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  • There are two defined areas as to where ascaris comes in direct contact with mucosal linings. It is known that Treg cells can be preferentially induced at mucosal surfaces, in particular gut and respiratory tract. (32)

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  • 1. Ascariasis
    Melissa Torres
    Monday, December 14, 2009
  • 2. Defining relationships between humans and ascariasis
    Overview
    Prevalence
    Symptoms
    Ascarislifecycle
    Immunosuppressive activity
    Role of IL-10
    Role of PAS-1
    Hygiene hypothesis
    Evolution of the hypothesis and helminths
    Future implications
  • 3. Ascariasis
    Most common helminth
    Infecting 25% of the world population
    Most prevalent in children
    Highest prevalence = 2 – 10 y/olds
    Highest intensity = 5 – 15 y/olds*
    Intensity due to co-infections
  • 4. Warm, moist climates
    Bethony, S.B., et al. (2006). Soil transmitted helminth infections: ascariaisis, trichuriasis, and hookworm. The lancet 2006; 367, 1521-1532
  • 5. Symptoms
    • May manifest into
    • 6. Growth retardation
    • 7. Pneumonitis/ verminous pneumonia
    • 8. Intestinal obstruction
    • 9. Hepatobiliary and pancreatic injury
    • 10. Eosinophilia*
  • Ascarislumbricoides
    Bethony, S.B., et al. (2006). Soil transmitted helminth infections: ascariaisis, trichuriasis, and hookworm. The lancet 2006; 367: 1521-1532.
  • 11. Life cycle
  • 12. Conflicting reports
    Reports indicating ascariasis
    Induced inflamatory response (AHR)
    Suppressed AHR
    Increased versus suppressed AHR
    More cases in which suppression occurs
    Novel genes provide insight…
    Maizels, R.M., et al. (2004). Helminth parasites—masters of regulation. Immunological Reviews; 201: 89-116.
  • 13. Immunosuppressive activity
    1977 discovery of MW of nematode allergen
    10,000 – 50,000 MW
    1986 expanded weight range components
    14,000 – 410,000 MW
    Resulting in two distinct components
    Lower weight component (PIII)
    IgE-potentiating activity
    Higher weight component (PI)
    Protective antigen
  • 14. Immunosuppressive activity
    In 1998 immunosuppression is confirmed
    For high molecular weight components (PI)
    Faquim-Mauro, E.L., & Macedo, M.S.. (1998). The immunosuppressive activity of Ascarissuum is due to highmolecular weight components. Clin Exp Immunol; 114: 245-251.
  • 15. Cytokines
    In 2004, cytokines affected by Ascariswere starting to be confirmed.
    Th2 cytokines
    IL-4
    IL-5
    IL-10
    Th1 cytokine
    IFN-gamma
    Cooper, P.J., Chico, M.E., Sandoval, C., & Nutman, T.B.. (2004). Atopic phenotype is an important determinant of immunoglobulin E-mediated inflammation and expression of T helper cell type 2 cytokines to Ascarisantigens in children exposed to Ascariasis. The Journal of Infectious Diseases; 190: 1338-1346.
  • 16. Th1 and Th2 cytokines
    Romagnani, S.. (2004). The increased presence o fallergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?. Immunology; 112: 352-363.
  • 17. Conditioned or Th2 like response
    Macedo, M.S., et al. (1998). Immumomudulation induced by Ascarissuum extract in mice: Effect of anti-interleukin-4
    an inti-interleukin-10 andtibodies. Scand. J. Immunol; 47: 10-18
  • 18. Protein component of A. suum
    In 2005, PAS-1 was a strong candidate as a suppressive protein component
    Oshiro, T.M., Macedo, M.S., & Macedo-Soares, M.F.. (2005). Anti-inflammatory activity of PAS-1, a protein component of Ascarissuum. Inflammation Research; 54: 17-21.
  • 19. PAS-1
    Further confirmed in 2006
    Oshiro, T.M., et al. (2006). PAS-1, a protein affinity purified from Ascarissuum worms, maintains the ability to modulate the immune response to a bystander antigen. Immunology and Cell Biology; 84: 138-144.
  • 20. The goal
    Using what we know
    It has been demonstrated that nullifying T-cell activity can “cure” chronic helminth infection.
    By allowing immune system to operate at full potential
    Are there trade-offs?
  • 21. The hygiene hypothesis
    Much of what is known now is owed to this hypothesis
    ~1998 – present
    Although its definition has evolved…
  • 22. By definition:
    A hypothesis that states that exposure to allergens in the environment early in life reduces the risk of developing allergies by boosting immune system activity.
    Conversely, relatively clean environment in early life would sway the immune system towards allergy-promoting responses.
  • 23. Yasdanbakhsh, M., Kremsner, P.G., and van Ree, R.. (2002). Allergy, parasites, and the Hygiene Hypothesis. Science; 296: 490-494.
  • 24. Before a “cure”
    We need to think about the trade off:
    Increase in chronic inflammatory diseases
    Like rheumatoid arthritis
    There should be consideration of controlling infections
    Much is yet to be learned as to the extent of control
  • 25. Bibliography
    Working bibliography
    Altman, D.M.. (2008). Review on helminths, immune modulation and the hygiene hypothesis; Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology; 126: 1-2.
    Bethony, S.B., et al. (2006). Soil transmitted helminth infections: ascariaisis, trichuriasis, and hookworm. The lancet 2006; 367: 1521-1532.
    Carvalho, L., et al. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Mechanisms underlying helminth modulation of dendritic cell function. Immunology; 126: 1-2.
    Cooke, A.. (2008). Review series on helminthes, immune modulation and the hygiene hypothesi: How might infection mogulate the onset of type 1 diabetes?. Immunology; 126: 12-17.
    Cooper, P.J., Chico, M.E., Sandoval, C., & Nutman, T.B.. (2004). Atopic phenotype is an important determinant of immunoglobulin E-mediated inflammation and expression of T helper cell type 2 cytokines to Ascarisantigens in children exposed to Ascariasis. The Journal of Infectious Diseases; 190: 1338-1346.
    Crompton, D.W.T.. (2001). Ascarisand Ascariasis. Advances in Parasitology; 48: 285-375.
    Faquim-Mauro, E.L., & Macedo, M.S.. (1998). The immunosuppressive activity of Ascarissuum is due to high molecular weight components. Clin Exp Immunol; 114: 245-251.
    Fincham, J.E., et al. (2007). Ascaris, co-infection and allergy: the importance of analysis based on immunological variables rather than egg excretion. Transactions of the Royal Society of Tropical Medicine and Hygiene; 101: 680-682.
    Geha, R.S., Jabara, H.H., & Brodeur, S.R.. (2003). The regulation of immunoglogulin E class-switch recombination. Immunology; 3: 721-732.
    Haburchak, D.R.. (2008, September 12). Ascariasis. Emedicine. Retrieved September 18, 2009 from http://emedicine.medscape.com/article/212510
    Hotez…Forgotten people, Forgotten diseases.
    Hogarth-Scott, R.S.. (1967). The molecular weight range of nematode allergens. Immunology; 13: 535-537.
    Itami, D.M., et al. (2005). Modulation of murine experimental asthma by Ascarissuumcomponents. Clinical and Experimental Allergy; 35: 873-879.
  • 26. Jackson, J.A., et al. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Immunity against helminthes and immunological phenomena in modern human populations; coevolutionary legacies?. Immunology; 126: 18-27.
    Kennedy, M.W., Qureshi, F.. (1986). Stage-specific secreted antigens of the parasitic larval stages of the nematode Ascaris. Immunology; 58: 515-522.
    Lima, C., et al. (2002). Eosinophilic inflammation and airway hyper-responsiveness are profoundly inhibited by a helminth (Alscarissuum) extract in a murine model of asthma. Clinical and Experimental Allergy; 32: 1659-1666.
    Lochnit, G., et al. (1998). Structural elucidationandmonokine-inducing activity of two biologically active zwitterrionicglycosphingolipids derived from porcine parasitic nematode Ascarissuum. The Journal of Biological Chemistry; 371 (1): 466-474.
    Maizels, R.M., et al. (2004). Helminth parasites—masters of regulation. Immunological Reviews; 201: 89-116.
    Matricardi, P.M., et al. (2002). Hay fever and asthma in relation to markers of infection in the United States. J Allergy ClinImmunol; 110 (3): 381-387.
    Oshiro, T.M., Macedo, M.S., & Macedo-Soares, M.F.. (2005). Anti-inflammatory activity of PAS-1, a protein component of Ascarissuum. Inflammation Research; 54: 17-21.
    Oshiro, T.M., et al. (2006). PAS-1, a protein affinity purified from Ascarissuum worms, maintains the ability to modulate the immune response to a bystander antigen. Immunology and Cell Biology; 84: 138-144.
    Peng, W., Zhou, X., & Gasser, R.B.. (2003). Ascaris egg profiles in human faeces: biological and epidemiological implications. Parasitology; 127: 283-290.
    Platts-Mills, T.A.E. et al. (2005). Is the hygiene hypothesis still a viable explanation for the increased prevalence of asthma?. Allergy; 60 (79): 25-31.
    Romagnani, S.. (2004). The increased presence o fallergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?. Immunology; 112: 352-363.
    Rook, G.A.W.. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: The broader implications of the hygiene hypothesis. Immunology; 126: 3-11.
    Santra, A., et al. (2001). Serodiagnosis of ascariasis with specific IgG4 antibody and its use in an epidemiological study. Transactions of the Royal Society of Tropical Medicine and Hygiene; 95: 289-292.
    Schaub, B., Lauener, R., von Mutus, E.. (2006). The many faces of the hygiene hypothesis. J Allergy ClinImmunol; 117 (5): 969-977.
    Sherman, S.C., & Weber, J.M.. (2005). Visual Diagnosis in Emergency Medicine: The CT diagnosis of ascariasis. The Journal of Emergency Medicine; 28 (4): 471-472.
    Shultz, M.G.. (1982). Ascariasis: nutritional Implications. Review of Infectious Diseases; 4: 815-820.
    Silva, S.R., et al. (2006). Immunosuppressive components of AscarisSuum down-regulate expression of costimulatory molecules and function of antigen-presenting cells via an IL-10-mediated mechanism. Eur. J. Imunnol.; 36: 3227-3237.
    Van Riet, E., Hartgers, F.C, Yazdanbakhsh, M.. (2007) Chronic helminth infections induce immunomodulation: Consequences and mechanisms. Immunobiology; 212: 475-490.
    Von Hertzen, L., Haahtela, T.. (2006). Disconnection of man and the soil: Reason for the asthma and atopy epidemic ?. J AllgeryClinImmunol; 117 (2): 334-344.
    Williams, D., Burke, G., & Hendley, O.J.. (1974) Brief Clinical and Laboratory Observations: Ascariasis: A family disease. The Journal of pediatrics; 853-854
    Yang, J., et al. (1995). The structure of Ascariasis hemoglobin domain I at 2.2 resolution: Molecular features of oxygen avidity. Proc. Natl. Acad. Sci. USA; 92: 42224-4228.
    Yasdanbakhsh, M., Kremsner, P.G., and van Ree, R.. (2002). Allergy, parasites, and the Hygiene Hypothesis. Science; 296: 490-494.
    Wiess, S.T.. (2001) Parasites and asthma/allergy: What is the relationship?. J Allergy clinImmunol; 105 (2): 205-210.