Only recently did the advent of better sanitation and potent drugs break up this marriage. Shoe-wearing put hookworms out of business in the United States. But the 20th century also ushered in asthma, allergies, and a host of autoimmune diseases that had been uncommon previously and remain so in less developed countries. All are marked by out-of-control immunity. Vanquishing worm parasites in particular might have disrupted an equilibrium that kept humans healthy.
Of course, parasitic worms have not really gone away. Some estimates suggest that more than 1 billion people, mainly in the tropics, are infected, giving scientists a chance to study the link between immunity and parasites in context.
In 2003 researchers at the University of Nottingham in England and colleagues found that toddlers living in an Ethiopian city were twice as likely to wheeze—a symptom related to asthma—as kids living in less sanitary rural areas. Similarly, Ethiopian kids with roundworm infections were half as likely to wheeze as those free of parasitic worms.
At about that time in Argentina, physicians Jorge Correale and Mauricio Farez began a study that brought the helminth issue into sharp focus. Previous studies had shown that mice with a disease similar to multiple sclerosis, marked by damage to the fatty sheaths insulating nerves in the central nervous system, improved when they were infected with flatworms.
That prompted Correale and Farez to examine a group of MS patients and identify 12, average age 34, who had recently acquired a parasitic worm infection. Then the doctors found 12 other MS patients who matched the first group in age and other respects, but who didn’t have parasites. The rate of MS relapse had been similar in both groups.
As part of the study, which followed patients for an average of 4.6 years, those harboring parasites agreed not to be treated for them. Perhaps it’s just as well, because MS symptoms in this group became mild to nonexistent. Only three of the patients had a relapse—one apiece—during the study period. The other nine worm- infected patients had none at all. In contrast, the MS patients without parasites had 56 relapses in all, about one per year each.
MRI scans showed 14 new or enlarged brain lesions in the worm-infected patients during the study and 164 in the other group. Mild anemia showed up in four people with worms, but the other eight had no serious ill effects from the parasites. The results appeared in the Annals of Neurology in 2007.
Despite the dramatic difference, the scientists acknowledged that such observational studies need to be borne out in trials in which scientists randomly assign patients to one of two groups with different courses of treatment.
Maria Yazdanbakhsh, an immune-parasitologist at Leiden University Medical Center in the Netherlands, and colleagues had done just that in Gabon in equatorial Africa. To assess whether a parasitic worm infection protects against allergies, the scientists enlisted 317 schoolchildren, ages 5 to 13, in a study. All of the kids had intestinal parasites, mainly roundworms, but none had an active allergy to house-dust mites. Then researchers randomly assigned half the children to get drugs ridding them of the parasites.
Within a year, 14 percent of the children treated for parasites had developed a dust mite allergy, skin-prick tests showed, compared with fewer than 7 percent of those who retained their parasites. The report appeared in the Journal of Infectious Diseases in 2004.
Some people beset by allergies, asthma, or autoimmune disease saw these early findings and took to stomping around in less-than-sanitary conditions in Central Africa in hopes of acquiring a parasite to cure ailments. Anecdotal evidence suggests it can work, but the approach is unverified and dangerous. Health risks from worm infections can range from mild (pinworm) to debilitating and sometimes lethal (schistosomiasis).
Others have resorted to buying unregulated parasite eggs on the Internet. They are available through an underground market with mixed results, says gastroenterologist Jonathan Terdiman of the University of California in San Francisco. He doesn’t endorse the approach, but he does regularly see patients with inflammatory bowel disease even if they are using it. “A lot of these patients are in great need,” Terdiman says. “The pharmaceutical approach has failed them.”
So controlled clinical trials are needed. To get a treatment trusted and cleared, scientists need to test it on people randomly assigned to get either the real thing or a placebo. This is the gold standard of medicine and, unlikely as it might have seemed a decade ago, it’s where parasitic worm therapy has now arrived.
Joel Weinstock had a perfectly good career as a parasitologist in the early 1990s when he and Elliott, then colleagues at the University of Iowa, noticed the lack of autoimmune diseases in the tropics. They knew about the hygiene hypothesis, which suggests that early exposure to germs is crucial for normal immune function later on. And the two knew about the rise of autoimmunity in the West.
“We asked, ‘What’s missing in developed countries?’” Elliott says. “We still had viruses and bacteria, but we were missing a whole class—helminths—which used to be universal.” Lab work and tests in animals soon convinced Elliott and Weinstock that helminth infection could quell inflammation. By 2000 they were speculating openly that failure to get parasitic infections might contribute to inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.
The researchers found an innocuous gut parasite, the pig whipworm Trichuris suis, that didn’t cause disease in people. They asked patients with ulcerative colitis to drink a solution containing either a placebo or cleaned-up, microscopic T. suis eggs every two weeks for 12 weeks. Roughly half the patients were randomly assigned to receive each. Of 30 people getting the helminth therapy, 13 improved substantially, compared with only 4 of 24 people on the placebo.
