Helminthic therapy

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. 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. == Hypotheses ==

Although the mechanisms of autoimmune disease development are not fully understood, there is broad agreement that the majority of autoimmune diseases are caused by inappropriate immunological responses to innocuous antigens; these are generally called the hygiene hypothesis, but exist in several variants. One version proposes that the dysfunction is driven by a branch of the immune system known as the T helper cells (T or TH). Two other refinements to the hygiene hypothesis exist: The "old friends" hypothesis, and the "microbiome depletion" hypothesis. TH1 vs. TH2 response regulation Extra-cellular antigens primarily trigger the TH2 response, as observed with allergies, while intracellular antigens trigger a TH1 response. T 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 reduce the symptoms of many autoimmune disorders. Learned appropriate response The hygiene hypothesis proposes that appropriate immune response is in part learned by exposure to micro-organisms 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. Microbiome depletion hypothesis The microbiome depletion hypothesis posits that the absence of an entire class of organisms from the human inner ecology is a profound evolutionary mismatch that destabilizes the immune system, resulting in disease: the microbiome is "depleted". The biome depletion hypothesis departs from a drug model approach, which remains the current focus of helminthic therapy as evidenced by numerous clinical trials now underway for existing disease states. == Proposed mechanism of action ==

Experimental data support the hypothesis that clinically induced helminthic infections have the ability to alleviate or mitigate immune responses. Helminths secrete immunoregulatory molecules that promote the induction of regulatory T cells while inhibiting the function of antigen presenting cells and other T cells. As such, helminthic therapy attempts to restore homeostasis by shifting a hyperactive TH1 pro-inflammatory response to a TH2 response with reduced inflammation. Human and animal studies have provided evidence of decreased TH1 and TH17 immune responses with a shift to TH2 cytokine production resulting in significantly decreased levels of interleukin 12 and IFNy with simultaneous increases in the regulatory T cells, interleukin 4, interleukin 5 and interleukin 10 of test subjects. These observations indicate that helminth therapy can provide protection against autoimmune disease not only through prevention, since helminths can be present before autoimmune disease develops, but also after autoimmune responses are initiated. Furthermore, responses of type-2 T helper cells rarely kill the parasitic worms. Rather, the TH2 response limits the infection by reducing the viability and reproductive capacity of the parasite. Given the down regulation of TH1 and TH17 immune responses with helminthic therapy, immune responses to other pathogens and allergens may be suppressed. Consequently, unmonitored and uncontrolled helminthic infections may be associated with suppressed immunity to the viruses and bacteria that normally trigger TH1 and TH17 immune responses required for protection against them, leading to illness or disease. == Research ==

Evidence in support of the idea that helminthic infections reduce the severity of autoimmune diseases is primarily derived from animal models. Studies conducted on mice and rat models of colitis, multiple sclerosis, type 1 diabetes, and asthma have shown helminth-infected subjects to display protection from the disease. While helminths are often considered a homogenous group, considerable differences exist between species and the species used in clinical research varies between human and animal trials. As such, caution must be exercised when interpreting the results from animal models. Crohn's disease, multiple sclerosis, ulcerative colitis, and atherosclerosis. It is currently unknown which clinical dose or species of helminth is the most effective method of treatment. Hookworms have been linked to reduced risk of developing asthma, while Ascaris lumbricoides (roundworm infection) was associated with an increased risk of asthma. Similarly, Hymenolepis nana, Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, Enterobius vermicularis, and Trichuris suis ova have all been found to lower the number of symptom exacerbations, reduce the number of symptom relapses, and decrease the number of new or enlarging brain lesions in patients with multiple sclerosis at doses ranging from 1,180 to 9,340 eggs per gram. The use of Trichuris suis ova has been granted by the USA Food and Drug Administration as an investigational medicinal product (IMP). A patient will ingest the eggs so the worms can colonize the caecum and colon of the human gut for a short period of time and provide treatment. The beneficial effect is temporary because the worms only live for a few weeks. Because of this short life span, treatments need to be repeated at intervals. Trichirus suis removes any wider public health issues due to species-specificity and lack of chronic infection. Necator americanus larvae are administered percutaneously and migrate through the vasculature and lungs to the small intestine. They feed on the blood from the mucosa. although it can cause temporary gastrointestinal side effects, especially following the initial inoculation, or with increased doses. High doses can also cause anemia. The general ideal characteristics for a therapeutic helminth are as follows: • Little or no pathogenic potential • Can complete whole life cycle in host • Does not multiply in the host • Cannot be directly spread to close contacts • Produces a self-limited colonization in humans • Produces an asymptomatic colonization in humans • Does not alter behavior in patients with depressed immunity • Is not affected by most commonly used medications • Can be eradicated with an anti-helminthic drug • Can be isolated free of other potential pathogens • Can be isolated or produced in large numbers • Can be made stable for transport and storage • Easy to administer While the research is still rudimentary and the treatment is still being studied, helminthic therapy is a viable option as of current due to its lowered cost and seemingly high effectiveness in comparison to other treatments. == Potential side effects ==

Helminths are extremely successful parasites capable of establishing long-lasting infections within a host. If the side effects from helminthic therapy were to become unmanageable, they can be alleviated by the use of anti-helminthic medications. • Tumor promotion Outside of these initial symptoms that can arise, there are other worries attached to using live helminth parasites as treatment including: • Ethical perspective: using living things as treatment • Symptoms re-occurring post treatment • Worm adaption if in a colitis host == Self-administration ==

Social media has brought helminth therapy to the forefront of treatment discussion with many false claims and misinformation. Due to this increased online discussion on Helminth therapy, many people struggling with autoimmune diseases have turned to self-administering parasites to treat themselves. Patients have begun to travel or look in the black market to purchase helminths, as the treatment is still in testing stages and generally discouraged by most medical professionals. == See also ==