Toxoplasma gondii
Classification
Phylum: Apicomplexa
Class: Sporozoea
Subclass: Coccidia
Order: Eucoccidia
Suborder: Eimeriina
Genus: Toxoplasma
Species: gondii
Toxoplasma gondii
Worldwide distribution
Zoonotic parasite; Toxoplasma is an opportunistic
pathogen.
Infects animals, cattle, birds, rodents, pigs, and sheep.
and humans.
Causes the disease Toxoplasmosis.
Toxoplasmosis is leading cause of abortion in sheep and
goats.
Intracellular parasite.
Final host (Felidae family, cat)
Intermediate host (mammals )
Toxoplasmosis
1. All parasite stages are infectious.
2. Risking group: Pregnant women, meat handlers (food
preparation) or anyone who eats the raw meat
First Described: The organism that was ultimately
named Toxoplasma gondii was first described in
France in 1908 (Nicolle and Manceaux)
Affected Host Species: Cats are the definitive
host and are the only species known to complete
the sexual phase of T. gondii culminating in the
passage of oocysts in feces. Cats and most other
vertebrates can serve as intermediate hosts;
invertebrates can serve as transport hosts by
mechanical carriage of T. gondii oocysts
Toxoplasma gondii exists in three forms
. All parasite stages are infectious
1. Tachyzoites 2. Tissue cysts (bradyzoit)
3- Oocysts
Tachyzoite stage
Rapidly growing stage observed in the early stage of
infection.
(Acute phase) habits in the body fluid.
Crescent-shaped. One end is more pointed than the other
subterminal placed nucleus.
Asexual form.
Multiplies by endodyogeny.
It can infect phagocytic and non-phagocytic, cells.
Bradyzoites
Are slow-growing stage inside the tissue cysts.
Bradyzoites mark the chronic phase of infection.
Bradyzoites are resistant to low pH and digestive
enzymes during stomach passage.
Protective cyst wall is finally dissolved and
bradyzoites infect tissue and transform into
tachyzoites.
Bradyzoites are released in the intestine and are
highly infective if ingested.
Oocysts in the feces of cat
Cat ingests tissue cysts containing bradyzoites.
Gametocytes develop in the small intestine.
Sexual cycle produces the oocyst which is excreted in
the feces.
Oocysts appear in the cat’s feces 3-5 days after
infection by cysts.
Oocysts require oxygen and they sporulate in 1- 5
days.
The Oocyst
• The oocyst is noninfectious before sporulation.
• Unsporulated oocysts are subspherical to spherical.
• Sporulated oocysts are subspherical to ellipsoidal.
• Each oocyst has two ellipsoidal sporocysts.
• Each Sporocyst contains four sporozoites .
• Shedding occurs 3-5 days after ingestion of tissue cysts
• Sporulated oocyst remain infective for months .
Life cycle of T. gondii
ToxoplasmaZygote
Tissue cyst gondii Encapsulation of zygote
within a rigid wall: oocyst
Oocyst
Gametocytes
Multiplication
Bradyzoites infect Merozoites
cells and become
tachyozoites. Cat’s intestinal enterocytes
The life cycle of Toxoplasma can be divided into two stages;
I The asexual cycle with little host specificity i.e., the stage that occurs in sheep,
humans, rodents and birds
II The sexual stage of the life cycle, confined to the intestinal epithelial cells of cats,
which results in the production of oocysts.
The asexual life cycle of Toxoplasma
Tachyzoite stage:
1. Cats shed millions of unsporulated oocysts in their faeces, these take 1-5 days to
sporulate depending on the climatic conditions
2. The sheep ingests a sporulated oocyst
3. In the gut the sporozoites are released and they penetrate the intestinal wall and
migrate via the lymphatic and portal systems
Cats (young strays in particular) are the primary source of infective oocysts as they
shed millions in their faeces.
4. Tachyzoites penetrate host cells and become surrounded by a vacuole –
Toxoplasma gondii can infect cells in the reproductive system, central nervous system,
lung, liver and muscle tissue
5. The tachyzoites multiply asexually by a process called ‘budding’ 6. Once 8 – 16
tachyzoites have accumulated, the cell ruptures and new cells are infected
Some cases result in the death of the host, but more usually the host develops
immunity to the infection and chronic infection is established, which is called the
bradyzoite stage.
Bradyzoite stage:
1. Antibodies are produced by the host’s immune system and any extra cellular
parasites are eliminated
2. The antibodies limit the invasiveness of intracellular tachyzoites to new cells,
resulting in the formation of cysts which are found most frequently in the brain and
skeletal muscle
3. These cysts contain between a few and many thousands of organisms called
bradyzoites, which grow very slowly – this is the latent form. If immunity wanes, cysts
may rupture releasing bradyzoites.
The sexual stage of the life cycle of Toxoplasma
The sexual stage of the life cycle starts when a (usually) young cat ingests food
containing cysts, such as a rodent The walls of the cysts dissolve in the stomach and
small intestine The released bradyzoites penetrate the epithelial cells of the small
intestine and form gametocytes over the 3-15 days following infection The formed
microgametes are released and swim to and penetrate macrogametes The resulting
oocysts, each containing a fertilised gamete, are passed out of the cat and sporulate
within 1 – 5 days.
Transmission
start here
(Sporogony)
Sporulated
Oocyst
(infective)
T. gondii start here
in the
Intermediate
host
start here
(Sporogony)
Direct Life Cycle: T. gondii
Cat to Cat
Direct Life Cycle (homoxenous)
Definitive host = Felids only
Transmission -- fecal-oral, ingestion of oocyst
Invasion -- Sporozoites excyst from oocyst and invade
enterocyte
Asexual reproduction (in intestinal cells)
Endodyogeny AND Merogony
~ 5 cycles
Causes either no or mild pathology in the cat
Some sporozoites invade deep tissues (CNS, muscle, viscera) multiply &
disseminate as tachyzoites, and eventually form bradyzoite cysts
Pathogenesis: Toxoplasma gondii
Intestinal phase in felids → minimal
Systemic disease (extra-Intestinal phase) in felids, paratenic
hosts or humans
Explosive replication of tachyzoites causes:
massive direct destruction of host cells
acute immune response
Most often affects brain, liver, lungs and striated muscles.
Tissue cysts cause physical cell/tissue damage and are a source
for latent disease
Clinical Disease: Toxoplasma gondii
cats only
Intestinal/Acute Disease – usually no complaint
Oocysts noticed on routine fecal
10-20% of cats develop self-limiting small bowel diarrhea
Systemic Disease -
Non-specific disease: Fever, anorexia, vomiting, diarrhea,
myositis, uveitis, enlarged lymph nodes, pneumonia (especially
for FIV+ cats), encephalitis, nephritis, death
Can transmit congenitally to kittens
Development of clinical toxoplasmosis is dependent on both host
and parasite. Some strains of T. gondii may be more pathogenic
than others, and some strains may have specific tissue affinities,
such as a tendency to cause ocular disease in cats.
If a poor immune response is mounted after primary infection,
overwhelming tachyzoite replication that results in tissue necrosis
is the major cause of disease. Eosinophilic fibrosing gastritis was
recently described in a T. gondii–infected cat.
Fatal extraintestinal toxoplasmosis in cats can develop from
overwhelming intracellular replication of tachyzoites following
primary infection; hepatic, pulmonary, CNS, and pancreatic tissues
are commonly involved.Kittens infected by the transplacental or
transmammary routes develop the most severe signs of
extraintestinal toxoplasmosis and generally die of pulmonary or
hepatic disease. Common clinical signs in cats with disseminated
toxoplasmosis include lethargy, anorexia, and respiratory distress.
Toxoplasma gondii
Non-felid hosts
Cattle
Congenital toxoplasmosis (abortion, but
very rare), ingest oocyst from cat feces.
Horse
Systemic toxoplasmosis, low pathology,
ingest oocyst from cat feces
Rodents
Systemic toxoplasmosis, ingest oocyst from
cat feces or tissue cysts from prey
Decreased fear of cats
Major source of infection for cats and pigs
Toxoplasma gondii
Dogs
Non-felid hosts
Systemic toxoplasmosis, ingest oocyst from cat feces or tissue cyst from
prey
Less commonly develop clinical disease
May develop nonspecific signs: fever, neurological, ocular or respiratory signs
Rule-out Neospora caninum infection
Sheep & Goats
Systemic & Congenital toxoplasmosis,
ingest oocyst from cat feces
Systemic – CNS signs (circling, etc.)
Congenital – abortion
Toxovac S48 live vaccine available
Toxoplasmosis in Sheep
The signs of toxoplasmosis in sheep manifest following the exposure of a
naive pregnant ewe to oocysts. The sporozoites ingested excyst in the
digestive tract and penetrate the intestinal epithelium, before reaching the
mesenteric lymph nodes around day 4 post-infection. Here, they cause
lymphomegaly and focal necrosis before contributing to a parisitaemia from
day 5. Pyrexia is associated with the development of parasitaemia.Following
dissemination of T. gondii in the blood, many tissues become infected.
Parasitaemia ends when the maternal immune response becomes effective,
and protozoa start to encyst as bradyzoites. In pregnant animals, the uterus
is an immunoprivileged site, and the outcome of foetal infection is influenced
by the stage of gestation. In early pregnancy, the foetus is unable to mount
any immune response, and so cannot inhibit parasite multiplication. The
foetus rapidly dies and is resorbed. In a flock, this is visible clinically as large
numbers of barren ewes. In mid-gestation (70-120 days), infection can again
be fatal. This causes a mummified foetus which is often twinned with a lamb
that is stillborn or weak. Abortion due to infection at 70-120 days gestation
tends to occur in very late pregnancy. Because the foetal immune system is
well developed in late pregnancy, infection at this stage will be resisted, and
the lamb will be born transiently infected but alive.
Toxoplasma Transmission
in Man
Sources of infection :
Contaminated water or food by oocysts
Ingestion of tachyzoites and bradyzoites
(cysts) in flesh of infected host.
Undercooked meat.
Mother to fetus.
Organ transplant (rare).
Blood transfusion (rare).
Toxoplasma gondii
Non-felid hosts (important sources
of human infections)
Swine
Systemic toxoplasmosis, ingest oocyst from
cat feces or tissue cyst from prey.
Fever, respiratory signs
Highly prevalent in free-range pigs
Important source of infection for humans
Poultry
Systemic toxoplasmosis, ingest oocyst
from cat feces
Prevalent in free-range and back-yard
chickens
Important source of infection for humans
Many Humans at risk with
Toxoplasmosis
Implications on Human Health
In Humans
produces
1 Congenital
Toxoplasmosis
2 Post natal
Toxoplasmosis
Events on Development in man
When man ingests
Oocysts with eight
Sporozoites excreted
in Cats feces, can
establish an infection
and reproduces
Asexually
In humans Oocysts
open in duodenum and
releases eight
Sporozoites which pass
through the gut wall
Circulate in body and
invade various cells
Cycles of Development in Man
Toxoplasmosis in Pregnancy
In 1 st Trimester
May lead to still birth
Major central
nervous system
anomalies
In 2nd Trimester
Less severe
complications
Birth Anomalies still
common
Congenital Infection
Lead to
Still Birth
Chorioretinits
Intracellular calcification
Psychomotor
disturbances
Hydrocephaly
Microcephaly
Prenatal toxoplasmosis
may manifest with
blindness apart from
congenital defects
Babies infected with congenital
Toxoplasmosis manifest with
brain damage
enlarged spleen and liver
eye damage
jaundice
poor motor coordination
unusually small head
rash
Late Anomalies in
Toxoplasmosis
Clinical manifestation in infected fetus
may be delayed until long after birth
Even may present during early childhood.
Neurological problems of learning
difficulties may be caused by long delayed
effects of late prenatal infection.
Invasion of Lymphnodes lead to
chronic infections
Sporozoites invade
various cells especially
macrophages where
they from Trophozoites
further multiply break
out and spread the
infection to
lymphnodes and other
organs
The rapidly multiplying
Crescentric cell
(Tachyzoites ) initiate
the acute stage of
disease
Invade Organs
Brain involvement carries higher
Morbidity and Mortality
In futher development
they penetrate new
cells especially Eye
and Brain.
Further development
slows down in these
organs called ad
Bradyzoites to form a
quiescent tissue cysts
The event lead to
chronic stage of
disease
Systemic
Toxoplasmosis
Immunocompetent Person
1st exposure
“flu-like” illness that may last for weeks
Fever, myalgia, sore throat, lymphadenopathy
Often asymptomatic
Future exposures
immune-protected, no pathology
Can remain latently infected with cysts
Toxoplasmosis -
Immunosupressed
individua
Varying degrees of
disease may occur
in
Immunosupressed
indivudals results
in
Retinitis
Chorioretinits
Pneumonias
Other non specific
manifestions
Other Human Infections
Toxoplasmosis
produces severe
Human infections
in patient with
AIDS
The chronic
infection is altered
to Acute
manifestations
Direct microscopy Detection of
tachyzoites in blood and tissue cyst in tissue
biopsy
Staining methods:
1. Giemsa
2. PAS
3. Silver stains
4. Immunoperoxidase stain
Detection of Toxoplasma antigen by ELISA
Detection of Toxoplasma antibody by
1. Sabin feldman dye test
2. IgM ELISA
3. IgG ELISA
4. IgG avidity test
5. TORCH test in Newborn
Molecular diagnosis
Animal inoculation
Tissue culture
Imaging methods
Frankel's Intracutaneous test for epidemiological
purpose
Microscopic Examination of
Tissues
Smears and sections
stained with Giemsa’s
stain
Periodic acid Schiff
method preferred
The densely packed
cysts seen in the brain
or other parts of
nervous system
suggest chronic
infection
Diagnosis: System Disease
Aspirates or Necropsy
Tachyzoites from
effusion or aspirate
Bradyzoite cyst from Necropsy / Histology
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Gold standard antibody detection test
Done only in reference laboratories
Complement mediated neutralization test
that requires live tachyzoites
Live tachyzoites are incubated with
complement and test serum
Alkaline methylene blue dye is added and
reincubated
Toxoplasma antibodies in the serum bind to
the antigens in the live tachyzoites killed
due to complement mediated lysis
Killed tachyzoites thin, distorted and
colourless
The dilution of the test serum at which 50% of
the tachyzoites are killed antibody titer of
the test serum
Diagnosis: Toxoplasma gondii
cats only
Intestinal/Acute Disease
Oocysts in feces
Fecal float centrifugation (Zinc Sulfate)
Systemic Disease
Serologic tests – measure IgG and IgM antibodies
good to rule-out if seronegative; not as useful at proving Toxo
is cause of disease.
Thoracic radiographs if lung involvement (pneumonia)
Definitive diagnosis – detection of tachyzoites in
effusions, tissue aspirates or biopsy samples
Diagnosis: Fecal Float Centrifugation
cats only
Toxoplasma gondii
Cystoisospora felis
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Toxoplasma antigens in amniotic fluid
PCR
IgM antibodies in fetal blood by ELISA
Role of IgG antibodies in diagnosing
congential toxoplasmosis ?
Ultrasound of fetus at 20 to 24 weeks of
gestation
Immunity
Acquired immunity in
women is particularly
protective to the fetus.
In Immunosupressed
and AIDS patients
changes the host
resitance and causes
chronic infection
becomes fulminating
acute Toxoplasmosis
Treatment: Toxoplasma gondii
cats only
Intestinal / Acute Disease (shedding oocysts)
Pyrimethamine plus triple sulfa drugs
Clindamycin
Ponazuril
Hospitalize cat during oocyst shedding to reduce zoonosis
Systemic Disease (clinically ill)
Clindamycin for at least 4 weeks
Supportive treatment depending on clinical signs
No good treatment to clear tissue cysts
Treatment
Combination of Pyramethamine and
Sulphadiazine or Trisulfapyramidines
Other alternative Drugs
Spiramycin
Clindamycin
Trimethoprim – Sulphmethoxazole
In pregnancy – Spriamycin is
recommended drug
Control
It is difficult to control toxoplasmosis because of
wide range of animal reservoirs. Currently, there is
no effective vaccnine available for humans.
Primary control measure should be to protect
feedstuffs from access by cats.
A ‘clean’ flock should be prevented from ingesting
food and bedding contaminated by cats,
particularly young cats
A genetically engineered vaccine is under
development for use in cats.
Proper disposal of cat's litter and also the carcass
Control of Toxoplasmosis
Avoidance of human
contact with Cat feces
is highly important
measure.
Changing of Cat litter
and safe disposal can
prevent transmision
Pregnant women
should avoid
contact with kittens
Screening of pregnant women
Periodic screening
of pregnant women
with high risk for
IgG and IgM
antibodies to
Toxoplasmosis is
recommended
Care of the Meat
Avoid eating raw or
undercooked meat.
Freezing < -200c
Heating at 500c for
4-6 minutes
destroys the cysts
and sterilizes the
meat.
Prophylaxis
1- Individuals at risk, particularly pregnant women,
children, and immunocompromised persons should avoid
contact with cat and its feces.
2- Proper cooking of meat.
3- Proper washing of hands and washing of vegetables
and fruits before eating. Blood or blood products
from seropositive persons should not be given and
screening for T. gondii antibody should be done in all
blood banks.
4-For primary prophylaxis
Trimethoprimsulfamethoxazole is the drug of choice
5-Toxovac S48 live vaccine available for sheep
