Arguably man and woman’s best friend, the common cat began its longstanding friendship with the human race around 9,500 years ago, likely as a symbiotic relationship in which humans cared for cats who protected the fruits of agriculture from rodents. As happens in all relationships, our feline friends can cause us more than our fair share of headaches – in domestic life and as hosts of zoonotic diseases alike. The most prominent example of this involves the parasite Toxoplasma gondii, whose only host for sexual reproduction is the cat. While this parasite can alter the behaviour of intermediate hosts such as humans and rodents, presumably to facilitate transmission of T. gondii into cats, it remains unclear whether these behavioural changes are advantageous for the parasite’s long-term survival.
T. gondii was first described by the French medical doctors Nicolle and Manceaux in Tunisia. Since this discovery in 1908, it has taken the concerted efforts of clinicians, parasitologists, and veterinarians to unmask the multifaceted life cycle of the parasite. This is more than a story of mice and men and cats; while the sexual cycle takes place exclusively in the gut of species of the Felidae family, T. gondii can infect and divide asexually in all non-feline warm-blooded mammals. The products of these processes are oocysts and tissue cysts, respectively. Oocysts are shed into the environment via cat feces. As for tissue cysts, they result from parasite infection of muscle and/or the brain. Once either type of cyst is consumed, it invades host tissues and differentiates into gametocytes and oocysts in felines, or tissue cysts in non-felines, perpetuating the parasite’s life cycle. With its range of transmission routes and its capacity to infect in a zoonotic fashion – that is, between various species and not necessarily through cats – T. gondii is a highly successful pathogen, as evidenced by an estimated worldwide prevalence of 30% in humans.
So why is T. gondii not a major public health concern? In humans, infection causes transient flu-like symptoms before subsiding to lifelong latency in tissue cysts, with a few exceptions. In an immunodeficient individual, muscle and brain tissue cysts can reactivate and cause inflammation such as encephalitis. If a woman is infected for the first time during pregnancy, parasite invasion of the placenta can lead to encephalitis, visual impairment, and learning disabilities in the newborn or, more severely, miscarriage in the mother. Ultimately, the severity of T. gondii infection depends on immune status, as infection can remain asymptomatic for the entire lifespan of immunocompetent hosts.
If overt disease is rare in latent toxoplasmosis, why should we be concerned? Increasing evidence suggests that T. gondii brain cysts can cause behavioural and physiological changes. Studies have reported that infection in rodents can increase activity level and novelty seeking but impair learning and memory. In infected mice, these changes might explain a lesser aversion to cat urine and cat fur. Also alarming is the fact that researchers observe these behavioural changes in humans. In studies performed by Dr. Jaroslav Flegr, the Czech parasitologist found slower reaction times in T. gondii-positive patients, which worsened with prolonged latent toxoplasmosis. This may account for the higher rate of traffic accidents observed in infected individuals. In undergraduate cohorts, Flegr’s group found that infected male students are less sociable and tidy than their uninfected peers, whereas infected women trended in the opposite direction. Finally, T. gondii seropositivity is associated with a 2.7-fold increase in the risk of schizophrenia – over twice that linked to any known genetic polymorphism. On the one hand, the mechanism behind these changes likely involves increased synthesis of dopamine, which can be triggered by inflammation or directly synthesized by T. gondii tissue cysts. On the other hand, sex differences in toxoplasmosis may be due to an increase and decrease in testosterone, respectively, in infected men and women.
Fun fact: Male students with latent toxoplasmosis have shown evidence of increased attraction to cat urine, while female students showed the opposite!”
While researchers like Flegr continue to uncover the behavioural and psychiatric impact of T. gondii infection, others, such as Dr. R.C. Thompson, question whether host manipulation benefits the parasite or is simply a consequence of pathogenesis. For one, in rodents, there is no evidence that increased attraction to cat urine results in increased predation. Likewise, in men and women, T. gondii manipulation of humans is unlikely to benefit the parasite’s sexual reproduction – humans are not regularly preyed upon by felines. Rather, killing humans by inciting reckless behaviour prevents vertical transmission to future human hosts. Thus, foregoing sexual reproduction and opting for other transmission routes may be sufficient for permanence. For example, in the cat-free archipelago of Svalbard, Norway, an arctic environment one would presume to be inhospitable for the parasite (and cat-loving humans), T. gondii is nonetheless able to persist via asexual vertical transmission and carnivory among animals such as migratory geese, foxes, and walruses. Conversely, it has yet to be determined whether the parasite can also persist solely through vertical and oocyst transmission such as would occur on the Japanese island of Tashirojima, where cats outnumber humans 6 to 1. As with many resilient ecosystems, inclusive fitness and avirulence is the key to T. gondii survival, leaving transmission options open and maintaining host diversity.
Given its myriad transmission methods, how does one prevent T. gondii infection? Living in Canada is a good start; T. gondii seroprevalence is low in Canada, possibly owing to sanitation practices and our relatively colder climate. However, there are exceptions, as evidenced by the 1987 outbreak in the Inuit community of Kuujjuaq, northern Québec. Tissue cysts and oocysts can survive subzero temperatures as well as heating beyond 60°C. Thus, even with oocysts killed by frigid winters, tissue cysts can still be transmitted via consumption of undercooked animal flesh – food for thought before you decide to take a bite out of that rare steak. Barring glacial conditions, herbivores remain at risk for environmental exposure to oocyst-contaminated raw vegetables, unwashed fruit and unclean water. Thus, outdoor activities such as gardening and geophagia are also risk factors. Though it may sound cruel, pregnant women should also try to avoid cats or, at the very least, their litter boxes. When it comes to the cats themselves, indoor cats are less infectious than outdoor cats. Likewise, cats immune from a previous infection will shed fewer oocysts than cats infected for the first time. To minimize exposure indoors, litter boxes should be both cleaned with hot water and changed daily, as oocysts may take 1-5 days to become infectious. It is important to note, however, that the overall risk of T. gondii infection depends on a combination of environmental, cultural and sanitation factors, and studies show no correlation between parasite prevalence and cat caretaking alone. Infectivity is instead dependent on geocultural differences, which have culminated in disparate seroprevalences, ranging from 10% to 90% across human populations on Earth.
Fun fact: You can drink kopi luwak coffee (made from civet cat feces) without worrying about T. gondii infection because the civet cat is not a true felid!”
What about the evolutionary ramifications of mammalian coexistence with the parasite? In mice, T. gondii infection is lethal without toll-like receptors 11/12. However, these receptors recognize other pathogens and can also be found in giant pandas and horses, which are unlikely prey for cats. Stronger evidence for parasite pressure is found in reciprocal polymorphisms between a parasite kinase and a protective host GTPase. Laboratory mouse strains such as C57BL/6 lacking the GTPase cannot counteract the parasite kinase. Since the resulting lethality benefits neither host nor parasite, the kinase system likely evolved against host species with the capacity for prophylactic sterile immunity. So far, no human has been documented to have sterile immunity against the parasite. Interestingly, humans homozygous or heterozygous for the RhD blood group antigen are resistant to parasite-induced reflex impairment. This may explain the correlation between the geographic distribution of the RhD-positive group and T. gondii prevalence.
T. gondii is endemic worldwide and is likely to remain so due to its dynamic life cycle. However, given its capacity for numerous hosts and the sufficiency of asexual replication, we should attribute the parasite’s success to its evolutionary ingenuity rather than to the prevalence of our feline friends. In Toronto, homeless cats far exceed shelter resources, and T. gondii should not dissuade anyone from seeking a lasting friendship with one of the many shelter cats waiting to find a warm home.
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