Worm Therapy

Worm therapy, or more correctly helminthic therapy because the worms used are helminths, is the treatment of immunological dysregulation by means of deliberate infection with a helminth or with the ova of a helminth. Helminths are parasitic intestinal nematodes, a type of worm, such as hookworms or pin worms or whip worms.

Worm therapy has been or is being studied in humans as a treatment for several immunological diseases including Crohn's disease, Ulcerative Colitis, Multiple Sclerosis, Eczema or atopic dermatitis and allergies. Autoimmune liver disease has also been demonstrated to be modulated by active helminth infections and there are numerous animal studies that suggest it could be effective against almost any disease involving immune disorders, such as Autism, Rheumatoid arthritis, Lupus, etc.

The anti inflammatory effects of helminth infection are prompting research into diseases involving chronic inflammation that are not considered to include immune disorders as a factor. Heart disease and arteriosclerosis both have epidemiological profiles similar to autoimmune diseases and both involve chronic inflammation. It is accepted that the increase in their incidence in industrialized societies can not be solely attributed to environmental factors such as changes in diet. Recent research has focused on the eradication of helminths to explain this discrepancy.

Worm therapy involves inoculation of the patient with specific parasitic intestinal nematodes (helminths). There are currently two types of treatment available, either deliberate infection with Necator americanus, commonly known as hookworms, or Trichuris Suis Ova, commonly known as Pig Whipworm Eggs.

Worm therapy emerged from the the Hygiene Hypothesis, which suggests that our much cleaner environments in the industrialized world has resulted in immunological disorders due to stunted immune system development. The idea is that because we are exposed to so much less immune system stimuli, particularly growing up when our immune systems are developing, our immune systems do not develop properly.

Extensive research into the incidence of autoimmune diseases and allergies has demonstrated that diseases of immune regulation such as Multiple Sclerosis and Asthma are relatively rare in less developed countries, while there has been a significant and sustained increase in autoimmune and immunological diseases in the industrialized countries.

An explanation of how environmental factors play a role in autoimmune diseases has still not been completely developed. But, epidemiological studies, such as the meta analysis of many past studies in which large data sets are aggregated, have helped to established the link between parasitic infestation and its protective role in immunological disease development.

They Hygiene Hypothesis & Worm therapy

Although the mechanism of immunological disease development is completely worked out there is a general acceptance that the majority of immune disorders and the diseases they cause are due to inappropriate immune responses to innocuous antigens, driven by an arm of the immune system labeled as the TH1 type response. Extra-cellular antigens primarily trigger the TH2 response, as observed with allergies, while intracellular antigens trigger a TH1 response. The inter relationship and interplay between these two arms of the immune system is a central issue addressed by the Hygiene Hypothesis. The Hygiene Hypothesis states 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 the industrialized nations, undermined the Hygiene Hypothesis, and so it has been adapted to account for this observation.

This refinement of the Hygiene Hypothesis, that overcomes this apparent contradiction, is the Old Friends Hypothesis. The Old Friends Hypothesis modifies the Hygiene Hypothesis, proposing that T regulator cells (T regs) only become mature and completely effective if they are stimulated by repeated exposure to microorganisms and parasites that are relatively benign and which have coexisted with humans throughout our evolutionary history. As suggested by their name Tregs are the generals of the immune system, they determine to a large degree the response of the immune system to various pathogens and antigens. This model proposes that appropriate immune response is learned by repeated training of the Tregs through repeated exposure to these microorganisms and parasites.

In the industrialised nations, we live in a relatively sterile environment when it is compared to the one we evolved in. The development of vaccines, hygienic practices, waste disposal, sewers, antibiotics and effective medical care have diminished or eliminated the prevalence and impact of many dangerous organisms, as well as relatively benign ones. This has been of obvious benefit and hundreds of millions of lives have been saved.

However, our exposure to benign and apparently beneficial parasites and organisms has also been reduced as well. The central thrust of the theory is, therefore, that correct development of T regulator cells in individuals may depend on exposure to organisms such as lactobacilli, various mycobacterium and helminths. Lack of exposure to sufficient benign organisms, particularly during childhood, is now accepted as the cause for the increase in immunological diseases and diseases for which chronic inflammation is a major component in the relatively sterile industrialized world.

Depending on the immune disease in question infection with helminths results in remission of symptoms in approximately 70% of patients. While this is not absolute proof that the Hygiene Hypothesis and Old Friends Hypothesis are correct, it is very good evidence that a dysfunction of regulatory inflammatory response, is a key factor in the development of immunological diseases, and that a helminth infection can bring this immune response into a normal range for many.

Which worms are used in therapy?

For use as a therapeutic agent, the specific helminth should meet all the following minimum requirements:

    I should not cause any disease or harm to the subject at therapeutic doses

    It should not be able to reproduce in the host, or to proliferate, so that dose can be controlled.

  1. It should not be a vector for other parasites, viruses, or bacteria.

  2. It should not represent an infection risk to others.

  3. It should not interact harmfully with any existing medicines being used to treat the subject.

  4. It would ideally have a significant period of residence in the host since the benefit of helminths only prevails so long as the patient hosts them. Ideally dosing would only be required infrequently and after long intervals to save costs.

  5. It should be easily eradicated from the host, if required

Only Necator Americanus meet all these requirements, although Trichuris Suis Ova only misses on number 6 above, so it is more expensive.

Neither hookworm nor TSO is known to cause any specific disease in man at therapeutic doses. Since in both cases the parasite can not proliferate in the host they are safe on this score. Neither helminth is known to be a vector for the infection of the host with other parasites, viruses or bacterium. Given that close to a billion people are currently infected with hookworm the fact that there is no recorded case of anyone catching an opportunistic infection due to infection with hookworm is very encouraging on this score.

Neither helminth reproduces in the host; in both cases, the reproductive cycle requires a period outside the host, with both worms requiring several weeks' incubation in moist soil. As a result, the therapeutic dose can be tightly controlled. The complexity of both helminths' life cycles also means that cross-infestation, even with people living in very close proximity to the host, is highly improbable. Hookworm require a period of eight days outside the body in ideal conditions after being passed in feces to become infectious and then must come into direct contact with bare skin to infect someone. Such a situation in the industrialized world is hard to imagine.

The main difference between N. americanus and T. suis is residency time, because T. suis has a lifespan of only 2-3 weeks in humans, while N. americanus has an average life span of 5 years. Frequency of dose and therefore expense is therefore higher for TSO.

Both helminths have been demonstrated to have beneficial effects when used in conjunction with existing (conventional) therapies.

If eradication of helminths from the host is required at any point, both respond to a single 400 mg dose of albendazole administered orally as a pill or in suspension for juveniles.

Worm Therapy Treatment and Side Effects

TSO (Trichuris Suis Ova - pig whipworm eggs) is contra-indicted in patients experiencing acute symptoms associated with their respective autoimmune disease. Treatment with TSO is achieved by multiple oral doses. Patients are normally started with four separate doses taken every one to three weeks. Starting dose is normally 500 ova/dose, for the first 4 doses. Failure to respond after the first four doses will result in an increase in dose to 1000 ova/dose, up to a maximum of 2500 ova/dose every two weeks. A clinical trial of TSO in patients with Ulcerative Colitis, indicated that 13 of 30 patients (43%), given 2500 ova/dose bi-weekly for a twelve week period, showed improvement in their disease index activity. Better results were obtained in Crohn’s patients, with a 72% remission rate following eight doses of 2500 ova over a 24 week period. No side effects were reported in either study.

Treatment with hookworm is accomplished by a either single application of the infectious L3 larvae to the skin, or by giving multiple smaller doses over a period of time; In both cases the total dose is set at up to 35 larvae because it is estimated that the most common population size for those infected with hookworm in the third world is roughtly 20-25 hookworm. In single dose therapy a dose of 35 gives the best balance between the chance of achieving remission and the occurrence of the transient side effects associated with inoculation.

The side effects of treatment with hookworm vary widely, from nothing more than a mid rash at the site of inoculation to disabling fatigue and severe epigastric pain, diarrhea and cramping. There is no correlation between any of the side effects, so that some may experience the rash but no intestinal side effects, others no rash and severe intestinal side effects, and every permutation in between.

Immediate side effects of inoculation can include any, all or none of the following. A rash at the inoculation site that can last from a few hours to three weeks. Gastrointestinal symptoms to some degree in a majority of individuals over the following 12 weeks, usually episodic in nature, and generally starting either at day three or four in reactive individuals or at the end of week three in everyone else. Side effects are to some degree dose dependent although the relationship is not linear. Gender, disease profile, timing and age all effect side effects so treatment plans must be tailored to individuals and it is impossible to make generalizations that are of any use.

However in a small minority of clients with certain characteristics they experience severe side effects at any dose over 4 or 5 larvae. For these individuals a custom treatment plan is developed based on an evaluation of their risk factors in relation to those treated previously at the clinic. For them only multi-dose therapy is appropriate, often requiring treatment six to ten times to achieve a therapeutic dose while avoiding side effects. The good news is that it is possible for this group to avoid any side effects using this approach. It is estimated that approximately five percent of the population requires this approach.

Worm therapy compared to approved approaches

The potential benefits of Worm therapy are quite startling when compared to the success rates and side-effects experienced by people on currently accepted medications that are immune-modulating and or anti-inflammatory.

Success rates for Worm therapy, as measured by the number of people achieving remission range from 56% for Ulcerative Colitis using TSO as the helminth, 72% for Crohn's using TSO. No studies regarding the efficacy of hookworm have been published at this time, except for one weak Proof of concept study into Crohn’s showing a 100% remission rate using hookworm after a few months. However, although the hookworm paper is encouraging, the study was only intended to prove safety and is a not an appropriate study from which to determine efficacy.

Contrast that with the remission rates for the new biologicals as described below, in one study sponsored by the drug maker, Humira achieved only a 52% remission rate in Crohn's patients. As well, side effects of helminthic therapies are not universal and are temporary, usually lasting only two to four weeks. They consist of abdominal pain, cramping, gas, diarrhea and fatigue (medical)|fatigue. The side effects of conventional immune-modulating drugs, such as Beta-interferon and Remicade, or of anti-inflammatories such prednisone, are much more severe and potentially harmful. As with any immunosuppressive therapies patients using Worm therapy are likely to be more susceptible to certain infectious diseases.

Front line treatment for inflammation, whether in autoimmune disease or other, has relied on synthetic glucocorticoids (steroids) such as prednisone. Treatment is generally highly effective for acute inflammation, but the doses required and the need for prolonged use results in side effects referred to as Cushing's disease or syndrome. These side effects include immunosuppression, thinning of the bones, truncal obesity, moon face, glucose intolerance, mood swings and many other side effects.

Maintenance therapy once front line therapy has gotten the inflammaion under control in many diseases is immunosuppressive. The use of such drugs as azathioprine or 6-mercaptopurine (6-MP) is common. While these approaches can be very effective in some patients they are generally very expensive, do not work in many patients and carry the risk of complete immunosuppression and cause their own host of often severe side effects.

Several new therapies are becoming available or are undergoing trials. These new drugs are based on antibody targeting of specific molecules or factors involved in the immune response. Specifically the monoclonal antibodies, which target specific inflammatory provoking cytokines. Drugs such as Infliximab (Remicade), which is a chimeric (transgenic, involving the dna of multiple organisms, hence chimera) IgG monoclonal antibody that neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor, and Adalimumab (Humira), which is a human IgG monoclonal antibody specific for human tumor necrosis factor (TNF).

These drugs can be very effecting in patients who have become refractory (non responsive or resistant/allergic) to other therapies. However, the risk of side effects is significant. Immune response modulation by these drugs is reported to have resulted in patients being susceptible to tuberculosis (including re-emergence after apparent cure) and septic shock. Other side effects, such as the development of demyelinating disorders (similar to multiple sclerosis), hypersensitivity reactions (anaphylaxis), pancytopenia (a decrease in all types of blood cells), congestive heart failure, Lupus-like syndrome and an increase in the incidence of lymphoma in those treated have been reported

A series of recent studies at the Mayo Clinic suggests that patients are at an increased risk of a variety of cancers, including lymphoma, skin, gastrointestinal system, breast and lung cancer.

Worm Therapy Research

Worm therapy with both hookworm and TSO has been investigated in research published by the University of Nottingham and University of Iowa. Both TSO and Hookworm are well tolerated, and safe at therapeutic doses. Neither organism is by any standard definition infectious in the industrialized world. That is, it neither presents an infection risk to others from a treated individual, nor does either organism proliferate within the host once established.

Hookworms depend upon a period of eight to ten days outside the host within narrow environmental parameters to become infectious after being passed in stool. ''Trichuris suis'' is similar to the human whipworm ''Trichuris trichiura'', but its definitive host is pigs. ''T. suis'' can colonize people but only for a short term and the worms cannot reach maturity except in rare instances.

For this reason treatment with TSO requires regular doses, at intervals of two weeks. Treatment with hookworm requires inoculation at intervals of approximately five years. This is because the average life expectancy of necator americanus is on average 5 years.