Lecture 3- Taxoplasma gondii Flashcards
What family is taxoplasma gondii in?
Apicomplexan family- so has an apical complex and uses its apical complex and organelles within it to invade cells
What kind of parasite is it? Where does it like to live?
Obligate intracellular protozoan parasite. It doesn’t spend any time living in particular stages outside cells, likes living inside cells
What does the family include?
Plasmodium
What organisms does it infect?
Infects almost any warm blooded mammal or bird
affects 12-80% of the human population, depending on where you live
Incidence of seropositivity
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!
If you have antibodies against Toxoplasma in your blood what does that show?
Shows you have been infected with it at some point. Very likely you are still infected due to their lifecycle
History of toxoplasma
-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
What did William Hutchison demonstrate?
Toxoplasma gondii was a parasite of cats which shed oocysts in faeces
T gondii life cycle
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.
How are T gondii transmitted from mother to child?
Tachyzoite transmitted through placenta, congenital transmission, can damage babby
Detailed life cycle
- felines ingest oocytes(containing sporozoites) or tissues infected with bradyzoite cysts
- These bust out of custs and invade gut
- Both forms differentiate into male and female gametes and after fertilisation become oocysts containing sporozoites.
- Any warm blooded animal eats these and sporozoites released into gut.
- They differentiate into tachyzoite stage and disseminate throughout body, invading cells and become bradyzoite cysts
- If another animal eats infected tissue, bradyzoites released into gut, differentiate back into tachyzoites and disseminate where they become bradyzoite cysts again.
- 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
What happens if another warm blooded animal eats infected tissue?
If another animal eats infected tissue, bradyzoites released into gut, differentiate back into tachyzoites and disseminate where they become bradyzoite cysts again.
What happens if a bradyzoite cyst is ingested by a cat?
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
Why are they called bradyzoites?
brady means slow. They have slow turnover rate
tachyzoite=fast dividing
Describe sexual stage of T. gondii
- 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
Asexual stage (tachyzoite)
- 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
Asexual stage (bradyzoite)
- Intermediate hosts
- Slow reproduction rate
- Form cysts in neural and muscular tissue
- persist and cause Chronic Disease
- If immunocompromised: can cause acute encephalitis
How does the toxoplasma parasite move?
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.
Why has it been studied as model organism?
Readily genetically manipulated. (malaria is difficult to manipulate)
Briefly how does it invade?
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)
What measurements are used to tell how significant a health issue the parasite is?
DALY=YLL+YLD
DALY= Disability Adjusted Life year
YLL= Years lost to mortality
YLD= No. of years lived with disability
What are the clinical manifestationd of toxoplasma?
- usually asymptomatic
- outbreaks occasionally
- short incubation period 4-21d
- focal lymphoadenopathy
- flu-like symptoms
- altered behaviour
Taxoplasmosis: immuno-compromised patients cause what?
- reactivation of latent disease
- fatal pneumonia common
- ocular problems
- encephalitis, coma and death
Why is toxoplasma so high in France?
Because they like eating rare meat so higher chance of ingestion
Vertical transmission (infants) effects?
Spectrum of disease: Vision problems Premature birth Hydrocephalus and CNS problems Miscarriage/still born
How does the time the mother gets infected affect the severity?
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)
What causes the parasite to differentiate into the bradyzoite cysts stages?
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
How does Toxo help the hosts immune response?
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
Why does toxo help the hosts immune response?
The parasite helps the immune response to slow itself down so it doesn’t kill the host and can survive
What altered behaviour do infected people exhibit?
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
How does toxoplasma influence sex ratios?
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
Treatment
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
