Toxoplasma gondii infects a large
proportion of the world's human
populations, but it is an uncommon
cause of disease.
The prevalence of anti-Toxo
seropositivity is as high as 75% by
the fourth decade of life.
Toxoplasmosis
• Congenitally infected fetuses , newborns
and immunologically impaired individuals
with defects in T-cell-mediated immunity
are at high risk for severe or life-threatening
disease due to this parasite.
Toxoplasma gondii
•
-
T.gondii exists in nature in three forms:
the oocyst (which releases sporozoites),
the tissue cyst (which releases bradyzoites),
the tachyzoit (is the hallmark of primary or
reactivated infection)
Toxoplasmosis-transmission
• Tranmission of T. gondii occurs through
- the ingestion of raw or undercooked meat (pork,
lamb) that contains cysts,
- the ingestion of water or food contaminated with
oocysts,
- congenitally through transplacental transmission
from a mother who acquired her infection during
gestation
- the transplantation of an infected organ or
transfusion of contaminated blood cell
The life cycle of
T gondii
The life cycle of T gondii
http://images.google.pl/images?svnum=10&hl=pl&lr=&q=Toxoplasmosis+cycle&btnG=Szukaj
Toxoplasma gondii
http://images.google.pl/images?svnum=10&hl=pl&lr=&q=Toxoplasmosis+cycle&btnG=Szukaj
Toxoplasma gondii - strains of
the parasite
• Type I strains are associated with human
congenital toxoplasmosis
• Type II strains are associated with reactivation of
chronic infections and accounted for 65% of
strains isolated from AIDS patients
• Type III strains are common in animals but
observed less often in cases of human
toxoplasmosis
Toxolasma gondii-strains
Most cases in humans were caused by type
II strains
Toxoplasma gondii
• The life cycle of T. gondii has two phases.
- The sexual part of life cycle takes part only
in domestic and wild cats.
- The asexual part of the life cycle can take
place in mammals and birds.
Toxoplasma gondi-Oocyst
• The definitive host, in which the sexual
cycle takes place is the domestic cat.
• Cats shed oocysts, that remains viable for as
long as 18 months and may be ingested by
many annimals and penetrate the epithelial
cells of the small intestine.
Toxoplama gondii- tissue cyst
• Tachyzoite undergo conversion into
bradyzoite which form tissue cysts.
• The central nervous system, eye, skeletal
smooth and heart muscles are the most
common site of latent infection.
Toxoplasma gondii
• Organisms may spread first to the
mesenteric lymph nodes and then to distant
organs by invasion of lymphatics and blood
• Cyst formation takes place in multiple
organs and tissues during the first week of
infection
Toxoplasmosis
Toxoplasmosis is conveniently considered in
categories:
• (1) acquired in the immunocompetent
patient,
• (2) acquired or reactivated in the
immunodeficient patient,
• (3) ocular,
• (4) congenital
Toxoplasmosis in
immunocompetent patients
• T. gondii infection leads to a chronic or
latent infection without clinical significance.
This chronic asymptomatic infection
corresponds to the persistence of the cyst
form in multiple tissues.
• In most cases the clinical course of
toxoplasmosis in the immunocompetent
patient is benign and self-limited.
Toxoplasmosis in
immunocompetent patients
• Only 10 to 20% of cases of T. gondii infection are
symptomatic. Most often, toxoplasmosis manifests as
asymptomatic cervical lymphadenopathy, fever, malaise,
night sweats, myalgias, sore throat, maculopapular rash,
hepatosplenomegaly, or small numbers of atypical
lymphocytes (less than 10%)
• Toxoplasmic chorioretinitis can be a manifestation of the
acute acquired infection
Toxoplasmosis in
immunocompetent patients
• Eye infection in immunocompetent patients
produces acute chorioretinitis characterized
by severe inflammation and necrosis.
• Other manifestation of Toxoplasmosis
myocarditis, myositis, hemorrhagic gastritis
and colitis are rare.
Toxoplasmosis in
immunocompromised patients
• The clinical course of toxoplasmosis in
immunocompromised individuals is
potentially life threatening. The brain is the
most commonly affected organ. The
presence of multiple brain abscesses is the
most characteristic feature of TE in patients
with AIDS.
Toxoplasmosis in
immunodeficient patients
• In the United States, TE has been reported in 1 to
5% of patients with AIDS
• The incidence of Toxoplasmosis encephalitis
among HIV-infected individuals correlates with
the prevalence of T. gondii antibodies among the
general HIV-infected population, the degree of
immunosuppression (CD4<200), and the
institution of effective prophylactic treatment
against the development of TE
Toxoplasmosis in HIV patients
• Clinical manifestations of toxoplasmosis in
AIDS patients commonly reflect
involvement:
- the brain (toxoplasmic encephalitis-TE),
- the lung (pneumonitis),
- the eye (chorioretinitis).
Toxoplasmic encephalitis -CT
Toxoplasmic encephalitis-MRI
Toxoplasmosis in HIV patients
• Clinical manifestations of toxoplasmic
encephalitis include:
- mental status abnormalities,
- focal motor deficits, focal neurologic findings
- sensory aberrances,
- seizures, cranial nerve disturbances,
• cerebellar signs,
• meningismus,
• movement disorders
• neuropsychiatric findings
Congenital Toxoplasmosis
• Congenital toxoplasmosis-occurs when a mother
aquires the infection during pregnancy.
• Infants born of mothers who acquire their infection
in the first and second trimester more frequently
show severe congenital toxoplasmosis.
• The majority of children born of women who
acquire their infection during the third trimester are
born with the subclinical form of the infection.
Congenital Toxoplasmosis
• The congenital toxoplasmosis during the first trimester of
pregnancy can cause spontaneous abortion of the fetus or
can cause severe malformation at birth.
• However, it is during the third trimester that the highest
level of transmission occurs. The transmission rate from a
maternal infection is about 45%. Of these 60% are subclinical infections, 9% result in death of the fetus and 30%
have sever damage such as hydrocephalus, intracerebral
calcification, retinochoroiditis and mental retardation.
Congenital Toxoplasmosis
• In utero transmission is lowest in the Ist trimester (15%)
and highest in the 3 rd (60%).
• However, severity is greatest when infection occurs in the
Ist trimester.
Clinical course of Congenital
Toxoplasmosis
• 1) neonatal disease
• 2)disease (mild or severe) occuring in the
first month of life
• 3)relapse of previously undiagnosed
infection during infancy
• 4)subclinical infection
Clinical manifestations of severe
congenital toxoplasmosis
•
•
•
•
epilepsy,
strabismus, blindness,
psychomotor or mental retardation,
anemia, jaundice, rash, petechiae encephalitis,
pneumonitis, microcephaly, intracranial
calcification, hydrocephalus, diarrhea,
hypothermia,
• chorioretinitis which appears at a mean age of 3.7
years,
Clinical manifestations of milder
congenital toxoplasmosis
Full-term infants frequently develop a
milder disease manifested by
hepatosplenomegaly and lymphadenopathy
that usually appear in the first 2 months of
life. In these infants, disease reflecting
damage to the CNS may occur later, and eye
disease may occur months to years after
birth.
Congenital toxoplasmosis
• Congenital toxoplasmosis must be differentiated from
rubella virus, CMV, and herpes simplex virus infections;
syphilis, listeriosis, and other bacterial infections; other
infectious encephalopathies; erythroblastosis fetalis; sepsis.
Congenital Toxoplasmosis
• Treatment of the mother with acute Toxoplasmosis
infection with spiramycin throughout pregnancy
reduces the incidence of congenital infection by
about 60%.
• Congenital infection after the thirst trimester of
gestation is treated additionally with
pyrimethamine and sulphadiazine.
Ocular Toxoplasmosis in
Immunocompetent Patients
• chorioretinitis is a late sequela of the infection acquired in
utero
• is frequently in the second and third decades of life
• is bilateral disease with retinal scars, and involvement of
the macula
Ocular Toxoplasmosis in
Immunocompetent Patients
• In most cases, toxoplasmic chorioretinitis is diagnosed by
ophthalmologic examination, and empirical therapy
directed against the organism is often instituted based on
clinical findings and serologic test results.
• Diagnosis may be made by demonstration of the organism
in retinal biopsies, isolation of the parasite from vitreous
aspirates, or amplification of the parasite DNA by PCR
Toxoplasmic chorioretinitis
Toxoplasmosis-DIAGNOSIS
• the isolation of T. gondii
• serologic tests for demonstration of anty-Toxo antibodies
(Sabin-Feldman Dye Test, ELISA, IFA)
• detection of T. gondii DNA by PCR or amplification in
blood or body fluids;
• demonstration of tachyzoites in histologic sections of
tissue or in cytologic preparations of body fluids;
• Antigen-Specific Lymphocyte Transformation and
Lymphocyte Typing
• computed tomography or magnetic resonance imaging
Toxoplasmosis- treatment
• Currently recommended drugs against T. gondii act
primarily against the tachyzoite form and thus do not
eradicate the encysted form (bradyzoite).
• The 'gold' standard' regimen for the treatment of
toxoplasmosis is the combination of :
- pyrimethamine (200mg loading dose followed by 50–75mg
qd)
- sulfadiazine (2.0–4.0g loading dose initially followed by
1–1.5g q6h)
- folinic (not folic) acid (10–50mg qd).
Toxoplasmosis- treatment
• Clindamycin (600mg q6h, up to 1200mg q6h) can be used
instead of sulfadiazine in patients intolerant of
sulfonamides.
• Duration of treatment should be 4–6 weeks after
resolution of all signs and symptoms (often for several
months or longer, untill CD4>200cells/ul). .
Toxoplasmosis- treatment
• atovaquone+pyrimethamine are considered
as an alternative treatment for patients
intolerant of sulfonamides
• atovaquone+sulfadiazine for patients
intolerant of pyrimethamine.
Toxoplasmosis- treatment
• No therapy is required for lymphadenitis!
• Steroids may be required in chorioretinitis !