April 10, 2007

Hookworms Are Dangerous Parasites, But They Could Also Cure Disease

By Julia Stuart

David Pritchard's wife thought he was barking. In the interests of science, the professor of parasite immunology agreed for a plaster bearing 50 hookworms to be stuck on to his skin. They burrowed into his flesh, crawled up his arm, travelled to his lungs and arrived in his gut, where they attached themselves and started to suck out his blood. "My wife said, 'What the hell are you doing? You've got a young family," he says.

Mrs Pritchard had already had to put up with her husband disappearing to Papua New Guinea every summer for the past 10 years to study the parasite, a species known as Necator americanus. He and his team from the University of Nottingham established that while in intimate contact with the immune system, the hookworm was never rejected by it. They worked out that the worm was manipulating it to survive. Professor Pritchard then published a speculative article arguing that the worms could actually be good for you.

Necator americanus can switch off the immune system, so it was possible that it could be used to control diseases driven by overactive immune systems, which are a feature of advanced societies. These conditions include allergies, and a whole range of autoimmune diseases such as cirrhosis, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease.

A colleague of Professor Pritchard's working in Africa noted that asthma seemed to be moderated by the presence of the same species of hookworm. He and his team decided to conduct a trial. "We applied to the funding authorities and we were told to prove that it was safe."

The hookworm can potentially cause disease. It enters the body from the soil as an infective microscopic lava, migrates through the circulation into the lungs, breaks through into the airways, migrates upwards, is swallowed and then lives in the gut for up to five years producing eggs. The eggs are excreted, hatch into infected larvae and the life cycle starts again. Too many worms can damage the lungs, and they can extract so much blood from the gut that the carrier can become anaemic. One way to avoid infection in the tropics is to wear shoes.

Ten people in the group agreed to be infected. Each scientist was given a plaster with a dose of either 100, 50, 25 or 10 worms, which was stuck on his or her arm. They then monitored their symptoms. The colleague who was given 100 vomited. The safe dose was 10 to 25 larvae, they concluded.

"You don't feel anything until they get to your gut," says Professor Pritchard. "Then you get this dull ache under the ribcage - the worms have hooked on. You get an inflammation that makes you feel unwell. Once in the gut, the worms are feeding on blood." And he was OK with this? "I didn't feel 100 per cent secure. You never know what else is being carried by a parasite. The key is that once you've taken them, forget you've got them - or you imagine all sorts of things going on."

The scientists took de-worming tablets to kill the parasites once they had reached their guts. They then started on the second phase of their trials, infecting volunteers suffering from hay fever. It showed that 10 larvae had no adverse effect.

"A treatment for asthma is the goal," he says. "The clinical monitoring is a lot more stringent. The message is: so far, so good. We haven't made anybody sick with 10 larvae."

The scientists are now recruiting volunteers for the asthma trial. None will be paid. They are also running a trial on Chrone's disease, which attacks the bowel and causes inflammatory disease. "Chrone's is a nasty disease. It's a big ask to expect 10 larvae to reverse it, but you have to start somewhere," he says. Both trials have secured funding.

The hope is not that patients will be infected with hookworms in the future, but that scientists will be able to synthesise a drug can be that mimics how they control the body's immune system. The latest theory is that the hookworms stimulate white blood cells called regulatory T-cells, which reduce overactive immune responses.

Professor Pritchard concludes: "We should be looking for drugs from organisms that live either in us or on us, rather than harvesting drugs from organisms that live in the soil."

Doctors have set up more than 450 centres in Britain offering maggot therapy to help treat leg ulcers, pressure sores and other wounds. Maggots clean wounds by dissolving the dead and infected tissue and disinfect them by killing bacteria.

The surgical materials testing lab at the Princess of Wales hospital in Bridgend has found evidence that maggot therapy can combat MRSA, the so-called superbug, which seems to be resistant to virtually all known antibiotics.

Leeches are particularly effective in microsurgery that involves the reattachment of skin or body parts. It is thought that a natural anticoagulant secreted by the leeches fights blood clots and restores blood flow to inflamed body parts.

A study found that patients with Chrone's disease who swallowed whipworm eggs of the species Trichuris suis, commonly found in pigs, for a 24-week period, showed significant improvement. Once the eggs hatch, the worms stay in the bowel and do not invade the rest of the body.