Ascariasis

Melissa TorresMonday, December 14, 2009

Defining relationships between humans and ascariasis

OverviewPrevalenceSymptomsAscaris lifecycle

Immunosuppressive activityRole of IL-10Role of PAS-1

Hygiene hypothesisEvolution of the hypothesis and helminths

Future implications

AscariasisMost common helminth

Infecting 25% of the world populationMost prevalent in children

Highest prevalence = 2 – 10 y/oldsHighest intensity = 5 – 15 y/olds*

Intensity due to co-infections

Warm, moist climates

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

Symptoms• May manifest into• Growth retardation• Pneumonitis/ verminous pneumonia• Intestinal obstruction• Hepatobiliary and pancreatic injury• Eosinophilia*

Ascaris lumbricoides

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

Life cycle

Conflicting reportsReports indicating ascariasis

Induced 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.

Immunosuppressive activity1977 discovery of MW of nematode allergen

10,000 – 50,000 MW1986 expanded weight range components

14,000 – 410,000 MWResulting in two distinct components

Lower weight component (PIII) IgE-potentiating activity

Higher weight component (PI) Protective antigen

Immunosuppressive activityIn 1998 immunosuppression is confirmed

For high molecular weight components (PI)

Faquim-Mauro, E.L., & Macedo, M.S.. (1998). The immunosuppressive activity of Ascaris suum is due to high molecular weight components. Clin Exp Immunol; 114: 245-251.

CytokinesIn 2004, cytokines affected

by Ascaris were 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 Ascaris antigens in children exposed to Ascariasis. The Journal of Infectious Diseases; 190: 1338-1346.

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.

Conditioned or Th2 like response

Macedo, M.S., et al. (1998). Immumomudulation induced by Ascaris suum extract in mice: Effect of anti-interleukin-4 an inti-interleukin-10 andtibodies. Scand. J. Immunol; 47: 10-18

Protein component of A. suumIn 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

Ascaris suum. Inflammation Research; 54: 17-21.

PAS-1Further confirmed in 2006

1.Oshiro, T.M., et al. (2006). PAS-1, a protein affinity purified from Ascaris suum worms, maintains the ability to modulate the immune response to a bystander antigen. Immunology and Cell Biology; 84: 138-144.

The goalUsing 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?

The hygiene hypothesisMuch of what is known now is owed to this

hypothesis~1998 – presentAlthough its definition has evolved…

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.

Yasdanbakhsh, M., Kremsner, P.G., and van Ree, R.. (2002). Allergy, parasites, and the Hygiene Hypothesis. Science; 296: 490-494.

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 infectionsMuch is yet to be learned as to the extent of

control

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