1. Toxoplasmosis in pregnancy

2. 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

3. 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

4. Transmission Food Organ transplantation
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

6. 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

7. 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

8. 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 rupture
Releasing organisms to invade other cells

10. 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

11. 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%)

12. 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

13. 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

14. 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.

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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.

22. 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

23. 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

24. 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

26. 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

27. 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

28. 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

29. 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

30. 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

32. Many thanks . . .