Lecture-7- Hazem Al-Khafaji 2016

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TOXOPLASMOSIS Lecture-7- Hazem Al-Khafaji 2016

TOXOPLASMOSIS It is a disease caused by Toxoplasma gondii which is a protozoan parasite that is infects a variety of mammals and birds throughout the world. The acute acquired infection in humans is usually asymptomatic. However, clinical or pathologic evidence of disease (i.e., toxoplasmosis) may occur, particularly in the immunocompromised patient, the congenitally infected fetus and child, and those in whom chorioretinitis develops during the acute acquired infection. Infection is characterized by two stages: acute (i.e., recently acquired) and chronic (i.e., latent).

Historical Facts Toxoplasmosis T.Gondii was first discovered in 1908 in Tunis within the tissue of the gondi, in the same year it was also described in Brazil in rabbits. Re-discovered in 1935 in the br ain tissue of guinea pigs. In 1939 it was found as the cause of encephalitis in a 31 day old infant. In 1969 infective cysts were detected in the stools of cats. T. Gondii

Toxoplasmosis Toxoplasmosis is one of the zoonotic diseases. Etiologic agent = Toxoplasma gondii.

LIFE CYCLE There are three forms of the parasite: 1- The tachyzoite, which is the asexual invasive form. 2- The tissue cyst, containing bradyzoites, which persists in tissues of infected hosts during the chronic phase of the infection. 3-The oocyst, containing sporozoites, which is produced during the sexual cycle in the intestine of members of the cat family, the definitive host.

Host Intermediate host Mainly domestic and wild cats. Human, birds, pigs, rodents, and sheep.

Toxoplasma gondii, Life-cycle

Toxoplasma gondii ACUTE PHASE CHRONIC PHASE Immunity + Tachyzoites: rapidly dividing forms Immunity - Bradyzoites: slowly dividing forms

Tachyzoite stage Toxoplasmosis oocyst

EPIDEMIOLOGY In the United States, there is no significant difference in prevalence of antibodies to T. gondii between men and women. Depending on geographic locale and population group, 3 to 67% of adults have serologic evidence of infection. In other parts of the world, including tropical countries and some areas of Western Europe, up to 75% of adults are seropositive.

Transmission to humans 1-Ingestion of tissue cysts or oocysts(contaminated with cat faeces). 2- The transplacental route. 3- Blood product transfusion. 4-Solid organ transplantation (i.e., kidney, heart, or liver from a seropositive donor into a seronegative recipient). 5-Laboratory accident. 6- Outbreaks of toxoplasmosis due to eating of undercooked meat or exposure to oocysts (e.g., contaminated water) have occurred. Commercial cuts of lamb, beef, and pork may contain tissue cysts that remain infectious unless the meat is frozen to 20 C or heated throughout to 66 C

TOXOPLASMA TRANSMISSION DEFINITIVE HOST Sources of infection : _ Contaminated water or food by oocysts _ Undercooked meat. _ Mother to fetus. _ Organ transplant (rare). _ Blood transfusion (rare). INTERMEDIATE HOST Ingestion of tachyzoites and bradyzoites (cysts) in flesh of infected host.

Types of o infection 1: Congenital. 2: Acquired :Primary or Reactivation of latent infection in case: Immunocompromised e.g. AIDS Immunosuppression e.g. drugs

congenital toxoplasmosis Transplacental infection resulting in congenital infection can occur in immunocompetent pregnant women with recently acquired T. gondii infection and in immunocompromised pregnant women with reactivation of their chronic infection. The frequency of transmission to the fetus probably depends on maternal parasitemia, maturity of placenta, and competency of the maternal immune response to T. Gondii. Congenital transmission has been shown to vary considerably, depending on the time during gestation the mother acquired her infection. Approximately 85% of infants with congenital infection appear normal at birth..

Although the severity of the fetal illness is inversely proportional to gestational age, the vertical transmission rate is directly proportional to the pregnancy stage of the mother when acquiring the infection for the first time.

Vertical transmission to fetus: % of fetal infection according to trimester: Before pregnancy I II III 0% 15% 30 % 60% severity of congenital 0 +++ ++ + disease NB * 1-2/1000 live births in USA have neonatal toxoplasmosis *

Congenital Toxoplasmosis 1-Intracerebral calcification. 2-Chorioretinitis. Ocular toxoplasmosis 3-Hydrocephaly. 4-Microcephaly. 5-Convulsions. 6-Mental retardation. 7-Cardiomegaly. toxoplasmic encephalitis Congenital disease

Congenital toxoplasmosis is a problem in 1-5/1000 pregnancies * Intracerebral calcification. If a woman is infected for the first time during pregnancy the parasite can cross the placenta and cause fetal disease. Both the* probability and severity of the disease depend on when the infection takes place during pregnancy. Early: low transmission, but severe disease Late: high transmission, more benign symptoms. Hydrocephaly.

Intracranial calcification

Clinical features Immunocompotent Infection is mostly asymptomatic in healthy individuals. In acute infection: Lymphadenitis is the most common feature. (generalized lymphadenopathy) Flu-like symptoms (Headache, fever, muscle pain) the infection is generally self limited & symptom usually resolve in few months. Acute choroido-retinitis which may result in blindness.

Clinical features Immune compromised Causes Encephalitis, for immunosuppressed patients and people infected with (AIDS). immunocompromised individuals, infection results in generalized parasitemia involvement of brain, liver,lung and other organs, and often death.

DIAGNOSIS Toxoplasmosis can be diagnosed by: 1- Isolation of the organism. A- Polymerase chain reaction (PCR) methods. B- Direct identification & demonstration of tachyzoites in peripheral blood, amniotic fluid, body fluids & tissues & by histologic or cytologic analysis. 2- Serologic testing. Whereas direct demonstration of the parasite is often used for diagnosis of the infection in immunocompromised patients, serologic analysis is most commonly used for diagnosis in immunocompetent patients.

Lab Diagnosis of Toxoplasmosis: 1-The demonstration of the Toxoplasma gondii organism in blood, body fluids, or tissue. 2-Detection of Toxoplasma gondii antigen in blood or body fluids by enzyme-linked immunosorbent assay (ELISA) technique. 3-The Sabin-Feldman dye test: is a sensitive and specific neutralization test. It measures IgG antibody and is the standard reference test for toxoplasmosis. High titers suggest acute disease. 4-Serologically: IgM fluorescent antibody test detects IgM antibodies within the first week of infection, but titers fall within a few months. 5-Polymerase Chain Reaction on body fluids, including CSF, amniotic fluid, and blood. 6-Animal inoculation: inoculation of suspected infected tissues into experimental animals. 7-Culture: inoculation of suspected infected tissues into tissue culture.

The significances of Sabin- Feldman dye test The Sabin-Feldman dye test: is a sensitive and specific neutralization test. It measures IgG antibody and is the standard reference test for toxoplasmosis. IgG antibodies usually appear within 1-2 weeks of infection.reach its peak within 2-3 months of infection then persist for life,although its level declines after 5 years. So positive test indicate exposure to infection & negative test rule out exposure to infection(unless the patients immune compromised). High titers suggest acute disease( increasing titer up to 1/8 or 1/16 on the 2 nd reading which repeated after 2-3 weeks of initial test.

Diagnosis Interpretation of the serological test.

Amniocentesis Done around 18 th week of pregnancy(if highly suspicion of fetal infection) A long needle is inserted into the Amniotic sac and amniotic fluid is drawn.

Spiramycin at a dose of 3 g/day (obtained from the U.S. Food and Drug Administration) has been stated to reduce the incidence of fetal infection by about 60%. If prenatal diagnosis reveals infection in the fetus, the pregnant patient should receive Sulfadiazine and pyrimethamine plus folinic acid to treat the fetus. Because of potential teratogenicity, pyrimethamine should not be administered in the first trimester. If necessary, sulfadiazine may be used, but its efficacy when used alone for this purpose has not been studied..

Prevention & Control Hands should be washed after contact with raw meat or in contact with soil. Vegetables should be washed well. Avoid undercooked meats. If you are owned by a cat Keep it inside if possible. Don t feed it raw meat. Avoid contact with cat during pregnancy..

T. gondiiis still constitute a public health problem among pregnant women and considered one of the abortion factor Seroprevalence gradually increased with age, from 31.7% at 15-24 years to 90.0% at 35-45 years. Regression analysis showed that seroprevalence of toxoplasmosis is positively correlated with age and residence. Consumption of undercooked meat and contact with soil were significant risk factors.

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