morbidity and Mortality Weekly Report. Seroprevalence was highest in the state of Arkansas, and levels were higher in men than in women.

AGS is a serious, potentially life-threatening allergy to mammalian meat or mammalian byproducts such as dairy or gelatin. The condition is caused by bites from lone star ticks, and its true burden in the US remains unknown, said senior author Johanna Salzer, DVM, PhD, veterinary medical officer in the CDC’s Division of Vector-Borne Diseases.

Diagnosis of AGS is made by immunoglobulin E (IgE) testing and a clinical evaluation; however, individuals can have alpha-gal IgE antibodies without having the disease, the researchers noted.

To determine the association between seroprevalence and diagnosed cases, the researchers reviewed 3000 residual blood donor samples collected from 10 states during 2024-2025. The donors ranged in age from 16 to 95 years, with a median of 62 years; 56.2% were men, 92.9% were White, and 93.4% were non-Hispanic.

The researchers calculated the odds of seropositivity based on age, sex, race, ethnicity, and urban-rural designation (urban, suburban, or rural).

Overall, the combined estimated alpha-gal IgE seroprevalence was 24.0% across the five states with the highest numbers of cases (Arkansas, Kentucky, Missouri, Tennessee, and Virginia). Estimated seroprevalence ranged from 1.1% in Washington state to 31.2% in Arkansas, whereas the estimated mean alpha-gal IgE titers were highest in Kentucky and lowest in Washington state.

Seroprevalence was higher among men than among women (odds ratio [OR], 1.61), and higher among adults aged 55-64 years than among those aged 16-34 years (OR, 0.40). Seroprevalence was lower in Hispanic donors than in non-Hispanic donors (OR, 0.43), but Hispanic donors accounted for a relatively small (4.8%) percentage of samples.

The state-level seroprevalences in the current study represent a significant increase from the 2022 estimate of approximately 450,000 individuals in the US. The estimated alpha-gal IgE seroprevalence was higher in states with established populations of lone star ticks than in the four analyzed states outside the lone star tick range. The 10.6% estimated seroprevalence in Maine, almost double that of the other states outside the lone star tick range (≤ 5.5%) was surprising.

However, recent evidence indicates that bites from blacklegged ticks (Ixodes scapularis), which are found in Maine, can cause AGS and might contribute to the relatively high seroprevalence, the researchers noted.

Arkansas, with the highest seroprevalence, had no donors from counties classified as urban, but blood donors with positive results appeared in urban counties in Kentucky, Missouri, Tennessee, and Virginia. Overall, the probability of seropositivity decreased by approximately 30% for each 10-fold increase in county population density.

“Continued surveillance strategies that include both laboratory and clinical criteria can help track how many people are impacted by AGS in the United States, identify geographic risk, and guide tick-bite prevention and provider education,” Salzer said.

Unexpected Sensitization

“What stood out was how common alpha-gal IgE sensitization was compared with the estimated number of people who have clinical symptoms of AGS,” said Salzer. Approximately one fourth of individuals aged 16 years or older in the five highest prevalence states might test positive, even though most seropositive people do not have symptoms, she said.

The findings that seropositive donors were identified in urban counties, and that Maine had relatively elevated seroprevalence despite not having an established lone star tick population also piqued the researchers’ interest, and suggest that exposure risk if not limited to rural areas, and that other tick species may cause AGS, she said. Further studies should examine the role of tick species other than the lone star tick in AGS in order to explain geographic findings such as the relatively high seroprevalence in Maine and low prevalence in South Carolina, Salzer noted.

Clinical Takeaways

“Clinicians should order alpha-gal IgE testing only when a patient has a history and symptoms compatible with AGS,” Salzer emphasized. “A positive blood test alone indicates sensitization and does not establish a clinical diagnosis,” she said. However, clinicians should consider AGS if patients experience allergic or gastrointestinal symptoms approximately 2-6 hours after exposure to red meat, dairy, gelatin, or other alpha-gal-containing products, Salzer said. “Diagnosis should combine a detailed history, physical examination, and appropriate testing, while disease management should be individualized with an allergist or other healthcare provider,” she added.

The study was limited by several factors including the assessment of only 3000 blood donors from 10 states, with limited demographic and geographic representation, as well as a disproportionate number of type O blood samples, and larger, more diverse studies are needed, said Salzer.

In addition, more research is needed to determine what proportion of people with alpha-gal IgE sensitization eventually develop clinical AGS, and which factors increase that risk, along with more specific diagnostic methods to distinguish symptomatic disease from asymptomatic sensitization, she said.

Seeking More Surveillance and Solutions

“Conducting a seroprevalence study helps understand some of the underlying aspects of this important tick-associated allergic disease,” said Paul G. Auwaerter, MD, MBA, FIDSA, professor of medicine and infectious diseases specialist at Johns Hopkins School of Medicine in Baltimore. “We have only limited information at a population-level, although seroprevalence doesn’t equate directly with alpha-gal syndrome,” he said.

The finding that seroprevalence highest in states with established lone star tick populations was unsurprising, Auwaerter said. “What was eye-opening was the rate of positivity in the five highest states at an estimated detectable alpha-gal IgE at 24% in adults, with Arkansas leading at 31.2%,” he said.

A key unanswered question for public health is why some people with alpha-gal antibodies develop clinical symptoms while many others remain asymptomatic, said Auwaerter. “The substantial geographic differences are also noteworthy; for example, seropositivity was 10.6% in Maine, even though the state lies near the northern edge of the lone star tick’s range, but only 5.5% in South Carolina, where the tick is well established,” he said. “This pattern indicates that the presence of lone star ticks is not the only determinant of risk, and factors including regional ecology, patterns of human-tick contact, exposure to other tick species, and differences in diagnosis or reporting may also be important,” he added.

More research is needed to understand the mechanisms that do or do not trigger AGS, said Auwaerter. Anti-tick strategies are needed as well, including improvements in personal protection and ecological interventions to reduce tick populations, he said. “Greater knowledge of tick populations, especially in emerging disease areas, and the pathogens they carry would help inform clinicians and patients of risks and the pathogens to consider in their area,” he said.

Disclosure information for the authors is available in the original study publication. Auwaerter disclosed scientific consulting and serving on the Clinical Adjudication Committee for Tarsus Pharmaceuticals.