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by Arabel Luscombe Published on 7th Dec 2015
by Arabel Luscombe Published on 7th December 2015
Rates of multiple sclerosis, inflammatory bowel disease, asthma and Celiac disease have all gone up significantly in economically developed countries in recent decades. While the causes of these diseases are complex and controversial, they are all related in some way to a malfunctioning of the immune system. What these conditions also have in common is that they tend to be chronic and difficult (or even impossible) to treat. However, an increasing number of scientists believe that they are among a group of disorders that can be treated with a rather bizarre, experimental new treatment known as helminthic therapy, i.e. deliberate infection of the patient with parasitic worms.The Hygiene HypothesisThe theoretical basis for helminthic therapy is provided by the 'hygiene hypothesis', which was initially proposed by David Strachan in 1989. Strachan's idea was that exposure to infection in childhood prevents the development of allergic disorders, and that higher rates of allergies such as hay fever can therefore be explained by improved rates of hygiene and cleanliness. While the theory has never been without controversy, and even its supporters have reworked it significantly in the decades since it was first proposed, the theory has generated a large body of research looking at the role of hygiene as a cause of allergies and other inflammatory, immunoregulatory disorders.One area of research inspired by Strachan's hypothesis relates specifically to the role of parasites in the human body. Until very recently, parasitic infection was an endemic problem all over the world – indeed, in many parts of the world it still is a major issue. Parasitic worms (also known as helminths) can enter the body in a number of ways, for example from undercooked food or from skin contact with infected soil. Once they are inside the human body, they lay eggs and feast on their host's blood or tissue, disrupting the body's absorption of nutrients and causing a number of problems, such as diarrhoea and malnutrition. Although the infected person does not always suffer from particularly serious symptoms, in other cases parasitic infection can be fatal.In economically developed countries these types of infection have been very nearly eradicated. While this is in some ways undoubtedly a good thing, many scientists believe that it has contributed to the rise of autoimmune disorders. This is due to the way in which parasites interact with the human immune system. The majority of autoimmune diseases are caused by the hyper-activity of a particular type of immune response known as the Th1 mechanism, which causes inflammation. Parasites, however, have a means of keeping this type of immune response in check, so as to prevent themselves being removed from the body. The presence of parasites in the intestine triggers a different type of immune response – the Th2 mechanism – that actively combats inflammation.While the idea that parasites have a positive effect on the human body may sound strange, it is worth remembering that bacteria also used to have a pretty bad reputation. Nowadays, however, probiotic yoghurt drinks are top-sellers and an increasingly large body of research points to the role of a large and varied intestinal bacteria population as a central element of good health. Recent research suggests that a healthy gut flora can prevent or hinder the development of a range of diseases, including depression and anxiety disorders. Many experts even support the idea of fecal microbiota transplants – otherwise known as stool transplants – as a treatment for certain diseases.Helminthic TherapyOn the basis of the hygiene hypothesis – in particular regarding the positive role of parasites for regulation of the human immune system – researchers have developed a new form of treatment for autoimmune diseases, known as helminthic therapy. The patients taking the treatment may drink a liquid that has been mixed with parasitic eggs, or apply a preparation of worm larvae directly to their skin. While the former is apparently no different to drinking any other type of liquid (i.e. one doesn't notice the eggs), people who have undergone the latter form of helminthic therapy describe feeling a tingling or itchy sensation as the parasites burrow their way through the skin. In order to minimise the risk of side-effects, researchers are very careful about the type of parasites they use. Pig whipworms are considered to be particularly safe, because they cannot survive for long periods in the human body and there is correspondingly no risk of developing a chronic infection. In addition to pig whipworms, however, researchers are also experimenting with the human hookworm – a major cause of medical complications in some parts of the world. There is a higher risk of chronic infection with hookworm, as it can potentially live for years within the human intestine, but it is nonetheless considered to be relatively safe in a clinical, controlled setting.The EvidenceOne of the earliest trials involving deliberate infection with parasites was in the late 1990s, when David Elliott and Joel Weinstock discovered that this could protect mice against ulcerative colitis, a form of irritable bowel disease. This news triggered a wave of other experiments – some on animals, some on humans – that tested the effects of helminthic therapy on a range of different diseases. While results have been mixed, a number of these experiments have had positive results.In one trial on patients with ulcerative colitis, for example, 43% of patients who were given pig whipworm eggs improved, against only 17% of test subjects who had taken a placebo. Another (very small scale) trial infected nine ulcerative colitis patients with the more dangerous hookworm: seven of these improved, while the condition of the other two deteriorated. A recent trial involving 40 patients with Celiac disease also suggested that hookworm treatment could be effective; by the end of the trial, participants were able to eat medium-sized bowls of spaghetti without the negative consequences this would normally have caused. Furthermore, small scale trials with multiple sclerosis patients have suggested that helminthic therapy can slow progression of the disease.It must be stressed, however, that research is still at an early stage and evidence remains unclear. For example, a recent systematic review on the effects of helminthic therapy on patients with irritable bowel disease concluded that there was insufficient evidence for its safety and efficacy. And while a number of animal studies have demonstrated a significant positive effect of helminthic therapy on preventing the development of allergies, there is little evidence that it can reduce allergic symptoms in either humans or animals who have a pre-existing allergy. Overall, more research is required before we can expect helminthic therapy to become an approved treatment for any disease.The Online MarketIn the meantime, however, this has not stopped people from taking things into their own hands. Although helminthic therapy has yet to receive regulatory approval, on the internet it is possible to buy almost anything – including preparations of hookworm and whipworm larvae or eggs. It is not easy to get hold of these in the United States, as the country's Food and Drugs Administration (FDA) has categorised helminthic therapy as an Investigational New Drug, but potential customers in other countries can easily access a range of options. A three-year course of hookworm can be bought for $3050 from one company, for example, while another offers a single dose of 25 larvae for $200.It seems that the initial positive evidence for the effect of helminthic therapy – as well as the lack of effective alternative options for many diseases – has created a significant market for these products. And it doesn't take long to find testimonials on the internet from people swearing that they have benefited as a result of using them. However, negative side-effects are possible and use of hookworm entails the risk of developing a chronic infection. Even Joel Weinstock, one the most vocal proponents of helminthic therapy and author of several studies on its efficacy, warns against taking parasites bought online: “Patients are not doctors or scientists... The online sites are not monitored. What they sell and say may not be as advertised or true” (quoted in Vice magazine).Indeed, some scientists are sceptical about the whole idea of using parasites as a form of treatment. For example, Peter Hotez from the National School of Tropical Medicine in Texas argues that helminthic therapy “makes absolutely no sense at all”, and that the risks of worm infestation significantly outweigh the benefits (quoted in Science Line). He therefore supports the idea of isolating the anti-inflammatory molecules produced by helminths and developing these into pharmaceutical drugs. However, while some progress has been made in this area, research remains at an early stage, and no clinical trials using helminth-derived molecules have been conducted so far. In the meantime, one can assume that the online trade in parasites will continue to flourish.