Helminthic therapy

Infectious Necator americanus L3 larva.
Invisible to the naked eye, from 10 to 35 are applied to the skin in therapy, either in a single dose or in multiple smaller doses over the course of two or three months.

Helminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms.

Helminthic therapy consists of the inoculation of the patient with specific parasitic intestinal nematodes (helminths). There are currently three closely related treatments available. which include noculation with Necator americanus,^[1] commonly known as hookworms, or Trichuris suis ova (TSO),^[2] commonly known as pig whipworm eggs, or inoculation with Trichuris trichiura ova,^[1] commonly referred to as human whipworm eggs.

Current research and available therapy are targeted at, or available for, the treatment of Crohn's disease, ulcerative colitis, inflammatory bowel disease (IBD), multiple sclerosis, asthma, eczema, dermatitis, hay fever, and food allergies.

Helminthic infection has emerged as one possible explanation for the low incidence of autoimmune diseases and allergies in less developed countries, together with the significant and sustained increase in autoimmune diseases in industrialized countries.^[3][4][5][6]

Incidence of autoimmune diseases and parasitic infestation

While it is recognized that there is probably a genetic disposition in certain individuals for the development of autoimmune diseases, the rate of increase in incidence of autoimmune diseases is not a result of genetic changes in humans; the rise of autoimmune related diseases in the industrialized world occurring in too short a time to be explained in this way. There is evidence that one of the primary reasons for the increase in autoimmune diseases in industrialized nations is the significant change in environmental factors over the last century. It is posited that the absence of exposure to certain parasites, bacteria, and viruses is playing a significant role in the development of autoimmune diseases in the more sanitized Western industrialized nations.^[7][8] Environmental factors include exposure to certain artificial chemicals from industrial processes, medicines, farming, and food preparation.

Lack of exposure to naturally occurring pathogens and parasites may result in an increased incidence of autoimmune diseases. This is consistent with the hygiene hypothesis.^[3][9] A complete explanation of how environmental factors play a role in autoimmune diseases has still not been proposed. However, epidemiological studies, such as the meta-analysis by Leonardi-Bee et al.,^[3] have helped to establish the link between parasitic infestation and its protective role in autoimmune disease development.

Genetic research on the interleukin genes (IL genes) shows that helminths have been a major selective force on a subset of these human genes. In other words, helminths have shaped the evolution of at least parts of the human immune system, especially the genes responsible for Crohn's disease, ulcerative colitis, and celiac disease — and provides further evidence that it is the absence of parasites, and in particular helminths, that has likely caused a substantial portion of the increase in incidence of diseases of immune dysregulation and inflammation in industrialized countries in the last century.^[10]

Hypothesis

Although the mechanism of autoimmune disease development is not fully defined, there is broad agreement that the majority of autoimmune diseases are caused by inappropriate immunological responses to innocuous antigens, driven by a branch of the immune system known as the TH1 type immune response. Extra-cellular antigens primarily trigger the TH2 response, as observed with allergies, while intracellular antigens trigger a TH1 response. The relationship between these two types of immune response is a central theme of the hygiene hypothesis, which suggests that there is a regulatory action between the two types of response. However, the observation that allergies and autoimmune response are increasing at a similar rate in industrialized nations appears to undermine the hygiene hypothesis.

A refinement of the hygiene hypothesis, which overcomes this apparent contradiction, is the "old friends hypothesis."^[11] The old friends hypothesis modifies the hygiene hypothesis by proposing that T regulator cells can only become fully effective if they are stimulated by exposure to microorganisms and parasites that have low levels of pathogenicity and that have coexisted universally with human beings throughout our evolutionary history. This hypothesis has recently been given more credibility by a study demonstrating the impact of infectious organisms, and helminths in particular, upon genes responsible for the production of various cytokines, some involved in the regulation of inflammation, in particular those associated with the development of Crohn's Disease, ulcerative colitis, and celiac disease.^[10]

The hygiene hypothesis proposes that appropriate immune response is in part learned by exposure to these microorganisms and parasites, and in part regulated by their presence. In industrialized nations, humans are exposed to somewhat lower levels of these organisms. The development of vaccines, hygienic practices, and effective medical care have diminished or eliminated the prevalence and impact of many parasitic organisms, as well as bacterial and viral infections. This has been of obvious benefit with the effective eradication of many diseases that have plagued human beings. However, while many severe diseases have been eradicated, humans' exposure to benign and apparently beneficial parasites has also been reduced commensurately. The central thrust of the hypothesis is, therefore, that correct development of T regulator cells in individuals may depend on exposure to organisms such as lactobacilli, various mycobacteria, and helminths.^[6] Lack of exposure to sufficient benign antigens, particularly during childhood, is sometimes suggested as a cause of the increase in autoimmune diseases and diseases for which chronic inflammation is a major component in the industrialized world.

Research

Helminthic therapy is currently being studied as a treatment for several (non-viral) auto-immune diseases including celiac disease,^[12] Crohn's disease,^{[13][14][15][16]} multiple sclerosis,^[17] ulcerative colitis,^[18] atherosclerosis^[19]

Hookworms have been linked to reduced risk of developing asthma, while Ascaris lumbricoides (roundworm infection) was associated with an increased risk of asthma.^[3]

See also

• Gut flora
• Helminths
• Hookworm
• Medical leech
• Ichthyotherapy
• Whipworm
• Immunotherapy
• Disease of affluence
• Effects of parasitic worms on the immune system
• trematodes

References