Toxoplasma gondii: The Puppeteer

Over a third of the world is infected.

It subtly manipulates the chemicals in the human brain, influencing our behavior.

It’s been at work for thousands of years.

And now it’s coming to harvest the fruit of its labors.

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Toxoplasma gondii; Source: Wikimedia

          Okay, the last line was added for dramatic effect. However, despite sounding like a cliché science-fiction movie, the rest is actually true! Toxoplasma gondii is a parasite that has been infecting warm-blooded creatures for thousands of years—in fact, it is one of the most common parasitic infections of animals worldwide and has even been found in arctic foxes and polar bears [7].

Life Cycle

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Source: vetpda.ucdavis.edu

T. gondii  is an infectious protozoan, which means it is a motile, single-celled organism. It has a bizarre life cycle; it requires a feline (such as our darling house cats) as a host to sexually reproduce, but it also requires an intermediate creature in which it can asexually reproduce. We’re not sure exactly why such strange life cycles have evolved, but the fact is that T. gondii can only produce its oocytes (reproductive cells) in the intestinal cells of felines. These are then excreted, contaminating both cat feces and the soil around them [4,7,9].

This is where things may start to sound familiar; the infamous, schizophrenia-causing cat-litter parasite is indeed T. gondii. If it makes you feel any better, it takes 1-5 days to become infective, so if you clean your cat litter regularly you don’t need to worry (this is a great way to make sure your child or spouse does the chore on time; just tell them if they don’t, their brains will become infected by an insidious parasite) [4].

In any case, these oocytes can survive in the soil for over a year and persist through freezing temperatures for 18 months [3]. This allows ample time for an intermediate host to come in contact with the parasite while grazing, eating seeds, or touching feces [4,7]. The oocytes then invade the animal’s intestinal cells, undergo asexual reproduction and enter the blood and lymphatic system [1]. The parasites form cysts in the muscle tissue and make themselves at home in the host’s brain, where they remain for the entirety of the host’s life [9].

This is where things get very interesting. Because the parasite needs to get back into a feline host to reproduce sexually and start the cycle all over again, extreme selective pressures have acted upon traits that increase its transmission efficiency back into a feline [10]. As it gets back into cats by being consumed (consequently, humans and carnivores can also become infected by eating raw or undercooked meat of infected animals [7]), the parasite has evolved mechanisms to manipulate its host’s behavior to increase the chances of it being eaten.

Behavior Modification

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Source: thegatewaypundit.com

               By zeroing in on the brain, T. gondii is in the prime location to pull the strings controlling its host’s behavior. This is clearly evident in rodent hosts, which are the most common prey for felines. Infected mice and rats develop a fatal attraction for the pheromone found in cat urine, causing them to seek out the felines against their natural instincts [9].  While this is an extremely specific behavioral change, but studies have found more general impacts as well: dopamine levels in infected brains rise. Dopamine is a neurotransmitter in the brain with a plethora of functions, influencing emotional responses, reward-driven learning, movement, and other functions. In rodents, this increase results in an increase in activity and decrease in natural fear, causing behavior that would attract a cat’s attention and increase the likelihood of the rats being caught and eaten [2,5,6,10].

Toxoplasmosis: The Human Infection

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T. gondii infection, toxoplasmosis; Source: musee-afrappier.qc.ca

               When a human becomes infected, the parasite causes toxoplasmosis. Most human hosts are asymptomatic after the initial infection, which explains why a third of the world is infected and yet we rarely hear about it. Despite this, it is the third leading infectious cause of death in food-borne illnesses [3].

               In people with healthy immune systems, the parasite often presents with a brief, acute infection after a 1-2 week incubation period, causing flu-like symptoms including enlarged lymph nodes, headaches, fever, muscle pain, and a sore throat. In immunocompromised individuals, the infection is more serious: confusion, fever, headaches, blurred vision, seizures, and death.  The parasite forms cysts in muscles, eyes, and the brain of its intermediate host, causing encephalitis and nerve degeneration over time [4,5,8].

               Toxoplasmosis is particularly a problem during pregnancy. If the primary infection is acquired during pregnancy, or if the infection reactivates due to the immunocompromised status of pregnant women, the infection is passed to the fetus (congenital toxoplasmosis) and is far more severe. It can result in severe neurological disease and blindness in the child [3,11].

               Normally, however, the infection becomes chronic and latent. The parasite settles into the intermediate host’s brain, causing immunity to the acute toxoplasmosis infection. Its presence also causes an immune response which enforces the dormancy, altering cytokine levels in the brain which influences levels of neurotransmitters and signal transduction—dopamine levels are increased, possibly several-fold [5].

Schizophrenia

               This increase in dopamine (and possibly other undiscovered effects) is what causes the parasite’s schizophrenia-causing reputation. Schizophrenia itself is largely due to an increase in dopamine. It is not surprising then that the risk factors of the toxoplasmosis infection are higher than the environmental and genetic factors of schizophrenia [5]. Before you panic, these chances are still quite low, but the association does exist. It’s also interesting to note that the anti-psychotic drugs used to treat schizophrenia are as effective as the antibiotics for T. gondii at preventing the development of behavioral changes caused by the parasitic infection in rodents.

The Impact on Human Culture

               Several studies have suggested that Toxoplasma gondii has actually influenced the development and shape of human culture by impacting brain activity. Considering the breadth of the infection, it doesn’t seem like an utterly crazy idea. All warm-blooded animals can carry the infection and pass it between each other: migratory birds have brought the infection across continents and even to the feline-free regions of the Arctic [7]. Human consumption of meat, the history of close relationships between humans and cats, and interacting with infected soil has allowed the infection to spread through populations. However, the percent of people with antibodies to the disease, which means they carry the infection, ranges from 0-100% between cultures [2].

               This variance in infection rates theoretically could result in variations in personality at a population level: subtle behavioral alterations of a majority of a population would influence their culture as a whole. Four categories are often used to describe a culture: individualism, sex roles, uncertainty avoidance, and class distinction. The behavioral changes that can occur in a chronic infection of T. gondii influence all of these categories by altering their host’s intelligence, conscientiousness, tendency to conform, morals, outgoingness, novelty-seeking behavior, self-doubt, depression, and suicidal behavior[2]. Over the course of thousands of years, these behavior changes could influence society and culture.

              Of course, these studies are mainly speculative and the evidence provided is strictly correlative and not causative, but it is nonetheless fascinating and somewhat disturbing to consider that an infectious pathogen, especially one this pervasive, could actually be influencing our behavior, culture, and history.

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Source: Gradydoctor.com

Benefits and Treatment

               Before this post causes anyone to have a massive panic attack, I would like to assure you that the infection is treatable and there are actually benefits to it as well. Generally if one is asymptomatic there is no need for treatment (but if you’re really concerned, there are diagnostic tests you can take before seeking treatment). For those with symptoms, specific antibiotics tend to do the job of cleaning up the infection [7,8].

               Furthermore, a recent study in rats has shown that the infection’s tendency to cause higher anti-inflammatory cytokine levels in brain tissues actually slows down and reduces damage from Alzheimer’s disease! A majority of the neuronal degeneration in Alzheimer’s is partially caused by inflammation, and, consequently, this is dampened by the already heightened anti-inflammatory response in T. gondii infected brains [1]. While I wouldn’t recommend trying to get infected to stave off Alzheimer’s, it’s possibly useful for future Alzheimer’s research and a great way to convince your spouse to allow you to get a cat.

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Source: dreameyce.deviantart.com

References

[1] Jung, B., et al. “Toxoplasma gondii Infection in the Brain inhibits Neuronal Degeneration and Learning Impairments in a Murine Model of Alzheimer’s Disease.” Plos One. 2013; 7(3).

[2] Lafferty, Kevin. “Can the Common brain Parasite, Toxoplasma gondii, Influence Human Culture?” Proc. R. Soc. 2006; 273: 2749-2755.

[3] Paquet, C., et al.  “Toxoplasmosis in Pregnancy: Prevention, Screening, and Treatment.” SOGC Clinical Practice Guideline. 2013; 285.

[4] “Parasites – Toxoplasmosis (Toxoplasma infection).” Centers of Disease Control and Prevention. 2011-04-05.

[5] Prandovszky, E., et al. “The Neurotropic Parasite Toxoplasma gondii Increases Dopamine Metabolism.” Plos One. 2011; 6(9).

[6] Quieroz, M., et al. “Behavioral Changes in Rattus norvegicus coinfected by Toxocara canis and Toxoplasma gondii. Rev. Inst. Med. Trop. Sao Paulo. 2013; 55(1): 51-3.

[7] Sandstrom, C., et al. “Latitudinal Variability in the Seroprevalence of Antibodies Against Toxoplasma gondii in Non-Migrant and Arctic Migratory Geese.” Veterinary Parasitology. 2013; (Preprint).

[8] “Toxoplasmosis.’ PubMed Health. National Center for Biotechnology Information. 2012.

[9] Vyas, A., et al. “Behavioral Changes Induced by Toxoplasma Infection of Rodents are Highly Specific to Aversion of Cat Odors.” PNAS. 2007; 104(15).

[10] Webster, J., et al. “Parasites as Causative Agents of Human Affective Disorders? The Impact of Anti-Psychotic,  Mood-Stabilizer and Anti-Parasite Medication on Toxoplasma gondii’s Ability to Alter Host Behaviour.” Royal Society Publishing. 2006; 273(1589): 1023-1030.

[11] Zhou, H., et al. “Differential proteomic profiles from distinct Toxoplasma gondii strains revealed by 2D-difference gel electrophoresis.” Experimental Parasitology. 2013; (Preprint).

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3 thoughts on “Toxoplasma gondii: The Puppeteer

  1. I believe there was a recent study that showed that the T. gondii genome codes for an enzyme known to produce dopamine. Does that match the explanation in your references as to how the parasite produces dopamine?

    Second, though 1/3 of the population has the parasite antibody, is there any estimation as to the proportion of humanity that has the parasite in the brain?

    And third, a different study showed that infected people were involved in car accidents at twice the background rate. Apparently, reaction time is slowed if you’re infected. That might be an interesting way to detect infected people!

    Given that infected rats are attracted to cat urine, is there a similar behavior in humans?

    • Sorry for the delay!
      The Prandovszky article in my references does indeed mention a tyrosine hydroxylase being encoded in T. gondii’s genome. This is an enzyme that catalyzes the formation of a dopamine precursor, which would increase dopamine levels. Additionally, the scientists found that potassium-induced release of dopamine was increase, potentially suggesting a dual-mechanism for the increase in dopamine.

      From what I can glean from the research, if you have the infection, even if latent, it is likely in your brain. The extent to which the neurological effects occur depends on the strain, latent state, mode of initial infection, and your immune system.

      You know, I did wonder if the high infection rate in humans could be contributing to our obsession with cats (from Egyptian worship to the internet’s burning passion for them!)… unfortunately I couldn’t find any correlative studies regarding that relationship. It would be pretty interesting and amusing to look into, though 🙂

  2. Pingback: Mind Control and Zombie Hosts: Parasitic Invasions | Biogeekery

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