Helminthic Therapy

Helminthic therapy is the use of certain medically prepared species of helminths to treat allergic and autoimmune diseases (source: www.ncbi.nlm.nih.gov/mesh/68061147, accessed 8/30/12).

Helminths are roundworms, many of which live at least part of their adult life in the intestines of vertebrate animals. Many helminths were (and in some countries still are) part of the normal intestinal flora of the human gut for tens of thousands of years.

Helminths have now found their way back to the human gut, intentionally, for the treatment of such immune-related disorders as type I diabetes, asthma, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, multiple sclerosis, eczema, inflammatory bowel disease (IBD), dermatitis, hay fever, and food allergies.

This page describes the following issues:


 


History of Helminth Therapy

In the late 1980s, a popular theory arose entitled “The Hygiene Hypothesis” to explain why people living in developed countries have a high prevalence of atopic, or allergic, disorders. The theory was put forth by David P Strachan in the British Medical Journal after he studied hay fever in British children (Strachan, David. “Hay fever, hygiene, and household size.” British Medical Journal. 1989 Nov; 299 (6710):1259–60). Essentially, the Hygiene Hypothesis states that the human immune system is dependent upon exposure to a variety of organisms, in particular helminths, for proper development and functioning. The reason for this is believed to be that we co-evolved with these organisms, because they have almost always been present in our bodies. The recent and relatively rapid removal of these organisms from our bodies by modern medicine is believed by many scientists to be a major factor in the malfunction of many people’s immune systems.

Under controlled conditions, at least some helminth species interact with humans in highly complex and apparently beneficial ways, modulating the immune system in preliminary studies and positively impacting allergic and autoimmune diseases. In small quantities, the right species may more accurately be described as having a symbiotic rather than parasitic relationship with the human body. 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 (source: www.microbemagazine.org/index.php/04-2012-home/4700-a-darwinian-view-of-the-hygiene-or-old-friends-hypothesis, accessed 8/30/12).

Note that helminthic therapy is just one step in restoring the natural environment in our bodies. The growing probiotic industry and the availability of natural yoghurts are other attempts to expose our bodies, once again, to the naturally occurring microflora that used to cohabit our gastrointestinal tract.

 


Clinical Practice of Helminthic Therapy

THE SCIENCE OF HELMINTHIC THERAPY
According to Joel Weinstock, MD, Professor of Medicine at the Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, recent science has revealed what may be a “perfect correlation” between the rise in allergic and autoimmune states and the timing of helminth eradication programs in industrialized countries (source: www.youtube.com/watch?v=JpxMUwSOYQY, accessed 8/30/12). It’s thought that the elimination of an entire class of co-evolved organisms from the human body, as was done with helminths in the early 20th century, may be at least in part what’s driving the current epidemic of allergic and autoimmune diseases in developed nations (ibid).
Supporting this assertion, encouraging experimental research has already been performed and more is either being planned or is currently underway to test the use of helminths in the treatment of Crohn’s disease, ulcerative colitis, asthma, allergies, multiple sclerosis, autism, celiac disease and rheumatoid arthritis (source: www.clinicaltrials.gov, accessed 8/30/12).

SPECIES CURRENTLY IN USE AS THERAPY
Two main helminth species have been used in formal studies, Necator americanus, or human hookworm, and Trichuris suis, or pig whipworm (http://www.ncbi.nlm.nih.gov/pubmed/19050918). A third species, Trichuris trichiura (human whipworm) has been mentioned in the medical literature as a therapeutic agent but has not been formally studied. However, P’ng Loke, PhD, Assistant Professor, Department of Microbiology, New York University, reported a case of an individual who self-treated for ulcerative colitis with T. trichiura and experienced remission of symptoms (http://www.ncbi.nlm.nih.gov/pubmed?term=loke%20trichuris, accessed 8/30/12 ). T. trichiura has been referred to by David Elliott, MD, Professor and Division Director of Gastroenterology-Hepatology at the University of Iowa, as a commensal organism (Sleisenger and Fortran's Gastrointestinal and Liver Disease 9th edition, via MDConsult at: www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-6189-2..00110-4&isbn=978-1-4160-6189-2&type=bookPage&from=content&uniqId=357891209-2, accessed 9/4/12).

One species has achieved Investigational New Drug (IND) status from the FDA, and is being studied clinically in the U.S.: Trichuris suis ova, or TSO®, produced by Ovamed GmbH and made available for clinical trials by the U.S.-based corporation Coronado Biosciences.

Necator americanus appears to have similar investigational status in Australia and the UK, as evidenced by use in authorized clinical trials in those countries.

 


Producers and Distributors of Helminths and Helminthic Therapy Products

All three species mentioned herein are commercially available as treatments, however in the U.S., the Food and Drug Administration appears to have classified therapeutic helminths as biological agents, i.e. drugs. Thus far, no helminth has been approved by the FDA for use in humans, and only one (the non-human species, Trichuris suis) has been approved for clinical testing.

Producers and distributors of helminths for medical use or research include the following sources:

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How to Find a Helminthic Therapy Expert

We are in the process of assembling a searchable database of helminthic therapy experts. Anyone with interest, knowledge or experience with helminthic therapy is encouraged to add your resources or contact information to this list, by contacting the Foundation.

Current therapists include:

  • InTAAI
    Jorge A. LLamas MD
    Paseo Ensenada # 1912
    Playas de Tijuana
    Mexico
    Ph.: (664) 6801484
    Cell: (664) 188 5533
    USA: (903) 742 8025
    dr_llamas @ hotmail.com (personal)

 


Related Topics, Links, and References


Helminthic Therapy Forum - http://health.groups.yahoo.com/group/helminthictherapy/

Scientific Publications & Presentations


Hanauer SB: Evolving Biologic Therapies for IBD

(Medscape Conference Coverage, based on selected sessions at the:
Digestive Disease Week 2004; May 15 - 20, 2004, New Orleans, Louisiana)

Diet of worms can cure bowel disease.

Porcine Whipworm Ova Safe for Treatment of IBD.

Abner SR, Hill DE, Turner JR, Black ED, Bartlett P, Urban JF Jr, Mansfield LS (2002) Response of intestinal epithelial cells to Trichuris suis excretory-secretory products and the influence on Campylobacter jejuni invasion under in vitro conditions. J Parasitol 88:738-745

Albonjco M, Stoltzfus RJ, Savioli L, Tielsch JM, Chwaya HM, Ercole E, Cancrini G (1998) Epidemiological evidence for a differential effect of hookworm species, Ancylostoma duodenale or Necator americanus, on iron status of children. Int J Epidemiol 27:530-537

Aoyama H, Hirata T, Sakugawa H, Watanabe T, Miyagi S, Maeshiro T, Chinen T, Kawane M, Zaha O, Nakayoshi T, Kinjo F, Fujita J (2007) An inverse relationship between autoimmune liver diseases and Strongyloides stercoralis infection. Am J Trop Med Hyg 76:972-976

Bee RJ (1976) The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig. Res Vet Sci 20:47-54

Belizario VY, Amarillo ME, de Leon WU, de los Reyes AE, Bugayong MG, Macatangay BJ (2003) A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp. Bull World Health Organ 81:35-42

Cookson, W. O. C. M., and M. F. Moffatt. 1997. Asthma: an epidemic-in-the-absence-of infection? Science 275:41.

Correale J, Farez M (2007) Parasite infections modulate the immune response in multiple sclerosis. Ann Neurol 61:97-108

Croese J, Speare R (2006) Intestinal allergy expels hookworms: seeing is believing. Trends in Parasitol 12:547-550

Croese J, O'neil J, Masson J, Cooke S, Melrose W, Pritchard D, Speare R (2006a) A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors. Gut 55:136-137

Croese J, Wood M, Melrose W, Speare R (2006b) Allergy controls the population density of Necator americanus in the small intestine. Gastroenterology 131:402-409

de Silva NR, Brooker S, Hotez PJ, Montresor A, Engels D, Savioli L (2003) Soil-transmitted helminth infections: updating the global picture. Trends Parasitol 19:547-551

Doetze, A., J. Satoguina, G. Burchard, T. Rau, C. Loliger, B. Fleischer, and A. Hoerauf. 2000. Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by Th3/Tr1-type cytokines IL-10 and transforming growth factor-Beta but not by a Th1 to Th2 shift. Int. Immunol. 12:623.

Elliott DE, Summers RW, Weinstock JV (2007) Helminths as governors of immune-mediated inflammation. Int J Parasitol 37:457-464

Fleming J, Fabry Z (2007) The hygiene hypothesis and multiple sclerosis. Ann Neurol 61:97-108

Fox, J. G., P. Beck, C. A. Dangler, M. T. Whary, T. C. Wang, H. N. Shi, and C. Nagler-Anderson. 2000. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces Helicobacter-induced gastric atrophy. Nat. Med. 6:536.

Hadley C (2004) Should auld acquaintance be forgot. EMBO Rep 5:1122-1124

Holgate ST, Lack G (2005) Improving the management of atopic disease. Archives of Disease in Childhood 90:826-831

Hotez PJ, Pritchard DI (1995) Hookworm infection. Sci Am 272:68-74

Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S (2004) Hookworm infection. New Eng J Med 351:799-807

Hsu S-J, Tseng P-H, Chen P-J (2005) Trichuris suis therapy for ulcerative colitis: nonresponsive patients may need anti-helminth therapy. Gastroenterology 129:768-769

Hunter & McKay: Helminths as therapeutic agents for inflammatory bowel disease. Aliment-Pharmacol-Ther. 2004 Jan 15; 19(2): 167-77.

Hunter M, Wang A, McKay D (2007) Helminth infection enhances disease in a murine TH2 model of colitis. Gastroenterology 132:1320-1330

Jacobson DL, Gange SJ, Rose NR, Graham NM (1997) Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopath 84:223-243

Joven J, Hotez PJ, Brooker S, Bethany J (2005) Hookworm infection. New Eng J Med 352:205

Lynch, N. R., I. Hagel, M. Perez, M. C. D. Prisco, R. Lopez, and N. Alvarez. 1993. Effect of anti-helminthic treatment on the allergic reactivity of children in a tropical slum. J. Allergy Clin. Immunol. 92:404.

Magen E, Borkow G, Bentwich Z, Mishal J, Scharf S (2005) Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases. Med Hypoth 64:904-909

Mansfield LS, Gauthier DT, Abner SA, Jones KM, Wilder SR, Urban JF (2003) Enhancement of disease and pathology by synergy of Trichuris suis and Campylobacter jejuni in the colon of immunologically naïve swine. Am J Trop Med Hyg 68:70-80
McKay DM (2006) The beneficial helminth parasite. Parasitology 132:1-12

Mortimer K, Brown A, Feary J, Jagger C, Lewis S, Antoniak M, Pritchard D, Britton J (2006) Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg 75:914-920

Radford-Smith GL (2005) Will worms really cure Crohn's disease? Treatment of Crohn's disease patients with the intestinal helminth Trichuris suis appears safe and effective in the short term, even with concurrent immunosuppressive therapy. Gut 54:6-8

Reddy A, Fried B (2007) The use of Trichuris suis and other helminth therapies to treat Crohn's disease. Parasitol Research 100:921-927

Reddy A, Fried B (2008) Atopic disorders and parasitic infections. Adv Parasitol 66:149-191

Rook GA, Adams V, Hunt J, Palmer R, Martinelli R, Brunet LR (2004) Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. Springer Seminar Immunopathol 25:237-255

Shi, H. N., C. J. Ingui, I. Dodge, and C. Nagler-Anderson. 1998. A helminth-induced mucosal Th2 response alters non-responsiveness to oral administration of a soluble antigen. J. Immunol. 160:2449.

Shoenfeld Y, Harats D, Wick G (2001) Atherosclerosis and autoimmunity. Elsevier, UK, pp 1-396

Stoltzfus RJ, Dreyfuss ML, Chwaya HM, Albonico M (1997) Hookworm control as a strategy to prevent iron deficiency. Nutr Rev 55:223-232

Strachan, D. P. 1989. Hay fever, hygiene and household size. (The Hygiene Hypothesis) Br. Med. J. 299: 1259.

Summers RW, Elliott DE, Qadir K, Urban JF Jr, Thompson R, Weinstock JV (2003) Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 98:2034-2041

Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV (2005a) Trichuris suis therapy in Crohn's disease. Gut 54:87-90

Summers RW, Elliott DE, Weinstock JV (2005b) Is there a role for helminths in the therapy of inflammatory bowel disease. Nature Clinical Prac Gastroent Hepatol 2:62-63

Summers RW, Elliott DE, Weinstock JV (2005c) Why Trichuris suis should prove safe for use in inflammatory bowel diseases. Inflamm Bowel Dis 11:783-784

Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV (2006) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128:825-832

Svoboda E (2006) Scientist at work: David Pritchard, The worms crawl in-New York Times article http://www.nytimes.com/2008/07/01/health/research/01prof.html?_r=2&pagewanted=1&sq&st=nyt&scp=2&oref=slogin

Turton, J.A. (1976) IgE, parasites, and allergy. The Lancet ii:686 (text not available online, too old)

van den Biggelaar, A. H. J., R. van Ree, L. C. Rodrigues, B. Lell, A. M. Deelder, P. G. Kremsner, and M. Yazdanbaksh. 2000. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 356:1723.

Van Kruiningen HJ, West AB (2005) Potential danger in the medical use of Trichuris suis for the treatment of inflammatory disease. Inflamm Bowel Dis 11:515

Wang, C.-C., T. J. Nolan, G. A. Schad, and D. Abraham. 2001. Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin. Clin. Exp. Allergy 31:493.

Wills-Karp, M., J. Santeliz, and C. L. Karp. 2001. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat. Rev. Immunol. 1:69.

Yazdanbakhsh, M., P. G. Kremsner, and R. van Ree. 2002. Allergy, parasites and the hygiene hypothesis. Science 296:490.

Links & News Stories

International Biotherapy Society

Hanauer SB: Evolving Biologic Therapies for IBD
(Medscape Conference Coverage, based on selected sessions at the:
Digestive Disease Week 2004; May 15 - 20, 2004, New Orleans, Louisiana)

Diet of worms can cure bowel disease.

Yahoo group devoted to users of helminthic therapy (worm therapy).

Porcine Whipworm Ova Safe for Treatment of IBD

http://blogs.discovermagazine.com/discoblog/2009/07/22/are-hookworms-the-next-claritin/

http://abcnews.go.com/Health/AllergiesNews/story?id=8114307&page=1

BioTherapeutics, Education and Research (BTER) Foundation
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Phone: 949-246-1156;     Fax: 949-679-3001
E-mail: info@BTERFoundation.org
www.BTERFoundation.org
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