Toxoplasmosis and its Impact on the Nervous System

Question 1

What is Toxoplasma gondii?

Answer 1

Infects multiple Intermediate hosts (warm-blooded mammals)
* Cat → Definitive host through oocysts in faeces
* Infection is common but often benign
* In epithelial cells of small intestine of cat

Question 2

Stage of T. gondii - Tachyzoite

Answer 2

Appearance - crescent-shaped, pointed anterior & rounded posterior

Function - divides asexually

Question 3

Stage of T. gondii - Bradyzoite

Answer 3

Appearance - Spherical cyst that is more prevalent in the nerves + muscles

Function - Cyst cell wall can be destroyed by pepsin or trypsin but is resistant to gastric juices

Question 4

Stage of T. gondii - Sporozoites

Answer 4

• Infects epithelial cells
• Converts to tachyzoites

Question 5

Hosts of T. gondii

Answer 5

Cat faeces
- Intermediate host (unwashed veg or undercooked meat)
- Environmental e.g in the soil
- Blood transfusion/organ transplant
Transplacental

Question 6

Tranmission of T.gondii - Congenital

Answer 6

• Mother to offspring
• Tachyzoites through placenta or milk

Question 7

Tranmission of T.gondii - Organ Transplant

Answer 7

e.g. heart, kidney, liver, bone marrow

Question 8

Tranmission of T.gondii - Faecal-oral

Answer 8

Through cat feces (oocysts)

Question 9

Tranmission of T.gondii - Carnivorism

Answer 9

• Undercooked meat results in bradyzoite survival after cyst wall is degraded by enzymes
• Also can happen with unpasteurised milk

Question 10

Most to least common meats that T. gondii cysts are found

Answer 10

• Highest : pigs, sheep, goats
• Then: free-range poultry, pigeons, farm deer, game animals, dogs
• Then: horses + commercially raised poultry
• Least : Buffaloes, cattle

Question 11

T. gondii is a zoonotic disease in cats - Symptoms + means of infection

Answer 11

• Symptoms: fever, ocular inflammation, anorexia, lethargy, neurological abnormalities
• Cats shed oocysts after ingesting tissue cysts more often than with tachyzoites or oocyst
  • 1 bradyzoite ingested infection = ~1000 oocysts

Question 12

Stages of asexual development in intermediate host

Answer 12

• Tachyzoites (endogeny) in many
  host cell types & some form cysts
• Bradyzoites (slow endogeny) in
  cysts in neural & muscular tissue
  (terminal stage)

Question 13

T. gondii’s prevalence in humans

Answer 13

• Differs from geographical areas - the more meat eaten, the higher the prevalance
• Sabin-Feldman dye test- gold standard (labour
  intensive, need live parasites)
• Many antibody tests are now available

Question 14

Methods of prevention from zoonotic transmission

Answer 14

• Washing hands, fruit + veg
• Only drink treated water
• Wear gloves when gardening
• Clean litter tray to prevent accumulation

Question 15

T. gondii’s effects in humans

Answer 15

• Most cases are asymptomatic
• Lymphadenopathy, encephalitis, sepsis syndrome, myocarditis,
  hepatitis
• Infection prior to 4-6 months before conception may infer protective
  immunity EXCEPT in immunocompromised women e.g. AIDs

Question 16

Ocular Toxoplasmosis

Answer 16

• 0.4/100 000/year in British-born patients
• Symptoms 20-40 years old
• Most common symptom (28-50%)- chorioretinitis (inflamed choroid)
• White wisp appearance
• Recurrent(2/3 symptomatic infections

Question 17

How toxoplasmosis affects the nervous system

Answer 17

• Enters endothelial cells
• Then enters neuron as a cyst]
• Reactivation suppression
• Increases excitatory + decreases inhibitory neurotransmitters
• Leads to seizures

Question 18

Results of toxoplasmosis in the nervous system

Answer 18

• Reduced mental/physical wellbeing in 2
  months following infection
• Risk of suicidal behaviour increased
• Concentration reduced
• Chronic infection - risk of schizophrenia, bipolar
  disorder, addiction, OCD

Question 19

Reason for mental issues from chronic infection - Immune response

Answer 19

• PAMPs (profilin)
• Chronic immune
  response can cause brain inflammation

Question 20

Reason for mental issues from chronic infection - Cyst location

Answer 20

• In dendritic spines could reduce neuron function
• Reduction in function could be linked to schizophrenia

Question 21

Reason for mental issues from chronic infection - Neurotransmitter change

Answer 21

• Reduction of dopamine + increase in norepinephrine &
  serotonin
• In mice - competitive
  binding for dopamine could lead to behaviour change
• May damage dendritic spine