TOXOPLASMOSIS IN PREGNANCY

Introduction

A zoonoziz , caused by T.gondii , an intracellular protozoan parasite

Its more common in tropical & coastal regions

is less common in regions that are either cold ,warm or at high elevation

1 of every 900 pregnancies in the USA

Transmission Cats

host for T. gondii They acquire infection by

eating infected wild rodents and birds

A week after infection, the cat begins to shed oocysts in its feces

Shedding of the oocysts persists for about 2 weeks

within days to weeks these oocysts sporulate and become extremely infectious

Transmission

Food ingestion of

contaminated food is an important cause of toxoplasmosis

Meat is the most common infected food

unpasteurized milk and unfiltered water sources also are at risk

Organ transplantation

Pathophysiology Acute toxoplasmosis generally is well tolerated

in immunocompetent adults may result in vertical infection to the fetus and

lead to potentially serious consequences

In immunocompetent adult, symptoms usually are mild or inapparent

In about 10%: fever fatigue Malaise headache myalgias lymphadenopathy

These symptoms will resolve in weeks to months without specific therapy

Pathophysiology

In immunosuppressed : signs and symptoms often will be more pronounced can result in significant ocular and CNS abnormalities

Reactivation infection in immunosuppressed pregnant women also can cause fetal infection

T. gondii

three forms trophozoites or proliferative tissue cysts Oocytes

Trophozoite is seen in the acute phase of the infection in the human

Mulitiplies every 4-6 hours

cells ruptureReleasing

organisms to invade other cells

Utero Transmission

Newborns become infected in utero by transplacental passage of the parasite when the mother has acute infection

Chronic infections (onset precedes pregnancy) do not lead to congenital infection except in the rare circumstance of an

immunocompromised host with reactivation likelihood of fetal infection increases with each

trimester of pregnancy Fetal infection is :

15% in the first trimester, 25% second, 60% in third trimester

Utero Transmission

The severity of damage associated with timing of maternal infection the risks decrease toward term

Severe fetal disease or fetal death: occurs in about 10% of cases when infection

occurs during the first trimester extremely rare with infection during the third

trimester Mild damage is more frequent in the

second and third trimesters (about 5%)

Utero Transmission

Subclinical infections increase from about 2% with first-trimester infections to 50% with third-trimester infections

acute infection could be associated with preterm delivery and stillbirth but not with spontaneous abortion

TRANSPLACENTAL TRANSMISSION

Time of infection Likelihood of transmission in

untreated mothers

Disease in infant

>6 months before conception

No Risk ---

<6 months before conception

Very Low Risk

---

First trimester 10-25% Most severe

Second trimester 30-54% Less severe

Third trimester 60-65% Usually Asymptomatic

Diagnosis in Pregnancy

1. Maternal Infection usually is asymptomatic 10% to 20% of infected mothers have

lymphadenopathy (Posterior cervical is the most frequent )

The infection also can result in a mononucleosis like syndrome with:

fatigue assitude and rarely, can cause encephalitis The clinical picture can be much more severe in

immunocompromised adults.

1. Maternal Infection

clinicians are forced to rely on serologic tools for the diagnosis of toxoplasmosis in pregnancy

diagnosis of primary infection : demonstration of a seroconversion to this

organism significant rise in antibody titer obtained from

maternal sera taken at two different times detection of toxoplasma-specific IgM antibody

Maternal Infection

Adults with primary infection develop IgG and IgM antibody to toxoplasma rapidly

Toxoplasma-specific IgG antibody: develops within after infection peaks in 6 to 8 weeks2 weeks drops down over the subsequent several months then persists for life

Toxoplasma-specific IgM develops within 10 days after infection remains elevated for 6 months to more than 6 years

Maternal Infection

IgM titers may not provide useful information to document recent primary infection in pregnant women

The IFA test frequently is more useful than ELISA in differentiating remote from recent primary infection of a pregnant woman

In any case, the presence of IgG and the absence of IgM suggest an infection that is probably at least a year old

Maternal Infection

Up to 40% of positive toxoplasma-specific IgM are false positives

Avidity testing is a newer type of testing

Approximately 50% of placentas of congenitally infected infants will show T. gondii cysts on histologic slides

Additional cases can be detected by the presence of parasites in the cord blood

Maternal Infection

The organism also has been isolated from placental tissue of acutely infected mothers in 2% to 25% of cases

Isolation of organisms from tissue specimens, buffy coat heparinized blood body fluids

2. Prenatal Diagnosis

Antenatal diagnosis of fetal toxoplasmosis culture of amniotic fluid fetal blood

The main difficulties with culture techniques: some assays may take up to several weeks few laboratories are able to perform the assay

amniocentesis performed too early in gestation occasionally can be falsely negative

Prenatal Diagnosis

Toxoplasma-specific IgM, when present in fetal blood from cordocentesis, also has been used to diagnose fetal infection prenatally

fetal-specific IgM antibody frequently does not develop until after 21

to 24 weeks gestation is positive in only about 50% of infected

cases

Additionally, cordocentesis is a procedure that entails some risk.

Prenatal Diagnosis

the PCR has been used to detect T. gondii in amniotic fluid and has been shown to be useful in the detection of in utero infections

Prenatal ultrasound also may demonstrate abnormalities

Ventriculomegaly and hydrocephalus as well as microcephaly will be poor prognosticators

Intracranial calcifications, placentomegaly, hepatomegaly cataracts, and hydrops may be other signs

3. Neonatal Infection

Most congenitally infected newborns are asymptomatic at birth

Literature has shown that detection of toxoplasma-specific immunoglobulin A (IgA) may be a reliable method for the diagnosis of toxoplasmosis in the newborn

Demonstration of toxoplasma-specific IgM infection may be diagnostic, although in newborns approximately 20% of infections are not detectable by

toxoplasma-specific IgM at birth

A number of these asymptomatic, untreated infants will go on to have delayed and potentially serious manifestations

Neonatal Infection

20% with clinically obvious symptoms at birth will exhibit multiple findings

The most frequent clinical findings are : Chorioretinitis jaundice Fever Hepatosplenomegaly

in severe cases : Hydrocephaly microcephaly cerebral calcifications

Treatment

Treatment of acute toxoplasmosis in immunocompetent, nonpregnant adults is primarily supportive

the prognosis following acute infection is good, except in cases of profound immunosuppression

The treatment in pregnancy is a bit more complex

Treatment In Europe spiramycin is the first-line agent

used agent generally does not cross the

placenta, and if fetal infection is detected, women also are treated with a combination of pyrimethamine folinic acid sulfonamide

Treatment Although not definitive, treatment with these

regimens may prevent maternal-to-fetal transmission of the infection or improve the outcome among infected fetuses

The standard dosage is : 25 mg of pyrimethamine by mouth given daily 1 g of sulfadiazine by mouth four times daily for 1 year Folinic acid, 6 mg given intramuscularly or by mouth every

other day

***Pyrimethamine is a folic acid antagonist and therefore may have teratogenic effects when given in the first

trimester

Prevention

avoid eating raw or undercooked meat Fruits and vegetables should be peeled and

washed before eating proper hand hygiene Gloves should be used for gardening and

during any contact with soil or sand Pregnant women should avoid close contact

with cat feces need for obstetricians to educate pregnant

patients about these important preventive steps

Prevention

routine serologic screening programs screening of newborns and the institution

of treatment during the neonatal period to minimize the morbidity

Many infections in children that otherwise would be missed on routine clinical examination can be detected with IgM assays

Treatment of these infected infants has been associated with very low rates of subsequent neurologic or retinal disease

Many thanks . . .