NYT: toxoplasmosis

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NYT: June 20, 2006

A Common Parasite Reveals Its Strongest Asset: Stealth

By CARL ZIMMER

On paper, Toxoplasma gondii looks as if it ought to be the most famous

parasite on earth. This single-celled pathogen infects over half the world's

population, including an estimated 50 million Americans. Each of Toxoplasma's

victims carries thousands of the parasites, many residing in the brain. As if

that were not enough of an accomplishment, Toxoplasma is equally adept at

infecting all other warm-blooded animals, as disparate as chickens and

kangaroos.

Scientists are now discovering some of the secrets of Toxoplasma's

success. Researchers in Sweden

report that the parasite fans out through the body by manipulating mobile cells

that are part of the immune system. Toxoplasma hijacks these so-called

dendritic cells and makes them race around the body and ignore commands from

other immune cells to commit suicide. The

dendritic cells sneak the parasites into the brain and other organs, acting

much like a Trojan horse.

Strategies like this one have made Toxoplasma incredibly widespread and

incredibly obscure. Mention the parasite to most people and chances are you

will draw a blank. Pathogens that infect far fewer people, like the Ebola and West Nile viruses, are far

more famous.

Toxoplasma's obscurity is in fact a great tribute to its powers.

" To the parasite's credit, it's incredibly successful, " said Dr.

Lloyd Kasper of Dartmouth

Medical School.

" It's adapted itself to be a benign infection. "

For the vast majority of people, Toxoplasma causes no serious effects.

It manages this feat by hijacking our cells and immune system, and establishing

a careful harmony between parasite and host. " Once you get infected with

Toxoplasma, you're infected for life, " Dr. Kasper said.

Toxoplasma can, however, cause serious brain damage in those with weak

immune systems, like fetuses and adults with AIDS.

Cats play a major role in the parasite's success. They can carry it in

their intestines, where they can produce egglike cysts called oocysts. A single

infected cat can shed 100 million oocysts in its droppings. The oocysts can

survive in the soil for over a year and can contaminate drinking water.

Oocysts can infect humans, as well as other mammals and birds.

Undercooked pork, chicken and other meat is another route Toxoplasma can take

into our bodies.

Once Toxoplasma enters a host, it spreads quickly. Within hours it can

be detected in the heart and other organs. It is even able to infect the brain,

which is protected from most pathogens by a tight barrier.

Barragan and his colleagues at the Karolinska Institute in Stockholm were puzzled at

first about how Toxoplasma managed this swift journey. " When we looked for

parasites in the blood, we found very few that were just swimming around, "

said Dr. Barragan, an associate professor. But the scientists observed many of

the parasites inside immune cells known as dendritic cells.

Dr. Barragan was intrigued. Dendritic cells, common in the gut, often

come into contact with pathogens. They respond by crawling to the lymph nodes

or the spleen, where they communicate with other immune cells.

" That led us to think, what if this parasite is directing these

cells to move and to disseminate through the body? " Dr. Barragan said. He

and his colleagues put dendritic cells in a dish and injected them with

Toxoplasma. They noticed that the parasites triggered a peculiar change: the

dendritic cells became hyperactive, crawling for an entire day.

Next, the scientists observed how Toxoplasma spread through a living

animal. They added a firefly gene to the parasites so that they produced a

glow. When they injected the parasites into mice, a little of the light escaped

from the animals. By putting the mice in a darkened box, Dr. Barragan and his

colleagues could track the parasites as they spread.

Injecting dendritic cells carrying Toxoplasma spread the parasites to

the brain and other organs far faster than injecting Toxoplasma alone. The

researchers concluded that Toxoplasma was taking charge of the dendritic cells

and riding along with them. Their results are published online in the journal

Cellular Microbiology.

As Toxoplasma spreads through the body, it invades cells. Unlike other

pathogens, Toxoplasma can enter almost every type of cell in the bodies of

thousands of host species. The parasite slips into a cell by latching onto its

surface and pulling the membrane over itself. " You can think of it like

sticking your finger into a balloon, " said Vernon B. Carruthers of the University of Michigan.

Sibley, an associate professor of molecular microbiology at Washington University in

St. Louis, said, " It just sits there, and the host doesn't recognize it as

a foreign body it should destroy. "

If Toxoplasma simply spread from cell to cell, it could cause serious

harm. But killing its host is not in the parasite's best interests: its goal is

to get into its final host, cats, the only creature in which Toxoplasma can

reproduce by making oocysts that are shed in feces. And cats do not like eating

dead animals. Instead, Toxoplasma has evolved to be extremely contagious, but

not very harmful.

" This is an organism that has very cleverly worked out a way to go

from one host to another, " said Alan Sher, chief of the Laboratory of

Parasitic Diseases at the National

Institutes of Health. Dr. Sher studies how Toxoplasma manipulates its

host's immune system. In the early stages of infection, the parasite sets off

the production of signaling molecules called cytokines. They cause the immune

system to attack Toxoplasma, killing off free-floating parasites.

The parasites that happen to be inside cells during the attack somehow

recognize what is happening and enter a kind of hibernation. Their host cell

turns into a cyst in which they can hide from the immune system.

The strong response Toxoplasma provokes from the immune system carries

a risk of its own. " These cytokines just get out of control and cause

tissue damage, " Dr. Sher said. In experiments with mice, this response can

be fatal, he said.

Toxoplasma steers its hosts away from this danger, Dr. Sher has found.

It causes its host to make molecules that rein in the immune system.

An infection with Toxoplasma may feel like nothing more than a mild

case of the flu, and the

symptoms pass once the parasite has snuggled itself away in its cysts. In later

years, cysts occasionally break open, but the immune system quickly destroys

most of the free parasites. The few survivors invade new cells.

" That's the key of this infection, " Dr. Barragan said.

" I think this is why this parasite is so tremendously successful

worldwide. "

Toxoplasma becomes a menace when it does not have a healthy immune

system to control. Pregnant women infected for the first time by Toxoplasma may

pass it to their unborn children. Without a strong immune system to keep the

parasite in check, a fetus can suffer massive brain damage. Up to 4,000

children are estimated to suffer toxoplasmosis in the United States each year.

Toxoplasma is also dangerous to adults with weakened immune systems.

The cause may be AIDS or immune-suppressing drugs given to people who receive organ transplants.

A quiet Toxoplasma infection can suddenly explode.

For decades, most scientists believed that people with healthy immune

systems had no effects from Toxoplasma. But some studies in recent years have

hinted that the parasite can exert surprising effects on behavior, at least in

animals.

In 2000, British scientists demonstrated that rats infected with

Toxoplasma lost their fear of cats. They proposed that this strategy increased

the parasite's chances of getting into its final host.

Scientists at Stanford University

recently followed up on these experiments, studying rats and mice. " They

actually show a mild attraction to the cat odor, " said Ajai Vyas, a

Stanford neurobiologist. " It's not just the loss of an old behavior. A new

behavior is being induced. "

Dr. Vyas and his colleagues found that Toxoplasma's effects were

precisely aimed at cat odor. The rats were still afraid of dog odor but not of

rabbit odor. They could also acquire new fearful responses. " Only the

innate fear to the cat was different, which was very surprising, " he said.

" We don't really know how fear of a cat is hard-wired in the brain. "

How Toxoplasma incites this change is a mystery. It is possible that

the parasite alters the production of certain neurotransmitters. " But I

don't know how some global change could have such a specific effect, " Dr.

Vyas said. He reported his results in May at the annual meeting of the

International Behavioral Neuroscience Society.

Some scientists suspect Toxoplasma may influence the human brain.

Several studies suggest a correlation between Toxoplasma and schizophrenia,

but the claims for a connection are not widely accepted.

Dr. H. Yolken, the director of the Stanley Laboratory at s Hopkins University,

and his colleagues reviewed military medical records. They found that soldiers

who developed schizophrenia were twice as likely as other soldiers to show

signs of Toxoplasma infection in blood samples.

Toxoplasma's dangers, both proven and potential, are cause for concern,

experts say. " It's a substantial public health risk, " Dr. Sibley

said.

Recent studies suggest that Toxoplasma is rare in meat sold in stores

in the United States.

However, experts still recommend cooking meat thoroughly to kill any parasites.

Dr. Milton M. McAllister, a parasitologist at the University

of Illinois at Chicago, has called for controlling the

spread of Toxoplasma by cats. He notes that oocysts from cats can also infect

wildlife. Toxoplasma has even been detected in sea otters, suggesting it can

reach the ocean.

" It's perfectly safe to keep a cat, " he said. " Just keep

it inside. "