Geographic Distribution of Suspected Alpha-gal Syndrome Cases — United States, January 2017–December 2022

Thompson, Julie M.; Carpenter, Ann; Kersh, Gilbert J.; Wachs, Tyler; Commins, Scott P.; Salzer, Johanna S.

doi:10.15585/mmwr.mm7230a2

Cited by 27 publications

(15 citation statements)

References 10 publications

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“…Interestingly, epidemiologic surveillance studies have found a correlation between the geographic distribution of Aa ticks, high titer of α-gal sIgE antibody in AGS patients (Commins et al, 2014;Kersh et al, 2023). Beyond epidemiologic evidence from a recent case-control study, no direct and definitive evidence of tick bite induced AGS exists in humans.…”

Section: Discussionmentioning

confidence: 99%

Tick bite-induced Alpha-Gal Syndrome and Immunologic Responses in an Alpha-Gal Deficient Murine Model

Sharma,

Choudhary,

Vorobiov

et al. 2023

Preprint

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IntroductionAlpha-Gal Syndrome (AGS) is a delayed allergic reaction due to specific IgE antibodies targeting galactose-α-1,3-galactose (α-gal), a carbohydrate found in red meat. This condition has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases estimated in the United States alone. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate the levels of α-gal specific IgE. However, the precise mechanism by which tick bites influence the host’s immune system and contribute to the development of AGS remains poorly understood. This study investigates various factors related to ticks and the host associated with the development of AGS following a tick bite, using mice with a targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism.MethodsLone-star tick (Amblyomma americanum) and gulf-coast tick (Amblyomma maculatum) nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess the host immune response. Antibody responses in sensitized mice were also determined.ResultsOur results showed a significant increase in the titer of total IgE, IgG1, and α-gal IgG1 antibodies in the lone-star tick-sensitized AGKO mice compared to the gulf-coast tick-sensitized mice. Pork challenge inAm. americanum-sensitized mice led to a decline in body temperature after the meat challenge. Gene expression analysis revealed thatAm. americanumbites direct mouse immunity toward Th2 and facilitate host sensitization to the α-gal antigen, whileAm. maculatumdid not.ConclusionThis study supports the hypothesis that specific tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions or AGS, thereby providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.

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Section: Discussionmentioning

confidence: 99%

Tick bite-induced Alpha-Gal Syndrome and Immunologic Responses in an Alpha-Gal Deficient Murine Model

Sharma,

Choudhary,

Vorobiov

et al. 2023

Preprint

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“…Surveillance maps published by the Centers for Disease Control and Prevention (CDC) show the lone star tick’s expanding reach across the southern and eastern US . A CDC review of 233 521 individuals undergoing serological testing for alpha-gal syndrome suggests that suspected cases occurred primarily in the southern, midwestern, and mid-Atlantic US Census Bureau regions . Seroprevalence estimates of alpha-gal sensitization in the southeastern US range from 20% to 31% .…”

Section: Epidemiology Common Food Allergens and Natural Historymentioning

confidence: 99%

“…From 2011 to 2018, there was a 6-fold increase in alpha-gal–specific IgE antibody tests, suggesting that alpha-gal sensitization rates in the US may be increasing and/or testing is increasing. One CDC report estimates that between 96 000 and 450 000 individuals in the US may have developed alpha-gal syndrome since 2010 …”

Section: Epidemiology Common Food Allergens and Natural Historymentioning

confidence: 99%

Management of Food Allergies and Food-Related Anaphylaxis

Iglesia,

Kwan,

Virkud

et al. 2024

JAMA

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ImportanceAn estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US. IgE-mediated food allergies may cause anaphylaxis and death. A delayed, IgE-mediated allergic response to the food-carbohydrate galactose-α-1,3-galactose (alpha-gal) in mammalian meat affects an estimated 96 000 to 450 000 individuals in the US and is currently a leading cause of food-related anaphylaxis in adults.ObservationsIn the US, 9 foods account for more than 90% of IgE-mediated food allergies—crustacean shellfish, dairy, peanut, tree nuts, fin fish, egg, wheat, soy, and sesame. Peanut is the leading food-related cause of fatal and near-fatal anaphylaxis in the US, followed by tree nuts and shellfish. The fatality rate from anaphylaxis due to food in the US is estimated to be 0.04 per million per year. Alpha-gal syndrome, which is associated with tick bites, is a rising cause of IgE-mediated food anaphylaxis. The seroprevalence of sensitization to alpha-gal ranges from 20% to 31% in the southeastern US. Self-injectable epinephrine is the first-line treatment for food-related anaphylaxis. The cornerstone of IgE-food allergy management is avoidance of the culprit food allergen. There are emerging immunotherapies to desensitize to one or more foods, with one current US Food and Drug Administration–approved oral immunotherapy product for treatment of peanut allergy.Conclusions and RelevanceIgE-mediated food allergies, including delayed IgE-mediated allergic responses to red meat in alpha-gal syndrome, are common in the US, and may cause anaphylaxis and rarely, death. IgE-mediated anaphylaxis to food requires prompt treatment with epinephrine injection. Both food-protein allergy and alpha-gal syndrome management require avoiding allergenic foods, whereas alpha-gal syndrome also requires avoiding tick bites.

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“…13,14 Awareness of and testing for AGS appear to be increasing, with more than 90 000 individuals receiving positive test results between 2017 and 2022. 15 The most overt symptoms are similar to a typical food allergy, including angioedema, urticaria, and anaphylaxis. 16 In contrast, some individuals with elevated α-gal IgE levels may not experience any symptoms and are categorized as sensitized to α-gal.…”

Section: Introductionmentioning

confidence: 98%

“…In some individuals, α-gal IgE results in a delayed-onset reaction after ingestion of mammalian meat or its products, known as α-gal syndrome (AGS) . Awareness of and testing for AGS appear to be increasing, with more than 90 000 individuals receiving positive test results between 2017 and 2022 . The most overt symptoms are similar to a typical food allergy, including angioedema, urticaria, and anaphylaxis .…”

Section: Introductionmentioning

confidence: 99%

Tick-Borne Disease Infections and Chronic Musculoskeletal Pain

Zychowski,

Alvarez,

Abernathy

et al. 2024

JAMA Netw Open

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ImportanceTick-borne diseases (TBDs) other than Lyme disease, such as spotted fever group rickettsiosis, ehrlichiosis, and galactose-α-1,3-galactose (α-gal) syndrome, are an emerging public health issue. Long-term sequelae secondary to Ehrlichia or Rickettsia infection are uncommon; however, musculoskeletal symptoms are often attributed to prior tick exposure.ObjectiveTo evaluate the potential associations between prior exposure to TBDs and musculoskeletal symptoms, including radiographic osteoarthritis.Design, Setting, and ParticipantsThis cross-sectional study analyzed serum samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing longitudinal, population-based study in Johnston County, North Carolina. Biospecimen testing and analysis were performed between May 2022 and November 2023. Participants in the JoCo OA project are noninstitutionalized White and Black Johnston County residents 45 years or older.Main Outcome and MeasuresThe primary outcome was seropositivity with Ehrlichia IgG, Rickettsia IgG, and/or α-gal IgE and musculoskeletal symptoms. Secondary outcomes included risk factors associated with elevated α-gal IgE and weighted population point prevalence rates. Participants completed questionnaires, underwent physical assessments, and provided biospecimens for serological testing. Multivariable models were used to estimate associations of interest.ResultsOf the 605 participants who completed the fourth visit of the JoCo OA project, 488 (80.7%) had serum samples available for testing. The 488 participants had a median (IQR) age of 72 (68-78) years and included 336 females (68.9%) and 161 Black (33.0%) and 327 White (67.0%) individuals. The overall weighted point prevalence was 8.6% (95% CI, 5.9%-11.3%) for Ehrlichia IgG, 17.1% (95% CI, 12.6%-21.5%) for Rickettsia IgG, and 19.6% (95% CI, 15.3%-23.8%) for α-gal IgE level greater than 0.1 IU/mL. Only α-gal IgE was associated with knee pain, aching or stiffness (mean ratio, 1.30; 95% CI, 1.09-1.56). Antibodies to Rickettsia, Ehrlichia, and α-gal were not associated with symptomatic radiographic knee osteoarthritis. Male sex (odds ratio [OR], 2.63; 95% CI, 1.55-4.47), current smoker status (OR, 3.55; 95% CI, 1.38-9.18), and an attached tick bite in the past 5 years (OR, 3.99; 95% CI, 2.22-7.15) were all risk factors that were associated with α-gal IgE level greater than 0.1 IU/mL. Despite only 84 individuals (17.2%) recalling a tick bite in the past 5 years, 178 (36.5%) had evidence of prior tick-borne exposure, suggesting frequent human-tick interactions.Conclusions and RelevanceResults of this cross-sectional study indicate no association between Ehrlichia or Rickettsia seropositivity and chronic musculoskeletal symptoms or osteoarthritis. Further investigation is needed into the pathogenesis of α-gal syndrome and interventions to reduce human-tick interactions.

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Geographic Distribution of Suspected Alpha-gal Syndrome Cases — United States, January 2017–December 2022

Cited by 27 publications

References 10 publications

Tick bite-induced Alpha-Gal Syndrome and Immunologic Responses in an Alpha-Gal Deficient Murine Model

Tick bite-induced Alpha-Gal Syndrome and Immunologic Responses in an Alpha-Gal Deficient Murine Model

Management of Food Allergies and Food-Related Anaphylaxis

Tick-Borne Disease Infections and Chronic Musculoskeletal Pain

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