Helminthic therapy

Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hookworms, whipworms, and threadworms that have evolved to live within a host organism on which they rely for nutrients. These worms are members of two phyla; nematodes, which are primarily used in human helminthic therapy, and flat worms (trematodes). Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hookworms, whipworms, and threadworms that have evolved to live within a host organism on which they rely for nutrients. These worms are members of two phyla; nematodes, which are primarily used in human helminthic therapy, and flat worms (trematodes). Helminthic therapy consists of the inoculation of the patient with specific parasitic intestinal nematodes (helminths). A number of such organisms are currently being investigated for their use as treatment including: Trichuris suis ova, commonly known as pig whipworm eggs; Necator americanus, commonly known as hookworms; Trichuris trichiura ova, commonly referred to as human whipworm eggs; and Hymenolepis diminuta, commonly known as rat tapeworm cysticerci. While the latter four species may be considered to be mutualists – providing benefit to their host without causing longterm harm – there are other helminth species that have demonstrated therapeutic effects but which also have a potential to cause less desirable or even harmful effects and therefore do not share the ideal characteristics for a therapeutic helminth. These include Ascaris lumbricoides, commonly known as human giant roundworm; Strongyloides stercoralis, commonly known as human roundworm; Enterobius vermicularis, commonly known as pinworm or threadworm; and Hymenolepis nana, also known as dwarf tapeworm. Current research targets Crohn's disease, ulcerative colitis, inflammatory bowel disease, coeliac disease, multiple sclerosis and asthma. Helminth infection has emerged as one possible explanation for the low incidence of autoimmune diseases and allergies in less developed countries, while reduced infection rates have been linked with the significant and sustained increase in autoimmune diseases seen in industrialized countries. 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 increased rate of autoimmune-related diseases in the industrialized world is 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. Environmental factors include exposure to certain artificial chemicals from industrial processes, medicines, farming, and food preparation. 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 and industrialized Western nations. Lack of exposure to naturally occurring pathogens and parasites may result in an increased incidence of autoimmune diseases. Correlational data has shown the prevalence of helminthic infections to be greatest south of the equator where the rates of autoimmune diseases such as multiple sclerosis are low.This is consistent with the hygiene hypothesis which suggests that helminthic infections protect individuals from developing auto-immune diseases rather than being an agent responsible for inducing them. A complete explanation of how environmental factors play a role in autoimmune diseases has still not been proposed. Epidemiological studies such as the meta-analysis by Leonardi-Bee et al., however, have helped to establish the link between parasitic infestation and their protective role in autoimmune disease development. Although the mechanism(s) 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. Th cells can be divided into subtypes based on the characteristic cytokines they secrete. Th2 immune responses result in the release of cytokines associated with inflammation reduction such as interleukin 4, interleukin 5 and interleukin 10. These cytokines are thought to improve the symptoms of many autoimmune disorders. Conversely, Th1 immune responses are characterized by the cytokines interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα), both of which are thought to increase inflammation and worsen the progression of autoimmune diseases and their symptoms. The relationship between these two types of immune response is a central theme of the biological basis 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. The hygiene hypothesis proposes that appropriate immune response is in part learned by exposure to microorganisms and parasites, and in part regulated by their presence. In industrialized nations, humans are exposed to somewhat lower levels of these organisms, potentially resulting in unbalanced immune systems. 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 regulatory T cells in individuals may depend on exposure to organisms such as lactobacilli, various mycobacteria, and helminths. 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.