Canadian Meat Lovers Beware: The American Hitch-Hiker!

On By hpiuofcIn Uncategorized

By Justyna Kruczalak

Edited by Emily DeMichele

The lone star tick species displays sexual dimorphism, the female is well characterized by the white dot on the scutum of the tick. © Katja Schulz, some rights reserved (CC-BY).

The Lone Star Tick and Alpha-gal

Tickborne illnesses have been increasing within the past decades as temperatures rise in regions that were previously characterized by cooler temperatures. Ticks are venturing into new areas due to their hosts shifting their native range, which are typically deer, rodents, and migratory birds. The ectoparasite Lone Star tick (Ablyomma americanum) is found throughout the southwest and midwestern United States [1]. Still, recent findings have suggested that this tick is also moving North with confirmed observations already in Ontario [2]. The Lone Star tick is a major vector of various pathogens, such as ehrlichiosis, and tularemia, and is well recognized for causing Alpha-gal syndrome (AGS), a rare red meat allergy commonly caused by the bite of the Lone Star tick [3]. When AGS individuals consume red meat and mammalian by-products, a severe allergic reaction occurs, resulting in individuals having to stop consuming red meat and products involving red meat entirely. There is no current cure for AGS, but dietary lifestyle changes are advised. Substitution of red meat is recommended to prevent allergic reactions and medical therapies can also be implemented depending on if patients with AGS are symptomatic or may have a high risk for exposure to products containing alpha-gal. Healthcare providers with knowledge of this condition have also reported complete remission of the food allergy in certain cases. However, a statement made by Scott Commins, an allergy specialist at the University of North Carolina at Chapel Hill and a co-author of the CDC HPC survey, indicated most people are not even aware of having AGS [4].

SHOW ME THE NUMBERS!  

In the United States, the CDC (Centers for Disease Control) recently reported a study where between 2010 – 2022, more than 34,000 individuals (about twice the seating capacity of Madison Square Garden) tested positive for AGS from alpha-gal–specific IgE (sIgE) antibody [5] . The number of individuals with AGS has increased by 6-fold from 1110 in 2011 to 7798 in 2018. The number is believed to be much higher due to misdiagnosis of the allergy for other conditions, such as Pork-Cat syndrome which is also another rare allergic condition, but to a protein found in pork and cat dander [6]. A recent survey released in 2022 by the CDC indicated United States healthcare practitioners (HCP) have little knowledge of AGS. Out of 1500 HCPs, 42% were not aware of AGS, and 35% within that group did not feel confident in their ability to diagnose it. Uniquely, 48% of HCPs that were aware of AGS did not know what diagnostic tests to order, and only 5% of that group were able to correctly answer questions regarding etiology, treatment, and patient counseling. Another report recorded over 90,000 cases from 2017 to 2022, which is almost three times the 34,000 cases mentioned previously between 2010 to 2018. Additionally, an epidemiologist at the CDC Rickettsial Zoonoses Branch reported to the National Post that patients usually must visit multiple healthcare providers and an allergist to be diagnosed [7]. A 2015 study found that 79% of patients took an average of 7.1 years for an individual to be accurately diagnosed with AGS, highlighting the shortcomings of the United States medical system in helping individuals with this allergy [8].  

The Displeasing Discovery

AGS is considered relatively new given it was first identified in 2009. When the chemotherapeutic drug Cetuximab was released at that same time, it was found to cause allergic reactions in patients as individuals presented with cases of hives and anaphylaxis after their first dose. Upon further research, individuals who were not on Cetuximab were also having similar reactions, but all patients felt sick after eating red meat and had at least one or more tick bites. Cases were more prevalent in the Southwest, which is where the tick is localized. Researchers then discovered that chemo patients had antibodies to the sugar molecule alpha-gal before drug administration, explaining the allergic reaction to the drug containing alpha-gal [9].

Life stages of the lone star tick (Abylomma americanum), from top left to right: larva, nymph, adult female, and adult male. Credit: Chris Holderman

Infographic of AGS made by Justyna Kruczalak

Alpha Who?

When Ablyomma americanum bites a person, the tick’s saliva releases a sugar molecule alpha-gal, also formally known as galactose-alpha-1,3-galactose, into the person’s skin [10]. Alpha-gal is found within nonprimate mammalian tissue so ticks carry these alpha-gal molecules due to the ingestion of bloodmeals from other non-primate animals, commonly cows and pigs.

After the tick bite, the immune system releases IgE antibodies which specifically target the alpha-gal antigen. When AGS individuals consume red meat, IgE antibodies bind to the alpha-gal antigens and the IgE-alpha–gal complexes trigger allergic reactions including hives, itchy and scaly skin, swelling of lips, tongue, and throat, as well as stomach pain, nausea, vomiting, and anaphylaxis [11].  

Alpha-gal is found in many products making it difficult to reduce exposure. Beef, pork, lamb, milk, and cheese are all notable examples of alpha-gal products. However, many other products also contain alpha-gal you may not know about, such as gelatin [12]. Gelatin is produced from the collagen, hooves, and bones of animals, so it may contain alpha-gal. Products such as gummies, medical tablets (acetaminophen), and vaccines (i.e. against Measles, Mumps, Rubella, and Shingles) also may all contain alpha-gal [13]. Allergic symptoms occur from 3-6 hours after exposure to mammalian meats, but symptoms are individual-specific. This variability in reaction has made recognizing the condition difficult.

Large allergic reaction to the bite of another suspected meat allergy tick, Australian Paralysis tick (Ixodes holocyclus). Reactions are most likely mediated by IgE antibodies.

Stephen L. Doggett, Senior Hospital Scientist, Pathology West, ICPMR (level 3), Westmead Hospital, Locked Bag 9001, Westmead NSW 2145, Australia.

World map highlighting different species of ticks implicated in alpha-gal. Credit: Olivera-Ardid, S., Bello-Gil, D., Tuzikov, A., Araujo, R. N., Ferrero-Alves, Y., García Figueroa, B. E., Labrador-Horrillo, M., García-Pérez, A. L., Bovin, N., & Mañez, R. (2022). Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases. Frontiers in Immunology, 13, 873019.

Not the only tick? ICK!

The Lone Star is not the only tick implicated in the food allergy. Alpha-gal syndrome has been identified in 17 countries on all continents, except Antarctica [14]. Scientific findings have found alpha-gal molecules in other tick species, and researchers are currently looking into the Australian Paralysis tick (Ixodes holocyclus), Ixodes (Endopalpiger) australialiensis), Castor Bean tick (Ixodes ricinus), and Asian long-horned tick (Haemphysalis longicornis) due to various reports of red meat allergies associated with these tick species [15]. Further identification of ticks associated with AGS is still ongoing, such as in South Africa where there have been reports of the allergy, but not the specific tick that may cause the condition [16].

Oh Canada?

As of 2023, there are no established populations of the Lone Star tick in Canada, but sightings have been increasing over the past five years. According to a private tick identification company (Geneticks Canada) there has been an increase in submissions of Lone Star tick to the company, from 1-2 identifications a year to 6 in the Ontarian spring season alone reported by the CBC at the time of this article [17]. Another tick-tracking website (etick.ca) also has reported a significant increase in Lone Star submissions. In 2019, the website reported 4 ticks within Ontario. This number has jumped to 22 in 2023, a 450% increase in four years. Within the 10 provinces and 3 territories of Canada, only 6 provinces (Manitoba, Alberta, Nova Scotia, Quebec, Saskatchewan, and Ontario) have reported Lone Star ticks to date. Presently, etick.ca has identified 110 lone star ticks from 2017 to 2023 in Canada, highlighting the increasing threat of these non-native species, particularly in Ontario. Climate modeling predicts range expansion[18] and the Public Health Agency of Canada (PHAC) projects a continued increase in Lone Star tick occurrences and establishment [19].

In all, AGS is a tickborne illness that does not have sufficient recognition due to being a recently discovered food allergy for less than two decades. This condition is a growing concern for medical entomologists and health care practitioners as AGS cases have increased significantly and there is no current cure. Further research into AGS and tick species is necessary to improve our understanding of AGS. Even though this condition is non-infectious: it is prevalent due to its global distribution, low recognition, and severity of symptoms that impact daily life. To reduce misdiagnosis of AGS, national surveillance programs and initiatives that aim to increase awareness and recognition of this condition are essential.

References

  1. CDC – Ticks Home – Regions Where Ticks Live [Internet]. 2023 [cited 2023 Nov 14]. Available from: https://www.cdc.gov/ticks/geographic_distribution.html
  2. Fowler PD, Nguyentran S, Quatroche L, Porter ML, Kobbekaduwa V, Tippin S, et al. Northward Expansion of Amblyomma americanum (Acari: Ixodidae) into Southwestern Michigan. J Med Entomol. 2022 Sep;59(5):1646-1659.
  3. Zhang B, Hauk M, Clyne J. Alpha-gal antibody due to Lone Star tick bite, a unique case of allergic reaction. IDCases. 2020 Jan 1;22:e00908.
  4. Erika Edwards. Doctors often miss symptoms of meat allergy linked to lone star ticks, CDC finds [Internet]. NBC News. 2023 [cited 2023 Nov 14]. Available from: https://www.nbcnews.com/health/health-news/alpha-gal-syndrome-red-meat-ticks-lone-star-rcna96636 
  5. Binder AM, Commins SP, Altrich ML, et al. Diagnostic testing for galactose-alpha-1,3-galactose, United States, 2010 to 2018. Ann Allergy Asthma Immunol 2021;126:411–16.e1. PMID:33422649
  6. Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients. Expert Rev Clin Immunol. 2020 Jul;16(7):667-677. doi: 10.1080/1744666X.2020.1782745. Epub 2020 Jul 8. PMID: 32571129; PMCID: PMC8344025.
  7. Carly Penrose. Carnivores beware: Tick that causes red meat allergy found in Canada [Internet]. National Post. 2022 [cited 2023 Nov 14]. Available from: https://nationalpost.com/news/canada/carnivores-beware-tick-that-causes-red-meat-allergy-found-in-canada
  8. Flaherty MG, Kaplan SJ, Jerath MR. Diagnosis of Life-Threatening Alpha-Gal Food Allergy Appears to Be Patient Driven. J Prim Care Community Health. 2017 Oct;8(4):345-348.
  9. Steinke JW, Platts-Mills TAE, Commins SP. The alpha-gal story: Lessons learned from connecting the dots. Journal of Allergy and Clinical Immunology. 2015 Mar 1;135(3):589–96.
  10. Sharma SR, Crispell G, Mohamed A, Cox C, Lange J, Choudhary S, Commins SP, Karim S. Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism. Front Cell Infect Microbiol. 2021;11:775371.
  11. CDC – Ticks – Alpha-gal Syndrome [Internet]. 2023 [cited 2023 Nov 14]. Available from: https://www.cdc.gov/ticks/alpha-gal/index.html
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  13. Stone CA Jr, Hemler JA, Commins SP, Schuyler AJ, Phillips EJ, Peebles RS Jr, Fahrenholz JM. Anaphylaxis after zoster vaccine: Implicating alpha-gal allergy as a possible mechanism. J Allergy Clin Immunol. 2017;139(5):1710–1713.e2. doi: 10.1016/j.jaci.2016.10.03
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  15. Kwak M, Somerville C, van Nunen S. A novel Australian tick Ixodes (Endopalpiger) australiensis inducing mammalian meat allergy after tick bite Asia Pac Allergy. 2018 Jul 26;8(3):e31. doi: 10.5415/apallergy.2018.8.e31. PMID: 30079309; PMCID: PMC6073180
  16. Gray CL, Zyl AV, Strauss L. “Midnight anaphylaxis” to red meat in patients with alpha-gal sensitisation : a recent discovery in the food allergy world and a case report from South Africa : guest review. Current Allergy & Clinical Immunology. 2016;29(2):102–4.
  17. Tara De Boer. As meat allergies from tick bites become more common in the U.S., here’s what we know about cases in Canada [Internet]. CTV News. 2023 [cited 2023 Nov 14]. Available from: https://www.ctvnews.ca/health/as-meat-allergies-from-tick-bites-become-more-common-in-the-u-s-here-s-what-we-know-about-cases-in-canada-1.6503163
  18. Bree Iskandar. Cases of alpha-gal syndrome caused by tick bites on the rise, CDC reports [Internet]. STAT News. 2023 [cited 2023 Nov 14]. Available from: https://www.statnews.com/2023/07/27/alpha-gal-syndrome-lone-star-tick-bite-red-meat-allergy/
  19. Jennifer La Grassa. A red meat allergy caused by ticks is rising in the U.S. Canada’s national health agency says it’s rare here [Internet]. CBC News. 2023 [cited 2023 Nov 14]. Available from: https://www.cbc.ca/news/health/lone-star-tick-climate-change-allergy-1.6921603#:~:text=AGS%20is%20an%20allergic%20condition,a%20sugar%20%E2%80%94%20into%20the%20blood.

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