Transcript No Slide Title

Toxoplasma gondii
• cosmopolitan distribution
• seropositive prevalence rates vary
• generally 20-75%
• generally causes very benign
disease in immunocompetent adults
• tissue cyst forming coccidia
• predator-prey life cycle
• felines are definitive host
• infects wide range of birds and
mammals (intermediate hosts)
Definitive Host
• adult forms
• sexual
reproduction
Intermediate Host
• immature forms
• asexual
reproduction
Typical Isospora Life Cycle in Felines
Typical Isospora Life Cycle in Felines
• fertilization within
infected host cells
• immature oocysts
in feces
• sporulation in
environment (1-4 d)
Tachyzoite Stage
• ingestion of oocysts
• sporozoites penetrate
intestinal epithelium
• rapid intracellular
replication (any cell)
• dissemination via
macrophages
Tachyzoite Stage
• merogony  'merozoites'
• typical apicomplexan
• motile invasive stages
• intracellular replication
• 'binary fission' =
endodyogony
Endodyogony
Tachyzoite Stage
• repeated rounds of
merogony
• acute stage infection
• primarily in reticuloendothelial cells
Bradyzoite Stage
• dormant, slowly replicating
• due to host immune
response
• chronic or latent infection
• tissue cysts primarily in
brain and muscle
Bradyzoite Stage
• dormant, slowly replicating
• due to host immune
response
• chronic or latent infection
• tissue cysts primarily in
brain and muscle
“Fatal Attraction in Rats Infected
with Toxoplasma gondii”
non-infected rats (n=32)
infected rats (n=23)
visits to scented areas
own
neutral
rabbit
cat
From Berdoy et al (2000) Proc. R. Soc. (Biol.) 267:1591
Human
Transmission
• ingestion of sporulated
oocysts (cat feces +
incubation)
• ingestion of zoites
(undercooked meat)
• congenital infection (only
during acute stage)
• organ transplants
• chronic infection in
donor
• immunosuppression
• blood transfusions (only
during acute stage)
Recent Expansion of Toxoplasma
Acquired Postnatal Toxoplasmosis
• 1-2 week incubation period
• acute parasitemia persists for several
weeks until development of tissue cysts
• often asymptomatic (>80%)
• a common symptom is
lymphadenopathy without fever
• occasionally mononucleosis-like
(fever, headache, fatigue, myalgia)
• likely persists for life of patient
• immunosuppression can lead to
reactivation (eg., organ transplants)
Toxoplasmic Encephalitis
• common complication associated
with AIDS during the 1980's
• recrudescence of latent infection
• multifocal disease associated with
immunosuppression
• lesions detectable with CT or MRI
• little spread to other organs
• symptoms include: lethargy, apathy,
incoordination, dementia
• progressive disease  convulsions
Congenital Toxoplasmosis
• 1o infection must occur during or
shortly before pregnancy
• can only occur once
• 1/3 will pass infection to fetus
• incidence ~1 per 1000 births
• severity varies with age of fetus
• move severe early in pregnancy
• more frequent later in pregnancy
• infection can result in: spontaneous
abortion, still birth, premature birth,
or full-term ± overt disease
• typical disease manifestations include:
retinochoroiditis, psychomotor disturbances,
intracerebral calcification, hydrocephaly,
microcephaly
Prevalences of Outcomes
5-10% death
8-10% severe brain and eye damage
10-13% moderate-severe visual
impairment
58-72% asymptomatic at birth, many
developing retino-choroiditis
or mental impairment
Ocular Toxoplasmosis
• retinochoroiditis: likely due
to both active parasite
proliferation and immune
hypersensitivity
• generally a recrudescence-rarely from primary infection
• congenital infection
• 20% exhibit ocular
symptoms at birth
• 82% by adolescence
• most lesions are focal and
self-limiting
• rapidly destructive in AIDS
patients
Ocular
Toxoplasmosis
• retinochoroiditis: likely due
to both active parasite
proliferation and immune
hypersensitivity
• generally a recrudescence-rarely from primary infection
• congenital infection
• 20% exhibit ocular
symptoms at birth
• 82% by adolescence
• most lesions are focal and
self-limiting
• rapidly destructive in AIDS
patients
Diagnosis
• various serological tests
• active (acute) vs chronic
infection
• compare samples at 2 week
intervals
• IgM > IgG;  Ab titers
• seldom by direct parasite
demonstration
• biopsy
• inoculation into mice or cell
culture (only acute stage)
Treatment
 recommended: anti-folates (pyrimethamine + sulfadiazine)
 clindamycin for children
 spiramycin for prophylatic use during pregnancy
Condition Duration
Comments
symptomatic
disease
active retinochoroiditis
asymptomatic
children (<5)
immunocompromised
until symptoms subside
and evidence of immunity
until symptoms subside
+ corticosteriod (antiand evidence of immunity inflammatory)
prevents
3-6 weeks
retinochoroiditis
4-6 weeks after symptoms
subside + continued
+ folinic acid in AIDS
prophylaxis
Prevention
Raw Meat
• cook meat thoroughly
o
o
(66 C, 150 F)
• wear gloves when
handling
• wash hands after
Cat Feces
• clean litter box
•
•
•
•
•
promptly (<24 hr)
wear gloves
keep cat in house
cover sand box
no cats in home
control strays
An Enigma
Several studies show no
correlation between cat
contact and Toxoplasma.
But dog contact is highly
correlated with Toxoplasma
transmission.
Frenkel et al (1995)
AJTMH 53:458