Lecture 3- Taxoplasma gondii

Question 1

What family is taxoplasma gondii in?

Answer 1

Apicomplexan family- so has an apical complex and uses its apical complex and organelles within it to invade cells

Question 2

What kind of parasite is it? Where does it like to live?

Answer 2

Obligate intracellular protozoan parasite. It doesn’t spend any time living in particular stages outside cells, likes living inside cells

Question 3

What does the family include?

Answer 3

Plasmodium

Question 4

What organisms does it infect?

Answer 4

Infects almost any warm blooded mammal or bird

affects 12-80% of the human population, depending on where you live

Question 5

Incidence of seropositivity

Answer 5

They take samples of blood and see if they have antibodies for this parasite. So shows how much of population has been infected with toxoplasma.
estimates that 22.5% in USA 12 yrs and over have been infected.
In some populations up to 95% have!

Question 6

If you have antibodies against Toxoplasma in your blood what does that show?

Answer 6

Shows you have been infected with it at some point. Very likely you are still infected due to their lifecycle

Question 7

History of toxoplasma

Answer 7

-Discovered in desert rodent called gundi (1908)
-then found in child, and carnivores, then people who ate meat, then in cat faeces by 1970,
then life cycle worked out in 1970 by William Hutchison

Question 8

What did William Hutchison demonstrate?

Answer 8

Toxoplasma gondii was a parasite of cats which shed oocysts in faeces

Question 9

T gondii life cycle

Answer 9

Definitive host = cat
When cat becomes infected, they release unsporulated (uninfectious) oocysts passed in faeces. Because these parasites invade the epithelial cells of the cat intestine and oocytes shed off in poo.
Then in external environment they sporulate. Contain the next infective stage (sporisolite?).
These are present in soil etc., intermediate hosts will ingest it (warm blooded animals that eat it).
Then humans get infected via contaminated food and water. Humans can also be infected by carnivorous phase of life cycle by the oocytes ingested by animal or human bursting out and infecting gut epithelium. Or humans eating meat contaminated with bradyzoite stage.

Question 10

How are T gondii transmitted from mother to child?

Answer 10

Tachyzoite transmitted through placenta, congenital transmission, can damage babby

Question 11

Detailed life cycle

Answer 11

1. felines ingest oocytes(containing sporozoites) or tissues infected with bradyzoite cysts
2. These bust out of custs and invade gut
3. Both forms differentiate into male and female gametes and after fertilisation become oocysts containing sporozoites.
4. Any warm blooded animal eats these and sporozoites released into gut.
5. They differentiate into tachyzoite stage and disseminate throughout body, invading cells and become bradyzoite cysts
6. If another animal eats infected tissue, bradyzoites released into gut, differentiate back into tachyzoites and disseminate where they become bradyzoite cysts again.
7. If a bradyzoite cyst is ingested by a cat, the bradyzoites invade the gut and differentiate into male and female gametes and then become oocysts again

Question 12

What happens if another warm blooded animal eats infected tissue?

Answer 12

If another animal eats infected tissue, bradyzoites released into gut, differentiate back into tachyzoites and disseminate where they become bradyzoite cysts again.

Question 13

What happens if a bradyzoite cyst is ingested by a cat?

Answer 13

If a bradyzoite cyst is ingested by a cat, the bradyzoites invade the gut and differentiate into male and female gametes and then become oocysts again

Question 14

Why are they called bradyzoites?

Answer 14

brady means slow. They have slow turnover rate

tachyzoite=fast dividing

Question 15

Describe sexual stage of T. gondii

Answer 15

• In definitive host (cat)
• In intestine
• Oocysts form in intestinal epithelium
• Unsporulated oocysts shed in faeces (3-18d)
• Sporulate within 3 week period
• Contaminate water, soil, food
• Very stable especially in warm and humid environments

Question 16

Asexual stage (tachyzoite)

Answer 16

• Intermediate hosts
• rapid intracellular growth and accumulation
• targets almost any nucleated cell
• secreted into blood stream
• causes acute disease (parasitemia)
• limited by immune response and transformation into cyst-forming bradyzoites

Question 17

Asexual stage (bradyzoite)

Answer 17

• Intermediate hosts
• Slow reproduction rate
• Form cysts in neural and muscular tissue
• persist and cause Chronic Disease
• If immunocompromised: can cause acute encephalitis

Question 18

How does the toxoplasma parasite move?

Answer 18

It glides. Complex molecular motor. Does not extend pseudopod extensions, it has intricate linear motor system which is sandwiched between the parasite’s PM and a pair of membranes known as the inner membrane complex. Use actin and myosin to link to trans-membrane adhesive proteins.

Question 19

Why has it been studied as model organism?

Answer 19

Readily genetically manipulated. (malaria is difficult to manipulate)

Question 20

Briefly how does it invade?

Answer 20

Attachment
Apical attachment
Turns on motor complex
Orientates
Rhoptry discharge, secretes
Activates molecular motor and parasite moves into the cell.
(into parasitic vacuole not cytoplasm)

Question 21

What measurements are used to tell how significant a health issue the parasite is?

Answer 21

DALY=YLL+YLD
DALY= Disability Adjusted Life year
YLL= Years lost to mortality
YLD= No. of years lived with disability

Question 22

What are the clinical manifestationd of toxoplasma?

Answer 22

• usually asymptomatic
• outbreaks occasionally
• short incubation period 4-21d
• focal lymphoadenopathy
• flu-like symptoms
• altered behaviour

Question 23

Taxoplasmosis: immuno-compromised patients cause what?

Answer 23

• reactivation of latent disease
• fatal pneumonia common
• ocular problems
• encephalitis, coma and death

Question 24

Why is toxoplasma so high in France?

Answer 24

Because they like eating rare meat so higher chance of ingestion

Question 25

Vertical transmission (infants) effects?

Answer 25

Spectrum of disease:
Vision problems
Premature birth
Hydrocephalus and CNS problems
Miscarriage/still born

Question 26

How does the time the mother gets infected affect the severity?

Answer 26

The earlier the mother gets infected during pregnancy, the more severe the problems are to fetus usually
(pregnant women should stay away from cat litter tray)

Question 27

What causes the parasite to differentiate into the bradyzoite cysts stages?

Answer 27

It is probable that it is actually the host immune system trying to control the parasite that causes them to differentiate into the bradyzoite cysts stages- a certain type of immune response called Th1 response- IFN-gamma

This immune response keeps the infection in check and dormant

Question 28

How does Toxo help the hosts immune response?

Answer 28

Th1 response secreted IFN-gamma which keeps parasite in check and dormant.
In fact Taxo secretes a molecule that enhances a Th1 response.
Cyclophilin 18

Question 29

Why does toxo help the hosts immune response?

Answer 29

The parasite helps the immune response to slow itself down so it doesn’t kill the host and can survive

Question 30

What altered behaviour do infected people exhibit?

Answer 30

People take more risks and have slower reaction times.
Infected people more than twice as likely to be in car crashes.
Rats become more attracted to cats, should be scared of them

Question 31

How does toxoplasma influence sex ratios?

Answer 31

women who are seropositive have more sons than unifected women,
Mice have more males
Theory is that males are known to roam more than females so will transmit the infection further. But unsure

Question 32

Treatment

Answer 32

Suldonamides and pyrimethamine.
Spiramycin to reduce congenital transmission
Is a live vaccine for sheep but no vaccine for humans
No good drugs that target the encysted bradyzoites that live inside you