The Arrizabalaga Lab

TOXOPLASMA GONDII: The most common parasite you never heard of

The common parasite Toxoplasma gondii has been attracting a lot of attention in past few years. Often called the “cat parasite”, Toxoplasma is actually capable of infecting humans and a wide variety of other animals. As we recently learned, not even beluga whales in the Arctic Ocean can escape the reach of this parasite. You may recall hearing that Toxoplasma can transform rodents into suicidal zombies, transform women into outgoing sex pots, and convert men into antisocial car wreckers. This parasite has become so engrained in pop culture that even good old Gregory House, M.D. had to take time from his devotion to pain meds to tackle an obscure case of toxoplasmosis. Unfortunately, the increased media attention has spawned a great deal of misinformation about this parasite. Toxoplasma infections have been erroneously connected to cat bites, the flushing of cat litter has been blamed for the demise of the sea otter, and this proud parasite has even been called a virus (I am looking at you, Dr. House). Here are a few actual amazing facts about this pesky and fascinating little parasite.                                                             Written by G. Arrizabalaga and B. Sullivan

Eureka hits twice

This parasite has been around a long time, but we humans did not discover it until 1908 almost simultaneously by scientists working in opposite sides of the world. In Tunisia, Charles Nicolle and Louis Manceaux isolated Toxoplasma from the rodent Ctenodactylus gundi while Alfonso Splendore isolated it from rabbits in Brazil. Nicolle and Manceaux christened the crescent-shaped  parasitic cell as Toxoplasma gondii (Toxo = bow, plasma = shape, gondii a reference to C. gundi), which is too bad because Splendore is a much cooler name for this sinistirely tricky parasite.

Pork: the infected white meat

Toxoplasma cysts tend to be more prevalent in sheep, goats, and pigs than cattle. Not surprisingly, cultures that routinely consume undercooked lamb tend to have higher levels of infection. While some studies show that up to 75% of lamb in the US can be contaminated with Toxoplasma, the most common source of foodborne infection in the US is pork, due to its higher level of consumption. The rates of farmed pigs infected with Toxoplasma have been as high as 40% in the past, but have been significantly reduced in recent years to as low as 1%. But we like pork, so a 1% infection rate equates to a million infected pigs going towards human consumption. Interestingly, the popularity of free-range farming appears to be responsible for a recent spike in Toxoplasma infected animals. Animals that are free to roam and feed on pasture are more likely to ingest infected rodents or encounter oocysts left behind by feral cats. But don't worry too much, cooking your pork fully should take care of the parasite.

Once infected you are always infected

In humans and almost all other warm-blooded animals Toxoplasma divides asexually – with parasite number doubling every 6-8 hours. After a few rounds of division these parasites burst out and proceed to infect new host cells. Luckily, animals have adapted to this intruder, sounding a red alert to the immune system that gets the infection under control. But Toxoplasma is full of surprises. Instead of being eradicated by the immune response, the parasite converts to a latent tissue cyst. These tissue cysts tend to form in brain and skeletal muscle tissue where they evade the immunity police and persist until the host’s dying day. Toxoplasma is parasitic baggage that you carry the rest of your life. 

Courtesy of David Ferguson, Oxfofd University

Pregnancy and toxoplasmosis

Congenital infections early in pregnancy can be devastating, resulting in spontaneous abortion or congenital birth defects. These birth defects vary widely in their severity and can include impaired vision and neurological anomalies. It is estimated that 400-4,000 cases of congenital toxoplasmosis occur annually in the U.S. Considered with the severity of congenital infection, pregnant woman are advised by their physicians to avoid areas where cats may have defecated, including kitty litters, sandboxes or gardens. Keep in mind is that it’s all about the poop - cat bites and scratches do NOT transmit Toxoplasma. In addition, since the oocysts require a day or two in the air to become infectious, and cats are obsessive groomers, there is virtually no risk of cats carrying oocysts on their fur.  

Eat me Mr. Kitty: Toxoplasma and Rodent Mind Control

Cat odors elicit an innate and powerful avoidance response in rodents, causing even lab mice that have never seen a cat to scurry away. Nonetheless, while rats and mice avoid areas that have been infused with a cat stench, Toxoplasma infected rodents do not seem to mind that its predator’s scent is right under its nose. Even more bizarre, these infected rodents appear to be attracted to the scent of a cat. This effect is not elicited by odors to other animals or by infections with other parasites that do not require transmission from a rodent to a feline. 

The likely consequence of this behavioral change: infected rodents are more likely to be eaten by a cat! By cleverly rewiring the brain’s fear and reward center, Toxoplasma learned long ago how to turn an intermediate host into a conduit that quickly gets it back to the cat where it can have sex and widely distribute its progeny into the environment. 

Toxoplasma everywhere

Toxoplasma gondii has turned up in every warm-blooded vertebrate that parasitologists have dissected regardless of  world location. Billions of animals on land, at sea, or in the air are playing host to this unwanted “guest”. Most recently it was reported that more than 10% of Beluga whales assayed in the Artic tested positive for Toxoplasma infection.  In the case of humans it is estimated that a third of the world population is infected. In the United States between 15% to 20% of people are infected.

So many ways to become infected

One of the reasons for the ubiquitous nature of this parasite is that it has many routes by which to infect you. Animals, including humans, become infected by ingesting Toxoplasma oocysts (parasite eggs) that are shed in the feces of infected cats or by eating raw or undercooked meat of infected animals. Finally, Toxoplasma is one of the few parasites capable of crossing the placenta and infecting the unborn child. 

Cats are cute parasite factories

For reasons we have yet to understand, the gut of the cat is a very romantic place for Toxoplasma, and it is the only place where

 the parasite has sex. Only in intestine of felines can Toxoplasma convert into male and female gametes, which then crank up the Barry White. The product of this cat gut mating ritual is expelled from the cat’s tail end in the form of oocysts. A cat infected with Toxoplasma can produce up to 800 million oocysts in the span of about 8 days and these oocysts can survive in soil or water for as long as 2 years. It has been estimated that there are 74-86 million household cats and about 50 million feral/outdoor cats in the US. That is a lot of cat poop and thus a lot of oocysts! 

Without the immune system Toxoplasma goes on a rampage

Your immune system is fairly good at detecting and controlling Toxoplasma so most infections are asymptomatic. As the immune system kicks in, the parasite cocoons itself as tissue cysts for a deep sleep. Over time, cysts can rupture or reconvert back to the fast growing form, but the immune system revs up and tucks the parasite back into bed. Without the immune system, the cysts reactivate and parasites start replicating freely, inadvertently tearing through critical bodily systems such as the brain and heart. Unfortunately, this is exactly what happens in individuals whose immune system is severely compromised by HIV, blood cancers and immunosuppressants. During the highpoint of the AIDS epidemics toxoplasmic encephalitis was a common cause of death. The advent of effective retrovirals, which successfully reduced the numbers of AIDS cases, also reduced the incidence of opportunistic toxoplasmosis.

A Whale of A Tale Like No Otter:  How Does Toxoplasma Infect Sea mammals? 

When southern sea otters, a threatened species that is super cute, started washing up dead on the beaches of California, great

efforts were put into

determining the cause of death. Surprisingly, over half the dead otters were

infected with Toxoplasma and meningoencephalitis due to toxoplasmosis was ruled the primary cause of death for many of them. Otters are not eating undercooked lamb (and no, the catfish does not qualify as a feline), so how are these furry creatures becoming infected? Southern sea otters live in giant kelp forests along the California coast and mostly eat turban snails. These snails feed by scraping nutrients off surfaces such as rocks and kelp. It turns out that kelp is covered with sticky biofilms made of bacteria and algae, perfect for trapping oocysts that get into coastal waters through agricultural runoff. Once stuck to the kelp, the oocysts are scraped off and consumed by the snails, which in turn are eaten by otters, completing an amazing journey from land to sea. 

Parasite Head:  The Correlations Between Chronic Toxoplasmosis and Human Diseases 

other neuropsychosis.

Although it is plausible that the presence of cysts in the brain could worsen existing diseases. 

The discovery that Toxoplasma infection alters the behavior of rodents prompts a rather unsettling question. What if this parasite, which is carried around by billions of people around the world, can alter human behavior? Will Toxoplasma evolve to bring about a zombie apocalypse? Interestingly, there appears to be strong correlation between schizophrenia and Toxoplasma infections, but to date no “smoking gun” has emerged that directly implicates the  parasite as a   cause   for this or any