Bacillus and Francisella bacterial research (28)Vector-borne infectious diseases (20)Poxvirus research and outbreaks (18)Herpesvirus Infections and Treatments (16)Zoonotic diseases and public health (14)
Saunders EF, Taylor ML, Jones ES, Biggerstaff BJ, Vorobiov JM, et al.
MMWR. Morbidity and mortality weekly report •
Alpha-gal syndrome (AGS) is an emerging, noninfectious tickborne disease characterized by an allergic reaction to galactose-α-1,3-galactose (alpha-gal), an oligosaccharide found in red (mammalian) meat and other mammalian products such as dairy and gelatin. As of 2022, AGS was estimated to affect up to 450,000 persons in the United States (1). Anaphylactic AGS reactions can be fatal, and AGS allergic reactions encompass a range of symptoms including urticaria, angioedema, wheezing, and gastrointestinal distress. AGS is primarily managed through an avoidance diet. The U.S. geographic distribution of AGS is closely associated with the range of the lone star tick (Amblyomma americanum); bites from this tick introduce alpha-gal through its saliva, which can trigger the allergy. Diagnosis of AGS requires both the presence of clinically compatible symptoms and the detection of serologic immunoglobulin E (IgE) antibodies against alpha-gal. Persons can have alpha-gal-specific IgE antibodies without clinical symptoms. The proportion of persons in the United States who are seropositive for alpha-gal IgE is unknown. To better understand the distribution and seroprevalence of alpha-gal IgE among U.S. adults, 3,000 serum samples collected during November 2024-April 2025 from blood donors living in 10 states were tested for the presence of alpha-gal IgE antibodies. States previously reported to have high numbers of suspected AGS cases were found to have correspondingly high seroprevalences. Among the 10 states, the highest estimated seroprevalences among persons aged ≥16 years were detected in Arkansas (31.2%) and Missouri (26.0%). These findings can guide the development of surveillance systems for AGS and help identify regions at increased risk.
Barnett KM, Maki CK, Nicholson WL, Beard CB, Kersh GJ, et al.
Ticks and tick-borne diseases •
In this Opinion, the authors investigated peer-reviewed publications on alpha-gal syndrome (AGS), also known as red meat allergy, since its first description in the literature in 2009 to October 2024 to understand academic discipline and geographic affiliation of associated authors. We raise the issue of disproportionate contribution between medical disciplines and ecology/entomology disciplines and emphasize the positive future impacts of increased collaboration between the fields to address current gaps in our fundamental knowledge of this unique tick-borne disease.
Butler WK, Oltean HN, Dykstra EA, Saunders E, Salzer JS, et al.
Emerging infectious diseases •
We describe a case of alpha-gal syndrome (AGS) in a resident of Washington, USA, after local Ixodes pacificus tick bites, which were associated with IgE increases after diagnosis. AGS should be considered a potential cause of anaphylactic and allergic reactions in persons with tick exposures, regardless of geographic residence.
In the United States, alpha-gal syndrome (AGS) is primarily associated with lone star tick (Amblyomma americanum) bites. We describe AGS onset after an Ixodes scapularis tick bite and present AGS surveillance in Maine, 2014-2023. US health and public health professionals should be aware of AGS outside the established lone star tick range.
Taylor ML, Kersh GJ, Salzer JS, Jones ES, Binder AM, et al.
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology •
Alpha-gal syndrome (AGS) is an allergy to galactose-α-1,3-galactose (alpha-gal), a carbohydrate found in most mammals. Evidence indicates that AGS develops after a tick bite, and in the United States, AGS is most associated with bites from Amblyomma americanum (lone star tick); however, not all persons bitten by ticks develop clinical AGS. To investigate intrinsic risk factors associated with the development of AGS. We performed a case-control study among adults presenting for diagnosis or management of AGS at an allergy clinic in North Carolina during 2019 to 2020 and compared them with controls enrolled from 2 nearby internal medicine clinics. A questionnaire gathered epidemiologic and tick exposure data, and blood was obtained for alpha-gal-specific IgE and other testing. The 82 enrolled case patients and 191 controls did not differ significantly by age or sex. Case patients were more likely than controls to have A or O blood types (non B-antigen), have experienced childhood allergies, and have a family history of AGS and other food allergies. Case patients were also more likely to report experiencing long healing times for insect bites or stings and a family history of allergy to stinging or biting insects. This study suggested that intrinsic factors contribute to risk of developing AGS. Some traits are genetic, but common behaviors among households and family units likely also contribute. Identification of these risk factors can inform personal risk, aid health care providers in understanding susceptible populations, and contribute to ongoing understanding of AGS epidemiology.
Carpenter A, Drexler NA, McCormick DW, Thompson JM, Kersh G, et al.
MMWR. Morbidity and mortality weekly report •
Alpha-gal syndrome (AGS) is an emerging, tick bite-associated immunoglobulin E-mediated allergic condition characterized by a reaction to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), which is found in mammalian meat and products derived from mammals, including milk, other dairy products, and some pharmaceutical products. Symptoms range from mild (e.g., a rash or gastrointestinal upset) to severe (anaphylaxis); onset typically occurs ≥2 hours after exposure to alpha-gal. No treatment or cure is currently available. Despite the potential life-threating reactions associated with AGS, most patients perceive that health care providers (HCPs) have little or no knowledge of AGS. A U.S. web-based survey of 1,500 HCPs revealed limited knowledge of AGS, identified areas for continuing medical education, and described self-reported diagnostic and management practices. Overall, 42% of surveyed HCPs had never heard of AGS, and among those who had, fewer than one third knew how to diagnose the condition. Two thirds of respondents indicated that guidelines for the diagnosis and management of AGS would be useful clinical resources. Limited awareness and knowledge of AGS among HCPs likely contributes to underdiagnosis of this condition and inadequate patient management, and underestimates of the number of AGS patients in the United States, which currently relies on laboratory testing data alone.
Thompson JM, Carpenter A, Kersh GJ, Wachs T, Commins SP, et al.
MMWR. Morbidity and mortality weekly report •
Alpha-gal syndrome (AGS) is an emerging, tick bite-associated allergic condition characterized by a potentially life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal), an oligosaccharide found in most nonprimate mammalian meat and products derived from these mammals. Specific symptoms and severity of AGS vary among persons, and no treatment or cure is currently available. During 2010-2018, more than 34,000 suspected cases of AGS were identified in the United States, but current knowledge of where cases occur is limited. This study examined alpha-gal-specific IgE (sIgE) antibody testing results submitted to the commercial laboratory responsible for nearly all testing in the United States before 2022 to assess the geographic distribution and magnitude of this emerging condition. During January 1, 2017-December 31, 2022, a total of 357,119 tests were submitted from residences in the United States, corresponding to 295,400 persons. Overall, 90,018 (30.5%) persons received a positive test result in the study period, and the number of persons with positive test results increased from 13,371 in 2017 to 18,885 in 2021. Among 233,521 persons for whom geographic data were available, suspected cases predominantly occurred in counties within the southern, midwestern, and mid-Atlantic U.S. Census Bureau regions. These data highlight the evolving emergence of AGS and can be used to help state and local health agencies initiate surveillance and target public health outreach and health care provider education to high-risk localities.
Kersh GJ, Salzer J, Jones ES, Binder AM, Armstrong PA, et al.
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology •
The disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal-specific IgE (sIgE) antibodies. To evaluate tick exposure as a risk factor for AGS and elevated alpha-gal sIgE level. We conducted a case-control study comparing patients with AGS from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tick-borne pathogens. The patients with AGS were more likely to recall finding a tick on themselves (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.97-25.15), live near wooded forest (OR, 2.27; 95% CI, 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR, 5.58; 95% CI, 2.56-12.19). The patients with AGS were also more likely to report 4 or more tick bites (OR, 33.05; 95% CI, 9.92-155.12) and reactions at the site of tick bites (OR, 7.93; 95% CI, 3.74-16.80). Furthermore, elevated alpha-gal sIgE level was observed in 33% of the controls and was associated with tick exposure in the controls (OR, 4.25; 95% CI, 2.21-8.18). The results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE level.