Parasitic Worms: An Untapped Potential for Bio-medicine?

Hookworms, whipworms, pinworms, flukes: mere mention of the panoply of parasitic worms that plague humans is enough to make most of us shudder. Not John Turton. In the mid-1970s, while working at the UK's Medical Research Council Laboratories in Surrey, he intentionally infected himself with hookworms in an attempt to relieve his chronic hay fever. It worked. For two summers while he harboured the parasites, his allergy abated, only to return when he was free of them (The Lancet, vol 308, p 686).

Turton's grim experiment came at a time when it was emerging that people living in regions where parasitic worm infections are rife tend to have fewer allergies. Nevertheless, he might have thought twice. In 1913, W. Herrick, a doctor from Columbia University in New York, noticed a very different link between parasitic worms, or helminths, and allergy. Lab workers whose duties included dissecting the gut-dwelling roundworm Ascaris often developed tenderness and swelling in their fingers, and more severe allergies after longer exposure, especially asthma.

Since the 1970s, researchers have been trying to make sense of these conflicting findings in the hope of being able to harness the power of parasites to help relieve allergies without making things worse. They know they are playing with fire - after all, helminths are responsible for some truly horrible diseases and cause great suffering around the world. Yet, as the effects of helminths on the human body become clearer, it looks as though their healing potential may be unleashed.

Not surprisingly, few researchers have been willing to take the risk of deliberately infecting themselves as Turton did. Instead, most studies are based on populations in countries where people are already infected. This research tends to focus on the three most commonly diagnosed allergic conditions: asthma, eczema and hay fever. The results have been confusing, but now researchers are beginning to understand why.

One study conducted in Taiwan, for example, showed that people infected with Enterobius vermicularis, a pinworm that is one of the most common gut parasites in the world, were less likely to have hay fever than the general population (Clinical Experimental Allergy, vol 32, p 1029). However, results from Ecuador tell a different story. Noting that hay fever was significantly more common in children living in urban than rural settings, researchers looked for a correlation between the allergy and levels of infection with the roundworm Ascaris lumbricoides. The parasite was equally common in both groups, so they concluded that something else must be responsible for the prevalence of hay fever (Clinical Experimental Allergy, vol 34, p 845).

The findings on eczema have proved just as difficult to interpret. For example, a study in Uganda found that eczema was less common among infants whose mothers had been infected with helminths while pregnant (JAMA, vol 294, p 2032). However, another study, this time in Ethiopia, discovered that children with Trichuris worms, whipworms that infest the large intestine, were more likely to have eczema than uninfected children (Journal of Allergy and Clinical Immunology, vol 115, p 370).

As for asthma, Herrick's finding that it can be triggered merely by contact with Ascaris was confirmed in the 1970s. However, hookworms reduced the severity of asthma in a group of Ethiopians (The Lancet, vol 358, p 1493) and similar benefits have been noted in Brazilian asthma sufferers infected with Schistosoma mansoni, the flatworm responsible for schistosomiasis, which damages internal organs.

What are we to make of all this? The crucial link between allergies and parasites is the human immune system. Allergies are triggered by an overactive immune response, and helminths have strategies to damp down our immune response to promote their survival; after all, they have evolved in lockstep with humans for millennia.

In people who don't have allergies, foreign material entering the body prompts the release of cytokines, molecules that sound the alarm to get the attention of other immune cells. As immune cells rally to attack the intruder, a second set of molecules is released to prevent the immune response from overreacting. One of the key molecules responsible for keeping reactions in check is interleukin-10, which inhibits the release of certain cytokines. People with allergies tend to have lower than normal levels of interleukin-10, so immune responses frequently get out of hand. Conversely, people infected with helminths have above-average levels of the molecule, and research on schistosomiasis patients indicates that this is at least partially because the worms release chemicals that stimulate the production of interleukin-10 in their host.

The mystery, then, is not so much that helminthic infections can damp down hay fever and other allergies, but that in some cases parasites do not. Clearly, different helminths interact with the immune system in different ways. "Parasitic worms are often treated as having the same effect on the body, but they probably do not," says Carsten Flohr at the University of Nottingham, UK, who recently published an article on the subject (Clinical Experimental Allergy, vol 39, p 20). What is not clear is the mechanism that sends the immune response in either direction.

One possible explanation is the helminths' lifespan. A short-lived worm, such as E. vermicularis, will not have much of a chance to tinker with the immune system and is less likely to be able to suppress the response than a hookworm, for example, a parasite that's in for the long haul. Worms responsible for chronic infections would be unlikely to survive without evolving mechanisms that allow them to strike up an immunological balance with their host.

In addition, different species may have specific effects on immunity depending on the areas of the body they inhabit. Trichuris, for example, is ingested and stays in the gut, escaping the intense immune response that schistosomes encounter as they burrow their way through the skin, which is heavily monitored by cytokines and highly reactive, explains Flohr. Hookworm larvae also enter through the skin and make their way through the bloodstream to the lungs, where they pass through the thin-walled blood vessels. They then travel up from the lungs into the trachea, only to be coughed up and swallowed, allowing them to reach the small intestine where they develop into adult worms. "The potential protective effects of hookworm infections on asthma may be related to these parasites' lung migration phase," Flohr says.

It is this specificity that makes parasitic worms attractive as a potential treatment for allergic conditions. "The nice thing about a worm is it does the work of entering the body and interacting with the immune system for you. It has evolved excellent techniques that allow it to get to where it wants to go and lower the ensuing immune response," says immunologist Klaus Erb from Boehringer Ingelheim Pharmaceuticals in Germany.

Could there really ever be a demand for worm therapy? With a growing understanding of which parasites have the most potential to alleviate allergies, some researchers are convinced worms have a future. That's partly because allergies are a huge and increasing problem, particularly in the developed world where they affect around 1 in 5 children, and partly because there is no treatment that resolves the underlying problem of an overreactive immune system. The choice is antihistamine tablets, which only work as long as you keep taking them, or a painful and time-consuming course of injections to desensitise you to the materials that prompt the immune system to overreact.

In an attempt to bring helminthic therapy a step closer, researchers at the University of Nottingham are testing the suitability of hookworms as a treatment for asthma. First they infected healthy people with the worms and discovered that a dose of 10 larvae resulted in a high enough level of infection to confer immune benefits; studies in Ethiopia indicate that this occurs when infected individuals are excreting at least 50 hookworm eggs per gram of faeces. Side effects included itching and sometimes minor intestinal discomfort, but they were only mild. The researchers then recruited asthma sufferers to test the effectiveness of hookworm therapy. "We monitored airway responsiveness during the period when we knew the larvae were migrating through the airways to determine if the migration made respiratory disease worse," says Johanna Feary, a member of the Nottingham team. And, most recently, they have conducted a 16-week, placebo-controlled trial on 34 people with asthma.

The results of these ground-breaking studies have yet to be published. Even if the treatment proves highly effective, it may well be difficult to convince people that worm therapy is the way to go. Many doctors find the idea repellant. "These things are disgusting. People are never going to allow themselves to be infected with them," says clinical immunologist Asif Rafi at the University of California, Los Angeles. "You really don't want to treat people with worms if you don't have to," adds Erb.

Aside from the yuck factor, there is another problem: helminths could ultimately make patients more susceptible to other diseases. It is an oversimplification to suggest that worms just reduce the immune response, says Rafi. What they are doing is changing the type of activity the immune system engages in. When reacting to parasites, bacteria and viruses, the immune system must balance the release of molecules that sound the alarm and increase inflammation, against those that calm things down, reducing inflammation and repairing tissue. Parasitic worms are particularly adept at shifting the balance towards an anti-inflammatory state, as it's the ability to control inflammation that allows them to survive for years in a human. That's good for them, but may make their host vulnerable to other infectious diseases.

"There may well be a downside to worm infection," admits David Pritchard from the Nottingham team. "The great challenge we face is finding the correct balance between alleviating disease and propagating it."

There may be another way to exploit the healing powers of helminths, however. "What we really need, is to find useful compounds being produced by these worms, rather than trying to use the worms themselves," says Rafi.

That is exactly what William Harnett and colleagues are doing at the University of Strathclyde in Glasgow, UK. They have shown that a complex protein called ES-62 - produced by Acanthocheilonema viteae, a parasitic filarial nematode worm that infects rodents - dramatically reduces inflammation associated with allergic conditions in mice. Intriguingly, ES-62 affects multiple aspects of the immune system simultaneously. As well as inducing production of anti-inflammatory cytokines such as interleukin-10, it also inhibits production of pro-inflammatory cytokines and proliferation of lymphocytes - the immune system's white blood cells - and blocks the activation of mast cells, which play a key role in promoting inflammation. Now Harnett and his team are attempting to create small drug-like molecules that mimic the effects of ES-62.

Treating allergies with "essence of parasite" might sound like an ambitious goal, but the ES-62 research could be just the start. Parasitologist Jan Bradley at the University of Nottingham points out that there is far more to helminths than just how they influence allergic reactions. For example, Murray Selkirk at Imperial College London has discovered that infection with parasitic worms gives animals some protection against pneumonia caused by influenza. "Things are going to get a whole lot more complicated when we start considering the effects generated by interactions between different parasites, and the interactions between parasites and certain viruses," says Bradley.

Who's for worm therapy?

Some species of parasitic worm are better at suppressing allergies than others. Likewise, some people get greater benefits from worm infections than others. Researchers suspect that a person's age, diet and the environment in which they became infected may make a difference. In rural settings in developing countries, for example, children are often repeatedly infected from an early age. "This leads to a degree of host immunity and is probably the reason why helminths such as hookworms can survive in the same host for years, often causing only mild symptoms," says Carsten Flohr of the University of Nottingham, UK. In this case, the parasites are more likely to help alleviate allergies. Where people are infected later in life, however, exposure to helminths can actually lead to allergies.

Another factor that seems to influence the link between parasites and allergies in different individuals is genes. "Genetics are known to play a role in whether people are susceptible to both allergies and parasites," says immunologist Padraic Fallon at Trinity College in Dublin, Ireland. "Both of these susceptibilities could be under common genetic control." It may be that people who are prone to allergies have immune systems that naturally respond more aggressively towards invading parasites. Such highly reactive immune systems would have been selected for in areas where infections from parasitic worms were high. In today's developed world, where such infections are rare, these individuals will be more prone to allergies. However, they may also be more likely to respond to helminthic therapy.

Parasites

Its nice that the press are finally waking up to this idea, but disappointing that so many basic errors are repeated again.

Hookworms impact on asthma has nothing to do with their migration through the lungs.

More disappointing still is that the author did not contact me for at least some background information.

Because I have treated over 90 people using hookworm or whipworm and the results have been spectacular. I probably know more about it than many you quote.

The author needs to check his facts better, and New Scientist needs to do a better job editorially. If this is typical it is hard to trust anything published here.

90% of those we have treated for Crohn's for instance have shown an improvement of 4.5 on a scale of 5 after six months for instance, and our success rates for RR MS, allergies, IBS, asthma and Sjogren's are equally, if not more, impressive.

I have no doubt that the practice of immunology in the future is going to largely consist of managing the yeasts, bacteria, protozoa and helminths, from a very early age, and based on genotype, that inhabit our intestinal tract.

With respect, aren't these internet medical websites usually shoutey, shoutey. If it's private business (esp. internet) and medical I tend to stay away. That might be tarnishing you with the snake-oil label though. Why isn't this at a university base with the director holding the "chair for such and such" or "Professor this of that".

It reminds me of those natural remedy websites that say, oh take Selenium and NAC and your asthma will be cured. Have a look at what all these people say. You try it and whoa! comes a day when you call the ambulance and you're in A&E.

Anyway, I guess when one looks at the eukaryotic cell, in the future an in-vivo, long-term, self-sustaining, man-made nano-machine that delivers a dose of medicine (say insulin or whatever) is I guess, just a symbiot and a parasite...

Mixed Article Tue Jul 14 01:01:56 BST 2009 by Jasper Lawrence http://autoimmunetherapies.com

I myself used, and continue, to shy away medical sites on the internet. Ours, the one you link to is, I hope, different in substance and in approach, if one gets past one's immediate reaction to the idea of infection with parasites being uniformly bad.

Our site is littered with scientific references and anecdote, both. Our claims are conservative and factual, and always referenced or supported by the literature. Often that literature is available on the same page and if not we provide links to references. We also repeatedly offer the full text of articles throughout our site.

Each disease specific page contains not just science but the personal account of at least one client.

But, most people are not interested in the science, oddly. If they were we would have treated many more than the roughly 90 we have.

Please Dr Lawrence, don't give up on reductive science. Please find just what it is that these worms produce and then make that 'essence of worm'.

Is it naive to think that they can be put in a blender and the allergens then given as a pill or even skin patch?

Is it possible to wear some of skin patch with live worms and some kind of semi-permeable barrier (ultra-pore membrane) that allows small molecules to pass to-and-from but not to let the parasite burrow into the skin?

Are you seriously suggesting that "natural" remedies are more dangerous than the long list of negative side effects of nearly ALL pharmaceuticals? And what makes universities so great? I work at Ohio State and they have a whole hospital dedicated to treating cancer - The James, yet they don't condone or provide for natural remedies that ARE working elsewhere. It is just this kind of thinking - that remedies have to come from some proven medical entity in order to be viable, instead of what is really true - that our bodies used to be perfect, until humans started messing with our physiology and introducing foreign materials, manmade "better than nature" chemicals, and non-foods cloaked as foods which have completely disrupted our natural ability to heal our own bodies either by themselves or via truly natural remedies. The knowledge exists. We need to let it flourish - should we test things? sure. But we shouldn't discount them just because they don't cure every little thing that we humans have inflicted upon ourselves. Most of the time, when people have negative reactions to holistic or natural remedies it is because they are not following the directions or have not done enough research themselves or simply don't know what their underlying root cause is and are simply treating a symptom (just like all pharmaceuticals do).

My son is very ill and I'm looking into all types of remedies. This worm article and the doctor's comments were extremely helpful. Conventional medicine is not working for my son, but this and other types of holistic remedies have given us hope. I do my research, and not just on the internet. I don't want my son harmed in any way by a natural remedy that I'm administering so I do seek out medical advice. but guess what - most doctors refuse to buy into anything but what the pocket lining pharmaceutical companies offer them. The internet has become a wonderful source of information - we just have to be vigilant and smart enough to investigate - and no, I certainly don't need a university's name tied to something - their money comes from questionable sources as well. They are no different than doctors and legislators being paid by Big Pharma and Big Food.

What really interests me is how can a person get information so that they can tune their lifestyle to

When people have a way to do that for themselves a lot can change for those who take the option.

Mixed Article Fri Jul 17 23:12:58 BST 2009 by Jasper Lawrence http://autoimmunetherapies.com

You will have to hunt me down, I was not allowed to post my contact information, it must be in breach of their policies here.

I have an issue with people being infected with parasitic worms and then being "released" into the general population. Surely most societies aim to reduce the incidence of parasitic infection not to deliberately increase the risk of collateral infection of otherwise healthy people through dubious intervention. I get annoyed when colleagues bravely stuggle into the office with streaming colds. Imagine how I would feel knowing that they were shedding worm eggs.

Whoa There! Fri Jul 10 03:03:32 BST 2009 by Jasper Lawrence http://autoimmunetherapies.com

Which is a legitimate concern and why we only use helminths that cannot be transmitted, in any practical sense, by an infected person living in the US or Western Europe.

Neither hookworm or whipworm are communicable unless an infected person is in the habit of defecating on the ground, and then after respectively a minimum of 9 or 21 days of ideal tropical conditions, an uninfected person either comes in bare skin contact with feces contaminated soil or ingests feces contaminated food. By idea conditions I mean high humidity, rainfall and around the clock warm conditions (approx 30°C). Both aridity and sunlight will kill these parasites' larvae or embryos.

In fact hookworm are so benign that the CDC diagnosis and treatment algorithm shows that for light infections the CDC recommends doctors not treat light infections. This implies also that they are not an infection risk to others, as I assert based on the life cycle of hookworm and whipworm above. After all the CDC is a political as much as a medical animal and if they woke up to find the Eastern seaboard was infected with hookworm having made such a recommendation to doctors heads would roll.

Simply introducing toilets with sewers and widespread use of shoes breaks the lifecycle of these parasites, which helps put the tropics in perspective.

I am very surprised that there is no mention of the work of Joel Weinstock and David Elliott. They have presented compelling experimental and clinical studies on the therapeutic efficacy of nematode worm treatments. Wikipedia is also rather more informative.

This has been known for at least 20 years. One other factor in the play is the actual immune response of the body, that is now targetted at something more threatening than (e.g.) some pollen, but at the worm. Because even with all its supressing tricks, the immune system will still try to fight the worm.

Back then, someone also suggested that a ravies shot should have simillar effects.

Suffering from severe allergies, I have to say though, that I am not eager to try eithe treatment. The problem is that you will want a working immune system in case something really severe comes along (say swine flu).

Not So New News. . . Fri Jul 17 23:22:49 BST 2009 by Jasper Lawrence http://autoimmunetherapies.com

It is a common misconception that hookworm suppress immune response substantially.

A number of studies have clearly demonstrated that those suffering from bad allergies actually enjoy a heightened immunity, even to forms of cancer. A study in late 2007 into glioma and allergies showed that the highly allergic had a 30% lower chance of developing Glioma.

The hygiene hypothesis proposes exactly that, that in the absence of helminths and other immune modulating infections, our immune systems are over active and mis-directed because our immune systems evolved to account for the presence of these organisms.

So according to that theory you are sick because you do not have as rich an intestinal ecosystem as you are adapted to.

Hence the issue is not that you will be immuno compromised or suppressed if you have parasites, but that you are not sufficiently immuno suppressed to be healthy now.

In reference to the Glioma study it is entirely plausible that were you infected with hookworm your chances of developing Glioma would increase by about 30%. But you would still have the same chances of developing Glioma as someone with a normal immune system.

So this issue is not a simple matter of hookworm or whipworm making people more vulnerable to infectious disease or cancer.

As well, when this possibility has been studied, epidemiologically, the affect of parasites even on the world's poorest is not strong or strictly one way.

For instance, various immunizations in the third world have been demonstrated to make children more vulnerable to death to malaria. Why? Their immune response, no longer modulated by the disease they were vaccinated for, is so over the top to malaria that their immune response kills them when infected with malaria.

An Article I Wrote In The Same Vein Tue Jul 14 21:25:39 BST 2009 by Beverly Richards-Smith

A PubMed (http://www.pubmed.gov) search using the terms "worms" and "atopy" retrieves 82 publication records. Searching for "worms" and "allergy" yields 2158 results

Very nice article. I was wonder if Parasites worms can cause cancer. High level of Treg who protect him from immunology system can help cancer grow. That way we won't be allowed to do this care on ourselves hand

Parasitic Worms: Just What The Doctor Ordered? Wed Sep 02 20:17:22 BST 2009 by R H Davies

I love the way doctors just dismiss out of hand the possibility of a Hookworm treatment on the grounds that patients wouldn't want to cope with the "Yuck" factor. What does he know arrogant prat? Years of the misery of asthma and allergies and you really don't care much about a few worms if there's any hope of a reprieve.

Plus there's more than a few medical procedures patients are expected to endure with a high "yuck" factor and we're just dismissed as pathetic if we complain it hurts or is unpleasant. Cervical smears spring to mind.

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Who's for worm therapy?

Parasites

Parasitic Worms: An Untapped Potential for Bio-medicine?