Gut nematodes

Question 1

How do we currently treat gut-dwelling nematodes?

Answer 1

• drugs don’t prevent reinfection
• drug resistance developing
• need immunotherapy
• no vaccines
  nice

Question 2

What are the main species of gut-dwelling nematode?

Answer 2

Trichuris trichura - Whipworm
Ascaris lumbricoides - Roundworm
Anclyostoma duodenale - Hookworm
Necator Americanus - Hookworm

Question 3

what is the prevalence of gut-dwelling nematodes like?

Answer 3

Very high
children born in endemic areas harbour worms most of their lives due to constant repeated exposure

Question 4

Biological features of nematode infections

Answer 4

• long-term persistence - chronic
• elicit immunity only after years
• complex life cycle
• aggregated distribution
• predisposition to infection

Question 5

Which nematode effects educational achievment?

Answer 5

Trichuris trichiura - whipworm

Question 6

Symptoms associated with high intensity of nematode infection

Answer 6

Anaemia, abs pain, Colitis, Diarrhoea
Rare - finger clubbing and rectal prolapse

Question 7

What are immunoepidemiological studies?

Answer 7

immune factors controlling patterns of infection in community

Question 8

What is the epidemiology of gut-dwelling nematode infections?

Answer 8

• they are not normally distirbuted - overdispersed!
• Prevalence high in children (geophagia)
• There is a predisposition to infection

Question 9

Why are worms more prevalent in children

Answer 9

acquired immunity over time

Question 10

Why do we study immunity to infection?

Answer 10

Diagnosis
Control - identify candidate antigens
Understanding - types of IR involved in immunity

Question 11

how would you conduct a GI nematode field study?

Answer 11

• 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

Question 12

Evidence for acquired immunity?

Answer 12

human trichuriasis - T. Trichirua
Infects 1/5
we actually have a predisposition to worm infection

Question 13

Hookworm infection stats

Answer 13

average worm load is 40 worms
each worm casues 0.1ml blood loss per day
5.4 M litres blood loss/day worldwide

Question 14

What is a Hookworm’s latin name and where are they prevalent

Answer 14

Necator Americanus
Papua New Guinea

Question 15

What is the evidence for acquired immunity in hookworms?

Answer 15

Correlation between high IgE and low parasite weight and fecundity
Resistance associated with IL-5

Question 16

What is the global incidence for gut dwelling nematodes?

Answer 16

10000M

Question 17

What 4 species of intestinal nematodes in rodents do we study in the lab?

Answer 17

Nippo
H. poly
Trichinella Spriallis
Trichuris mursis
Each have unique life cycle

Question 18

What are the important differences between the rodent parasites?

Answer 18

• 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

Question 19

What is the role of T cells in intestinal helminths?

Answer 19

• 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

Question 20

Which parasite is the most useful lab model in human

Answer 20

Trichuris trichirua - host strain variation in ability to expel parasite, therefore study IR involved acute and chronic infection

Question 21

Which Th cells make gamma interferon

Answer 21

Th1, not Th2

Question 22

Which Th cell is important in resistance in T. muris (mice)

Answer 22

Th2 - it protects against gut-dwelling helminths

Question 23

What is the significance of IL-4 and IL-13 in Trichiuris infection

Answer 23

• produced by T cells
• IL-4 KO can’t make Th2 so susceptible to infection
• Same with IL-13 KO mice

Question 24

Is IL-4 important in all the lab models of nematodes?

Answer 24

In trichiruis yes, also important in trichinella and H.poly
Not in nippo