Worms, your unlikely allies

Parasites show promise in treating immune disorders

Although hookworms, shown here in the intestines, didn’t lessen the symptoms of people with asthma in a recent study, scientists are finding that other parasitic worms can help people with immune disorders. CDC

Back in the Stone Age, humans had to put up with all sorts of creepy crawlies. Parasites — organisms that live on or in another organism — lingered inside our bodies, living off of our blood. Because internal parasites go mostly unnoticed, they were able to keep living with humans. People can survive a long time with tiny parasitic worms in their intestines.

This seems like a win-lose situation — with humans the losers. But scientists now say that may not be so. Parasitic worms might have something to offer humans in return for getting free meals and housing. In parasites’ efforts to turn people into friendlier hosts, these tiny worms have developed the ability to tone down the human immune system. This system is that invisible “sixth sense” inside us all that fights infections and disease, including parasites. The part of the immune system the worms really target is inflammation.

Inflammation is usually a good thing. If you cut your foot, you might notice the area around the cut becoming warm and swollen. That’s a sign of inflammation — the immune system sending in an army of professional cells and proteins to kill germs. But too much inflammation for too long is not healthy. And that’s where parasitic worms come in.

By releasing chemicals that lessen inflammation, parasitic worms make life easier for themselves. And while reducing inflammation might lower immunity in some people, it might also offer a golden opportunity in others to cool off an overheated immune system.

Many people have immune problems, which include allergies and asthma. Their bodies generate too much inflammation on the skin or in the lungs, creating a rash, a cough or other symptoms. Doctors try to knock down the inflammation with an inhaler, pills or whatever it takes.

Inflammation can show up in more serious immune problems, too, such as autoimmunity, when the immune system gets so out of whack that it actually causes disease instead of curing it. Autoimmune diseases tend to be more severe than allergies and asthma, and include rheumatoid arthritis (affecting joints, such as knees), multiple sclerosis (in nerves and muscles), Crohn’s disease (in intestines), psoriasis and lupus (in skin) and the kind of diabetes that occurs in young kids. In all of these cases, the immune system generates out-of-control inflammation.

Scientists are now trying to put parasitic worms to work helping people with immune problems. It’s hard to believe, but doctors have shown that treating patients with the live microscopic eggs or larvae (young) of parasitic worms can calm some autoimmune diseases without creating new ones.

Itty-bitty worms

Wait a sec. Aren’t parasites the bad guys?

Yes and no.

Hookworms, illustrated here, are parasites that often enter the human body by way of bare feet. Eraxion/iStock

Like a burglar who steals from your house but also fixes the plumbing, parasitic worms can offer some benefits. It’s true these tiny worms can cause anemia (a lack of red blood cells) and more serious conditions. But because a parasite gets no benefit from bumping off its host, the worm doesn’t do too much damage right away. And in the meantime, its inflammation-fighting routine might come in handy.

The 20th century’s medical advances meant the end of most parasites in the United States and other high-income, developed countries. But those same regions also saw increases in asthma, allergy and many kinds of autoimmune diseases. Meanwhile, parasites continue to infect millions of people in the tropics, where autoimmunity is rare and asthma and allergy are less common than in wealthier, temperate countries.

Coincidence? Some people don’t think so.

David Elliott, a doctor at the University of Iowa in Iowa City, noticed the increase in autoimmune diseases, asthma and allergies in the United States. Elliott says, “We asked, ‘What’s missing in developed countries?’ We still had viruses and bacteria, but we were missing a whole class [of microbes] that used to be universal.” That would be parasites. Better sanitation and simple changes like wearing shoes (to keep hookworms from getting into the skin) had put parasites out of business in the United States long ago.

The tropic zone

Elliott wasn’t the only scientist fascinated by these trends. Researchers at the University of Nottingham in England began working with Ethiopian scientists to study parasites and immune disorders. In 2003, the team reported finding that Ethiopian kids with parasitic worms were half as likely to wheeze — a symptom related to asthma — as were kids without the worms.

Around the same time, Argentine scientists began tracking 24 people who had multiple sclerosis, also known as MS. In people with this disease, the immune system damages nerves that control muscles. Half of the people in the South American study also had a parasitic worm infection. As part of the study, people with the worms agreed not to be treated for their parasites.

And just as well. Only three of the 12 patients with worm infections developed an MS attack — and only one attack each — during the next four years. The 12 MS patients without worms suffered a total of 56 attacks over the same time period. These results suggested the parasites were fighting inflammation.

In Gabon, a country in equatorial Africa, another study found that school children with a parasitic worm infection were about half as likely to develop an allergy to dust mites as were kids with no parasites. Again, it seemed these worms were keeping inflammation at bay.

Armed with this knowledge, some scientists decided to see if deliberately giving parasitic worms or their eggs to people already sick with an autoimmune disease would offer them any benefit.

Cringe-worthy treatment

Elliott and his colleagues at the University of Iowa identified patients with ulcerative colitis, a condition in which the intestines become inflamed, causing pain, diarrhea and other symptoms. The researchers assigned patients to get a drink every two weeks for 12 weeks. Some patients received a drink that contained a cleaned-up version of eggs from a parasite called a whipworm. The team used the kind of whipworm that infects pigs because these worms don’t bother people. The other patients in the study were given an egg-free drink.

The results weren’t spectacular, but 13 of 30 people getting the parasite eggs improved substantially, compared with only 4 of 24 people who didn’t get the eggs.

Taken with a microscope, this image of a hookworm shows its young, noninfectious stage. CDC

Despite the promising findings, worm therapy isn’t a slam dunk. A test in the European country of Denmark found patients with hay fever, a kind of allergy, received no benefit from whipworm eggs given over three weeks. Another study at the University of Nottingham showed that people with asthma receiving very small doses of hookworm larvae experienced no benefits.

But those results haven’t dimmed interest in parasite therapy. Several human studies with parasites are underway or being planned.

Purposely taking parasitic larvae or eggs requires some courage, says John Fleming, a brain doctor at the University of Wisconsin–Madison. Fleming is working on one of those studies and acknowledges that “it doesn’t seem like mainstream science at first pass.”

Not surprisingly, some people do find this whole idea of using worms to treat illness a bit hard to swallow.

“The problem with giving people [parasitic worms] is you’re introducing a foreign organism, and that has the [risk] of unforeseen consequences,” says Derek McKay. He’s an immune-system expert at the University of Calgary in Canada.

But McKay is convinced that worms can stop inflammation by changing how the human immune system acts. So he is trying to find out just what those changes are. McKay’s team has found that parasites slow inflammation by revving up the production of a protein called interleukin-10, which reduces heat and swelling.

Joel Weinstock, a researcher at Tufts University Medical Center in Boston who worked on the Iowa studies, thinks that parasites smother inflammation by manipulating two kinds of immune cells: dendritic cells and macrophages. Parasites can steer these cells away from promoting inflammation and toward stopping it.

The next step is to find out which chemicals the parasites themselves release to trigger these changes. “Identifying these [parasite] products,” McKay says, “could be the blueprints for new drugs.”

Several chemicals already have been identified. David Elliott says all of a parasite’s different compounds might be necessary to effectively halt the inflammation caused by disease. “It’s a lot like getting a kid to clean his room,” he says. “You offer money, turn off the TV, hide the video games — then the room gets cleaned. Any one thing won’t do it.”

Power words:

parasite Organisms that live on or in another organism.

immune system A bodily system of organs, tissues, cells and cell products — such as antibodies — that identifies threats to the body and rids it of harmful substances or organisms.

inflammation The body’s response to cellular injury; often involves swelling, redness, heat and pain.

tropics The region near Earth’s equator. Temperatures here are generally warm.

temperate Regions just above and below the tropics. Temperate regions have a moderate climate with fewer temperature extremes.

microbe An organism (such as a bacterium) that is very tiny and visible only with a microscope.

dendritic cell A type of immune system cell that initiates the primary response to a foreign substance.

macrophage A type of immune system cell that aids in the destruction of foreign objects such as bacteria.

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