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  • Writer's pictureP.K. Peterson

Virulent Toxoplasma gondii Rears Its Ugly Head

“They’re considered one of the most widely successful parasites globally because they have so many tricks up their sleeves to move themselves around and hide in hosts.”

- Melissa Miller, DVM, PhD, wildlife veterinary specialist, California Department of Fish and Wildlife

“We’ve been characterizing other types of toxoplasmosis in sea otters for 20 years, but this was a complete doozy—a strain that linked to a really severe form of disease we’ve never seen before. We needed to let people know.”

- Karen Shapiro, DVM, PhD, associate professor, University of California, Davis School of Veterinary Medicine

Recently, scientists were alarmed by the death of four wild sea otters caused by an extremely virulent, previously unrecognized strain of Toxoplasma gondii— a strain that could pose a threat to other mammals, including humans. (See May 31, 2023 National Geographic, “Why 4 California sea otters have scientists so alarmed.”) In this Germ Gems post, I provide a brief overview of toxoplasmosis, including a discussion of who’s at greatest risk of developing life-threatening disease.

What is T. gondii? T. gondii is aruably the most successful protozoan parasite on our planet. Many warm-blooded animals including most pets, livestock, birds, and humans can become infected with T. gondii. While nearly all of these animals can harbor parasites in their muscles, cats are a special case. They’re the only definitive host for T. gondii. This parasite can only undergo sexual reproduction in the cat intestine, where it forms zygote-containing cysts, called oocysts, which are shed in cat feces.

How is T. gondii transmitted? Most often humans acquire T. gondii by eating poorly cooked meats that contain cysts. Undercooked meat (pork, lamb, and venison) or contaminated shellfish (for example, oysters, clams, or mussels) pose the biggest risk for acquiring T. gondii.

Exposure to cat feces is another route of infection. T. gondii can spread through the bloodstream to multiple organs, including the uterus. Therefore, pregnant women are particularly vulnerable hosts as they can pass the parasite on to the unborn fetus resulting in a condition called congenital toxoplasmosis. Approximately 200,000 cases of congenital toxoplasmosis occur per year globally. (In the U.S., 300-4,000 cases are diagnosed annually.)

What are the symptoms of toxoplasmosis? It’s estimated that half the world’s population is infected by T. gondii and that about 11% of Americans are infected. But almost all of these people are completely unaware of their infection because asymptomatic infection is the norm. Some people do, however, develop acute toxoplasmosis, a mono-like illness with fever, headaches, fatigue, and swollen lymph nodes. Although the swollen lymph nodes can persist for many months, people with a normal immune system usually clear the infection rapidly.

Healthy people ordinarily don’t require treatment for toxoplasmosis, as symptoms are mild and disappear within a few weeks. But for pregnant women and people with a compromised immune system the story is quite different; the consequences of infection can be disastrous.

Babies born with congenital toxoplasmosis typically have a small head (microcephaly), inflammation of the brain, heart, lungs, or eyes, jaundice, enlarged liver and spleen, and a rash. Toxoplasmosis in immunosuppressed individuals is most often the result of reactivation of latent infection, which presents with neurological signs, including headache, disorientation, drowsiness, hemiparesis, reflex changes, and convulsions. For these reasons, pregnant and immunocompromised people need to strictly follow the precautions against acquiring toxoplasmosis by avoiding cat feces and not eating undercooked meats.

Reactivation of latent infection. In immunocompetent people, upon ingestion of T. gondii oocytes, the parasite rapidly transforms into tachyzoites that localize in muscle and the brain. In these tissues, they transform into latent bradyzoite cysts. Thus, toxoplasmosis is considered a chronic infection. In almost all cases that’s the end of the story.

Because bradyzoites have the ability, if the immune system becomes compromised, to reconvert into rapidly growing tachyzoites, chronic toxoplasmosis can cause severe and even fatal disease. Immunodeficiency conditions that impair cell-mediated immunity, particularly the function of T lymphocytes, put people at high risk of reactivation of latent toxoplasma infection. For example, in the early years of the HIV/AIDS epidemic, central nervous system toxoplasmosis was a remarkably common, and often fatal, opportunistic infection.

Neuropsychiatric and behavioral effects of toxoplasmosis. Past studies have shown that T. gondii causes a phenomenon known as “fatal attraction” in infected mice and rats. This manifests as a loss in these rodents of their innate fear of cat odors making the rodents easier to catch and eat.

These cat and mouse studies raised the provocative question of whether T. gondii can cause permanent changes in brain structure, and if so, whether this is relevant to human infection. An article published in 2020 in Frontiers in Psychiatry,“Negative Effect of Latent Toxoplasmosis on Mental Health,” provides evidence of a statistically significant correlation between latent toxoplasmosis and a variety of mental illnesses, such as, schizophrenia, autism, attention-deficit/hyperactivity disorder, and obsessive compulsive disorder. A causative link for any of these correlations, however, has not been established.

Why the big worry about T. gondii in sea otters? Sea otters are especially vulnerable to T. gondii infection because they live near the shoreline where they may be exposed to the parasite’s eggs in rainwater runoff, and they eat marine invertebrates that can concentrate the parasites.

The four sea otters mentioned earlier that are described in the May National Geographic were found dead between 2020 and 2022. Melissa Miller, a veterinarian and wildlife specialist who reported their demise, described “astronomically high levels of parasites and massive numbers in the fat, which was severely inflamed. . . a notable contrast to other types of toxoplasmosis, which typically affect an animal’s brain and central nervous system.”

The nature of the infection in these fatal cases also shocked her co-author, veterinarian Karen Shapiro. The massive number of parasites and their distribution had never been seen before in sea otters in California. Genetic studies revealed another surprise—a match with two Canadian mountain lions nearly 30 years ago. That strain, dubbed COUG for its origin, was detected and identified after residents of Victoria, British Columbia contracted toxoplasmosis from contaminated drinking water.

Exactly how the incredibly virulent strain of T. gondii that killed the four sea otters arose in California remains a mystery. Drs. Miller and Shapiro suggest water contamination related to flooding with a link to climate change could be involved. Of course, the most pressing question for us is, “Can this virulent strain be transmitted to Homo sapiens?”

Because of T. gondii’s unique ability to infect so many different animal species, there is a legitimate concern that this virulent strain could find its way into cats or food sources of humans (meats or shellfish). The good news so far, however, is this hasn’t been observed, and for now, we can be thankful for the veterinary medicine specialists who raised the alarm for increased surveillance.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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