Dear Toxoplasma gondii, do you feel neglected?

fotovapl / stock.adobe.com

As the world continues to plod through what has apparently become “The Age of SARS-CoV-2,” it behooves the well-rounded veterinarian to remember that other pathogens remain. Toxoplasma gondii is perhaps the least appreciated parasite in relation to its ability to cause disease. T gondii has perhaps the broadest host range of any parasite; it infects most species of warm-blooded animals and is considered a ubiquitous organism.¹ Despite the fact that toxoplasmosis is considered a leading cause of death from foodborne illness in the United States, it is also categorized as a neglected parasitic infection. A surprisingly large number of infected or at-risk individuals, likelihood of underreporting or missed diagnoses due to lack of awareness and effective diagnostic tests, and lack of effective treatments or disease prevention all land T gondii in the neglected category.² Why is T gondii so neglected?

The basics

First, let’s focus on the basics of the T gondii life cycle—how does this intracellular protozoan parasite survive? For T gondii (and for my great-grandmother’s neighbor, Vivian), the world revolves around cats. Felids are the only definitive hosts of T gondii, and therefore the only ones that shed oocysts. The oocysts must then sporulate to become infective, which takes 1 to 5 days, following excretion in the cat feces. Intermediate hosts, such as rodents or birds, ingest the oocysts in contaminated food or water. Once in the gut, the oocysts transform into tachyzoites, which then make their way into muscle or neural tissue and become bradyzoites, encysted in the tissue. When a felid consumes the intermediate host, the bradyzoites in the tissue are released into the feline gut, where they invade intestinal epithelial cells. Some of them mature into merozoites and begin sexual reproduction to yield oocysts that are shed in the cat’s feces. Tachyzoites are capable of asexual reproduction while in the intermediate host. Triggers for the different stages of the life cycle and criteria for asexual vs sexual reproduction remain largely unknown.³

Clinical manifestations

T gondii can infect and affect nearly any warm-blooded animal.¹ Yet, clinical presentations can vary widely and typically have a long period between initial infection and the manifestation of clinical disease. As tachyzoites migrate through tissue, they are the stage of the parasite that is typically responsible for clinical disease. The period from initial infection to clinical disease is determined by the immune status of the infected host. Immunocompetent animals effectively control tachyzoite activity and spread, limiting toxoplasmosis to a subclinical illness.⁴ Animals lacking robust immune systems are vulnerable to the development of clinical disease at initial infection, or later in life once the immune system weakens. Young and older animals are more likely to manifest clinical illness such as pneumonia, myocarditis, hepatic necrosis, myositis, encephalitis, etc.⁴ If a pregnant animal is infected, the tachyzoites can cause placental necrosis or directly affect the fetus, producing necrosis in multiple organs or, ultimately, fetal death. Even though cats are the definitive host for T gondii, felids are not immune from clinical toxoplasmosis. If a cat is immunocompromised, either from feline immunodeficiency virus or because of chronic organ disease, then clinical toxoplasmosis may develop.⁴

Treatment

No vaccine is available for the prevention of toxoplasmosis, and clinical treatment is less than ideal following the determination of clinical disease. Although arresting the tachyzoite stage may be accomplished with either sulfa-based drugs or, more recently, ponazuril, the tissue damage produced by the parasite may be ultimately irreversible. In addition, bradyzoites are not affected by currently recommended therapies and may remain encysted only to cause illness at a later stage. All this only applies once the diagnosis has been made, which is tricky. Between equivocal antibody titers, intermittent shedding, and long-term encysting in tissues, it is difficult to establish which diagnostic method is best or even the most reliable.

Prevalence

How prevalent is T gondii in humans? In the United States? And precisely how deadly is it in humans? If you thought we had all “outgrown” this parasite as a real threat, consider that the Centers for Disease Control and Prevention says “toxoplasmosis is considered to be a leading cause of death attributed to foodborne illness in the United States.”⁵ Roughly 11% of the US population older than 6 years has been infected with T. gondii.⁶ Beyond mortality statistics, a “significant relationship between T. gondii seroprevalence and bipolar disorder type I for respondents [with] both manic and major depression symptoms” has been established, although still perceived as controversial in some circles.⁷ What about us? Risk factors for seropositivity among veterinarians in a recent report included older age, rural living, tasting beef during cooking, and not doing small animal practice.⁸ I have never been more enthusiastic about my next shift at a small animal practice. The good news is that a robust immune system keeps clinical disease in check. So take that vitamin D supplement each morning with some gusto.

What’s in it for me?

Beyond the statistics, though, sit some real issues for veterinarians and support staff in any type of practice. Despite the dogma that active nonlethal management strategies are effective, the feral cat population continues to rise, indicating that T gondii is not going away anytime soon. As the veterinary profession continues to beat the drum for responsible ownership and annual examinations of all cats, more cat owners will be visiting their local veterinarians. Veterinarians should make an effort to remind, if not provide initial information, about all zoonotic risks presented by pets, including cats. I am not advocating a focus on T gondii; however, I am in favor of working to alter its neglected status. Multiple reliable and credible organizations provide free client-appropriate handouts on toxoplasmosis risk to practitioners—leverage this resource to get your clients’ attention. Commit to breaking your habit of tasting beef while cooking and recognize the silver lining for your career in small animal practice. A decade from now, let’s work together to change the answer when we ask the question, “Hey Toxoplasma gondii, do you still feel neglected?”

References

1. Toxoplasmosis. Centers for Disease Control and Prevention. Updated November 10, 2020. Accessed June 20, 2021. https://www.cdc.gov/dpdx/toxoplasmosis/index.html
2. Parise ME, Hotez PJ, Slutsker L. Neglected parasitic infections in the United States: needs and opportunities. Am J Trop Med Hyg. 2014;90(5):783-785. doi:10.4269/ajtmh.13-0727
3. Sharma J, Rodriguez P, Roy P, Guiton PS. Transcriptional ups and downs: patterns of gene expression in the life cycle of Toxoplasma gondii. Microbes Infect. 2020;22(10):525-533. doi:10.1016/j.micinf.2020.09.001
4. Dubey JP. Overview of toxoplasmosis. Merck Veterinary Manual. Updated October 2013. Accessed June 20, 2021. https://www.merckvetmanual.com/generalized-conditions/toxoplasmosis/overview-of-toxoplasmosis
5. Parasites - toxoplasmosis (toxoplasma infection). Centers for Disease Control and Prevention. Updated August 29, 2018. Accessed June 20, 2021. https://www.cdc.gov/parasites/toxoplasmosis/index.html
6. Parasites - toxoplasmosis (toxoplasma infection). Centers for Disease Control and Prevention. Updated September 4, 2018. Accessed June 20, 2021. https://www.cdc.gov/parasites/toxoplasmosis/epi.html
7. Pearce BD, Kruszon-Moran D, Jones JL. The relationship between Toxoplasma gondii infection and mood disorders in the third National Health and Nutrition Survey. Biol Psychiatry. 2012;72(4):290-295. doi:10.1016/j.biopsych.2012.01.003
8. Siponen AM, Kinnunen PM, Koort J, et al. Toxoplasma gondii seroprevalence in veterinarians in Finland: older age, living in the countryside, tasting beef during cooking and not doing small animal practice associated with seropositivity. Zoonoses Public Health. 2019;66(2):207-215. doi:10.1111/zph.12550

Jenifer Chatfield, DVM, DACZM, DACVPM, is staff veterinarian at 4J Conservation Center, an instructor for FEMA/DHS courses, and a regional commander for the National Disaster Medicine System Team. She graduated from Texas A&M University’s CVM and has pursued emergency medicine and zoo medicine throughout her career. She owned 2 emergency clinics and has been the senior veterinarian in a zoo. She completed fieldwork in Madagascar and South America and continues to explore new areas of medicine as an associate editor for the Journal of Zoo and Wildlife Medicine for more than 10 years. She is a Medical Reserve Corps member and developed “Veterinary Support to Zoological Animals in a Disaster” for the National Veterinary Response Teams training curriculum. She has chaired the Florida Veterinary Medical Association’s (FVMA) One Health Committee and cochaired FVMA’s Disaster Response Committee.