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Sunday, October 14, 2012

Helminthic Therapy


For this week’s post, I decided to cover a subject rather than a particular parasite. This is the subject of Helminthic Therapy.  So what is helminthic therapy you ask? Great question! Let’s delve in and explore this somewhat counter-intuitive idea.  Perhaps in the end you won’t think it’s quite so counter-intuitive after all!
The word “helminth” comes from the Greek word “hélmins”, which is a kind of worm.  For parasitologists, this term refers to any type of parasitic worm, be it a flat worm, roundworm, hairworm, etc.  The study of parasitic worms and how they effect their hosts is called “helminthology”.  Helminthic therapy is a type of treatment that utilizes helminthes or their eggs (a.k.a. “ova”) to heal patients with immune disorders or autoimmune diseases. This is a form of “immunotherapy”, a type of treatment that involves inducing, suppressing, or even enhancing an immune response in order to treat a disease. In this case, parasitic worms or their ova are introduced intentionally into a patient.

So, why would anyone think this was a good idea? 

Research has shown that people in well-developed, industrialized countries are at greater risk for autoimmune diseases and allergies than people living in less developed countries. Over time, epidemiologists (people who study the spread of diseases) have begun to link parasitic infestations to lower instances of autoimmune diseases.  Sure, you might be genetically predisposed to certain types of autoimmune diseases, but the rate of increased numbers of people afflicted with autoimmune diseases is not a result of genetic changes.  If this were the case, the emergence of autoimmune diseases would be able to be traced back much further. Since these diseases have a relatively recent emergence, environmental changes (rather than genetic changes) seem to be far more likely explanations.

Environmental factors that could induce such an emergence may include exposure to different medicines, foods (or food preparations), industrial chemicals, etc.  These factors are great for subduing particular diseases such as those associated with infection by bacteria, viruses, and yes, parasites.  However, because there is a lack of exposure to these diseases, human bodies may be likely to develop the antibodies needed to fight off a major infection by the aforementioned disease-causing agents. Therefore, by not ever being exposed to naturally occurring pathogens/parasites, you may be at a greater risk for developing autoimmune diseases and allergies.

This idea is consistent with what epidemiologists call “the hygiene hypothesis”. This hypothesis states that by not exposing people to infectious agents during childhood, the development of the immune system is naturally suppressed. This leads to increased susceptibility to allergic diseases.  Immunologists (people who study the immune system in all of its mind-boggling complexity) have shown that many types of bacteria and viruses elicit an immune response that is mediated by Th1 cells. These cells cause a down-regulation of responses by Th2 cells. If a human is not exposed to pathogens that induce a response mediated by the Th1 cells, then that human’s body does not have a way of initiating the down-regulation of response by Th2 cells.  The result is that the Th2 cells respond excessively. When these cells respond to a harmless antigen inappropriately, you have an allergic reaction. When it comes to more complex issues, such as full-blown autoimmune diseases, it is hypothesized that immune systems that were never exposed to stimuli from infectious agents or parasites do not develop regulatory T cells adequately. Since these regulatory T cells don’t develop properly, they are not sufficient at repressing Th1 or Th2 immune responses, and therefore the immune system is more susceptible to autoimmune diseases. This second hypothesis regarding more complex issues is endearingly called the “old friends hypothesis”. The hypothesis is aptly named as such because it relies on the idea that exposure to microorganisms and parasites at low levels of pathogenicity instigate the development of regulatory T cells. It further implies that these organisms have evolved alongside humans throughout our own evolutionary history.
I rarely take quotes directly from sources, but this was much better than the way that I put it. So, for your reading pleasure I present a quote about the hygiene hypothesis from a paper titled “Helminths and Harmony” that was published by Gut in January of 2004 (authored by JV Weinstock, R Summers, and DE Elliott….53(1): 7-9):

“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 theory is, therefore, that correct development of T regulator cells in individuals may depend on exposure to organisms such as lactobacilli, various mycobacteria, and helminths.”

I have to muse at the fact that I’ve also heard the “old friends hypothesis” referred to as the “lost friends theory” or the “depleted biome theory” in various papers. This is just such a novel and interesting way of thinking about human evolution with regard to parasitism! But, I digress…back to helminthic therapy!

Researchers have established a link between parasitic infections and how these infections play a protective role against the development of autoimmune diseases! Geneticists have found that helminths have helped to shape part of the evolution of the human immune system based on a subset of interleukin (IL) genes. The immune system is highly dependent upon these particular genes. In fact, deficiencies in some of the IL genes seem to be the cause for autoimmune diseases. A lack of helminth exposure can be associated with deficiencies in the IL genes associated with Crohn’s disease, celiac disease, and ulcerative colitis. 

What types of diseases might helminthic therapy be useful for treating?

I’ve already mentioned a few here, but just to reiterate and to add in a few others:
-Asthma
-Celiac Disease 
-Crohn’s Disease                             
-Eczema
-Dermatitis        
-Hayfever
-Inflammatory Bowel Disease
-Multiple Sclerosis

-Ulcerative Colitis
Whipworm Ova
-Various Food Allergies 

So what types of helminths are used for this therapy? 

I’m glad you asked! As of now, the only organisms used have been hookworms (Necator americanus) and both pig and human whipworms (Trichuris suis and Trichuris trichiura respectively). From what little I know about the subject, adult hookworms are used while it is the ova of whipworms that are used.

How effective is helminthic therapy?

From some of the papers and forums I have run across researching this topic, I have found that this has a great success rate. Use of Trichuris suis ova have Crohn’s disease and ulcerative colitis remission rates of 55%. Use of Necator americanus has Crohn’s disease remission rates of 85%! Use of Trichuris trichiura has Crohn’s disease and ulcerative colitis remission rates of 85%. Remission rates for a combined use of hookworms and whipworms (while taking vitamin D supplements) are over 90%!!!


How do you introduce the parasites into a patient’s body? 

Vial containing 15 adult hookworms.
Photo from http://coloncomrades.wordpress.com/
Most people are a little creeped out by the idea of parasites living within their bodies. (Though some of us parasitophiliacs may like the thought of contracting a parasite just long enough to remove it and save it as a testament to our strengths as a biologist…) The medical world takes this fear into consideration. Apparently, the whipworm eggs come in a liquid suspension (eggs are in a buffer solution). The patient is to drink half a cup or so of this suspension, which, from forum posts, should taste no different than drinking a glass of water.  Administration of the hookworms is a little more involved. Patients pour a small vial of hookworms in a liquid medium onto a piece of gauze and apply the gauze to the inside of the arm. They secure the gauze with either medical tape or a band-aid for a little bit. The only symptoms associated were some minor itching and little red dots from where the worms burrowed into the patients. The hookworms don’t have to be reapplied for 3-5 years when the parasites will start to die off.
Application of Adult Hookworms
Photo from http://coloncomrades.wordpress.com/
So a treatment regime that can have anywhere from 55%-90% remission rates MUST be expensive, right? 

WRONG! True, some of the companies that sell the pig whipworms charge a pretty penny, but from what I understand, purchasing the hookworms or human whipworms is extremely inexpensive. (And those species have better remission rates anyway!) Some estimates show that you can be treated for less than $3 a day using hookworms!  The lump sum is fairly high, but when you take into account that you only have to dose once every 3-5 years and that most people are relieved of allergies to foods and to allergic reactions such as hay-fever, you are actually saving money in the long run. (No more medications like Zyrtec or Claritin and you can often eat foods you love once more without going into anaphylactic shock! Talk about a bonus!!!) 

Keep in mind that helminthic therapy is NOT FDA approved. From what I understand, you cannot patent a biological organism (though some companies patent the production of media for administration of these parasites). If it did become FDA approved, it would be something that anyone could produce for very little money. On average, it takes about 10 years and millions of dollars to get a drug approved, so most companies wouldn’t be able to recoup their costs from hookworm media production due to how cheaply it can be produced, and theoretically sold. Thus, big pharmaceutical companies don’t have an interest in funding drugs that can’t be patented and won’t have a big return on their investment. While we are on the subject, you should check out this link to a DIY for growing hookworms and whipworms at home. Just keep in mind that this is a “at your own risk” sort of thing. You don’t want to infect anyone too heavily as these ARE parasites we are working with here, and heavy infestations can have some nasty clinical manifestations. As you might have guessed, you are really better off having a doctor monitor your intentional infections.

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