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Intestinal Parasites and Immunomodulation in Neuroinflammatory Disease

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Neuro-Immuno-Gastroenterology
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Abstract

Some intestinal parasites are major human pathogens, and deworming is rightly advocated to prevent helminth-induced morbidity. Actual understanding of the immunoregulatory responses induced by helminths, in combination with epidemiological and animal studies, suggests however that intestinal worms may have therapeutic potential in autoimmune diseases such as multiple sclerosis (MS). The epidemiology of MS shows an inverse correlation with helminth infections. Positive effects of helminths in animal models of MS and observational studies in people with MS naturally infected with helminths suggest that those organisms can act as immune regulators and led to clinical trials of helminth therapy. This chapter reviews the animal studies, the rationale for and the safety and efficacy results of clinical trials of helminth therapy in MS. Studies on helminth treatments in MS may provide information that could lead to advances in our understanding of MS pathogenesis.

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References

  1. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299(6710):1259–60. Pubmed Central PMCID: 1838109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bjorksten B. The hygiene hypothesis: do we still believe in it? Nestle Nutr Workshop Ser Paediatr Program. 2009;64:11–8; discussion 8–22, 251–7.

    Article  CAS  Google Scholar 

  3. Kemp A, Bjorksten B. Immune deviation and the hygiene hypothesis: a review of the epidemiological evidence. Pediatr Allergy Immunol Off Publ Eur Soc Pediatr Allergy Immunol. 2003;14(2):74–80.

    Article  Google Scholar 

  4. Rook GA. Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):5–15.

    Article  CAS  PubMed  Google Scholar 

  5. Okada H, Kuhn C, Feillet H, Bach JF. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160(1):1–9. Pubmed Central PMCID: 2841828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fleming JO, Weinstock JV. Clinical trials of helminth therapy in autoimmune diseases: rationale and findings. Parasite Immunol. 2015;37(6):277–92.

    Article  CAS  PubMed  Google Scholar 

  7. Elliott DE, Weinstock JV. Helminthic therapy: using worms to treat immune-mediated disease. Adv Exp Med Biol. 2009;666:157–66. PubMed PMID: WOS: 000271245900012. English.

    Article  CAS  PubMed  Google Scholar 

  8. Tanasescu R, Constantinescu CS. Helminth therapy for MS. Curr Top Behav Neurosci. 2015;26:195–220. doi: 10.1007/7854_2014_361.

    Google Scholar 

  9. 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(6):1395–408. PubMed PMID: WOS: 000267133700017. English.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lundmark F, Duvefelt K, Iacobaeus E, Kockum I, Wallstrom E, Khademi M, et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet. 2007;39(9):1108–13.

    Article  CAS  PubMed  Google Scholar 

  11. Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Bresolin N, Clerici M, et al. The landscape of human genes involved in the immune response to parasitic worms. BMC Evol Biol. 2010;10:264. PubMed PMID: WOS: 000282768700002. English.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Fleming JO. Helminth therapy and multiple sclerosis. Int J Parasitol. 2013;43(3–4):259–74.

    Article  CAS  PubMed  Google Scholar 

  13. Parker W, Ollerton J. Evolutionary biology and anthropology suggest biome reconstitution as a necessary approach toward dealing with immune disorders. Evol Med Public Health. 2013;2013(1):89–103. Pubmed Central PMCID: 3868394.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Correale J. Helminth/Parasite treatment of multiple sclerosis. Curr Treat Options Neurol. 2014;16(6):296.

    Article  PubMed  Google Scholar 

  15. Alter M, Leibowitz U, Halpern L. Multiple sclerosis in European & Afro-Asian populations of Israel. A clinical appraisal. Acta Neurol Scand. 1966;42 Suppl 19:47–54.

    PubMed  Google Scholar 

  16. Leibowitz U, Antonovsky A, Medalie JM, Smith HA, Halpern L, Alter M. Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation. J Neurol Neurosurg Psychiatry. 1966;29(1):60–8. Pubmed Central PMCID: 495985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 2010;9(5):520–32.

    Article  PubMed  Google Scholar 

  18. Koch-Henriksen N, Sorensen PS. Why does the north–south gradient of incidence of multiple sclerosis seem to have disappeared on the Northern hemisphere? J Neurol Sci. 2011;311(1–2):58–63. PubMed PMID: WOS: 000297893400010. English.

    Article  PubMed  Google Scholar 

  19. Fleming JO, Cook TD. Multiple sclerosis and the hygiene hypothesis. Neurology. 2006;67(11):2085–6. PubMed PMID: WOS: 000242750900042. English.

    Article  PubMed  Google Scholar 

  20. Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Buss P. Hookworm: “the great infection of mankind”. Plos Med. 2005;2(3):187–91. PubMed PMID: WOS: 000228382500005. English.

    Article  Google Scholar 

  21. http://www.msif.org/includes/documents/cm_docs/2013/m/msif-atlas-of-ms-2013-report.pdf. 2013.

  22. Sawcer S. The major cause of multiple sclerosis is environmental: genetics has a minor role – no. Mult Scler J. 2011;17(10):1174–5. PubMed PMID: WOS: 000295695100006. English.

    Article  Google Scholar 

  23. Hutchinson M. The major cause of multiple sclerosis is environmental: genetics has a minor role – commentary. Mult Scler J. 2011;17(10):1176. PubMed PMID: WOS: 000295695100007. English.

    Article  Google Scholar 

  24. Taylor BV. The major cause of multiple sclerosis is environmental: genetics has a minor role – yes. Mult Scler J. 2011;17(10):1171–3. PubMed PMID: WOS: 000295695100005. English.

    Article  Google Scholar 

  25. Fleming JO. Helminths and multiple sclerosis: will old friends give us new treatments for MS? J Neuroimmunol. 2011;233(1–2):3–5.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Correale J, Farez M. Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms. J Immunol. 2009;183(9):5999–6012.

    Article  CAS  PubMed  Google Scholar 

  28. Correale J, Farez M, Razzitte G. Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol. 2008;64(2):187–99.

    Article  PubMed  Google Scholar 

  29. Correale J, Farez MF. Parasite infections in multiple sclerosis modulate immune responses through a retinoic acid-dependent pathway. J Immunol. 2013;191(7):3827–37.

    Article  CAS  PubMed  Google Scholar 

  30. Correale J, Farez MF. The impact of parasite infections on the course of multiple sclerosis. J Neuroimmunol. 2011;233(1–2):6–11.

    Article  CAS  PubMed  Google Scholar 

  31. Kuerten S, Angelov DN. Comparing the CNS morphology and immunobiology of different EAE models in C57BL/6 mice – a step towards understanding the complexity of multiple sclerosis. Ann Anat = Anatomischer Anzeiger: Off Organ Anatomische Gesellschaft. 2008;190(1):1–15.

    Article  Google Scholar 

  32. Mix E, Meyer-Rienecker H, Hartung HP, Zettl UK. Animal models of multiple sclerosis–potentials and limitations. Prog Neurobiol. 2010;92(3):386–404.

    Article  PubMed  Google Scholar 

  33. t Hart BA BA, Gran B, Weissert R. EAE: imperfect but useful models of multiple sclerosis. Trends Mol Med. 2011;17(3):119–25.

    Article  Google Scholar 

  34. Constantinescu CS, Farooqi N, O’Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol. 2011;164(4):1079–106. Pubmed Central PMCID: 3229753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Farooqi N, Gran B, Constantinescu CS. Are current disease-modifying therapeutics in multiple sclerosis justified on the basis of studies in experimental autoimmune encephalomyelitis? J Neurochem. 2010;115(4):829–44.

    Article  CAS  PubMed  Google Scholar 

  36. Hasseldam H, Hansen CS, Johansen FF. Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis. Parasite Immunol. 2013;35(3–4):103–8.

    Article  CAS  PubMed  Google Scholar 

  37. Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M, et al. Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol. 2003;15(1):59–69.

    Article  CAS  PubMed  Google Scholar 

  38. Zheng X, Hu X, Zhou G, Lu Z, Qiu W, Bao J, et al. Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. J Neuroimmunol. 2008;194(1–2):107–14.

    Article  CAS  PubMed  Google Scholar 

  39. La Flamme AC, Ruddenklau K, Backstrom BT. Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun. 2003;71(9):4996–5004. Pubmed Central PMCID: 187318.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kuijk LM, Klaver EJ, Kooij G, van der Pol SM, Heijnen P, Bruijns SC, et al. Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation. Mol Immunol. 2012;51(2):210–8.

    Article  CAS  PubMed  Google Scholar 

  41. Donskow-Lysoniewska K, Krawczak K, Doligalska M. Heligmosomoides polygyrus: EAE remission is correlated with different systemic cytokine profiles provoked by L4 and adult nematodes. Exp Parasitol. 2012;132(2):243–8. PubMed PMID: WOS: 000309737900020. English.

    Article  CAS  PubMed  Google Scholar 

  42. Sofronic-Milosavljevic LJ, Radovic I, Ilic N, Majstorovic I, Cvetkovic J, Gruden-Movsesijan A. Application of dendritic cells stimulated with Trichinella spiralis excretory-secretory antigens alleviates experimental autoimmune encephalomyelitis. Med Microbiol Immunol. 2013;202(3):239–49.

    Article  CAS  PubMed  Google Scholar 

  43. Zhu B, Trikudanathan S, Zozulya AL, Sandoval-Garcia C, Kennedy JK, Atochina O, et al. Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis. Clin Immunol. 2012;142(3):351–61. Pubmed Central PMCID: 3288504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wu Z, Nagano I, Asano K, Takahashi Y. Infection of non-encapsulated species of Trichinella ameliorates experimental autoimmune encephalomyelitis involving suppression of Th17 and Th1 response. Parasitol Res. 2010;107(5):1173–88.

    Article  PubMed  Google Scholar 

  45. Walsh KP, Brady MT, Finlay CM, Boon L, Mills KH. Infection with a helminth parasite attenuates autoimmunity through TGF-beta-mediated suppression of Th17 and Th1 responses. J Immunol. 2009;183(3):1577–86. PubMed PMID: WOS: 000268519500013. English.

    Article  CAS  PubMed  Google Scholar 

  46. Wilson MS, Taylor MD, O’Gorman MT, Balic A, Barr TA, Filbey K, et al. Helminth-induced CD19 + CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol. 2010;40(6):1682–96. Pubmed Central PMCID: 3179601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Reyes JL, Espinoza-Jimenez AF, Gonzalez MI, Verdin L, Terrazas LI. Taenia crassiceps infection abrogates experimental autoimmune encephalomyelitis. Cell Immunol. 2011;267(2):77–87.

    Article  CAS  PubMed  Google Scholar 

  48. Gruden-Movsesijan A, Ilic N, Mostarica-Stojkovic M, Stosic-Grujicic S, Milic M, Sofronic-Milosavljevic L. Mechanisms of modulation of experimental autoimmune encephalomyelitis by chronic Trichinella spiralis infection in Dark Agouti rats. Parasite Immunol. 2010;32(6):450–9.

    Article  CAS  PubMed  Google Scholar 

  49. Chiuso-Minicucci F, Van DB, Zorzella-Pezavento SF, Peres RS, Ishikawa LL, Rosa LC, et al. Experimental autoimmune encephalomyelitis evolution was not modified by multiple infections with Strongyloides venezuelensis. Parasite Immunol. 2011;33(5):303–8.

    Article  CAS  PubMed  Google Scholar 

  50. Radovic I, Gruden-Movsesijan A, Ilic N, Cvetkovic J, Mojsilovic S, Devic M, et al. Immunomodulatory effects of Trichinella spiralis-derived excretory-secretory antigens. Immunol Res. 2015;61(3):312–25.

    Article  CAS  PubMed  Google Scholar 

  51. Tundup S, Srivastava L, Harn Jr. DA. Polarization of host immune responses by helminth-expressed glycans. Ann N Y Acad Sci. 2012;1253:E1–13.

    Google Scholar 

  52. Wilson MS, Taylor MD, Balic A, Finney CA, Lamb JR, Maizels RM. Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med. 2005;202(9):1199–212. Pubmed Central PMCID: 2213237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Taylor MD, van der Werf N, Harris A, Graham AL, Bain O, Allen JE, et al. Early recruitment of natural CD4+ Foxp3+ Treg cells by infective larvae determines the outcome of filarial infection. Eur J Immunol. 2009;39(1):192–206.

    Article  CAS  PubMed  Google Scholar 

  54. Tadokoro CE, Vallochi AL, Rios LS, Martins GA, Schlesinger D, Mosca T, et al. Experimental autoimmune encephalomyelitis can be prevented and cured by infection with Trypanosoma cruzi. J Autoimmun. 2004;23(2):103–15. PubMed PMID: WOS: 000223912200002. English.

    Article  CAS  PubMed  Google Scholar 

  55. Wallberg M, Harris RA. Co-infection with Trypanosoma brucei brucei prevents experimental autoimmune encephalomyelitis in DBA/1 mice through induction of suppressor APCs. Int Immunol. 2005;17(6):721–8. PubMed PMID: WOS: 000230346000007. English.

    Article  CAS  PubMed  Google Scholar 

  56. Gong D, Shi W, Yi SJ, Chen H, Groffen J, Heisterkamp N. TGFbeta signaling plays a critical role in promoting alternative macrophage activation. BMC Immunol. 2012;13:31. Pubmed Central PMCID: 3406960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Maizels RM, Pearce EJ, Artis D, Yazdanbakhsh M, Wynn TA. Regulation of pathogenesis and immunity in helminth infections. J Exp Med. 2009;206(10):2059–66. Pubmed Central PMCID: 2757871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wan YY, Flavell RA. TGF-beta and regulatory T cell in immunity and autoimmunity. J Clin Immunol. 2008;28(6):647–59. Pubmed Central PMCID: 2837280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Beer RJ. The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig. Res Vet Sci. 1976;20(1):47–54.

    CAS  PubMed  Google Scholar 

  60. Navarro S, Ferreira I, Loukas A. The hookworm pharmacopoeia for inflammatory diseases. Int J Parasitol. 2013;43(3–4):225–31. PubMed PMID: WOS: 000315975700005. English.

    Article  CAS  PubMed  Google Scholar 

  61. Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S. Hookworm infection. N Engl J Med. 2004;351(8):799–807.

    Article  CAS  PubMed  Google Scholar 

  62. Blount D, Hooi D, Feary J, Venn A, Telford G, Brown A, et al. Immunologic profiles of persons recruited for a randomized, placebo-controlled clinical trial of hookworm infection. Am J Trop Med Hyg. 2009;81(5):911–6.

    Article  CAS  PubMed  Google Scholar 

  63. Pritchard DI, Brown A. Is Necator americanus approaching a mutualistic symbiotic relationship with humans? Trends Parasitol. 2001;17(4):169–72. PubMed PMID: WOS: 000169933900011. English.

    Article  CAS  PubMed  Google Scholar 

  64. Quinnell RJ, Bethony J, Pritchard DI. The immunoepidemiology of human hookworm infection. Parasite Immunol. 2004;26(11–12):443–54. PubMed PMID: WOS: 000227673900003. English.

    Article  CAS  PubMed  Google Scholar 

  65. Geiger SM, Caldas IR, Mc Glone BE, Campi-Azevedo AC, De Oliveira LM, Brooker S, et al. Stage-specific immune responses in human Necator americanus infection. Parasite Immunol. 2007;29(7):347–58. PubMed PMID: WOS: 000247855700003. English.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Palmer ED. Course of egg output over a 15 year period in a case of experimentally induced necatoriasis americanus, in the absence of hyperinfection. Am J Trop Med Hyg. 1955;4(4):756–7. PubMed PMID: WOS: A1955XG09400014. English.

    CAS  PubMed  Google Scholar 

  67. Feary J, Venn A, Brown A, Hooi D, Falcone FH, Mortimer K, et al. Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2009;39(7):1060–8. Pubmed Central PMCID: 2728895.

    Article  CAS  Google Scholar 

  68. Mortimer K, Brown A, Feary J, Jagger C, Lewis S, Antoniak M, et al. Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg. 2006;75(5):914–20. PubMed PMID: WOS: 000242189100025. English.

    CAS  PubMed  Google Scholar 

  69. Maxwell C, Hussain R, Nutman TB, Poindexter RW, Little MD, Schad GA, et al. The clinical and immunologic responses of normal human volunteers to low dose hookworm (Necator americanus) infection. Am J Trop Med Hyg. 1987;37(1):126–34.

    CAS  PubMed  Google Scholar 

  70. Falcone FH, Pritchard DI. Parasite role reversal: worms on trial. Trends Parasitol. 2005;21(4):157–60. PubMed PMID: WOS: 000228286500003. English.

    Article  PubMed  Google Scholar 

  71. Pritchard DI, Blount DG, Schmid-Grendelmeier P, Till SJ. Parasitic worm therapy for allergy: is this incongruous or avant-garde medicine? Clin Exp Allergy. 2012;42(4):505–12. PubMed PMID: WOS: 000301532800005. English.

    Article  CAS  PubMed  Google Scholar 

  72. Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, et al. Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clin Exp Allergy. 2010;40(2):299–306. PubMed PMID: WOS: 000273547500015. English.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Croese J, O’Neil J, Masson J, Cooke S, Melrose W, Pritchard D, et al. A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors. Gut. 2006;55(1):136–7. Pubmed Central PMCID: 1856386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Daveson AJ, Jones DM, Gaze S, McSorley H, Clouston A, Pascoe A, et al. Effect of hookworm infection on wheat challenge in celiac disease–a randomised double-blinded placebo controlled trial. Plos One. 2011;6(3):e17366. Pubmed Central PMCID: 3050888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Fleming JO, Isaak A, Lee JE, Luzzio CC, Carrithers MD, Cook TD, et al. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Mult Scler. 2011;17(6):743–54. Pubmed Central PMCID: 3894910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bager P, Kapel C, Roepstorff A, Thamsborg S, Arnved J, Ronborg S, et al. Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial. Plos One. 2011;6(8):e22346. PubMed PMID: WOS: 000293511900005. English.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. http://clinicaltrials.gov/show/NCT00645749/msif-atlas-of-ms-2013-report.pdf.

  78. Moynagh PN. The roles of Pellino E3 ubiquitin ligases in immunity. Nat Rev Immunol. 2014;14(2):122–31. PubMed PMID: WOS: 000331022400014. English.

    Article  CAS  PubMed  Google Scholar 

  79. Fleming JHL, Maksimovic J, Nace S, Luzzio C, Koehn M, Ritter A, Risa T, Lawler B, Maser A, Mundt P, Rolak L, Cook T, Field A, Fabry Z. Clinical Trial of Helminth-induced Immunomodulatory Therapy (HINT 2) in relapsing-remitting multiple sclerosis AAN annual meeting. Philadelphia: Neurology; 2014. p. P3.149.

    Google Scholar 

  80. Benzel F, Erdur H, Kohler S, Frentsch M, Thiel A, Harms L, et al. Immune monitoring of Trichuris suis egg therapy in multiple sclerosis patients. J Helminthol. 2012;86(3):339–47.

    Article  CAS  PubMed  Google Scholar 

  81. Lammie PJ, Katz SP. Immunoregulation in experimental filariasis. II. Responses to parasite and nonparasite antigens in jirds with Brugia pahangi. J Immunol. 1983;130(3):1386–9.

    CAS  PubMed  Google Scholar 

  82. Graham SP, Trees AJ, Collins RA, Moore DM, Guy FM, Taylor MJ, et al. Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in a bovine model of onchocerciasis. Infect Immun. 2001;69(7):4313–9. Pubmed Central PMCID: 98501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Rosche B, Werner J, Benzel FJ, Harms L, Danker-Hopfe H, Hellweg R. Serum levels of brain-derived neurotrophic factor (BNDF) in multiple sclerosis patients with Trichuris suis ova therapy. Parasite. 2013;20:55. Pubmed Central PMCID: 3866952. Niveaux seriques du facteur neurotrophique derive du cerveau (BNDF) chez des patients atteints de sclerose en plaques sous therapie par les oeufs de Trichuris suis.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Rosche B, Wernecke KD, Ohlraun S, Dorr JM, Paul F. Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial. Trials. 2013;14:112. Pubmed Central PMCID: 3680966.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Voldsgaard A, Bager P, Kapel C, Roepstorff A, Thamsborg S, Soendergaard H, et al. Trichuris suis ova therapy for relapsing multiple sclerosis – a safety study. Neurology. 2012;78:S30.005. PubMed PMID: WOS: 000303204802022. English.

    Article  Google Scholar 

  86. http://clinicaltrials.gov/show/NCT01470521/msif-atlas-of-ms-2013-report.pdf.

  87. Rook GA, Lowry CA, Raison CL. Hygiene and other early childhood influences on the subsequent function of the immune system. Brain Res. 2015;1617:47–62. doi: 10.1016/j.brainres.2014.04.004.

    Google Scholar 

  88. Vanderlugt CL, Miller SD. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol. 2002;2(2):85–95.

    Article  CAS  PubMed  Google Scholar 

  89. Wammes LJ, Mpairwe H, Elliott AM, Yazdanbakhsh M. Helminth therapy or elimination: epidemiological, immunological, and clinical considerations. Lancet Infect Dis. 2014;14(11):1150–62.

    Article  CAS  PubMed  Google Scholar 

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Tanasescu, R. (2016). Intestinal Parasites and Immunomodulation in Neuroinflammatory Disease. In: Constantinescu, C., Arsenescu, R., Arsenescu, V. (eds) Neuro-Immuno-Gastroenterology. Springer, Cham. https://doi.org/10.1007/978-3-319-28609-9_11

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