Toxic parasite

Pediatrician Rima McLeod has spent more than three decades battling the bug that causes toxoplasmosis.

By Lydialyle Gibson
Photography courtesy Rowley and Gemma Samuel

Toxic parasite
“Although Fin”—with his father, Rowley Samuel—“still has serious problems that remain a challenge,” McLeod says, “he is a playful, sweet, cheeky little boy cherished by his family.”

The discovery that led Rima McLeod toward a live vaccine for a parasite that infects up to one-half the world’s population was partly an accident. Researchers in McLeod’s laboratory were poking and prodding at Toxoplasma gondii, the parasite that causes toxoplasmosis, which can lead to blindness, deafness, and brain damage in children born with the disease. The scientists suppressed first one gene and then another, looking for those most essential to the parasite’s function and thus a good target for drugs. Among the genes the researchers suppressed was a ribosomal protein associated with the parasite’s growth and reproduction.

Then a student research assistant—Samuel Hutson, AB’05, who went on to medical school at the University of Illinois at Chicago—went home for Thanksgiving and accidentally left the altered strain in a tissue culture. When he returned, the parasite had disappeared from the culture. McLeod thought it had died. The researchers tried reviving it with tetracycline, and a month later, it started growing again: “It was just sleeping in the tissue culture,” explains McLeod, medical director of the University’s Toxoplasmosis Research Institute and a pediatrician who has studied the disease for more than 30 years.

A few weeks later, when Hutson went home for winter break, “he forgot another flask in the incubator,” McLeod says. And again the parasite went dormant and then was awakened. The researchers decided to see how it would respond if it were injected into mice. After a week, it disappeared entirely and never regrew.

But before the parasite vanished, the researchers discovered, it had trained the mice’s immune systems to fight off a toxoplasmosis attack. As a live vaccine, the altered parasite proved 100 percent effective. This past November, McLeod and her coresearchers, including Hutson, published their findings in PLoS One.

A month later McLeod coauthored two other papers, in Vaccine and Immune Research, offering an alternative to the live vaccine, one that uses only fragments of the parasite rather than the whole organism. She and collaborators from Johns Hopkins and the United Kingdom identified the parasite peptides that bind to hosts’ immune cells and formulated an injection that protected 80 percent of mice from the disease. That’s good, but McLeod hopes to do better. If this vaccine could work as effectively as the live vaccine, she says, “we would have something that could be synthesized, that could be easy, cheap, that could be nontoxic.”

A parasite smaller than a human cell, Toxoplasma gondii infects 2 to 3 billion people worldwide. It’s commonly found in uncooked meat or infected cats’ excrement. “But you don’t have to have eaten raw meat or changed your cat’s litter box,” McLeod says. “You just have to live in the world. It’s in the water; it’s in the soil; it’s in the food that doesn’t get washed in the restaurant.”

Many people infected as adults never show symptoms. But for children who contract toxoplasmosis in the womb—from mothers who acquire the parasite for the first time while pregnant—or for people with compromised immune systems, the disease can be devastating. It can cause blindness, hearing loss, seizures, palsy, mental retardation, hydrocephalus, heart disease, pneumonia, and brain disease. Some of these symptoms can be prevented or lessened with prenatal or postnatal treatments, which McLeod’s and her collaborators’ research helped develop. But so far the parasite cannot be eliminated from the body once it’s acquired.

McLeod first encountered toxoplasmosis as a Stanford postdoc in the late 1970s. Her adviser, infectious-disease expert Jack Remington, was one of only a few US researchers studying toxoplasmosis then. “I answered a lot of phone calls from patients,” McLeod says, “and I realized this was a really unstudied and important disease.”

In December 1981, three years after arriving in Chicago to practice at Michael Reese Hospital and teach at the U of C Medical Center, she was called in to consult on a toxoplasmosis patient, a newborn girl. “At the time, we knew that all kids with toxoplasmosis were going to have problems later,” McLeod says. But the powerful, toxic medicines used to treat the disease—sulfadiazine and pyrimethamine, which remain the mainstays today—were recommended for only a month’s use at a time (“they were afraid it would wipe out the bone marrow”), and dosages for children had not been worked out. “We knew a month wasn’t enough,” McLeod says.

So she and a large team of researchers began a clinical trial that continues today, to determine what medicine strength, duration, and formulation works best to treat congenital toxoplasmosis in newborn babies. “The first parents were really, really brave,” she says. Through the 1980s, about 15 families and their infected newborns—some mildly affected, some severely so—took part. “At the end of each year, we had walking, talking, seeing, hearing kids. Eighty percent of them were OK.” The newborn girl McLeod examined in 1981, “the baby that started it all,” she says, is now healthy and a mother herself. 

The clinical trial now follows about 215 families and their children, some of whom have recovered with treatment. McLeod, as much a clinician as a researcher, keeps many photos of children that parents have sent her: a little girl who was adopted by an ICU nurse and recovered; a boy, Fin Samuel, whose family was told when he was a baby that he would “never be interactive or capable of anything,” McLeod says. Now 4, he is walking, and he asks for “more book” when his parents read to him.

Although treatment can avert some of the worst symptoms of toxoplasmosis, the risk of recurrence remains ever present, especially for those whose immune systems falter: AIDS patients, transplant patients on immunosuppressant drugs, patients with autoimmune disorders.

One of McLeod’s most promising projects involves developing “transductive” peptides that can travel into the parasite cysts, carrying small molecules—drugs—that would disrupt and destroy the organism. “We’ve been focusing on the proteins that regulate” the parasite, the ones “that make it able to grow or go to sleep, so that we can target those uniquely,” she says. “Because if we could treat it for a week with something that was nontoxic and kill it, we would be able to eliminate the recurrences that people get.”

McLeod has also become an activist for toxoplasmosis prenatal screening—a bill mandating it is moving through the Illinois legislature. “You can be diagnosed when you first get it,” she says. “You can prevent it from being transmitted. You can treat it in the fetus. You can do all those things; we just don’t do it in this country.”


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