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Flashcards in Parasitology lecture 3 Deck (11):
1

cause of Schistomiasis?

1 - the Schistosoma genus of helminths
2 - primarily the species:
- S.mansoni - africa, s.america
- S.japonicum - china philippines (also in domestic animals so zoonotic - cattle, water buffalo, pigs, dogs)
-S.haematobium - africa and middle east

2

Schistosome life cycle

eggs into water - miracidium - two generations of sporocyst in snails (all flukes have snails as an intermediate host) for about 3 weeks - motile cercaria - attracted to skin secretions and penetrates skin of host - schistosomulum - enters circulation - migrates to ortal vessels of liver to mature into the adult - migrates to mesenteric veins of gut (mansoni and japonicum) or bladder (haematobium) where the males and females mate. major pathological problem is backwash of eggs to the liver rather than into the lumen of the gut/bladder.

3

5 features of Schistosome life cycle

1 - worms pair in liver as juveniles and paired for life. female lives in the male's gynecophoral canal.
2 - eggs have characteristic morphology that is used in taxonomy
3 - the miracidium are highly motile and have only 5-6hrs to find a snail host.
4 - cercaria - approx 200mm long, live 2-3 days, attracted by skin secretions
5 - adult schistosomes may live 20-30 years.

4

overview of pathology in schistosomiasis

1 - morbidity almost entirely due to immunopathological response to the eggs, not the adults
2 - invasion - if they fail to get past the skin (usually avian schistosomes) they cause a cercarial dermatitis called swimmers' itch
3 - acute phase - 4-8weeks, fever headache etc, response to sudden high antigen exposure, corresponds to onset of egg deposition.
4 - chronic phase - characterised by granuloma formation around eggs as the immune system cant clear them so walls them off with macrophages/eosinophils/fibrocytes. probably more than half of eggs fail to be excreted.
5 - in S.haematobium the deposition of eggs is in the bladder, ureters and some in genital organs
6 - s.mansoni and s.japonicum deposit in the walls of the intestine but some are swept back into the liver and get stuck in the portal system too.
7 - eggs secrete antigens and form the focus of T cell mediated recruitment of macrophages, eosinophils, and fibrocytes and subsequently granuloma formation with fibrosis (type 4 delayed hypersensitivity)

5

describe the pathogenesis of the chronic phase in S.haematobium

1 - early stages cause painless haematuria, but eggs may cause intense inflammation
2 - later - inflammation decreases, fibrosis increases. may ulcerate the bladder wall. strong evidence it may predispose to bladder cancer.
3 - concern that female genital schistosomiasis may have a significant impact on health and may be a risk factor in HIV transmission due to broken epithelium. also other STIs.

6

describe the pathogenesis of the chronic stage in S.mansoi and S. japonicum

1 - most severe manifestation is hepatosplenic disease as eggs swept into the presinusoidal capillary bed secrete antigens - CD4 Th2 (IL-4/5/13) recruitment of eosin/macroph/fibroblasts.
- eggs live for 3 weeks in tissues but the granulomas are fibrotic and block blood flow causing portal hypertension. (fibrosis = deposition of collagen)
2 - liver and spleen enlarge, blood shunted and causes oesophageal varices which can rupture causing torrential haematemesis (due to high BP) - can be fatal.

7

immune responses of the host to Schistomiasis

1 - no multiplication within host so increased worm burden via increased infection.
2 - egg causes granuloma formation
3 - adaptive response to the schistosomula formed involves Th2-like response - high IgE production, mast cells and eosinophils.
4 - IgE coats parasite, eosinophils have FceR - ADCC (antibody dependent cell-mediated cytotoxicity)

8

methods of schistosome immune evasion?

can survive 20-30 years (av about 7) so must have lots of effective mechs.
uses host imune system for transmission of eggs into gut lumen.
1 - blocking antibodies - stimulates specific IgE and IgG4. IgG4 seems to have no effector function. also stimulates large non-specific polyclonal IgE response, these bind eosinophile FceR to block binding of specific IgE to sites.
2 - the schistosome tegument - surrounds it, double lipid bilayer. rapidly replaced if damaged, few antigens, most membrane proteins present on inner bilayer. adsorbs host MHC/blood group proteins/antibodies (via Fc)/lipids to appear as 'self'.
3 - anti immune response - loads of mechanisms inc proteases, some of which cleave host IgE.
4 - immunosuppression - produce number of molecules to suppress inc ACTH (adrenocorticotrophic hormone)

9

how is schistosomiasis controlled?

1 - chemotherapy - one dose of off patent praziquantel kills all species but can reinfect.
2 - sanitation and education to prevent eggs entering water (hygenic waste disposal) and prevent collection of likely infected water (sand filter).

Vector control
3 - molluscosides - expensive, continuous, environmental damage
4 - modify environment - change snail breeding environment, improve drainage (eradicated it in some parts of lowland china), remove acquatic plants.
5 - biological control - introduce schistosome resistant snails to replace host (martinique), use crayfish to reduce snail pop.
6 - provide safe water - 40% of the world pop without it. impact other diseases eg giardia, cholera.
7 - vaccinate - not currently available

10

why is it important for macroparasites to prevent host immunity?

Their life cycles require chronic infections unlike microparasites. would go extinct if immunity was acquired as repeated infections are needed to get male and females together to breed. but would go extinct if the host was too susceptible as it would die. hence natural selection favours intermediate levels of pathogenicity.

11

what factors affect parasite population sizes in a host?

1 - parasite density/crowding
2 - host genetics ie immune response and mutations that prevent entry
3 - parasite genetics
4 - host sex differences - men are generally more susceptable possibly as testosterone is immunosuppressive