Let's Talk Toxo
Most of us are, on some level, intrigued with infectious diseases in the same sense that we are intrigued with true crime. And often for similar reasons. We're fascinated by the lurking sense of danger, our interest is piqued by the curious nature of disease processes, and we also have many points of relation. Each of us has known illness, both personally and through our connection with others.
If you're an epidemiologist, at some point you will inevitably be asked something like, "what's your favorite disease/microbe?" For me, the answer has always been Toxoplasma gondii.
I've long had a soft spot for parasites. They deeply fascinate me. Their life-cycles - often complex and at times requiring multiple, disparate host species - seem almost counterintuitive to the precepts of natural selection, and yet they've adapted to a point of near perfection. Most parasites are deceptively simple creatures, but they wield powerful influence over their hosts and the environment.
My love for parasites began many years ago, in my biological anthropology undergraduate coursework, while studying the Rockefeller Institute's pre-CDC-era public health efforts. After reading Greer William's book, The Plague Killers, I was hooked [1]. The book weaves together three related tales of monumental 19th-Century public health work: the elimination of yellow fever, hookworm, and malaria from the United States. (Many people don't realize that all three of these were endemic in the U.S. prior to these efforts.)
That book was my gateway drug to public health, and after reading it, I became rather obsessed with epidemiology. My passion for parasites only grew, exploding upon the discovery of Professors Dickson Despommier and Vincent Racaniello, and their wonderful podcast, This Week in Parasitism [2]. Throughout my explorations and all of the wonderfully diverse academic encounters with parasites, T. gondii keeps returning to the forefront of my mind.
Toxoplasma gondii is a protozoan parasite, specifically Apicomplexa, which is single-celled and spore-forming. Like Plasmodium spp. (the parasites which cause malaria), T. gondii has a relict plastid organelle, called an apicoplast, which is vital for metabolic functions. This is fairly unique and plastids are more commonly found in algae or plants than in microbes (at least outside of Apicomplexa, the phylum name derived from this feature). The apicoplast is important from a clinical standpoint, as it serves as a target for herbicides and drugs like tetracycline [3,4].
T. gondii is an obligate intracellular parasite with just one definitive host: cats (felidae). Although cats are required for T. gondii to sexually reproduce and complete its life cycle, the parasite is adept at infecting virtually all warm-blooded animals. T. gondii is ubiquitous! Indeed, studies have found global pooled seroprevalence in hosts at 35% for domestic cats, and 59% for wild cats [Fig 1.][5]. In humans, seroprevalence is also high - estimated to be around 25.7% globally, with a very broad range across geographic regions (0.5-87.7%) [6]. There is a very reasonable chance, dear Reader, that you yourself have been infected with this parasite.
The life cycle of T. gondii begins with sexual reproduction in a felid host, and the host shedding of unsporulated oocysts in stool. These oocysts sporulate in the environment and are consumed by a variety of intermediate hosts. If the host is a prey animal (rodent), it might be consumed by a felid, where the sexual cycle will continue inside the definitive host. In other intermediate hosts, infection can be transmitted through tissue cysts and tachyzoites (Fig. 2.). (This is a very brief overview of the life cycle - there are already textbooks and website articles which expound in greater detail, if you are curious. See [7] in references below.)
Intermediate host infection may result in acute toxoplasmosis, which can cause severe damage to the central nervous system and even lead to host death, but in the majority of cases infection remains chronic and "benign." In these non-acute cases, T. gondii infection manifests in some very interesting ways. Infected rodents tend to lose their instinctive fear of cats, making them easier prey and increasing the parasite's chance at successful reproduction. Their aversion to cat urine wanes, sometimes becoming inverted to the point of attraction, so rodents become more likely to wander in a cat's territory or even seek it out.
Infection in humans can cause elevated dopamine and testosterone production, increased risk-taking behavior, and higher levels of aggression. Similar findings have been observed in other social animals, like wolves [8]. Considering the high seroprevalence of T. gondii in humans and other mammalian species, these effects may have important implications for our understanding of social dynamics, hierarchies, and leadership (fig. 3.). Indeed, toxoplasmosis has been associated with schizophrenia, suicidality, road rage incidence, and entrepreneurship!
In addition to the significance of T. gondii's ability to modify intermediate host behavior, the parasite may also play a role when it comes to other health conditions, particularly autoimmune disease. Recent studies suggest that toxoplasmosis might actually have a protective effect when it comes to conditions like Multiple Sclerosis (MS) [9]. Similar effects have been demonstrated with other parasites, such as sheep or pig whipworms, where benign infection in humans has resulted in immunomodulation and reduced inflammatory response, effectively relieving some symptoms of IBD and MS [10].
T. gondii is an endlessly-fascinating parasite, and we are only just beginning to understand its ecological and social implications. This blog entry barely begins to scratch the surface, but I hope it helps pique your interest to know more. And who knows - after your own obsessive deep-dive, maybe the next time someone asks you about your favorite microbe, you'll feel compelled to answer, "Toxoplasma gondii!"
REFERENCES
1. Williams, Greer (1969). The Plague Killers. https://a.co/d/bq7sFXi
2. This Week in Parasitism, TWiP (2024). https://www.microbe.tv/twip/
3. Dubey, J.P. (1996). Medical Microbiology, 4th Ed. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK7752/
4. Despommier et al. (2019). Parasitic Diseases, 7th Ed. https://a.co/d/1VNpLtr
5. Montazeri, M. et al (2020). The global serological prevalence of Toxoplasma gondii in felids during the last five decades (1967–2017): a systematic review and meta-analysis. Parasites and Vectors: 13(82). https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-020-3954-1
6. Molan, A. et al (2019). Global status of Toxoplasma gondii infection: systematic review and prevalence snapshots. Tropical Biomedicine: 36(4). https://pubmed.ncbi.nlm.nih.gov/33597463/#:~:text=The%20search%20identified%20152%20published,to%20be%200.5%20%2D%2087.7%25.
7. Attias, M. et al (2020). The life-cycle of Toxoplasma gondii reviewed using animations. Parasites and Vectors: 13(588). https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-020-04445-z
8. Meyer, C.J. et al (2022). Parasitic infection increases risk-taking in a social, intermediate host carnivore. Communications Biology: 5(1180). https://www.nature.com/articles/s42003-022-04122-0
9. Pawełczyk, A. et al (2024). Seroprevalence of Toxoplasma gondii and Borrelia burgdorferi infections in patients with multiple sclerosis in Poland. Scientific Reports: 14(11015). https://www.nature.com/articles/s42003-022-04122-0
10. Science Daily (2014). Pig whipworm genome may aid to treat autoimmune diseases. https://www.sciencedaily.com/releases/2014/06/140620103205.htm
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