Toxoplasma gondii: The Beast Lurking in the Litter Box

Sufana Noorwez

Illustrations by: Abigail Schoenecker

You are a parasite, drifting through the world with no objective other than to infect. You need nutrients, and you need them quickly, so what do you do? You can’t produce them yourself; it takes too much energy. Why would you waste time hunting and killing when you could just attach yourself to another organism and sap them of their energy and nutrients instead? First, you find yourself inside of a mouse. It seems to have picked you up from your previous home in some rotting meat. How lucky! The mouse is good; it will take you far, and quickly too. But you can’t live here forever, so you’ll need to copy yourself and find as many new hosts as possible. You send a message to the mouse’s brain: get me as close as possible to a cat. And like a puppet under your control, the mouse loses its fear of cats, gets a little close, and — GULP! Now, this is more like it. Inside a cat, you have room to grow and you’re able to reproduce as much as you want. There are millions and millions of cats in this world, all living snugly inside the homes of humans [1, 2]. When their humans pick the cats up and cuddle them — BAM! Now you’re inside the human, too. You wiggle your way to the most delicious part of these strange, two-legged creatures: the brain. Finally, the ultimate feast begins. Your name? Toxoplasma gondii. 

The Tiny Monster Inside Your Cat

Toxoplasmosis is a deadly disease capable of ravaging the human body, caused by a parasite so small that the human eye cannot perceive it: Toxoplasma gondii. Parasites thrive by exploiting another organism called a host [3]. Leeches are an example of a common parasite; these vampiric creatures attach to warm-blooded mammals and suck on their skin to draw blood, benefiting the parasite but harming the host, who loses dangerous amounts of blood [4]. T. gondii is far smaller and less bloodthirsty than a leech, but still has the ability to cause great harm to humans [5]. When T. gondii infects any organism, it first multiplies into millions of copies [6]. These copies officially set up camp in the host organism within small tissue capsules known as cysts. Then, if T. gondii is lucky enough to come in contact with its preferred host, the cat, it produces eggs that are released in cat feces. T. gondii benefits the most when expelled through cat feces, which comes into contact with a wide variety of organisms, such as humans [7]. By multiplying and forming cysts, T. gondii reproduces and thrives in humans, an excellent and readily available source of nutrients [6].

The Secret Life of a Worldwide Parasite

For T. gondii to thrive, it must seek new hosts to exploit, and it is extremely successful in doing so. An estimated 30-50% of the world’s human population is infected with T. gondii, many of whom are without symptoms [8]. One of the main strategies the parasite uses to spread itself so widely is to live in environments frequented by both cats and humans. T. gondii is commonly found in raw or undercooked meat, which cats and humans often handle and eat [9]. Despite its small size, the parasite is estimated to be one of the top leading causes of death from foodborne illness in the United States [9]. Because of its ubiquity in raw, spoiled food, it can come into close contact with vermin, such as mice, who are then infected [2]. The parasite has an uncanny ability to exert a zombie-like influence on rodents, removing their innate aversion to the smell of cat urine and their fear of the animals themselves [1]. This change in their senses causes rodents to accidentally wander right in the path of their predator, and the parasite is able to jump into cats — their favorite host [1, 2]. Now that it has infected humans, cats, and mice, T. gondii can continue its journey to the human brain. 

Your Brain on T. gondii

T. gondii takes up residence in both our nervous system and muscles, but exerts its most unique effects on the central component of the nervous system: the brain [12]. The brain is an incredibly sensitive organ responsible for processing sensations, organizing voluntary and involuntary movements, and carrying out necessary daily behaviors. Pathogens that invade the brain can wreak havoc on this fragile tissue. To guard against unwanted entry, the human brain is surrounded by a thick network of blood vessels called the blood-brain barrier, which regulates all of the substances that move between the blood into the brain [10]. T. gondii’s small size allows it to slip through this barrier easily, leading it to permanently establish itself in the form of cysts — round, raised bumps with protective walls that harbor millions of copies of the parasite. Under certain conditions, these cysts can rupture and widely distribute copies of the parasite, ready to make even more cysts [6]. When the cysts burst open, the parasite’s proteins can cause the death of neurons, the brain’s primary communication cells [11]. The simple presence of T. gondii can also trigger the immune system, which causes the brain to swell [12]. Although this swelling is often an effective way to stop infection, it can actually harm the brain; in some cases, swelling in structures of the brain that are crucial for normal function can cause permanent tissue damage [13, 14]. All of these disruptions to the central nervous system prevent the brain from functioning properly, producing severe neurological damage.

When Signals Don’t Stop: Your Brain Without Traffic Control

Although most people are not severely impacted by T. gondii, some develop an acute version of the infection, meaning the parasite suddenly and dramatically impacts their health [15]. Acute infections can interfere with neurotransmission, the process that allows us to sense and react to our surroundings [12]. Neurons, the workhorses of neurotransmission, pass chemical signals from one cell to the next. T. gondii blocks a particularly important signal called glutamate. When glutamate is present in the gaps between neurons, it gives neurons the green light to fire and pass the chemical signal along to the next cell [16, 17]. Neurons are repeatedly stimulated when glutamate remains in the space between neurons for a long period of time. To prevent signals from being transmitted, the brain needs to vacuum up the glutamate from this neuronal gap. T. gondii prevents the brain from doing this, resulting in a buildup in the levels of glutamate between neurons. This buildup causes neurons to fire continuously — the glutamate light is stuck on green forever. Like cars zooming through an intersection with nothing to stop them, the neuron is repeatedly activated, increasing neurotransmission to a dangerously high frequency. This constant stimulation overwhelms neurons and releases toxic compounds that can lead to cell death [12]. Further, an excess of glutamate in the space between neurons is strongly correlated to the onset and progression of various neurodegenerative diseases [18, 19]. 

T. gondii also impacts another important signaling chemical, GABA. GABA inhibits signaling in neurons, acting as a kind of stop sign [12]. Because of this, GABA and glutamate have opposite functions: GABA prevents neurons from being excited. T. gondii consumes GABA from between neurons rather than allowing it to build up, and the subsequent lack of this chemical causes neurotransmission to speed up once again — perhaps similar to if  someone were to steal all the stop signs on a busy road . The combination of increasing glutamate levels and decreasing GABA levels gives rise to imbalanced neurotransmission, leading to a variety of dangerous symptoms in those afflicted. For example, seizures can occur due to this heightened activity in the brain [12]. While these symptoms are uncommon in most healthy individuals, people who contract an acute infection may experience some of these more extreme consequences of infection with T. gondii [20]. 

En Garde! Raising an Immune Response to T. gondii

While the most debilitating symptoms of toxoplasmosis usually occur in immunocompromised individuals, a small fraction of people with functioning immune systems may contract acute infections with T. gondii, displaying symptoms similar to those of a bad case of the flu [20]. In rare cases, people may even suffer from more serious symptoms, such as swelling in their brain [12]. The majority of cases in non-immunocompromised people are harmless — they develop the characteristic cysts, but these cysts generally go undetected. However, even asymptomatic toxoplasmosis is correlated with an increased chance of developing certain behaviors and conditions, including suicidal ideation, schizophrenia, and personality changes [21, 22, 23, 24]. One potential explanation for this phenomenon is that T. gondii primarily targets structures of the brain responsible for emotions, sensory processing, and thought processing [25]. Similar patterns of damage are also observed in other neurological diseases and disorders, such as post-traumatic stress disorder (PTSD), which may explain why the symptoms of toxoplasmosis mirror those of other conditions [25, 26]. Strangely, high levels of T. gondii in the blood also are correlated with a higher probability of being in traffic incidents [27]. Since this field of study is relatively new, however, these results don’t necessarily indicate causation, and many of the mechanisms behind T. gondii’s behavioral symptoms remain unknown [12].

For the vast majority of people with healthy immune systems, their bodies are able to easily fight off infection by T. gondii [28]. When T. gondii enters a healthy individual, the body produces immune cells that hunt down the parasite and neutralize it, preventing it from replicating [28]. However, illnesses like cancer and HIV/AIDS can disrupt and incapacitate these immune cells, leaving the body vulnerable to infection [29, 30]. Around 10 million adults in the United States have suppressed immune systems, meaning they may be unable to fight off even relatively common infections, such as the common cold or the flu [31]. Without the body’s natural warriors, pathogens are likely to run rampant, developing into more serious diseases that may even cause death. For immunocompromised individuals, T. gondii is a particularly tricky adversary. When the parasite enters the brain and begins to develop cysts, compromised immune systems are unable to detect it and mount a response [32]. An unchecked T. gondii infection can trigger a range of devastating neurological issues, anywhere from seizures to paralysis to death [32]. Immunocompromised people who experience  neuronal death and brain lesions can begin to exhibit some behavioral changes associated with schizophrenia and bipolar disorder [33]. However, these symptoms often manifest very shortly before death, so they are relatively unstudied [34]. These behavioral symptoms are also seen in individuals without immune deficiencies who aren’t suffering from acute infections [25, 35]. 

Parasites, Placentas, and Pregnancy

Immunocompromised people are not the only population at risk for infection by T. gondii. Pregnant people are also particularly at risk of developing severe symptoms when infected by T. gondii, as are their fetuses [36]. The risk of parasite transmission from the parent to the child increases because these fetuses are entirely dependent upon their pregnant parent for nutrients through the blood. Therefore, when a pregnant individual is infected, the parasite can be passed on to the fetus through a phenomenon known as congenital toxoplasmosis [37]. In the same way that the parasite can sneak through the blood-brain barrier in an adult host, it can also travel through the placenta, which provides nutrients and oxygen straight to the fetus [36]. The rate at which the parasite is passed to a fetus is dependent on when the pregnant person is infected [38]. In late-stage pregnancies, transmission rates can climb up to 65%. Fetuses do not have a developed and strong immune system, so they can have trouble fighting off the parasite. Infection without a mature immune system can severely impede the fetus’ development and lead to neurological damage, often impacting the eyes. However, the effects of fetal infection may not even manifest until the second or third decade of life. At this point, cysts formed while a person was in the womb may rupture and cause blindness in both eyes [38]. The severity of these symptoms and their effects on young children point to a need for effective prevention and treatment of the infection.

Taming the Beast 

Although the symptoms of toxoplasmosis are frightening, there are a multitude of ways to prevent and treat the disease. Avoiding places where T. gondii may be found is the first step in preventing infection [39]. This includes staying away from untreated water, wearing gloves when coming into contact with soil, and avoiding consumption of raw or undercooked meat. High-risk populations, such as those who are immunocompromised or pregnant, should also avoid contact with cat feces or their litter. While this kind of physical prevention is the best way to avoid a T. gondii infection, for some high-risk individuals, there are drugs called prophylactics that can prevent T. gondii from forming cysts [40, 41]. These prophylactics work by stopping the life cycle of T. gondii upon the initial exposure, but will not work for individuals already experiencing active infection. Post-infection, a range of drugs can be used to mitigate the symptoms of toxoplasmosis. Many factors determine the type of drug that works best for an individual, such as the symptoms they experience, pregnancy status, and the state of their immune system [39]. Some antimicrobial drugs are available to help the body fight off T. gondii infection before it spreads out of ruptured cysts, but there are currently no known drugs that can remove cysts from the brain [40, 42]. Additionally, some strains of T. gondii are developing resistance to drugs traditionally used to treat the disease [43]. Another possible treatment for toxoplasmosis is the administration of antipsychotic drugs, which have the potential to reverse the behavioral changes associated with infection, though their mechanisms are not well understood [44]. Physically preventing the parasite from entering the brain by reducing exposure may be the best way of ensuring that infection does not occur. 

Toxoplasma gondii is an extremely efficient parasite, able to spread itself far and wide by utilizing an extremely ubiquitous host, the domestic cat [8]. It moves about in a constant cycle of transmission — from contaminated food, to a mouse, to a cat, to a human. While the average infected person will carry on with their lives, completely unaware of the presence of this foreign invader in their brain, toxoplasmosis presents a particularly unique threat to others [45]. The human immune system can fail to keep the parasite in check, leading to a whole host of devastating symptoms [32]. Modern medicine has provided a range of solutions to this issue, from prophylactics to antimicrobial drugs, but preventing the parasite from entering your body in the first place is always the best way to ensure that you remain uninfected [39]. Something to think about the next time you clean your furry friend’s litter box! 

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