Gut nematodes Flashcards
How do we currently treat gut-dwelling nematodes?
- drugs don’t prevent reinfection
- drug resistance developing
- need immunotherapy
- no vaccines
nice
What are the main species of gut-dwelling nematode?
Trichuris trichura - Whipworm
Ascaris lumbricoides - Roundworm
Anclyostoma duodenale - Hookworm
Necator Americanus - Hookworm
what is the prevalence of gut-dwelling nematodes like?
Very high
children born in endemic areas harbour worms most of their lives due to constant repeated exposure
Biological features of nematode infections
- long-term persistence - chronic
- elicit immunity only after years
- complex life cycle
- aggregated distribution
- predisposition to infection
Which nematode effects educational achievment?
Trichuris trichiura - whipworm
Symptoms associated with high intensity of nematode infection
Anaemia, abs pain, Colitis, Diarrhoea
Rare - finger clubbing and rectal prolapse
What are immunoepidemiological studies?
immune factors controlling patterns of infection in community
What is the epidemiology of gut-dwelling nematode infections?
- they are not normally distirbuted - overdispersed!
- Prevalence high in children (geophagia)
- There is a predisposition to infection
Why are worms more prevalent in children
acquired immunity over time
Why do we study immunity to infection?
Diagnosis
Control - identify candidate antigens
Understanding - types of IR involved in immunity
how would you conduct a GI nematode field study?
- select population (100-200)
- Estimate current intensity of infection
- blood samples pre- and post treatment
- assess reinfection levels over 1-2 years
- analyse peripheral IRs
Evidence for acquired immunity?
human trichuriasis - T. Trichirua
Infects 1/5
we actually have a predisposition to worm infection
Hookworm infection stats
average worm load is 40 worms
each worm casues 0.1ml blood loss per day
5.4 M litres blood loss/day worldwide
What is a Hookworm’s latin name and where are they prevalent
Necator Americanus
Papua New Guinea
What is the evidence for acquired immunity in hookworms?
Correlation between high IgE and low parasite weight and fecundity
Resistance associated with IL-5
What is the global incidence for gut dwelling nematodes?
10000M
What 4 species of intestinal nematodes in rodents do we study in the lab?
Nippo
H. poly
Trichinella Spriallis
Trichuris mursis
Each have unique life cycle
What are the important differences between the rodent parasites?
- Trichinella and Nippo expelled from mouse within weeks
- H. poly primary infection chronic. Studies on protective immunity use a challenge model - readily expelled
- Trichuris - ability to expel stain dependent
What is the role of T cells in intestinal helminths?
- Despite differences in effector mechanisms, they have common underlying T cell regulation.
- Central role for CD4+ T cells in resistance - adoptive transfers, in vivo depletions
Which parasite is the most useful lab model in human
Trichuris trichirua - host strain variation in ability to expel parasite, therefore study IR involved acute and chronic infection
Which Th cells make gamma interferon
Th1, not Th2
Which Th cell is important in resistance in T. muris (mice)
Th2 - it protects against gut-dwelling helminths
What is the significance of IL-4 and IL-13 in Trichiuris infection
- produced by T cells
- IL-4 KO can’t make Th2 so susceptible to infection
- Same with IL-13 KO mice
Is IL-4 important in all the lab models of nematodes?
In trichiruis yes, also important in trichinella and H.poly
Not in nippo