TOXOPLASMOSIS

TOXOPLASMA GONDII

Toxoplasma gondii-- Obligate intracellular parasite

produces a wide range of clinical syndromes in humans,
land and sea mammals, and various bird species.
Nicolle and Manceaux first described the organism in
1908 after they observed the parasites in the blood,
spleen, and liver of a North African rodent,
Ctenodactylus gondii.
The parasite was named Toxoplasma (arc like form)
gondii (after the rodent) in 1909.

Toxoplasma Gondii

Scientific classification

T. gondii
tachyzoites

Kingdom:

Protista

Phylum:

Apicomplexa

Class:

Conoidasida

Subclass:

Coccidiasina

Order:

Eucoccidiorida

Family:

Sarcocystidae

Genus:

Toxoplasma

Species:

T. gondii

Toxoplasma gondii is a protozoa. The definitive

host, in which the sexual stages takes place is the
domestic cat.

There are many intermediate hosts, including man rodent and farm
animals.

Man

Rat

farm animals

 A cat becomes infected with toxoplasmosis by

eating the raw flesh of infected animals
Cat transmits the infection to her unborn
kittens through the placenta or to her new litter
through her milk.
An infected kitten may die,
An infected otherwise healthy cat may show no
signs of disease.

Inside the cat Toxoplasma infects the intestinal epithelial cells

and divides.
In the cat the sexual phase of the life cycle occurs resulting in
the production of oocysts (eggs).
The eggs are excreted in fecal matter.
The intermediate host becomes infected by eating the oocysts.

Definitive host

Tissue cysts containing

Bradyzoites
Eaten by cat

Oocyst contains
two sporocysts
with 4
sporozoites
Intermediate host

Three forms of parasite involve man:

1) Tachyzoite: the
intracellular parasitic stage
which rapidly proliferates by
binary fission, usually seen in
the early acute stage of
infection
2) Bradyzoite: quiescent
forms within a cyst which is
formed during chronic latent
(asymptomatic) infection;
persists for years in human
tissues (brain, retina, muscle
etc.)
3) Oocysts: shed in the stool
of cats, They sporulate in 3
days after passage in stool and
then can be infective in the
environment for a year. Man
swallows oocysts to become
infected.

MORPHOLOGY
Tachyzoite3-7 micrometre in length
Oval to crescent shaped with a pointed anterior end and a rounded
posterior end..
Ovoid nucleus at the posterior end
It is the actively multiplying form (tachy = fast, zoite = organism)
and can invade any cell in the host

Toxoplasma gondii
tachyzoites
(Giemsa stain).

Tissue cyst
After repeated divisions, tachyzoites become encysted in the body,

mostly in muscle and neural tissues.

The encysted stage (tissue cyst) contains relatively slowly multiplying
organisms called bradyzoites,( brady = slow).
Tissue cysts persist in the body as long as the host lives. The tissue
cyst is a dead end phase of the parasite in the intermediate host
waiting to be eaten by the definitive host, cat
In man found in brain, skeletal muscle and heart muscle.

PSEUDOCYST AND TISSUE CYST

In pseudocyst there are actively multiplying tachyzoites within

a cytoplasmic vacuole of the cell they infect.
Here they may appear rounded or enclosed in a host cell.
In tissue cyst it is the bradyzoites which are present and
encysted within the tissue especially in the brain and muscles.
Large in size:-12-100 micrometre in size with several 1000
bradyzoites.
Tissue cysts form as early as 7 days after infection.
They produce little or no inflammatory response but cause
recrudescent disease in immunocompromised patients or
chorioretinitis in congenitally infected older children.

Pseudocyst in human heart

pseudocyst

Pseudocyst in human heart -magnified

Pseudocyst of toxoplasma

Oocysts
In the environment, cysts take 48-72 hours to sporulate and become
infective.
Mature oocysts measure 10-12 m in diameter and contain two sporocysts. .
Cats may excrete millions of oocysts after ingesting as few as 1 bradyzoite or 1
tissue cyst, and many tissue cysts may be present in one infected mouse.
Oocysts are shed for only a short period (1-2 weeks) in the life of the cat,

A: Toxoplasma gondii sporulated oocyst

in an unstained wet mount
oocyst

B: Toxoplasma gondii sporulated

Epidemiology
Very common throughout the world; up to 50+% in other

developed or developing countries.

zoonosis affecting almost all mammalian carnivores and
mammals in contact with cats.
Toxoplasma gondii infection occurs commonly in many
animals used for food (for example, sheep, goats, pigs,
and rabbits).
The cat is the definitive host.
Many mammals and birds serve as intermediate hosts

Mode of infection

Ingestion of oocysts through contamination of

food, hands, etc. with cat faeces.
Ingestion of bradyzoites in uncooked meat, e.g.
lamb, pork, beef, caribou
Transplacental when mother develops acute
infection during pregnancy
Blood transfusion,
Organ transplant.

Life Cycle
The sexual cycle takes place exclusively in the intestinal enterocytes of
many members of the cat family
1) Ingestion of tissue cysts,
2) The parasites invade the enterocytes and divide repeatedly
3) Differentiate into microgametocytes and macrogametocytes.
4 ) The gametocytes fuse to form a zygote or oocyst that is shed into
the environment with the cats faeces.
5) The oocyst undergoes meiosis, producing eight infectious
sporozoites that are resistant to environmental damage and may
persist for years in a moist environment.
6)Ingestion (by a secondary host such as a mouse),

7) Sporozoites differentiate into the rapidly dividing

tachyzoite form, which establishes and sustains the acute
infection.
8) During the acute infection, congenital transmission to the
developing fetus can occur
9) In many hosts, a chronic phase of the disease ensues, as the
tachyzoite changes into a slowly dividing form known as the
bradyzoite. Latent bradyzoite tissue cysts persist for the life of
the host.
10) Ingestion of tissue cysts can lead to the infection of a new
host, allowing for an indefinite nonsexual propagation of T.
gondii.
11) In the cat, this will initiate the sexual cycle.
12) In man it is a dead end infection unless its in a pregnant
female.

Toxoplasma gondii in infected

monolayers of HeLa cells (Giemsa
stain).

C. Tissue cyst separated from

host tissue by homogenization
of infected brain. Note tissue
cyst wall (arrow) and hundreds
of bradyzoites (arrowheads
D. Schizont (arrow) with
several merozoites
(arrowheads) separating from
the main mass.
E. A male gamete with two
flagella (arrows). Impression
smear of infected cat intestine
A. Tachyzoites Note crescent-shaped
individual tachyzoites (arrows), dividing
tachyzoites (arrowheads) compared with
size of host red blood cells and leukocytes.
B. Tissue cysts in section of muscle. The
tissue cyst wall is very thin (arrow) and
encloses many tiny bradyzoites
(arrowheads).

F. Unsporulated oocyst in
fecal float of cat feces.
G. Sporulated oocyst with a
thin oocyst wall (large arrow),
2 sporocysts (arrowheads).
Each sporocyst has 4
sporozoites

Pathophysiology
Oocysts are ingested in material contaminated by feces from acutely
infected cats.
Sporozoites are released from oocysts and enter gastrointestinal
cells. They multiply, rupture cells, and infect contiguous cells. They are
transported via the lymphatics and disseminated hematogenously
throughout the tissues.
Tachyzoites proliferate, producing necrotic foci surrounded by a
cellular reaction. With the development of a normal immune response,
tachyzoites disappear from tissues.
In immunodeficient individuals and in some apparently
immunologically healthy patients, the acute infection progresses and
may cause potentially lethal consequences such as pneumonitis,
myocarditis, or necrotizing encephalitis
When a mother acquires the infection during gestation, the organism
may be disseminated hematogenously to the placenta. When this
occurs, infection may be transmitted to the fetus transplacentally or
during vaginal delivery

Clinical
1) Majority are asymptomatic In humans, severe disease is usually
observed only in congenitally infected children and in immunosuppressed
individuals, including patients with acquired immune deficiency
syndrome (AIDS).
2. Acute Toxoplasmosis:
Fever,
Lymphadenopathy Any node can be infected, but the deep cervical
nodes are the most commonly involved. Infected nodes are tender and
discrete but not painful; the infection resolves spontaneously in weeks or
months
Fatigue,
Muscle pains,
Sore throat, and
Headache
Rarely cause specific organ inflammation, e.g. encephalitis,
myocarditis.

3. Reactivation toxoplasmosis:
occurs in immunosuppressed such as AIDS,
transplant and cancer patients:
CNS disease occurs in 50% of patients
encephalitis,
meningoencephalitis,
Hemiparesis,
seizures, and
mental status changes
Patients report visual changes.
Myocarditis and pneumonitis

Clinical manifestations of toxoplasmosis in patients

with AIDS
Brain involvement (ie, toxoplasmic encephalitis), with or

without focal CNS lesions, is the most common manifestation

of toxoplasmosis in individuals with AIDS.

Clinical findings include an altered mental state, seizures, weakness,

cranial nerve disturbances, sensory abnormalities, cerebellar signs,
meningismus, movement disorders, and neuropsychiatric
manifestations.
The characteristic presentation is usually a subacute onset, with focal
neurologic abnormalities in 58-89% of cases.
Most commonly, hemiparesis and/or speech abnormality is the
major initial manifestation.
Brain stem involvement often produces cranial nerve lesions, and
many patients exhibit cerebral dysfunction with disorientation,
altered mental state, lethargy, and coma.

Clinical manifestations of toxoplasmosis in patients

with AIDS cont
Less commonly, parkinsonism, focal dystonia, hemichorea-

hemiballismus, panhypopituitarism, diabetes insipidus, or

syndrome of inappropriate antidiuretic hormone secretion
may dominate the clinical picture.
In some patients, neuropsychiatric symptoms such as
paranoid psychosis, dementia, anxiety, and agitation may be
the major manifestations.
Diffuse toxoplasmic encephalitis may develop acutely and can
be rapidly fatal; generalized cerebral dysfunction without focal
signs is the most common manifestation, and CT scan findings
are normal or reveal cerebral atrophy.
Spinal cord involvement

4.Pulmonary toxoplasmosis (pneumonitis)

Increasingly recognized in patients with AIDS who

are not receiving appropriate anti-HIV drugs or

primary prophylaxis for toxoplasmosis.
The diagnosis may be confirmed by demonstrating T
gondii in bronchoalveolar lavage (BAL) fluid.
Pulmonary toxoplasmosis mainly occurs in patients
with advanced AIDS (mean CD4+ count of 40
cells/L 75 standard deviation) and primarily
manifests as a prolonged febrile illness with cough
and dyspnea.

5. Congenital toxoplasmosis:
Transmission from mother to fetus when mother has developed
acute toxoplasmosis during pregnancy --- increased transmission
rate in third trimester, but increased severity of fetal disease in
first trimester.
Infection in the first trimester - approximately 17% of fetuses are
infected, and disease in the infant is usually severe.
Infection in the third trimester --65% of fetuses are infected, and
involvement is mild or inapparent at birth.
These different rates of transmission are most likely related to
placental blood flow, the virulence and amount of T
gondii acquired, and the immunologic ability of the
mother to restrict parasitemia

Congenital toxoplasmosis
Presents as
Hydrocephalus,
Hepatomegaly,
Cerebral calcifications,
Mental retardation
Choreoretinitis -Focal lesion in retina presenting as
Decreased visual acuity;
Rarely occurs during acute toxoplasmosis.


LABDIAGNOSIS
DemonstrationoftheT. gondiiorganism in blood, body fluids, or tissue.
IsolationofT. gondiifrom amniotic fluid is diagnostic of congenital infection
by mouse inoculation.
Lymphocytetransformationto T. gondii antigens is an indicator of previous
toxoplasmosis in adults
DetectionofT. gondiiantigenin blood or body fluids by enzyme-linked
immunosorbent assay (ELISA) technique indicates acute infection.
The Sabin-Feldmandyetest
Sensitive and specific neutralization test.
It measures IgG antibody and is the standard reference test for toxoplasmosis.
Live virulent tachyzoites of T gondii are used as antigen and are exposed to
dilutions of the test serum and to a complement accessory factor resembling
complement that is obtained from Toxoplasma-antibody free-human serum.
Its main disadvantages are its high cost and the human hazard of using live
organisms.

Lab diagnosis cont

The indirect fluorescent antibody test measures the

same antibodies as the dye test. Titers parallel dye test

titers.

The IgM fluorescent antibody test detects IgM antibodies

within the first week of infection, but titers fall within a

few months.

Indirect hemagglutination test

The results from a double-sandwich IgM ELISA are

more sensitive and specific than the results from other IgM
tests.

Diagnosis in pregnancy
Diagnosis is primarily made by serologic investigations.
Antibody Detection
The detection of Toxoplasma-specific antibodies is the primary
diagnostic method to determine infection with Toxoplasma.
Test kits are commercially available to detect T. gondii specific
IgG, IgM , IgA or IgE antibodies.
All suspected patients should be initially tested for the presence
of Toxoplasma-specific IgG antibodies to determine their immune
status.
The presence of IgG antibodies only means exposure because
asymptomatic humans can develop very high (>100,000) and
titres may remain elevated for several years or even whole life if
repeated exposures are encountered.
A 8-fold rise in antibody titre, taken two weeks apart, is
indicative of a recent infection,
IgM antibodies are short-lived, and they appear before IgG
antibodies

A negative IgM test essentially excludes recent infection, but a

positive IgM test is difficult to interpret because Toxoplasmaspecific IgM antibodies may be detected by EIA for 6-12 months
but rarely as long as 18 months after acute acquired infection.
Two situations occur frequently:
i) positive IgM but negative IgG, and
ii) positive IgG and IgM.
In the first situation, the patient's blood should be redrawn two
weeks after the first and tested together with the first specimen. If
the first specimen was drawn in early infection, the patient should
have highly positive IgG and IgM antibodies in the second sample.
If the IgG is negative and the IgM is positive in both specimens,
the IgM result should be considered to be a false positive and the
patient should be considered to be not infected.

 In a pregnant women whose sample is taken in

second or third trimester is found IgG positive but

IgM negative, it is more advisable to perform IgG
avidity test.
High avidity IgG tests indicate that she acquired the
infection more than 4 months ago. But the low
avidity is not a confirmatory test for recent infection.

New born infants suspected of congenital toxoplasmosis should be

tested by both an IgM- and an IgA-capture EIA. Detection of
Toxoplasma-specific IgA antibodies is more sensitive than IgM detection
in congenitally infected babies.
Polymerase chain reaction on body fluids, including CSF, amniotic
fluid, BAL fluid, and blood, may be useful in the diagnosis.

Treatment
1)Sulfonamides and
2) Pyrimethamine (Daraprim) are two drugs widely used to treat toxoplasmosis
in humans.
helpful when given in the acute stage of the disease,
usually they will not eradicate infection when active multiplication of the
parasite occurs.

No killed vaccine is currently available to reduce or prevent congenital

infections in humans and animals, but research to develop such an
agent is under way.
A live vaccine using a nonpersistent T gondii strain is available in
Europe and New Zealand to reduce abortion in sheep.

Precautions
1) Meat should be cooked to 66C throughout before eating.
2) Hands should be washed with soap and water after handling meat.
3) Raw meat should never be fed to cats; only dry or canned food or cooked
meat should be fed.
4) Cats should be kept indoors and litter boxes changed daily.
5) Cat feces should be flushed down the toilet or burned.
6) Litter pans should be cleaned by immersing them in boiling water.
7) Gloves should be used while working in the garden.