17 Responses

  1. Beth Stokes
    Beth Stokes at | | Reply

    The idea of parasites assisting the immune system is quite fascinating. Parasites, intestinal worms in particular, generally conjure a skin crawling reaction. However, there is a growing body of evidence indicating that they can actually be beneficial. Helminthic therapy has been used to treat a variety of disorders such as multiple sclerosis, irritable bowel syndrome, and Crohn’s disease. The “Hygiene Hypothesis” and the fact that immune disorders are rare in developing countries where helminth infections are higher are two bits of evidence that are pointing more researchers in the direction of using parasites as a treatment for immune disorders. Previously, it was found that helminth treatment increased production of interleukin 22. IL-22 is linked to mucus production – helminth infections served to activate a population of IL-22 producing immune cells, therefore increasing the secretion of mucus. This increased mucus is thought to prevent gut bacteria from causing inflammation characteristic of many immune disorders localized to the intestines. Zaiss’ study shows a much different side and unique way of how the immune system interacts with helminths. This is a topic that I look forward to reading more about.

    http://www.bbc.com/future/story/20130422-feeling-ill-swallow-a-parasite
    http://gut.bmj.com/content/54/1/6.full
    http://abcnews.go.com/Health/Wellness/drinking-pig-worms-fight-crohns-disease/story?id=17148676
    http://www.scientificamerican.com/article/helminthic-therapy-mucus/

    1. Trisha Cardillo
      Trisha Cardillo at | | Reply

      I agree, Beth, that the hygiene hypothesis has great merit, and many people in the U.S. are not doing themselves or their children any favors by overuse of antibiotics, Lysol disinfectants and hand sanitizers, while simultaneously limiting exposure to dirt, and the organisms it contains – like helminths. The studies correlating increased helminth infection with lower incidence of autoimmune disorders like multiple sclerosis and diabetes are fascinating, but correlation does not imply causation. Further, there are a great many differences environmentally and culturally between U.S. populations and those in areas with higher helminth infection rates, yet lower autoimmune disorder incidence. Increased ingestion of food additives, poorer air quality from increased carbon emissions, and chronic exposure to environmental toxins – both inside and outside the home – may all be playing a part in increased autoimmune incidence in this country. How does one go about isolating any of these factors to prove causation? Or, is it more likely a combination of factors that are impacting genetic mutation and increased autoimmune disease rates? While helminth infection has been shown to inhibit type I diabetes – which may certainly impact the reduced incidence of this disease in those areas of the world where sanitation is poor and helminth infection is widespread – it is also true that the diet and exercise/activity level of those same individuals is radically different than that of the average American.

      I think the role of helminths and our immune functioning deserve further exploration, but I will remain skeptical that helminth treatment in the absence of changes in diet, exercise, and overall chemical exposure will have a dramatic impact on disease rates in the U.S.

    2. Vishakh
      Vishakh at | | Reply

      The helminths are able to survive inside their host with minimum collateral damage due to the modification of the host immune response. This is achieved by the expansion of Forkhead box P3+Tregs in addition to the production of transforming growth factor β and IL-10. These cytokines and Tregs lead to suppression of parasite-specific T cell proliferation, reduced levels of Th2 cytokines, and Th1 cytokines. But the overall outcome of immunoregulatory effects of helminths on the host in the presence of another immune stress is still not clear. Helminths can suppress various bystander immune responses, such as the suppression of anti-tumor, antibacterial, antiviral, and antiprotozoal immunity. It may also affect the vaccine efficacy due to suppressed immune responses. Hence, helminthic therapies should be used with caution.
      Source:
      McSorley HJ, Maizels RM. Helminth infections and host immune regulation. Clin Microbiol Rev. 2012;25:585–608.

      1. Torrellas Beasley
        Torrellas Beasley at | | Reply

        While I agree with the uncertainty of helminth worms as addition to the immune response, I disagree with the statement of it masking “anti tumor properties.” I am recently conducting research on ways to reduce T regulatory cell (T regs) populations in tumor bearing mice. This study shows that helminths has T reg suppressor properties. There are several studies that show that suppression of T reg populations is what’s necessary to help the immune system fight off tumors. Helminths would actually work quite oppositely when it comes to anti tumors because it reduces the inflammatory environment which is what helps tumors spread in the first place.

        Works cited:
        Nahas GR, Walker ND, Bryan M, Rameshwar P.A Perspective of Immunotherapy for Breast Cancer: Lessons Learned and Forward Directions for All Cancers. Breast Cancer . 2015 Nov 2;9(Suppl 2):35-43.

      2. Courtney Masset
        Courtney Masset at | | Reply

        Although I agree that helminth based therapies should be used with caution, I disagree with the statement that these parasites have minimal collateral damage to the host. Helminth infections, as discussed in Peter Hotez’s article, can cause serious disorders such as elephantiasis, visual impairment, anemia, growth stunting, and poor cognitive development. The list of conditions associated with helminth infections is quite extensive and the fact that patients typically have secondary infections by other parasites just increases the long-term negative effects caused by these parasites. This type of infection is very serious and affects developing countries across the globe.
        Reference:Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J. Helminth infections: the great neglected tropical diseases. The Journal of Clinical Investigation. 2008;118(4):1311-1321. doi:10.1172/JCI34261.

  2. Aishwarya Parameswaran
    Aishwarya Parameswaran at | | Reply

    An interesting feature in this article is that parasite helps the immune system and it is in fact a little surprising. Helminths mostly doesn’t replicate with in a host unlike virus or bacteria. Its survival is based on immunomodulation. Helminths interfere with the maturation of dendritic cells, which affects the antigen presentation. Secondly it is also found to generate a network of regulatory cells, which secretes transforming growth factor-β and IL-10. These cytokines are found to regulate the immune responses in chronic allergies. This survival strategies by helminths could be beneficial for both parasite and host as the host will protected against strong inflammatory response. So a helminths infection may protect its host from autoimmune disorders like multiple sclerosis and inflammatory bowel disorder.

    References:
    Lior Zeller MD, Leonid Barski MD, Elena Shleyfer MD, Uri Netz MD, Vered Stavi MD and Mahmoud Abu-Shakra MD, Taenia Solium in a Patient with Systemic Lupus Erythematosus: Do Parasites Protect against Autoimmune Diseases, IMAJ • VOL 17 • April 2015.

    http://gut.bmj.com/content/54/1/6.full

  3. Vishakh
    Vishakh at | | Reply

    According to researchers, helminthic exposure could have three possible outcomes on the immune system of an individual.
    Outcome 1: The infected individual may be susceptible to the infection, will have long-lived active adult worms in their tissues. Will have high T-helper-2 responses, low T-helper-1 responses and apparently high T-reg cell activity. IgG4 antibody will be prominent with very less amount of IgE. This individual might not show any symptoms of infection but will serve as a carrier of the helminthic infection.

    Outcome 2: The infected individual may develop a high uncontrolled inflammatory T-helper-1 disease with low T-reg activity. This is due to a strong immune response against the eggs present in body tissues. There will be low levels of IgG4, IgE responses will be prominent. Lymphatic inflammation resulting in elephantiasis may be observed.

    Outcome 3: The infected individual may be resistant to the infections and will have a well-balanced T-helper-1 and T-helper-2 activity due adequate T-reg activity. There will be a less skewed levels of IgG4 and IgE antibodies. All these factors will contribute to preventing an helminthic invasion.

    Hence, it is important to understand the regulation and counter-regulation of immune responses to the helminthic infections to be able to identify the situations where helminthic infections assist our immune system and the situations where they may result in parasitic infestation and an immunopathological and inflammatory disease.

    Source:
    Maizels, R.M., M. Yazdanbakhsh. 2003. Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat. Rev. Immunol. 3:733–743. 10.1038/nri1183

  4. Dessica Hodges
    Dessica Hodges at | | Reply

    Hopefully in the future the FDA can approve the use of parasitic worms or parasitic worm products to help treat inflammatory diseases such as asthma, arthritis, dermatitis, lupus and fibromyalgia in the United States. Many of the drugs given for autoimmune inflammatory diseases can cause fever, kidney damage, liver damage, and leukopenia. Immunosuppressive drugs like methotrexate and azathioprine that are used to treat lupus have teratogenic effects and can cause abortion in pregnant women (3). According to the CDC, Ascaris lumbricoides parasitic helminth worm infection is asymptomatic especially in light infections (2). In a 2015 research study using mice, synthetic immunomodulatory parasitic worm products were used to prevent arthritis by inhibiting cytokine IL- 1β production through transcription factor NRF2 (1). This breakthrough in the use of parasitic worm immunomodulatory products is great because it allows a safer alternative where there is no need to use live parasitic worms to get the immunological benefits.

    References
    1. Rzepecka J, Pineda MA, Al-Riyami L, et al. Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome. Journal of Autoimmunity. 2015;60:59-73.

    2. CDC. Soil-transmitted helminths. Centers for Disease Control and Prevention. http://www.cdc.gov/parasites/sth/index.html

    3. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation for PDA: A reference guide to fetal and neonatal risk. Philadelphia: Lippincott, Williams & Wilkins; 2005.

    1. Shawn Friedland
      Shawn Friedland at | | Reply

      Dessica, I agree in that parasites can be a great therapeutic approach for autoimmune diseases, but I really don’t see parasites gaining popularity in treatment, at least for those already benefiting from conventional treatment. For example, a family member of mine has Multiple Sclerosis. She is doing very well with Tecfidera (conventional medicine), and a high dose of Vitamin D, with very little side effects. So, in her case, it wouldn’t be smart for her to use parasites in her treatment. There are many people in her situation, where they are treating their autoimmune disease and it is working for them. It would not be wise to change things, as disrupting a working treatment can make things worse. However, I think if someone is struggling with conventional medicine and things are not working for them, then parasites could be a great treatment approach. In many autoimmune diseases, it is not the disease that kills you, it’s the symptoms. Controlling the symptoms is a major part of treating autoimmune diseases. I am not sure if using parasites solely for treatment will be as beneficial as well researched FDA approved medicine. Also, without solid, heavy research on parasites benefiting those with autoimmune diseases, I highly doubt many people will be willing to try this. There needs to be solid long-term studies showing the benefits and no adverse risks in the long run, otherwise I don’t think many people will be willing to go this route.

      Correct me if I am wrong, but I thought the FDA has already approved certain parasites for treatment. I believe leeches are FDA approved and have been used as “medical devices” for blood cleansing and skin rejuvenation. I tried to search if other parasites are FDA approved, but it seems to be extremely difficult to find online. So, maybe not.

    2. Harveen Walia
      Harveen Walia at | | Reply

      I support the idea that helminths have or provide beneficial advantages to our immune systems. But like all products/drugs, I believe it has its advantages and disadvantages. Although helminths have been seen to be efficiently helping prevent conditions as you mentions, such as arthritis, but there are other conditions that it may make worse. A study I reference below finds that parasitic helminth worms are widespread in regions with high prevalence of tuberculosis. Studies have shown that helminth coinfection contributes not only to increased TB susceptibility but also increases the rate of TB reactivation. Globally, we all live in very diverse environments and people in other communities may be more or less susceptible to infections/conditions. So I am not entirely sure right now of using parasitic worms for preventing certain health conditions because at times an infection could be associated with another condition. Further research is definitely needed to explore this interesting mechanism of regulation utilized by helminths.

      Reference:
      Monin, Leticia. “JCI – Helminth-induced Arginase-1 Exacerbates Lung Inflammation and Disease Severity in Tuberculosis.” JCI – Helminth-induced Arginase-1 Exacerbates Lung Inflammation and Disease Severity in Tuberculosis. JCI, n.d. Web. 05 Dec. 2015. .

  5. Torrellas Beasley
    Torrellas Beasley at | | Reply

    While most people zoomed in on parasitic worms and the help they may or may not provide to the immune system, I noticed the part of the study where the worms may or may not affect fertility. During pregnancy, the immune response is generally lessened so that the body builds a tolerance for the developing fetus. While this is great in terms of pregnancy, I’m not sure that I would want this same kind of immunity when not with child. So helminths may be great when it comes to reducing inflammation. And the reduction of inflammation is more likely great when it comes to inflammatory diseases. But do we really want inflammation suppressed more or less? I would like to keep my inflammatory cytokines around when I need them in lieu of keeping around a parasite that suppresses my immune system.

    Works Cited:

    Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Hormonal Behavior. 2012 Aug: 62(3): 263-271.

  6. Shawn Friedland
    Shawn Friedland at | | Reply

    I have done a lot of research on Multiple Sclerosis and immune effects, as well as diet, environmental factors of MS (both preventing and treating the disease). This article has really piqued my interest and searches of helminths, and in particular, with MS. From my previous research, I learned that MS is mostly due to 2 factors- part genetics, part environment. There are a lot of studies showing a genetic link with family members and MS, about a 1 in 40 chance of someone having MS if they have a first degree relative with MS. The other factor is environmental, this is where my research came in- most people with MS live further from the equator, with less sunlight, less vitamin D. Low vitamin D levels are thought to be correlated with getting MS, along with a genetic factor (recent findings are suggesting). The hygiene hypothesis does strike interest. It is true that most people that have helminths in their body (about 2 billion in the world), according to the WHO, have decreased incidences of autoimmune diseases. However, this may not solely be due to helminths in their body. It could be due to genetics and environmental factors.

    An interesting study (Correale 2007) showed interesting results giving helminths to 12 people with MS. They quote in their results “During a 4.6-year follow-up period, parasite-infected MS patients showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imaging changes when compared with uninfected MS patients (Correale 2007).” They also quote “Increased production of IL-10 and TGF-beta, together with induction of CD25+CD4+ FoxP3+ T cells, suggests that regulatory T cells induced during parasite infections can alter the course of MS Correale 2007).” Interesting results, and promising. However, the way the helminths are beneficial to the immune system of MS patients can be similar to the effects of conventional medications to treat MS (Interferons, Tecfidera, etc.), as well as using high levels of Vitamin D to help with MS. So, I think helminths can be a good therapeutic approach to MS, with less side effects than conventional medicines, but there really needs to be more long term studies to show the beneficial effects of it.

    I don’t think one can strictly say the hygiene hypothesis is the sole factor related to autoimmune diseases. We need to take into account genetics and the environment too.

    Correale J1, Farez M. Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol. 2007 Feb;61(2):97-108.

    1. Courtney Masset
      Courtney Masset at | | Reply

      As someone who also has a family member that suffers from MS, I was intrigued by this possible new method of treatment. One thing that is interesting to me is how helminth infections also have helpful effects on patients suffering ulcerative colitis and Crohn’s disease. Vitamin D deficiency has been shown as a factor for all these diseases and in one study, they suggest that the decreased helminth infections in developed countries could be a cause for the increase of these diseases in addition to the vitamin D intake. Since gut microflora plays a key role in our immunity, maybe helminth treatment could help with MS patients who may have an imbalance in that area; although, I don’t necessarily agree with the hygiene theory since my family member lives in NYC and that place can in no way be deemed overly clean.
      Linlin Yang, Veronika Weaver, Jill P Smith, Sandra Bingaman, Terryl J Hartman, and Margherita T Cantorna.Therapeutic Effect of Vitamin D Supplementation in a Pilot Study of Crohn’s Patients. Clinical and Translational Gastroenterology (2013) 4, e33; doi:10.1038/ctg.2013.1

  7. Harveen Walia
    Harveen Walia at | | Reply

    This is a very interesting post. If I was asked on my response on whether I thought parasitic worms cause harm in our bodies or benefit us, I would have responded with harm. So this blog has been very interesting to read. The fact that parasitic worms provide beneficial effects and help us regulate our immune systems is fascinating to say the least. What I remain curious about is the way it all works/the mechanism by which this works in our body providing the beneficial effects. Our immune systems are critically dependent on immune cells to all work efficiently. The type 2 immune response, characterized by enhanced production of Th2 cytokines, is important since it enable the tolerance to the tissue damage caused by the infection. With the stimulation of type 2 cytokines and development of dendritic cells stimulating T regulatory cell activation and down-regulating type 1 cytokines, we would see promotion and enhancement of the type 2 immune response in our bodies. Altogether, it can be said that the host can both resist and tolerate helminth infections through these immune responses but it is to be noted, as stated in the referenced study below, that prolonged type 2 immunity may lead to immune pathology, including fibrosis. Therefore, I agree that helminths have several beneficial affects including helping down-regulating several health conditions such as asthma, but it also continues to have its disadvantages/malfunctions where prolonged immune response could potentially lead to other conditions such as fibrosis. More studies are definitely needed to figure out the mechanisms behind it all.

    Reference:
    Mishra PK, Palma M, Bleich D, Loke P, Gause WC (2014) Systemic impact of intestinal helminth infections. Mucosal Immunol 7: 753–762. doi: 10.1038/mi.2014.23

    1. Courtney Masset
      Courtney Masset at | | Reply

      Many studies have actually been released in the last few years discussing the benefits of helminth infections beyond increased regulatory T cell induction and suppressive cytokine release. I’ve listed some of the articles I found below in case you would like to research this topic further.
      Fleming J, Isaak A, Lee J, et al. Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study. Multiple sclerosis (Houndmills, Basingstoke, England). 2011;17(6):743-754. doi:10.1177/1352458511398054.
      Correale J, Equiza TR.Regulatory B cells, helminths, and multiple sclerosis.Methods Mol Biol. 2014;1190:257-69. doi: 10.1007/978-1-4939-1161-5_18.
      Linlin Yang, Veronika Weaver, Jill P Smith, Sandra Bingaman, Terryl J Hartman, and Margherita T Cantorna.Therapeutic Effect of Vitamin D Supplementation in a Pilot Study of Crohn’s Patients. Clinical and Translational Gastroenterology (2013) 4, e33; doi:10.1038/ctg.2013.1

  8. Courtney Masset
    Courtney Masset at | | Reply

    This post is quite intriguing to me since I have family members that suffer from MS and Crohn’s disease. After researching the negative effects helminth infections can cause, I’m not completely onboard with helminth based therapies since the benefits may not outweigh the long term effects of these parasites can cause. I did find some promising research however where the Trichuris suis ova were administered to MS patients. The patients showed decreased mean number of new lesions at the close of the study but did have an increase after therapy was stopped, which researchers concluded that helminth infection provides a transient suppression/enhancement of the immune system. If the helminth byproducts that triggered this response could be synthesized, the new treatments for autoimmune disease like MS, IBS, and Crohn’s could be not only more helpful in combating these diseases but also much easier on the patients’ bodies since many current methods can have adverse side effects. It will be interesting to follow this research and see what develops.
    Fleming J, Isaak A, Lee J, et al. Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study. Multiple sclerosis (Houndmills, Basingstoke, England). 2011;17(6):743-754. doi:10.1177/1352458511398054.

  9. Bukunmi Oyewole
    Bukunmi Oyewole at | | Reply

    The point in the paper that a parasitic worm can actually be found to be beneficial to an organism is intriguing. I find it surprising that an organism that should connote such negative bodily reactions can interact with the natural biome of the body to provide positive effects. This opens the possibility of introducing “parasites” with minimal negative effects that include greater known beneficial effects to a person in order to boost their immunity.

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