How I think helminthic therapy works*.

I believe that there are three mechanisms by which helminths can produce a therapeutic response.
The following is the result of reading and speculation on my part, and should not be taken as the definitive or the final answer. 

Host immune system modulation

This mechanism is the one of most interest to the scientific community. Because hookworms and whipworms have to remain in contact with our tissues to feed on us, they have to reduce or suppress the immune response that would otherwise be directed at them resulting in their death. [1]

To do so they secrete a variety of molecules that moderate our immune response to them. Molecules that are all drug candidates, hence the scientific interest. 

Evidence for this is easy to see in simple blood tests for a class of white blood cells called Eosinophils. If you have ever had a blood test you have likely been tested for Eosinophil levels (sometimes listed as EOS) for already. Absent infection by a parasite they can be an indicator of immune disorders, "ghost worm" syndromes, of which there is a variety.

Eosinophils exist only to fight parasites, and in subjects who have never been exposed to hookworms or whipworms or some other helminth, circulating numbers of eosinophils are usually very low. Within two months of first exposure to either organism numbers skyrocket, plateauing at a high level for about four months, before declining at around six months to levels very slightly above that prior to exposure. There is a lot of research indicating the relationship between the effects of helminths on circulating levels of eosinophils and diseases like allergies as one example.[2]

This is clear evidence of the ability of hookworms and whipworms to moderate our immune response.

There is also some excellent research showing that the effects on the human immune system extend to the production of autoantibodies. The research into the impact of helminths on Relapsing-Remitting Multiple Sclerosis is remarkable, if I had MS I would do whatever it took to obtain helminths. [3] and [4]

Our experience has shown that other strict autoimmune diseases also respond as well as MS, diseases like Sjögren's, etc. all respond very, very well.

It is for this reason that helminths used in other types of helminthic therapy, TSO and HDC, require frequent dosing. They do not modulate our immune system in any profound way, and as a result, are killed so quickly a new dose is required every two weeks or so.

Which leads us neatly to the next mechanism by which helminths can produce a therapeutic response.

"Distraction" of the host immune system

Please note that this portion is based on speculation by the author, I have not been able to find any papers to cite though I have not spent a great deal of time looking.

The immune system is one of limited resources, as all systems are. In someone who is sick if you present their immune system with an additional challenge such as helminths, it has to shift some of its resources from where it is getting up to mischief to deal with this new insult.

By presenting your immune system with a new challenge in the form of helminths the immune system will divert some proinflammatory resources away from where it is making mischief, your immunological disease, allergies or autoimmune condition, and towards fighting this new invader.

For this reason, we sometimes see a "bounce" in individuals when they take their first dose, where the subject can go into complete remission, often accompanied by euphoria so intense I get teased that I must use hookworms as people do beer or wine. Sadly not everyone experiences such a pleasant experience, and even in those that do it is short-lived and typically only occurs with the first and sometimes the second dose.

It should be noted that this distraction effect can have undesired consequences. If you suffer from an incurable infectious disease or cancer then it is possible that during this transient phase lasting a few days or weeks after early doses that you may experience more frequent outbreaks of whatever disease you carry, or speculating now a more rapid progression of your cancer. In these cases, the brief nature of the phenomena is a welcome one.

This is most common with herpes. With an estimated 60% of the population infected with herpes, and most unaware they have it, it is possible you may experience your first flare of herpes that you recognise as herpes as a result of taking your first dose of helminths.

If you suffer from frequent, severe outbreaks these will likely be more common and severe during the first six months of dosing with hookworms. Whipworms are more likely to have this effect.

I believe it is this mechanism which is responsible for the majority of well-documented benefits that come from using Trichuris Suis Ova (TSO) which are not adapted to humans.

The effect lasts only so long as the target of the immune system is present, and only in the initial period of the innate immune response, which is relatively brief. So that in the case of organisms that are not adapted to humans it is relatively short-lived as they are quickly killed by the immune system they have not evolved to resist and to control.

When helminths are used, as are those we provide, that are adapted to humans smaller doses must be used. The only known negative health effects resulting from infection with hookworm and whipworm come from very large populations, far larger than those we use. So this effect is much milder when using human-adapted helminths because dose sizes are so much smaller. A typical dose of TSO can range from 600 to 2,500 ova, where as a dose of TTO (our whipworm) is typically from 25 to 100 ova. 

Another reason that this effect for helminths adapted to humans is relatively short-lived is that as they exert control over our immune systems. When they do the immune system stops reacting to them as new interlopers, even with new doses.

This explains why the "bounce" effect is short-lived in those few who experience it, and only occurs with the first and sometimes to a lesser extent with the second dose.

Fortunately, as this effect fades the first mechanism discussed here comes to predominate in those who respond well, and so a therapeutic response is maintained but via a different mechanism.

In adjusting dose size and frequency early on when using Trichuris Trichiura Ova (TTO) the object is to optimise this distraction effect while building up the population using dose sizes that will not cause side effects until the other two mechanisms of action come to dominate the subject's therapeutic response to helminths.

A localised anti inflammatory effect at the helminth attachment site

This effect is the most important one for inflammatory diseases affecting the ileum and colon (Crohn's and Colitis), as well as being a major factor in inflammatory disorders that are not localised but that affect the intestinal tract, like Coeliac disease and food intolerances.

When we first started out we had excellent results in our first Crohn's clients using hookworms, which was the only organism we had at the time. They all had the most common variety of Crohn's. That affecting the ileum which happens [8] to be where hookworm live.

When our first group of Colitis clients showed up, for some reason we had a group of four in one month, April of 2008, we expected them to respond equally well. At that time only the systemic effect was one we had thought of.

All failed to respond.

In thinking about this I reasoned that perhaps this was because of a local effect rather than the systemic one which was the prevalent view at the time, or so I thought.

By luck a paper was published in that time frame looking at a different subject, but which showed there was a strong anti-inflammatory effect in subjects with Crohn's disease who were given hookworm.[5]

Capsule endoscopy showed "areas of profound" calm in the inflamed tissues of the two subjects surrounding where the hookworms were or had recently been attached to feed. Hookworms migrate once every 24 hours approximately to a new feeding site, so their effect is related to the size of the population in diseases involving inflammation in the areas they live. [6]. This research demonstrates why antihistamines like Benadryl can be so effective at controlling the symptoms of helminthic therapy in some individuals.

So I reasoned that to treat inflammatory diseases of the bowel, the colon, that we needed an organism with the safety profile of hookworms, one that also attached to feed but in the colon.

Whipworm was an obvious candidate, and I was fortunate to be able to obtain some with which to infect myself. Research has confirmed my belief and shown that whipworm do induce a strong change in the [7] epithelial cells lining the colon. Whipworm’s secrete molecules that suppress LPS-induced pro-inflammatory cytokines and increase production of other anti inflammatory cytokines.

Within four months we had ova with which to work and were able to isolate them and provide them to all those for whom hookworm had failed.

Every one of them responded well.

Except regrettably the young man who had come to me as his last hope before surgical removal of his colon. By the time I was able to offer him whipworm it was too late. The failures are the ones that stick, if I had been six months earlier I believe that like the others he would be in remission still. That this is illegal is an affront to decency and to common sense.

So in diseases involving inflammation of the intestinal tract, like Coeliac disease, Crohn's disease, Ulcerative and other Colitises, it is this local effect that is perhaps the most important component in achieving a therapeutic response. So that for inflammatory diseases of the intestines helminth population size, density and distribution all play an important role.

So with these disorders more than others how well a subject responds, if they respond, is directly related to the number of hookworms, whipworms or both are hosted.

In IBD this represents a unique challenge for the helminthic therapist as it is obvious that in many cases these diseases are the result of coevolution with hookworm and whipworm specifically, and likely with protozoa.

This obvious idea derived from amongst other things the observation of an almost one to one match in the initial symptoms of infection with hookworm and with the symptoms of Crohn’s disease of the ileum, has been born out by research. [8]

A consequence for those suffering from Crohn’s in the ileum for instance, where hookworm live, is a much higher level of innate immunity to hookworms. This results in the lifespan of hookworm in individuals with Crohn’s affecting the ileum being substantially reduced in comparison to someone with Crohn’s. So that they have to dose with hookworm larvae regularly in order to maintain a therapeutic response.

* It is my opinion and more generally that this type of Crohn's likely arises out of an adaptation to hookworms specifically and that similarly, some varieties of Colitis are likely an adaptation to whipworm and/or to protozoa.

Note: If my tone sounds detached, as when I speak of speculating as to why hookworm failed to help those with Ulcerative Colitis and Crohn's Colitis when it has succeeded so magnificently with those suffering from Crohn's in the ileum I apologise.

I spent many nights in those first three or four years whenever someone with a disease we had never treated showed up worrying I would fail them.

I find it impossible to avoid emotional attachment to clients and to their outcomes.

Failures are particularly hard, and if in time I fail you please allow me to apologise now.

No one should suffer from such illnesses, particularly given how preventable, never mind how treatable they all are. 

It is an outrage that helminthic therapy is not already integrated into mainstream medicine and prophylaxis because millions suffer needlessly, and they will be joined by millions more in time before the greed of the drug companies and the institutional intransigence of regulators and educators is overcome. 

I believe helminthic therapy is so safe, effective and cheap that it has historical inevitability. I find it hard to understand with so much evidence why so little research into the use of the organisms themselves, instead of as source of what will be dangerous drugs, is being conducted when the CDC says they are safe (See our FAQ for details).

Bibliography
1. J Immunol March 15, 2008, 180 (6) 4265-4272; DOI: https://doi.org/10.4049/jimmunol.180.6.4265 [Internet]. [cited 17 Jun 2018]. Available: J Immunol March 15, 2008, 180 (6) 4265-4272; DOI: https://doi.org/10.4049/jimmunol.180.6.4265

2. Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends Immunol. Elsevier Current Trends; 2001;22: 372–377.

3. Correale J, Farez M. Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol. 2007;61: 97–108.

4. Correale J, Farez M. Helminth Antigens Modulate Immune Responses in Cells from Multiple Sclerosis Patients through TLR2-Dependent Mechanisms. The Journal of Immunology. 2009;183: 5999–6012.

5. Intestinal allergy expels hookworms: seeing is believing. Trends Parasitol. Elsevier Current Trends; 2006;22: 547–550.

6. Website [Internet]. [cited 17 Jun 2018]. Available: DOI: https://doi.org/10.1053/j.gastro.2006.05.019

7. Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells. Mol Immunol. Pergamon; 2014;60: 1–7.

8. Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, et al. Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J Exp Med. 2009;206: 1395–1408.

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