This document discusses ascariasis, a common helminth infection caused by the roundworm Ascaris lumbricoides. It infects over 25% of the world's population, predominantly children. Symptoms can include growth retardation, pneumonia, and intestinal obstruction. The life cycle and immunosuppressive effects of ascariasis are described, including its role in modulating the immune system and suppressing inflammatory responses through molecules like PAS-1. The hygiene hypothesis, which proposes that lack of early childhood exposure to pathogens like helminths may increase risk for allergic diseases, is also discussed.

1. AscariasisMelissa TorresMonday, December 14, 2009

2. Defining relationships between humans and ascariasisOverviewPrevalenceSymptomsAscarislifecycleImmunosuppressive activityRole of IL-10Role of PAS-1Hygiene hypothesisEvolution of the hypothesis and helminthsFuture implications

3. AscariasisMost common helminthInfecting 25% of the world populationMost prevalent in childrenHighest prevalence = 2 – 10 y/oldsHighest intensity = 5 – 15 y/olds*Intensity due to co-infections

4. Warm, moist climatesBethony, S.B., et al. (2006). Soil transmitted helminth infections: ascariaisis, trichuriasis, and hookworm. The lancet 2006; 367, 1521-1532

5. SymptomsMay manifest into

6. Growth retardation

7. Pneumonitis/ verminous pneumonia

8. Intestinal obstruction

9. Hepatobiliary and pancreatic injury

10. Eosinophilia*AscarislumbricoidesBethony, S.B., et al. (2006). Soil transmitted helminth infections: ascariaisis, trichuriasis, and hookworm. The lancet 2006; 367: 1521-1532.

11. Life cycle

12. Conflicting reportsReports indicating ascariasisInduced inflamatory response (AHR) Suppressed AHRIncreased versus suppressed AHRMore cases in which suppression occursNovel genes provide insight…Maizels, R.M., et al. (2004). Helminth parasites—masters of regulation. Immunological Reviews; 201: 89-116.

13. Immunosuppressive activity1977 discovery of MW of nematode allergen10,000 – 50,000 MW1986 expanded weight range components14,000 – 410,000 MWResulting in two distinct componentsLower weight component (PIII)IgE-potentiating activityHigher weight component (PI)Protective antigen

14. Immunosuppressive activityIn 1998 immunosuppression is confirmedFor 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. CytokinesIn 2004, cytokines affected by Ascariswere starting to be confirmed.Th2 cytokinesIL-4IL-5IL-10Th1 cytokineIFN-gammaCooper, 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 cytokinesRomagnani, 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 responseMacedo, 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. suumIn 2005, PAS-1 was a strong candidate as a suppressive protein componentOshiro, 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-1Further confirmed in 2006Oshiro, 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 goalUsing what we knowIt has been demonstrated that nullifying T-cell activity can “cure” chronic helminth infection.By allowing immune system to operate at full potentialAre there trade-offs?

21. The hygiene hypothesisMuch of what is known now is owed to this hypothesis~1998 – presentAlthough 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.