Toxoplasmosis pdf - د. محمد العاني

Toxoplasmosis

Objective :

Describe the Life cycle

Mention the Infective stages

Define Congenital Toxoplasmosis

List the Lab.Diagnosis

Illustrate the Immunity to Toxoplasmosis

Show the relationship between
Toxoplasmosis & Pregnancy

Human

Toxoplasmosis

Toxoplasmosis is a

zoonotic disease

Caused by Coccidian
protozoan

gondii

Toxoplasma

Infectes a wide range of
animals, birds but
does not appear to
cause disease in
them

Toxoplasmosis

A disease of the blood and lymphatic system.

Cats are a critical part of the life cycle

It is usually acquired by eating undercooked meats
but can also be acquired by contact with cat
feces.

Primary problem is a

congenital infection

fetus, resulting in either a stillbirth or a child with
severe brain damage or vision problems.

Toxoplasmosis

The normal final
host is cat and
relatives in the
family Felidae,
only hosts in
which the Oocyst
is produced & the

sexual

stage of

Toxoplasma can
be developed

Toxoplasma gondii has very low host
specificity, and it will probably infect almost
any mammal.

Non species Specific &

Non organ specific)

, and has been found

in virtually every country of the world.

  Like most of the Apicomplexa, Toxoplasma
is an obligate intracellular parasite.  Its life
cycle includes two phases called the

intestinal (or enteroepithelial) and

extraintestinal phases.

Introduction

•The intestinal phase occurs in cats only (wild
as well as domesticated cats) and produces
"oocysts."

•The extraintestinal phase occurs in all infected
animals (including cats) and produces
"tachyzoites" and, eventually, "bradyzoites" or
"zoitocysts.“

•The disease toxoplasmosis can be transmitted
by ingestion of oocysts (in cat feces) or
bradyzoites (in raw or undercooked meat).

Tachyzoites are less resistant to stomach
secretions so less important sources of
infection than the other stages

Cats

• Cats are the only animal
species to

shed

the infectious

stage in their feces.
• All animals however,can disseminate

Toxoplasmosis if their

infected meat

eaten.

• cats get it by eating rodents,

raw meat,

cockroaches,

flies

, or by contacting

infected cats, infected cat feces, or
contaminated soil

Spread from Rats

– Cats to

Humans

Events on Development in man

When man ingests Oocysts with eight Sporozoites excreted in Cats
feces, can establish an infection in humans. Oocysts open in
duodenum and releases eight Sporozoites which pass through
the gut wall Circulate in body and invade various cells

In most humans infected with Toxoplasma, the
disease is

asymptomatic

. However, under

some conditions, toxoplasmosis can cause serious
pathology, including hepatitis, pneumonia,
blindness, and severe neurological disorders. This
is especially true in individuals whose

immune

systems are compromised (e.g., AIDS patients).

Toxoplasmosis can also be transmitted
transplacentally resulting in a spontaneous
abortion, a still born, or a child that is
severely handicapped mentally and/or
physically

Morphology

Acute stage:

The intracellular parasites

(tachyzoite) are 3x6µ,

crescent shaped

organisms that are

enclosed in the host cells

as Macrophages to form

the Pseudocyst

Toxoplasma gondii
tachyzoites.

Acute stage

Asymptomatic or

Flu like symptoms

Intracellular

tachyzoites of Toxoplasma
gondii.

In the psudocyst

As macrophages

Reproduction is by

Endodyogeny,

a process

of division where in 2
daughter zoites are formed
within the parent parasite,
which is destroyed when
the young zoites are
released

Invade Organs

In futher development they
penetrate new cells
especially Eye and Brain.

Further development slows
down in these organs
called ad

Bradyzoites

form a quiescent tissue
cysts

The event lead to

chronic

stage of

disease

Brain involvement carries
higher Morbidity and
Mortality if the
immunity is low

A zoitocyst of
Toxoplasma

gondii filled with
bradyzoites; this
zoitocyst (true cyst)
is in the
muscle ,eye or brain

Fate of Tissue Cysts

The tissue cysts are
infective when
ingested by cats or
eaten by other
animals.

In man it is a dead end
of disease or change
to acute stage
(tachyzoites) when
the Immunity is Low

Sources of infection

• Source of all oocytes ...

– Domestic (cats) and wild (zoo) cats
(

Cats are the only known full-life-cycle host of the

protozoan) parasite

Complete host

• Persist in environment (soil) if moist > one year

– reservoir of infective oocytes

• Many intermediate hosts

– reservoir of infective tissue cysts( farm animals—

cattle,sheep,rabbit)

• Cycle in humans

(an accidental host)

– Infected

• by ingesting infective oocytes

(

in >4 day old cat feces

)

• by ingesting tachyzoites or bradyzoites

in raw meat

• by receiving

blood

or tissues

with “-zoites”

• CONGENITALLY

by transplacental tachyzoites

– Proliferative stages in humans

• tachyzoites

result from all infective stages

• bradyzoites predominate within cysts

Humans become infected in several ways:

- ingestion of oocysts through contamination of

food, water, hands, etc. with cat feces.

- ingestion of bradyzoites in uncooked meat, e.g.

lamb, pork, beef, caribou.

- transplacental when mother

develops acute

infection during pregnancy.

- blood transfusion, organ transplant.

In immunocompetent adults,
toxoplasmosis, may produce flu-like
symptoms, sometimes associated with
lymphadenopathy.

In immunocompromised individuals,
infection results in generalized
parasitemia involvement of brain, liver
lung and other organs, and often death.

•

Toxoplasmosis

produces severe

Human infections in

patient with

AIDS

The chronic infection

is altered to Acute

manifestations

Toxoplasmosis

–

Immunosupressed patients

Varying degrees of disease
may occur in
Immunosupressed
indivudals results in

Retinitis

Chorioretinits

Pneumonias

severe neurological
disorders

Other non specific
manifestions

Immunology

Both humoral and cell mediated immune

responses are stimulated in normal individuals.
Cell Mediated Immunity is protective and
humoral response is of diagnostic value.

Immunity

Acquired immunity in women is
particularly protective to the fetus.

In Immunosupressed and AIDS patients
changes the host resitance and
causes the chronic infection becomes

fulminating acute
Toxoplasmosis

Premunition: a host may
recover clinically & be
resistant to specific challenge
but some parasites may
remain and reproduce slowly

Toxoplasmosis in Pregnancy

In 1 st Trimester

may lead to still birth

major central nervous system anomalies

In 2

Trimester

Less severe complications

Transmission to the fetus is more frequent if the
maternal infection occurs in the 3

trimester

Congenital Toxoplasmosis

Congenital infection
develop in fetus only
when non immune
mothers are infected
during pregnancy

Congenital infections occur in about 1-5
per 1000 pregnancies of which 5-

result in miscarriage,

% result in serious brain and eye

damage to the fetus,

-13% of the babies will have visual

handicaps.

Although 58-

% of infected women will

give a normal birth, a

small

proportion of

babies will develop active retino-
chorditis or mental retardation in
childhood or young adulthood

( Post natal

Toxoplasmosis is less severe)

Congenital Infection

Prenatal toxoplasmosis

Lead to

Still Birth

Sabin`s tetrad

Chorioretinits

Intracerebal calcification

Psychomotor disturbances

Hydrocephaly

Microcephaly

Prenatal toxoplasmosis may

manifest with blindness apart

from congenital defects

Summery of Clinical presentations :

1. majority are asymptomatic

2. acute toxoplasmosis: fever, lymphadenopathy (much like

infectious mononucleosis - EBV); can rarely cause specific

organ inflammation, e.g. encephalitis, myocarditis.

3. reactivation toxoplasmosis: occurs in immunosuppressed

such as AIDS, transplant and cancer patients: presents with

specific organ involvement e.g. encephalitis, pneumonitis.

4. choreoretinitis: occurs later in life in individuals who

acquired toxoplasmosis congenitally

Post natal toxoplasmosis

;

focal lesion in retina presenting as decreased visual acuity;

rarely occurs during acute toxoplasmosis.

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. Presents as

hydrocephalus, hepatomegaly, cerebral calcifications, mental

retardation with death at one end of spectrum and mental

retardation or just later choreoretinitis at the other end of

spectrum.

Diagnosis of Toxoplasmosis

Desired specimens,

Blood ( serum)

Sputum

CSF

Lymphnodes

Tonsil tissues

Striated muscle biopsy

Diagnosis

Suspected toxoplasmosis
can be confirmed by
finding the organism
from tonsil or lymph
gland biopsy.

Microscopic Examination of

Tissues

Smears and sections

stained with Giemsa’s
stain

Periodic acid Schiff method
preferred

Pseudocyst seen in the
acute stage.

The densely packed cysts
seen in the brain or other
parts of nervous system
suggest chronic infection

Immunological tests:

Tests which employ whole parasites include
• the

dye

test (Sabin-Feldman Dye Test (DT)

direct

agglutination and the

fluorescent

antibody test,

• whilst tests that use disrupted parasites as

an antigen source include

ELISA

latex

agglutination

indirect haemagglutination

and complement fixation.

Serology

Sabin Feldman dye

test

based on principle that
Antibodies to Toxoplasma
appear in 2-3 weeks that
will render the membrane
of the laboratory cultured

T.gondii

living
impermeable to Alkaline

methylene

blue

,So the

organism are unstained in the

presence of serum with antibodies

Newer Methods in Diagnosis

-Immuno florescent
assay method.

-ELISA for IgM and
IgG detection

-PCR

Frankel’s intracutaneous
test (Toxoplasmin skin
test )useful for
epidemiologcal purpose

fluorescent antibody test

ELISA Test

Acute infection

• Detectable levels of IgM antibody appear

immediately before or soon after the onset of
symptoms. IgM levels normally

decline within

4 to 6 months,

but may persist at low levels

for up to a year

• IgG levels begin to rise 1 or 2 weeks after

infection. Peak levels are reached in 6 to 8
weeks, then gradually decline over a period of
months or even years.

Low levels of IgG are

generally detectable for life

• immunocompromised individuals may not

produce any IgM. Antibody levels do not
correlate with severity of illness

Serologic Diagnosis of Toxo

• unreliable in immunodeficient (AIDS) pts
• normally IgM and IgG rise simultaneously

– IgG - persists for years
– IgM - undetectable after “cure”

• elevated IgM titer is diagnostic of recent infection in

persons with normal immunity

• A negative IgG or IgM test excludes Diagnosis

– a + IgM test confirms acute toxoplasmosis or current

Toxoplasma infection

(

measure IgM

antibodies, have low specificity )

• in the United States,

most

pregnant women are

not screened routinely

for toxoplasmosis

Only those with a

high risk.

Polymerase Chain Reaction

(PCR)

• PCR amplification is used to detect T. gondii DNA in

body fluids and tissues.

• It has been successfully used to diagnose

congenital,

ocular, cerebral and disseminated toxoplasmosis

• PCR performed on

amniotic fluid

has revolutionized

the diagnosis of fetal T. gondii infection by enabling an
early diagnosis to be made,

• PCR has allowed detection of T. gondii DNA in brain

tissue, cerebrospinal fluid (CSF), vitreous and aqueous
fluid, bronchoalveolar lavage (BAL) fluid, urine, amniotic
fluid and peripheral blood.

incidence

• Seroconversion rate  -----7.5%  in Egypt
•          30% in canada
    ----- 50 % in USA

-----

60% in France

Very common throughout the world; up to 50+% in
other developed or developing countries.

Care of the Meat

Avoid eating raw or
undercooked meat.

Freezing < -20

Heating at 50

c for 4-6

minutes destroys the
cysts and sterilizes
the meat.

Immunity to TG

• Active infection normally occurs

only once

in a lifetime.

• Although the parasite remains in the body indefinitely

latent infections usually persist for life

(

the immune system

reacts against the parasite, causing the parasite to hide in an
inactive form (cyst) in tissues throughout the body (usually the
skeletal muscles and the brain).

. ,

• True cyst generally is harmless and inactive

unless

the

immune system is not functioning properly in immuno-
compromised host -- the parasite can reactivate and
cause serious illness, characterized by inflammation of
the brain

• If a woman develops immunity to the infection at least

six to nine months before pregnancy, there is a very

rarely

any danger of passing it on to her baby because

immunity is developed to it

Widespread phobia

Toxoplasmosis is a part of TORCH syndrome

It is not a cause of habitual abortion

Only pregnant with primary active infection with
toxoplasmosis during pregnancy leads to congenital tox
and after primary infection there is persistence of cysts of
tox BUT development of active immunity protect
subsequent pregnancy

Very rarely

reactivation of previously latent T. gondii

infection induced

by severe

decrease of

immunity(People on chemotherapy , People with
congenital immune deficiencies , People with AIDS/HIV ,
long administration of corticosteroid drugs in the case of
transplant patients)
Many doctors believe that is the case which has created

a widespread phobia

among pregnant women and has

given some sort of satisfaction among some doctors by
treatment their pregnant women by chemotherapy which
is in fact unnecessary

Toxoplasmosis TTT

• Drugs of choice for pregnant women or

immunocompromised persons:
    Spiramycin or Pyrimethamine plus
Sulfadiazine

• Prophylaxis –in the primary prevention of

toxoplasmosis in persons with HIV who have
dormant or latent infection

- trimethoprim-sulfamethoxazole
• pyrimethamine plus folinic acid
• dapsone + pyrimethamine

Treatment of Infected Newborns

• Infected babies should be treated as soon

as possible after birth with pyrimethamine
and sulfadiazine which, as mentioned
earlier, can help prevent or reduce the
disabilities associated with toxoplasmosis.

Figure-5- Girl with hydrocephalus due to congenital toxoplasmosis.

Under research

• developing vaccines against Toxoplasma

gondii .

Thank You