John Scott investigates worms and parasites and their possible therapeutic uses in respiratory and gastrointestinal disease, and in allergy.

According to the hygiene hypothesis, we may have gone too far, too quickly, in our attempt to rid our lives of bugs, consequently leaving our immune systems out of sync with our suddenly squeaky clean lifestyles.

The fact that the human immune system is now redirecting its aggressive attentions onto non-threatening targets such as foods, and even attacking the body's own tissues, is seen as a direct consequence of it being deprived of many of its traditional targets – bacteria, viruses and parasites.

The theory continues to attract support from research, such as that which has recently revealed that the eradication of the stomach bug Helicobacter pylori can increase the risk of asthma (FM Sept 2007 p18 or on the FM website at http://tinyurl.com/4oh99h). It is also known that inflammatory bowel disorders, such as Crohn's disease, occur at a much higher rate in industrialised countries than in areas where gastro- intestinal parasites are still common.

The return of the worm
A parasite said to its host,
‘Though I’m not trying to boast,
My favourite trick
Is making you sick,
So your health will be better than most.’

When a hayfever-prone researcher from Nottingham University's School of Pharmacy contracted hookworms while on a field trip to New Guinea, the only obvious effect was that his sniffling, sneezing and sore eyes all cleared up. Intrigued by the possibility that a parasite infection might cause a down-regulation of the overactive immune response seen in allergies and auto- immune diseases, the School of Pharmacy team launched a study of Necator americanus, a hookworm which has been living in humans for millions of years.

The leader of the team gave himself 50 worms, causing diarrhoea, but also proving that the treatment was otherwise safe, while the researcher who had first contracted hookworms continued to enjoy the benefits of a more modest colony, without any adverse effects.

In order to win ethical approval for clinical trials involving patients, the Nottingham team had to overcome the conventional wisdom that all bugs – and parasites in particular – are bad. Nevertheless, approval was eventually granted, and preliminary studies were carried out in subjects with respiratory diseases, before commencement of the current trial to assess the effects of a hookworm infection in patients with Crohn's disease.

Hookworm alchemy
Necator americanus is clearly able to influence the human immune system and, while it is still not known exactly how it achieves this effect, some parts of the puzzle are beginning to fall into place.
It appears, for example, that, in order to protect itself from attack by the body, the worm stimulates the mechanism which is responsible for keeping the immune system under control.

An immune response depends on T-cells, of which there are two types – bacteria-fighting T-helper 1, and the worm-fighting T-helper 2 cells. If the former overreact, the result is diseases like Crohn's, psoriasis, and rheumatoid arthritis. If, on the other hand, the latter cells overreact, allergies develop.

Controlling these two types of immune cell are the regulatory T-cells, which are able to shut down the other defence cells before they become too aggressive and cause harm to the body. What the hookworm appears to do is somehow to increase the population of regulatory T-cells, effectively reducing the immune response.
The Nottingham researchers are seeking to establish exactly how the hookworm achieves this effect, with the eventual aim of synthesizing whatever chemicals it produces and using these in the creation of more effective medicines to combat allergies and auto- immune diseases and prevent organ transplant rejection.

Given the attitude to parasites that is common amongst the population at the present time, drugs rather than the bugs themselves may seem a much more attractive proposition to many patients. However, in view of the track record that synthesised medicines have for producing unpleasant and even harmful side effects (eg nearly 3,000 deaths from medication in the UK in the last three years – http://tinyurl.com/3v84nb) there is much to be said for installing a living chemical factory in one's gut which will produce the required medication on site, without interruption and without the risk of adverse side effects.

Desperately seeking infection
As someone who has multiple allergies and overwhelming food intolerance, as well perennial rhinitis, eczema and allergic asthma, I have been very keen to obtain a hookworm infection since I first heard about the Nottingham project.

I could have travelled to where the worms are endemic and picked up a hookworm infection by walking around barefoot in open air latrines, but the dose is difficult to control when obtained in this way and one could easily pick up something less desirable in the process.
The silver lining to my recent diagnosis of Crohn's disease was that this provided eligibility for inclusion in the current trial of hookworms in patients with this disorder, and I wasted no time in taking advantage of the opportunity.

At my first session at the Wolfson Digestive Diseases Centre at the Queen's Medical Centre in Nottingham, the project was explained in detail by Paul Fortun, the trial team leader, and my suitability for the study was assessed. After this, all of which took place in the 'Bored Room', I was examined in another room designated the 'Hide and Caecum'!

At the next session, a small amount of liquid was dispensed onto a plaster which was then applied to my arm. Contained within the liquid were either ten microscopic worm larvae, or a small quantity of histamine to act as a placebo by imitating the itch caused by the larvae as they make their way through the skin.
Which of these 'treatments' I received was dependent on whether I had been assigned to the active treatment group or the placebo group but, as this is a double-blinded trial, this detail was not revealed to me, nor known by the medical staff involved.

Living with wriggly lodgers
I settled into a routine of diary-keeping and of hospital visits every three weeks for blood tests and the completion of more questionnaires, while waiting for the worms – if these were what I had been given – to take up residence in my gut.
If I had received hookworm larvae, these would travel first, via my blood stream, from their point of entry on my arm to my lungs. They would then hitch a ride on the upward-moving escalator of hairs lining my airways, before being swallowed, passing through my stomach, and finally settling in pairs in the upper reaches of my small intestine. And all without the aid of a sat nav!

As the worms are still minute when they make this epic journey, the host is blissfully unaware of any of their activity. Even when fully grown, this hookworm only reaches approximately 1 cm long and, although it survives by drawing blood, this is also undetectable by the host, and the amount taken is miniscule.

Normal sanitation and hygiene procedures ensure that there is no danger of the worms proliferating in the host, or of infection being passed on to others. The eggs produced by the adult worms only become infectious after they have left the gut of the host and gone through a further stage of growth in soil. In order for a transfer of infection to take place, the next generation of larvae must then be picked up from the ground on bare skin, several days after the eggs were deposited.

The benefits of gut buddies
Quite suddenly, at about the fourth week of the trial, my bowel habits normalised somewhat and abdominal discomfort decreased. Itching at eczema sites eased, sleep improved, my perennial rhinitis dried up completely and a persistent nocturnal throat irritation also improved, completing this impressive list of chronic symptoms which were unexpectedly ameliorated.

What I was hoping for most was to regain some tolerance to normal foods but, eating small amounts of a few common foods (instead of my usual semi-elemental diet) produced only disappointing results initially. However, later in the trial period, several foods which had previously caused a variety of symptoms, including bloating, nausea and abdominal soreness, increased fatigue, headache and inappropriate shivering, began to produce less severe symptoms and, in a few cases, no symptoms at all.

Following eradication treatment at the end of the active phase of the trial, all the positive changes were reversed and I was forced to return to a solely semi-elemental diet, leaving me to ponder whether the benefits had all been due to the placebo effect, or whether I had actually found a remarkably simple solution to many of my health problems.
I am currently negotiating a reinfection with Necator, in order to further assess the possibility that this treatment might be of long-term benefit in my battle with multiple allergy and food intolerance.

Worm therapy opportunities
Many questions remain to be answered about worm therapy, such as what the ideal number of worms might be, and whether it is better to leave the same worms in place for a longer period or to eradicate and replace them every few months.

Further studies will be carried out at Nottingham to try to answer these and other questions, and are likely to involve other diseases as well as Crohn's. A study with asthma patients has already been completed and MS specialists are showing an interest in trialling hookworms with some of their patients.

Would-be worm hosts who are not eligible for a clinical trial could always acquire an infection the natural way, by walking barefoot on faeces-infected ground in a part of the world where hookworms are endemic, as did one adventurous worm hunter who was desperate to cure his asthma. Details of this brave man's exploits can be read in his practical guide to the use of hookworms in the treatment of asthma and hay fever, at http://tinyurl.com/nz46n.

A safer and more convenient, though much more expensive option would be to purchase the eggs of a different gastrointestinal worm – Trichuris suis – from Ovamed, a German pharmaceutical company.
(See http://tinyurl.com/4jhj9c)
Trichuris – a pig whipworm – has been researched at the University of Iowa in the US and found to be a safe and effective treatment for ulcerative colitis and Crohn's disease in humans. However, as this worm is not naturalised to our species, it does not survive long in the human gut, necessitating repeat infections every three weeks, in the form of a drink laced with the worm's eggs. (See http://tinyurl.com/4wvoxl)

Further information For an overview of the work with hookworms at Nottingham university, see http://tinyurl.com/6rx3zq

For more on specific hookworm studies, including contact details for the researchers involved in the trials, see:
http://tinyurl.com/6cdmyq (for Crohn's disease);
http://tinyurl.com/6zl9bf (for allergy and asthma).

For a fascinating and amusing read on the subject of our complex, and sometimes comical relationship with pathogens and parasites, see Riddled With Life: Friendly Worms, Ladybug Sex and The Parasites That Make Us Who We Are by Marlene Zuk, published by Harcourt.
For a review of this infectious read see http://tinyurl.com/694kct where a link is provided for those who wish to purchase the book.

Click here for more articles on digestive conditions

First Published in 2008

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