Helminths for health

Isn’t it fascinating to know that worms which we fear of having in our body are protecting the body from several auto-immune diseases? Wow! This was truly sensational to me to know how parasitic helminth modulate the immune system of the host to render it immune against autoimmune diseases like irritable bowel disease (IBD), asthma and allergic conditions.

So how important are worms to human body? Taking the message from the helminthology course, my perception regarding the parasitic helminth has changed drastically. What I feel now is, “the balance” if there’s balance between the diverse fauna inside you, nature has made all the arrangements to protect you from anything. The immune reactions and disorders are the result of imbalance between natural and acquired forces. Worm therapy (helminth therapy) uses the helminth as treatment of some immunological diseases by infecting deliberately with a helminth or ova of the helminth.

Parasites and hygiene hypothesis

Parasites have as long history as do Homo sapiens, history of human parasitology clearly explains that Human evolution and parasitic infections have run hand in hand (Nature Publishing Co. 2001. The human genome. Nature 409 (Suppl.):813-958). Parasites have been a part of people’s life since eternity. They were made to coexist in human body along with other organisms. With the advancements in knowledge and societies being more affluent, people have made significant achievements in being “worm-free” in developed world but no-one can refute the bitter truth that, they have also encouraged the auto-immune diseases like Ulcerative colitis, Crohn’s disease (CD), asthma, rheumatic arthritis etc. over the years. Looking at the CD incidence and prevalence, it appears to be higher in urban areas among people experiencing higher socio-economic class. In several studies it was found that, CD incidence was <1 per 100,000 in Asia and South America. 1-3 per 100,000 in southern Europe, South Africa. 16 per 100,000 in New Zealand and Australia, 14 per 100,000 in Canada and 7 per 100,000 in USA. The data above clearly speaks the truth. Asia, which comprises most of underdeveloped and developing countries have lower CD prevalence. The increasing rate in Asia is mostly contributed by developed countries of Asia, especially East Asia like Japan, a socio-economically advanced country. These developed countries have eradicated several parasites due to the availability of efficacious drugs and proper hygiene standards. In developing countries, however, helminth infection is still a major problem. (Weinstock et. al., 2005). These epidemiological studies at the end of the day convey the same message – “the frequency of worm colonization and prevalence of IBD is inversely related”. This is a basis of now world-famous “hygiene hypothesis”, which was first used by David P Strachan in the British Medical Journal after he studied hay fever in British children (D. Strachan 1989) .Elliott et al. in 2000 described it again putting forward the hypothesis that the loss of exposure to parasitic worms increases the risk of IBD. (Elliott et al., 2000). The Hygiene Hypothesis was further refined into the “Old Friends” hypothesis, which suggests that the human immune system had evolved with certain organisms for so long that they had become mutualistically symbiotic. In other words, we had evolved around the presence of certain parasites and that their absence could result in “abnormal” conditions. This positive relationship has been referred to as the “Old Friends” theory by Dr. Graham Rook, MD, Emeritus Professor of Medical Microbiology at University College London.

Researches in worm therapy

This underlying idea gave scientists a unique opportunity to try and experiment the concept of “worm therapy” which in the beginning looked weird as there were several ethical and practical difficulties. One of the early studies in 1980s by Neil Lynch et. al., suggested the inverse relation between the worms and the emergence of asthma and allergy in varying economic background. His overall findings reflects that worm burden was less and allergies was high in affluent Venezuelan society. After that a series of studies are published most of which tell the same story. Joel Weinstock and his colleagues at the University of Iowa are considered as the integral developers of this epidemiology. He has been involved in several studies which mainly aims at identifying worms as treatment of autoimmune diseases. In an attempt to test the hypothesis, he has yielded promising results. Presently he has been trying to explore more on helminth therapy and its relation to inflammation and IBD. (http://sackler.tufts.edu/Faculty-and-Research/Faculty-Research-Pages/Joel-Weinstock). Success stories over the years have made this approach more interesting and intriguing. The 2005 experiment by Weinstock involving 29 participants with Crohn’s disease, 23 patients given with whipworm eggs every 3 weeks for 6 months improved significantly and 21 experienced remission. Another success story involved 52 patients with colitis given with 2500 whipworm eggs or placebo. 13 of 29 who received eggs improved compared to 4 of 23 who received placebo. These trails and success stories are often considered as experimental evidence of global pattern. It is really interesting to read how this worm therapy have been accepted by so many people across the global and actually doing good for them.(Eg. http://www.hookworm4crohns.blogspot.ca/, http://www.hookwormdiary.com/, http://parasites-film.com/main/helminthic-therapy/ ). Even more fascinating to read is this piece reporting how actually helminth therapy is changing lives of so many people (http://www.foodsmatter.com/natural_medicine_comp_therapies/helminthic_therapy/articles/ht_success_stories.pdf )

How does it work?

Helminth therapy is just a means of restoring the natural environment of our body. Like the use of probiotic and natural products like yoghurt which contain the useful micro flora, these therapies attempt to replenish the lost fauna which used to coexist in the gastrointestinal world balancing the system. Our body have evolved along with the parasites so it expects them to be present in symbiosis with it. Reintroduction of parasites, such as hookworm and whipworm, is a step in redressing the natural evolutionary balance of the immune system, giving the immune system an appropriate target to work against, thus halting the destructive actions of the immune system on its own tissues or benign substances such as pollen, cat dander etc.

To understand the theory behind this phenomena the immune response should be understood first. The figure below summarizes all the responses when a body finds a foreign thing including parasitic helminth.

http://livingwellnessblog.wordpress.com/2012/10/12/am-i-th1-or-th2-or-th17/
Immune regulation in host in response to foreign antigens.

The logic behind the helminth therapy has found to be 3 fold

Mode of action of helminth therapy
Mode of action of helminth therapy
 1. Immunomodulation by the parasite. Helminth infection is associated with a special type of immune regulation called Th2 response. This type of response produces antibody-mediated immunity which is protective against extracellular parasites, asthma and allergic conditions. The inflammatory processes, autoimmunity disorders like IBD is the result hyperactive Th1 response in the gut which in natural condition is balanced by counter regulatory mechanism of Th2.
Counter-regulatory mechanism of Th1 and Th2 response
Counter-regulatory mechanism of Th1 and Th2 response

2. Secondly, they have been found to be associated with changes that activate regulatory T cells. These cells dampen immune responses and curb autoimmunity by maintaining the immune homeostasis and preventing the body from over stimulation of immune response.

3. Also studies suggest that they have probiotic like action, which alter the bacterial composition of intestinal flora. Research in mice suggest that, they are advantageous to gut micro-organisms thereby maintaining intestinal health and protecting from inflammatory diseases of the gut (DM McKay 1999).

Challenges

In spite of having promising results in few clinical trials and opinions of experts, many experts are still against it. Dr. Peter Hotez who is working in George Washington University to develop a hookworm vaccine refutes the theory and is in against deliberate infection of helminth. He says this “makes absolutely no sense at all” and says that this is based on false reasoning.  He explains that hygiene hypothesis ignores the fact that high rates of helminthic infection is still prevalent in the US and this has nothing to do with the allergies. He also bolstered his argument saying that whipworm infection is actually the leading global cause of IBD and allergies have been linked to toxicara infestation in American cities. In contrast, Elliot completely supports the hygiene hypothesis giving the example of South Korea, where Crohn’s disease appeared in the scene immediately after the helminth eradication program.( http://scienceline.org/2010/12/hookworms-and-whipworms-our-immune-system%E2%80%99s-attachment-to-parasites/) Popular name in this field Joel Weinstock is dedicating his life in this field and believes that worm therapy has sound logic and carry a huge potential.

In summary, this interesting approach has several challenges before to be unanimously accepted as therapeutic agent. Not all the people are brave enough to eat live worms or products of it in the hope to cure the next. Pharmaceutical companies have a huge challenge in accepting this treatment regime and commercialize it. There are still a lot of biological complication which may perpetuate as a result of immune modulation by worms. Although seems straightforward in paper, modulating one type of immune cell may create serious imbalance in this complex human immune system. The USFDA defined hookworms as investigational new drugs which requires much more clinical trials and regulations to be accepted. No any agency has approved this method of treatment which makes validating worm therapy more challenging.

The process for drug acceptance may be “marching along,” but it needs to move in double time. Millions of people suffer from autoimmune and allergic diseases which cause immense human suffering. This method seems to carry a possibility to relieve people’s suffering so needs greater attention. However, more clinical trials, double blinded trails, safety and efficacy studies should be carried out to convince the public to by worms and treat themselves.

 

References

J. V. Weinstock, R. W. Summers, and D. E. Elliott, “Role of helminths in regulating mucosal inflammation,” Seminars in Immunopathology, vol. 27, no. 2, pp. 249–271, 2005.

Strachan, David. “Hay fever, hygiene, and household size.” British Medical Journal. 1989 Nov; 299 (6710):1259–60

D. E. Elliott, J. F. Urban Jr., C. K. Argo, and J. V. Weinstock, “Does the failure to acquire helminthic parasites predispose to Crohn’s disease?” The FASEB Journal, vol. 14, no. 12, pp. 1848– 1855, 2000.

McKay DM. Intestinal Inflammation and the gut microflora. Can J Gastroenterol 1999; 13: 509–16.)

Posted by: Pratap Kafle

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