Lecture 20- Toxoplasma gondii Flashcards
Toxoplasma gondi was first seen by who?
Nicolle and Manceaux in 1908
When was the first human case diagnosed?
1923
When was the first disseminated case?
1940
What are the three main lineages with increasing virulence?
Lineage I, II, III
What are the three life stages?
- Tachyzoites
- Bradyzoites (in tissue cysts)
- Oocysts
What are the asexual stages?
- Tachyzoites
- Bradyzoites
What is the sexual stage?
Oocysts
Where does the asexual and sexual stages occur?
- Asexual = intermediate and definitive host
- Sexual = definitive host
____ are dead end hosts
Humans
What are the key elements in the lifecycle?
Cats
Who is the definitive hosts?
Cats
Oocysts can exist in the soil for a long time because?
They have a resilient shell arounf the mechanisms inside
Descrie horizontal transmission
- Intermediate host = ingests sporulated oocysts from contaminanted food or water and maintains the asexual reproductive cycle
- Oocysts can remain active in the soil up to one year
- Cat ingests tissue cysts, oocysts form in cat intestines, sporozoites develop in oocytes which are deposited in feces
- These sporozoites become infectious for 1-5 days after deposition
- Tachyzoites are rapidly dividing in macrophages
- Origin = tissue cysts or oocysts
- Dissemination in macrophages until adaptive immune response stops it and tissue cysts form (persistent form in tissues)
Describe verticle transmission
- Mother to fetus via placental transfer of tachyzoites
- Leads to congenital toxoplasmosis
How do humans get infected?
- Ingestion of tissue cysts with bradyzoites in undercooked or raw meat
- Infective oocysts can be ingested (fecal oral), releasing sporozoites that penetrate the gut wall and disseminate
- Blood transfusion/organ transplants
Worldwide distribution, incidences vary depending on ?
Cultural and social issues
There is a high prevalence where related to undercooked meat?
Northern Canada, Europe
What are the three categories of risk factors?
- Sociodemographic
- Biological
- Lifestyle
What are sociodemographic risk factors?
Increased age, increased warm climate
What are biological risk factors?
- Genetic predisposition (HLA DQ3)
- Immunodeficiency (common oppertunistic infection)
- Strain risk factors
What are Lifestyle risk factors?
- Contaminated food (raw meat with cysts are major source of human infection)
- Lamb and sheep > pork > beef
- Drinking untreated water
- Food habits (vegans and vegetarians less exposure)
- Exposure to cats (the feces)
T. gondii is a _____
Obligate intracellular protozoan
Can infect what as intermediate host?
Can infect all mammals
What does T. gondii infection and Toxoplasmosis mean?
- T. gondii infection = means both asymptomatic and symptomatic infections
- Toxoplasmosis = means symptomatic infection
____ of infections are asymptomatic in immunocompetent hosts
90%
What are symptomatic infections?
- Mononucleosis like disease
- Low grade fever
- Malaise
- Headache
- Cervical lymphadenopathy
What are some complications of T. gondii?
- Encephalitis
- Myocarditis
- Hepatitis
- Pneumonia
Describe the pathogenesis of T. gondii
- No host specificity, able to invade all cell types
- Ability to form tissue cysts that protect it from immune system
- Invasive at any stage of cell cycle
- Outcome of cell invasion dependent on type of cell
- Macrophages phagocytose into a phagosome which fuses with lysosomes and kills parasite
- Other cells = parasite enters a vacuole formed by plasma membrane invagination (PV), PV does not sude with lysosomes and does not acidify
- Toxoplasma cells do not have flagella but glide along host cell surfaces
- Relocation of surface bound molecules on Toxo (micronemes) = association with the cellular sub membranous actomyosin complex
- Attach then enter by apical complex into a PV
- Parasite causes formation of pores in PV
- Host cells infected with parasite undergo changes (changes caused by the parasite and by the immune response)
What are some alterations that occur in the host cells?
- Facilitate parasite nutrient acquisition
- Enhance host cell survival
- Avoidance of strong immune response allowing infection to continue
- Tissue cysts are likely a mechanism by which the parasite avoids interference from the immune system
What are the three special structures found in Apicomplexa?
- Micronemes
- Rhoptries
- Dense granules
What do micronemes do?
They function in cell-cell adhesion, motility, etc
What do Rhoptries do?
Modification of host cell and parasite, secretion only occurs during host cell invasion
Describe infection in immunocompetent individuals
Symptoms vary from short, self-limiting unspecific illness to severe symptoms with prolonged fever, fatigue and retinochoroiditis (predominant symptoms is cervical lymphadenopathy)
Describe infections in immunocompromised patients
- HIV infected patients = increased toxo encephalitis, often result of reactivation of latent infections after rupture of tissue cysts in the CNS
- SOT = increase CNS or pulmonary toxo, usually result of reactivation, usually within 3 months of transplantation
Is it easy or difficult to diagnose pregnant women?
Difficult because need seroconversion
What is congenital toxo?
Acute maternal infection where the tachyzoites transfer from blood to fetus
Risk of congenital toxo increased with?
Gestation time
More severe effects to fetus when infections are?
In early gestation (< week 26)
Describe early gestation infections
Severe disseminated infection with cerebral calcifications, cerebral abscess, retinochoroiditis, hydrocephalus or microcephalus and ascites, may lead to death in utero
Describe late gestation infections
- Baby is usually subclinical (not detectable)
- Neurological and intellectual sequelae can occur after birth in babies who were infected late in gestation
How to manage congenital toxo?
- Prenatal screening can be done to determine if the mother is already infected
- Repeated testing if mother not infected
- Testing of fetus (amniotic fluid), PCR, imaging if mother is symptomatic
- Prenatal treatment if infection found with spiramycin (parasitostatic) and/or pyrimethamine-sulfonamide (parasitocidal)
- Need for long term follow up of children when mother has had toxo = late effects can show up after years
What are some lab diagnostics available?
- Detection of tachyzoites or tissue cysts om body fluids or tissue
- EIA for toxoplasma antibodies
- Detection of parasite DNA (PCR) in body fluids or tissue samples
- PCR is very sensitive and specific
- Acute infection IgM positive or serial specimens (seroconversion)
- EIA sensitive and specific
What is the gold standard for diagnostic?
PCR
Is there a vaccine available?
- Animal vaccinations do exist (for sheep and goats)
- Human vaccination do not exist
What are some behavioural changes seen in rodents?
- Impaired motor performance
- Decreased reaction time
- Increased levels of dopamine
What is the manipulation hypothesis?
Parasite changes the organisms behaviour to benefit further survival and transmission of the parasite (increases chances for entering a feline)
Describe the host-parasite interaction
- Neutrophils have an early role in killing parasite
- Inactive macrophages to prevent killing
- Infected host cells resist apoptosis
- Needs glucose, iron, arginine, ornithine, cholesterol, calcium
- Toxoplasma can take up lysosomes and sequester them = this may be where they acquire iron and cholesterol
- Calcium is taken up from host cell cytosol
- Host cells have their ways of dealing with infection
- Toxoplasma growth is dependent on tryptophan. Depletion of arginine arrests parasite replication and induces the conversion from tachyzoites to bradyzoites
- Antibody production
- MHC I and MHC II presentation important for the adaptive immune response, especially MHC I
- Effective CD4 and CD8 cell activity important for controlling acute infections
- Toxoplasma rapidly overcomes hosts with impaired T cell function (AIDS)
- Interferon gamma produced by T cells (induced by IL-2 from CD4) important for limiting infection
- Infants have lower MHC I expression, dendritic cells are more immature, produce lower amounts of cytokines
Describe intestinal immunity
- Important = route of transmission is through the gut
- Cysts and oocysts susceptible to pepsin and release bradyzoites or sporozoites which are pepsin resistant
- Invasion of the gut epithelial cells, dissemination to lymph and blood
