Opening a good can of worms

Getting rid of parasitic worms in our bodies may seem like the sensible thing to do, however their ability to evade the body's powerful immune responses is central to research into new ways to to treat chronic conditions, writes CLAIRE O'CONNELL

RESEARCHERS struggling to find answers to diseases such as asthma and irritable bowel syndrome have help from an unusual ally – worms. Parasitic worms are artful dodgers, able to evade the body’s powerful immune responses and can survive without actually killing off their hosts. Yet by studying their survival techniques, researchers are discovering new approaches to the treatment of immune-related diseases.

It may not be the most appetising of thoughts, but some parasitic worms can live in humans for many years. These tiny hitchhikers come in many forms and today around three billion humans in the world are considered to have some type of worm infection.

But before you go right off your lunch, there’s a potential upside to paying attention to how these creatures work. Successful worm parasites have neat strategies for nobbling our defence mechanisms by just the right amount for both host and invader to survive – in other words they disarm our internal security systems before we can bounce them out.

Harnessing those subtle immune-dampening tricks could lead to new ways to address chronic conditions such as allergic asthma and inflammatory bowel disease, according to Prof Padraic Fallon, who carries out research into a type of flatworm called Schistosoma.

For humans, our relationship with schistosomes stretches back over millennia, and a complex dance appears to have developed between the invading parasite and our immune systems, explains Fallon, who is professor of translational immunology at Trinity College Dublin.

“Our immune system today is a by-product of co-evolution with pathogens, including worms,” he says, noting that worm parasite infections were more common in developed countries until relatively recently.

“Today if a child in a kindergarten displays signs of having a worm infection, then the child and the whole class is sent to the pharmacist to get drugs for the worms. But the reality is that removing worms is very recent practice, that’s maybe in the last 50 years.”

Getting rid of the worms seems like the sensible thing to do – parasitic worm infections may be fatal in some cases – but research indicates that some worms may also have a protective impact.

Studies of infections in Africa suggest that people with schistosomes tend to have fewer allergies, as Fallon explains. “Children who have schistosomes and other worms are less allergic, and if you give them drugs to remove the worms they start to get allergies.”

This links in with the “hygiene theory” that modern lifestyles in the developed world – including antibiotics and powerful cleaning agents – have meant fewer infections and less shaping of our immune systems.

“Thousands of years ago children were living in caves,” says Fallon. “Dirt, infections and worms were normal, there were no treatments. And those that survived were selected with genes that meant they tolerated worm infections.”

So that cascade of immune “insults” from viruses, bacteria and worms, may have helped to programme our immune systems, he says.

“But suddenly in the last 50 years we don’t have these worm infections – we have new drugs and hygiene. And our immune system and the genes that evolved for these infections are suddenly malfunctioning – the genes that go wrong today in Crohn’s disease, multiple sclerosis, asthma, all these modern diseases, those genes were programmed in evolution.”

Fallon has been studying what happens in animal models of the infection. And it seems there’s plenty to learn: he was part of a team that discovered a new type of immune cell, the nuocyte – details of which were published last year in the journal Nature.

“We used the worm to drive the immune responses and we discovered this new cell, the nuocyte,” says Fallon. “And the hypothesis, which is proving quite robust, is that this nuocyte cell evolved as an early response to worm infections.”

Introducing live infections of schistosomes can also have a positive effect on models of various diseases in the lab, according to Fallon.

“Using mouse models we have shown we can prevent experimental models of anaphylaxis, and we looked at allergic asthma, inflammatory bowel disease and models of multiple sclerosis,” he says. “Using a live Schistosoma infection we can ameliorate or reduce the severity of the diseases in the models.”

While several clinical trials are ongoing internationally to look at how infecting humans with worm parasites could impact on chronic diseases, Fallon cautions that it’s not something to be tried at home. “Live worm infections are not approved for clinical use,” he says. “Flatworms can kill people – approximately 10 per cent of people infected with schistosomes will get pathology that can be fatal.”

Meanwhile, efforts are under way to identify the particular molecules and mechanisms the worms use, because they may form the basis of useful therapies. Dr Sandra O’Neill at DCU is looking at a different flatworm – liver fluke – for such clues about immune modulation. While the fluke, Fasciola hepatica, causes disease in cattle and sheep, it can also infect humans, explains O’Neill, of DCU’s school of nursing.

“It is quite a successful parasite because it does infect humans but it doesn’t kill them,” she explains. “And if it can sit there and control immune responses and not kill the person, then from an evolutionary perspective it’s a parasite that has adapted quite well to its host.”

O’Neill gets plenty of liver fluke from abattoirs, and her research is particularly interested in how the isolated coat or tegument of the parasite can affect the host’s immune system.

“We are trying to find molecules that can be used or pinpoint a mechanism you can target with a therapy,” she says.

Prof Fallon and Dr O’Neill each receive research funding from Science Foundation Ireland and the Wellcome Trust.

Irrigation brought early Egyptians water - and infestation

THE EGYPTIANS were marvellous engineers, capturing the Nile's flood-waters to irrigate their crops. But these very canals also probably encouraged an unwanted invader.

Egyptian mummies dating back to 1,500 years ago bear signs of worm infection that may have been helped along by their irrigation practices, according to a recent study.

Today, more than 200 million people are thought to be infected with schistosomes, a type of parasitic worm that can cause the disease schistosomiasis.

To help build up a picture of the types of parasites that plagued people in ancient Egypt, researchers went looking for signs of the worm Schistosoma mansoni in tissue samples from mummies of the the Wadi Halfa, who lived by the Nile just south of the modern border between Egypt and Sudan.

Of the 46 mummies they screened, around a quarter of them showed evidence of infection with the worm, according to the findings published in the American Journal of Physical Anthropology.

"The prevalence of schistosomiasis shown in this study suggests that their parasite load was probably quite heavy," says study co-author and Emory University researcher George Armelagos.

The small worm may have had a boost from the farming practices of the time – farmers dug canals to irrigate their crops, and these channels may have been home to a type of aquatic snail that harbours the parasite.

"Often in the case of prehistoric populations, we tend to assume that they were at the mercy of the environment, and that their circumstances were a given," says the study's co-author Amber Campbell Hibbs. "Our study suggests that, just like people today, these ancient individuals were capable of altering the environment in ways that impacted their health."

– Claire O'Connell