David
Pritchard, an immunologist-biologist at the - Hookworms may stimulate human immune system against allergies
By ELIZABETH SVOBODA
In 2004, David Pritchard applied a dressing to his arm that was crawling with pin-size hookworm larvae, like maggots on the surface of meat. He left the wrap on for several days to make sure that the squirming freeloaders would infiltrate his system.
David
Pritchard, an immunologist-biologist at the
“The itch when they cross through your skin is indescribable,” he said. “My wife was a bit nervous about the whole thing.”
Dr. Pritchard, an immunologist-biologist at the
While carrying out field work in Papua New Guinea in the late 1980s, he noticed that Papuans infected with the Necator americanus hookworm, a parasite that lives in the human gut, did not suffer much from an assortment of autoimmune-related illnesses, including hay fever and asthma. Over the years, Dr. Pritchard has developed a theory to explain the phenomenon.
“The allergic response evolved to help expel parasites, and we think the worms have found a way of switching off the immune system in order to survive,” he said. “That’s why infected people have fewer allergic symptoms.”
To test his theory, and to see whether he can translate it into therapeutic pay dirt, Dr. Pritchard is recruiting clinical trial participants willing to be infected with 10 hookworms each in hopes of banishing their allergies and asthma.
Never one to sidestep his own experimental cures, Dr. Pritchard initially
used himself as a subject to secure approval from the National Health Services
ethics committee in
In the tropics, where it is common, hookworm kills 65,000 people a year and afflicts hundreds of thousands with anemia. In low numbers in adults in a controlled experiment, Dr. Pritchard said, the worms have not caused problems.
His interest in the immunology of parasite infection stretches back to 1977.
Intrigued by anecdotal reports from third world countries that parasites warded
off allergy symptoms, he completed his Ph.D. thesis at the
Afterward, he was an allergist at a pharmaceutical company, but the work
bored him, and he returned to academia at
“At that time,” he said, “I realized the definitive work had to be carried out in humans. So I began to make inquiries about possible tropical venues for this research.”
In the late 1980s, the Wellcome Trust issued a grant, and Dr. Pritchard and
his Nottingham team set up camp on
“We didn’t speak the language, and we were sparsely equipped,” he recalled. “But we established a rapport with the people. We gave them worm tablets and would ask them politely, in pidgin English, to collect their fecal matter in buckets for us.”
Hookworm infiltrates a victim’s system when the larvae, hatched from eggs in infected people’s excrement, penetrate the skin, often through the soles of the feet. From there, they enter the bloodstream, travel to the heart and lungs, and are swallowed when they reach the pharynx. They mature into adults once they reach the small intestine, where they can subsist for years by latching onto the intestinal wall and siphoning off blood. After sieving the fecal samples to extract hookworms eliminated when the worm treatment pill was given, the team reached an intriguing conclusion: Villagers with the highest levels of allergy-related antibodies in their blood had the smallest and least fertile parasites, indicating that these antibodies conferred a degree of protection against parasite infection.
And the hookworms seemed equipped to retaliate. After colonizing a digestive tract, the host often showed signs of a blunted immune response, leading Dr. Pritchard to suspect that the worms were reducing the potency of the body’s defenses to make their environment more hospitable.
“Sitting in the jungle for long periods gives you time to think,” he noted. “And this led to the idea that worm burdens of tolerable intensity could be beneficial under some circumstances.”
He began considering a left-field possibility. What if he could round up allergy sufferers, give them worms and see whether their wheezing and watery eyes disappeared?
Nearly 20 years later, his musing began to come to fruition. After Dr. Pritchard’s self-infection experiment, the National Health Services ethics committee let him conduct a study in 2006 with 30 participants, 15 of whom received 10 hookworms each. Tests showed that after six weeks, the T-cells of the 15 worm recipients began to produce lower levels of chemicals associated with inflammatory response, indicating that their immune systems were more suppressed than those of the 15 placebo recipients. Despite playing host to small numbers of parasites, worm recipients reported little discomfort.
Trial participants raved about their allergy symptoms disappearing. Word about the study soon appeared online among chronic allergy sufferers, and a Yahoo group on “helminthic therapy” sprung up.
“Many of the people who were given a placebo have requested worms, and many of the people with worms have elected to keep them,” Dr. Pritchard said.
Now he is recruiting patients for a larger-scale trial of the therapy, and he said he hoped to publish his results within the next year.
Some allergy sufferers cannot wait. The moderator of the Yahoo group, Jasper Lawrence, a Silicon Valley entrepreneur, has started a clinic in Mexico, to offer the unproven therapy (a basic worm “inoculation” costs $3,900).
Dr. Pritchard said he understood the motivations of such unregulated efforts. “It’s all become a bit scary,” he said. “There’s obviously a desperate cohort of patients out there, and they see this as a cure-all.”
An
infective hookworm larva.
Dr. Pritchard is the first scientist to infect patients with hookworms in a laboratory setting, but he is not the first to conclude that parasite infection might ease allergy symptoms. Previous studies have lent support to the idea.
In 2000, Maria Yazdanbakhsh, an immunologist at Leiden University in the Netherlands, studied 520 Gabonese children and found that those with Schistosoma haematobium, one of a family of parasites that cause schistosomiasis, had lower levels of allergic responses to dust mites, one of the most common environmental allergens.
When Dr. Pritchard and Carsten Flohr, another Nottingham scientist, returned
to Southeast Asia in 2006 to follow up on Dr. Yazdanbakhsh’s work with a survey
of 1,600 children in rural
Subjects with high worm infestation were less likely to have allergic
response to dust mites than noninfected children. Though reports of
parasite-conferred allergic resistance have been issued over the years, it was
not until 2005 that Rick Maizels, a biologist at
When Dr. Maizels and his colleagues infected a group of mice with the Heligmosomoides polygyrus parasite, a nematode similar to the hookworm that infects humans, they found that the mice started churning out more regulatory T cells for reasons that remain unclear.
The T cells, Dr. Maizels said, modulate the immune response by secreting interleukin-10, a compound that counteracts inflammatory effects that other immune system cells generate at the site of an allergic reaction.
“There’s a lot of evidence that allergy is just the immune system going a little over the top,” he said. “The worms are just turning down the volume.”
Based on his results, Drs. Maizels said Pritchard’s work looked promising. “I think it’s quite likely the hookworms will have a similar effect on the human immune system,” he said.
Some scientists say Dr. Pritchard is walking a fine ethical line by infecting patients with a parasite known to risk hosts’ health. Peter Hotez, a microbiologist at George Washington University who is developing a hookworm vaccine, said the parasite was among the primary causes of stunted growth and malnutrition in developing countries.
“If a kid is infected with 25 hookworms, he’s being robbed of his daily iron requirement, and because the worms suppress the immune system, they can increase the host’s susceptibility to diseases like AIDS and malaria,” Dr. Hotez said. “So in its current form, I think this therapy is too risky.”
Still, he supports Dr. Pritchard’s work from the perspective of proof of concept, saying, “The real question is could you isolate the molecules the worms are using to suppress the immune system and use them for therapeutic purposes?”
Because of the potential side effects, Dr. Pritchard does not envision thousands of patients lined up at clinics to receive parasites along with flu shots.
“The worst-case scenario would be to cause damage,” he said. “I’m nervous about deliberate infection, but I feel that my hypothesis should be tested rigorously.”
His long-term goal, he added, is to figure out exactly how the worms turn down the immune-system radar, so he can borrow the tactics to develop alternatives to immune-suppressant and allergy-fighting drugs.
“We’re looking at the molecular mechanisms the worms are using, and we’re hoping to find molecules that veer the immune response away from allergy,” he said.
A new class of drugs that mimics worms’ effects on the immune system could also potentially treat Crohn’s disease, arthritis and other autoimmune conditions.
Though he eventually hopes to eliminate hookworms entirely from his allergy treatment, Dr. Pritchard has few qualms about venturing where no parasite researcher has gone before.
“I gave myself 50 worms, and I felt it,” he recounted. “I had stomach pains and diarrhea. But with 10 worms, we’ve ascertained a dose that does not cause symptoms. The patients are happy. They’ve kept their worms, and I get an e-mail a day from people all over the world who want to be infected.”