Toxoplasmosis Flashcards

1
Q

Name two toxoplasmosis parasites

A

Toxoplasma gondii

Sporozoan- Apicomplexa

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2
Q

What is toxoplasmosis?

What does it infect and when was it first discovered?

A

Intracellular parasite infecting a huge variety of hosts including mammals, reptiles, amphibians, and birds (thought all warm-blooded animals infectable)- primary host is cat?

First discovered in 1908 in a wild rodents and rabbits

Cosmopolitan distribution in human population

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3
Q

When was toxoplasmosis’ medical importance recognised and what does it cause?

A

Its medical importance not recognised until 1939 when it was identified in tissues of congenitally infected infant

Causes a serious opportunistic infection in AIDS and major cause of birth defects in man and other mammals “Toxoplasmosis is considered to be a leading cause of death attributed to foodborne illness in the United States.”

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4
Q

What does Babesia cause?

A

The cause of red water disease in cattle

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5
Q

Name some more apicomplexan parasites and what they are common in

A

Babesia- cause of red water disease cattle

Plasmodium – 2 forms of malaria

Eimeria- common GI protozoal parasite in cattle and birds

Cryptosporidium- common GI protozoal parasite

Toxoplasma gondii

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6
Q

Tell me the following about toxoplasmosis parasites…

  • shape
  • What they can inhabit
  • What they require
  • Replication
A

Shape

Small crescent shaped parasite

Toxo- “bow” Greek

gondii- the North Africa Gundi, first identified host (a north African rodent)

Tachyzoites, (disease causing stage which is ‘bowed) possess a pellicle and subpellicular microtubules (gives the distinctive shape),

What they can inhabit

Can inhabit cytoplasm and nucleus of any nucleated mammalian or avian cell (amphibian / reptile- there is experimental evidence of infection – Stoner and Mannwell, 1969)

What they require

Requires cell to make new proteins so needs to be nucleated

Replication

Replicates within the cell in a parasitophorus vacuole (PV) before rupturing cell and infection of neighbouring cells be found in large numbers in various organs liver, bone marrow, lungs, kidneys brain

A thin layer supporting the cell membrane in various protozoa- seen at the tip

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7
Q

Tell me about the toxoplasma life cycle

A

cat is primary host- where sexual reproduction occurs

Produces oocysts which release spores to the environment

Sporulated oocyst

This is the only diploid stage the rest is haploid

The only miotic division

Rodent digests this –> GI tract –> sporocysts releases –> enter nucleated cell –> division –> Tachyzoites produced –> released as bradyzoites

Causes immune responses which causes release stage to be damaged

Tachyzoite stage  Cyst like bradyzoite stage

Can be life long

Dies or killed and eaten and enter cat

Cat can act as secondary host and repeat all of this

Merogony within the cat (another form of schizogony)

Gametes formed, male and female. Each is haploid which form diploid oocyst which is then shed

The oocyst can be ingested by animals that humans eat

If we eat uncooked met it will infect us, will cause immune response but can’t get rid of all

If cat faeces on veg for instance it can contaminate humans that way

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8
Q

What are the stages of the toxoplasma life cycle seen in the cat?

A

Merizoite in cat enterocyte, rapidly dividing and then enters meiosis

Gamete

Oocyst (red)and sporulated oocysts (black) in intestine

Encysted Bradyzoites in neuron – cat can be a secondary host too

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9
Q

What are the stages of the toxoplasma life cycle seen in the secondary host?

A

NB. All stages are infectious

Rapidly dividing tachyzoites

Slowly dividing (?) bradyzoites- found in tissue cysts

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10
Q

Whats the routine cycle of the toxoplasma?

A

Cats the definitive host (here sexual replication of Toxoplasma gondii takes place)

Merogony replication of merozoites followed by gametogony in cat enterocytes- both forms of schizogony- male and female T. gondii gametes forms and fuse to form diploid oocysts

Replication of merozoites in cat enterocytes (male and female T. gondii gametes formed and fuse to form diploid oocysts)

Oocysts shed in faeces and undergo meiosis in the environment giving eight haploid sporozoites. (All other stages are haploids other than the oocyst)

In the intermediate host (in most cycles rodents), asexual replication occurs.

  • Acute infection tachyzoites (rapidly replicating forms) that disseminate throughout the body.
  • chronic infection- tachyzoites differentiate (driven by host immune response) to slow-growing bradyzoites within tissue cysts

Ingestion of tissue cysts by cats, re-initiating the sexual phase of the life cycle (cats can also act as secondary hosts)

Oocysts survive in the environment for long periods of time, can sporulate and contaminate food and water.

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11
Q

What are some other toxoplasma hosts?

How do they become infected?

A

Many animals serve as intermediate hosts,

including human and farm animals-these become infected by

  1. eating undercooked meat containing tissue cysts
  2. ingesting sporulated oocysts in contaminated water and food
  3. congenital infection. - blood transfusion- tissue transplantation
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12
Q

Why is toxoplasma possibly one of the most widespread parasites in the world?

A

Cats release millions of oocysts after ingesting only one bradyzoite or one tissue cyst

Tens of thousands of tissue cysts may be present in one infected mouse (or other second host)

Sporulated oocysts survive for long periods under most ordinary environmental conditions.

Invertebrates such as flies, cockroaches, dung beetles and earthworms can mechanically spread these oocysts and carry them to food (vegetables etc)

Congenital infection can occur in cats (and secondary host), congenitally infected kittens can produce oocysts for contamination.

Infection rates in cats reflect the rate of infection in local avian and rodent populations as they serve as prey for cats

Huge range of secondary hosts

T. gondii may survive in intermediate host lifelong as tissue cysts- all edible portions of animal can harbour viable T.gondii. and all stages are infectious

Organ transplantation and blood transfusion: from implantation of an organ or bone marrow from an infected donor or from latently infected person

Usually doesn’t kill either of its hosts

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13
Q

Can Tachyzoites induce both cell mediated and humoral responses?

A

Yes

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14
Q

T. gondii invades host cells lives in intracellular niche- protected from much of the immune system, further the CNS shows immune restriction…

What does it cause?

A
  1. Causes a modified host lipid membrane to surround the parasite, the parasitophorous vacuole (PV)
  2. Inhibits apoptosis in host cell
  3. Prevents lysosomal fusion with the PV
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15
Q

Specific parasite organelles, called the micronemes, rhoptries and dense granules, contain proteins that alter host cell function –

What does it cause?

A
  1. cause a modified host lipid membrane to surround the parasite, the parasitophorous vacuole (PV).
  2. Inhibits apoptosis in host cell
  3. prevents lysosomal fusion with the PV. The membrane of PV contains parasite specific nutrient transporters
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16
Q

What is the “Host manipulation hypothesis”?

Tell me about it

A

“Host manipulation hypothesis”

T. gondii infected rats have a decreased aversion to cat urine and increased reaction times

epigenetic remodelling of neurons Jia et al., 2013

(Hypomethylation of arginine vasopressin-related genes in the medial amygdala. histone-lysine acetylation in cortical astrocytes)

amygdala - a primary role in the processing of memory, decision-making, and emotional reactions especially aggression and fear – mice show less fear of cats

17
Q

Global toxoplasmosis

A

In UK and USA it is estimated 16-40% seropositivity,

50-80% humans are infected in Central and South America

~4000 cases of congenital toxoplasmosis occur in each year in USA (3rd leading cause of food-borne deaths in USA)

In 1995, the world’s largest outbreak of waterborne toxoplasmosis occurred Canadian province of British Columbia, with 100 acute cases and 12 congenital cases

18
Q

What do Tachyzoites activate?

A

Tachyzoites activate a potent immune response that eliminates most of the

parasites, however, some escape and convert in to bradyzoites

19
Q

In immunocompetent humans, postnatal toxoplasmosis appears as what? What are the symptoms?

A

Immuno-competent humans, postnatal toxoplasmosis is either unapparent or mild

(Cervical lymphadenopathy, fever, joint pain, headache, and tiredness)

20
Q

What does toxoplasmosis clinical disease occur in?

A

Clinical disease occurs in immuno-compromised individuals or were congenital

here effects depend on the stage of pregnancy of expectant mother

21
Q

How is the growth of the bradyzoites effected in immuno-compromised individuals?

A

In immuno-compromised individuals (AIDS, Steroids) disseminated toxoplasmosis- the growth of the bradyzoites continues

22
Q

Tell me about the pathogenesis of toxoplasmosis

A

early-stage destruction of cells (Cell rupture due to mechanical pressure created by numbers of parasites in cells)

later stages due to hypersensitivity and foci of inflammation

23
Q

There are many organ deaths, most pathological are intracerebral lesions. Tell me about what happens and the symptoms

A

many organ defects- Most pathological are Intracerebral lesions

Death of bradyzoites causes an intense hypersensitive inflammatory reaction

Encephalitis headache, disorientation, drowsiness, convulsions coma- death

24
Q

Tell me about congenital toxoplasmosis…

A

Mother infected during pregnancy, - transplacental infection

Generalised infections in the foetus and placenta. Later, localise in the CNS

Still births and spontaneous abortions

Some congenitally infected infants are asymptomatic at birth but can develop clinical signs later

(Slower neurological and mental development and late chorioretinitis)

25
Q

The severity of congenital infection depends on what?

A

Severity of congenital infection depends upon stage of pregnancy when infected

  • Spontaneous abortions
  • Hepatic defects
  • Hydrocephalus,
  • Intra-cerebral calcifications,
  • Chorioretinitis
26
Q

The cat parasite is linked to what?

What is there an epidemiological correlation with?

A

Cat parasite linked to mental illness, schizophrenia

Preliminary evidence “suggests” that T. gondii can induce behavioural or personality changes may occur in humans (sex differences)

Epidemiological correlation of infection associated with

  • Schizophrenia
  • Depression
  • Reckless behaviour (car accidents)
  • Epilepsy

T. gondii cysts do modify tyrosine hydroxylase production of neurons

27
Q

What is the treatment for the acute stages of toxoplasmosis?

A