Toxoplasmosis in pregnancy

1. Benha University Hospital, EGYPT
E mail: elnashar53@hotmail. com
TOXOPLASMOSIS
IN PREGNANCY
Aboubakr Elnashar

2. DEFINE
Disease caused by an obligate intracellular
parasite;T. gondii
HISTORY
•Wolf & Cowen (1937): congenital Toxoplasmosis
•Sabin & Feldman (1948): dye test
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3. PREVALENCE
• Depend on:
1. Age: seroconversion increases by 1% /y
2. Eating habits
3. Exposure
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4. U.K Egypt Germany USA France
Sero +ve 25% 30% 35% 50% 75%
Seroconversion
in pregnancy
0.2% ? 0.6% 0.6% 1%
Acute infection complicates 1-5 ‰ of
pregnancies
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5. Aboubakr Elnashar

6. Bradyzoite Bradyzoite
Tachyzoite
Bradyzoite
Sporozoite
Tachyzoite
Bradyzoite
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7. FORMS
1. Oocyst:
excreted in farces of cats,
sporulate in the soil to form sporocyst.
2. Tissue cyst:
latent form,
contain bradyzoites,
represent chronic stage,
persist for life in humans Aboubakr Elnashar

8. 3. Tachzoites:
invasive form,
multiplies intracellularly,
found in tissues in acute stage or during
reactivation of the chronic infection
spread in blood & lymph,
disappear with development of the normal
immune response
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9. TRANSMISSION OF INFECTION
1. ORAL:
Tissue cysts: 10 % of lamb, 25 % of pork, beef, poultry. Pork
and lamb carry a higher risk of infection than beef or poultry.
Oocyst: 30 - 80 % of cats (low parasite dose)
2.TRANSPLACENTAl:
Primary acute infection during pregnancy
Maternal parasitaemia [Tachyzoites] (limited to 3 W): Placentitis:
Fetal infection
3 . BLOOD or LEUCOCYTES TRANSFUSION
(Tachyzoites) or
ORGAN TRANSPLANTATION (Tissue cysts): (Rare)
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10. Soil contact (cat
feces):17%
Eating infected
meat: 65%
Cook et al BMJ 2000;321:142-147(Multicenteric) [Evidence level 3]
Inadequately cooked meat is the main risk factor
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11. CLINICAL PICTURE
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12. Immunocomptent
•Mild & self-limited
•I.P :1-3 w
•90 %: asymptomatic
•10 %: lymphadenitis (painless, cervical LN), fever, sore
throat, rash
lymphocytosis, atypical lymphocytes
•DD: flu, inf. mononucleosis
Immunocompromised
•Severe, fulminate, CNS, Eye
Immunodeficient
•Fatal, CNS, Eye, heart &lung
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13. Congenital toxoplasmosis
•Effects: 67 % uninfected
2 % IUFD
31 % infected :
Before pregnancy: 0%
1st mo: 1 % (usually abortion)
2nd&3rd mo: 17 %
9 th mo: 90%
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14. •Incidence of fetal infection: greater in late
pregnancy
•Severity of fetal infection: greater in early
pregnancy
• Cl. forms: Triad
1 Attenuated:
chroretinitis, microphthalmia, hypotonia
2. Serious: 10%
IC calcification, icterus, encephalopathy
3. Latent:
convulsions, hydrocephalus, chorioretinitis
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15. Transmission risk
(mother to fetus)
Severity of
Damage to fetus
15% 25% 65%
Most less least
1st
Trimester
2nd
Trimester
3rd
Trimester
[Evidence level 3] Foulon et al. A.J. of Obst&Gynecology 1999;180:410–5
Hydrocephalus.
Intracranial calcification,
Retinochoroiditis
60% 20% 5%
Transmission To The Fetus
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16. As in rubella, toxoplasmosis
1. Is dangerous for the fetus only if the initial
infection occurs during pregnancy
2. Infection confers lasting immunity
(Fields,1990)
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17. INVESTIGATIONS
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18. Parasite
isolation
Parasite
detection
Serology Histology Other
Lymph
adenopathy
IgG
IgM
Excision
biopsy
Pregnancy IgG
IgM
IgG Avidity
Fetus Am F
Bl cells
Bl cells IgM
IgA
Total IgM
LFT
Neonate Placenta
Bl cells
Bl cells Seq IgG
IgM
IgA
Radiology of the
brain
Ocular
disease
Ocular
fluids
IgG
Local Ab
Ocular
examination
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19. Appear Maximum Disappear
Ig M
Ig G
1week
2 weeks
Few months
± few years
(6 mo to 6 yr)
Not
disappear
Individuals who have recovered from prior
toxoplasmosis may demonstrate Anamnestic spike in
IgG titer during subsequent episodes of other infections.
-ve IgM excludes acute infection
1 month
2 month
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20. Diagnosis of acute infection
1. IgG: dye test > 1/ 1000.
The gold standard test (sensitive & specific)
IFA > 1/ 512
Titer Increase 4 folds over 3 w
Seroconversion
Avidity: low
2. IgM: ELISA. Remains high for many yr after acute infection
IFA > 1/ 80. Remains elevated for 6 mo after acute
infection, then rapidly drops. More useful than ELISA
ISA > 6
The presence of IgM is suggestive but not diagnostic.
3. IgA or IgE: more sensitive than IgM
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21. Negative Negative No serological evidence of infection
Negative Positive Possible acute infection or false-positive IgM result
Positive Negative Infection for more than 1 year.
Positive Positive Possible recent infection within the last 12 months.
IgG IgM Report/Interpretation for All Except Infants
Equivocal IgG or IgM: obtain a new specimen for both IgG and IgM testing.
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22. IgG
Neg: Not infected, retest/ 1-3 ms for
seroconversion Pos: Infected
Neg: Infected for >1 y Pos: Infection within last 2 ys or
false positive
IgM
IgG avidity
High: Infected at >12 ws previously low: Recent infection possible
Obtain 2nd sample 2 ws after 1st; send both samples to toxoplasma
reference lab for confirmation before any intervention.Aboubakr Elnashar

23. The IgG avidity test
Discriminate between past and recently acquired
infection. Avidity (functional affinity) of toxoplasma-
specific IgG antibodies. Following an antigenic
challenge, the antibodies produced usually have a low
average affinity. During the course of the immune
response, there is maturation of antibody affinity that
increases progressively over weeks or months.
The avidity tests are helpful primarily to rule out that a
patient’s infection occurred within the prior 4 to 5
months. This is most useful in pregnant women in their
first months of gestation who have a positive test for
both IgG and IgM toxoplasma antibodies.
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24. Diagnosis of fetal infection
1. U/S
No findings: 80%
Specific findings:
Hydrops,
Ventriculomegaly (mild symmetrical to severe hydrocephalus),
Intracranial calcifications (periventricular)
Non specific findings:
ascites,
hepatomegaly,
liver calcification,
pericardial /pleural effusion,
oligohydramnios, IUGR, placental thickness
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25. 2. Amniocentesis or cordocentesis
. IgM
. High eosinophil count, LFT & low platelet count
. PCR: sensitive & specific
. Inoculation to mice or tissue culture
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26. Aboubakr Elnashar

27. •Depends upon:
prevalence rate & economic issues.
Cost benefit ratio
•Obligatory in: France, Austria, Belgium.
•Not done in UK, Egypt.
In USA (precomceptional)
In France (prenuptial)
NICE (2003):
Routine antenatal serological screening for
toxoplasmosis should not be offered because the
harms of screening may outweigh the potential
benefits. [B]
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28. •ACOG (2000): SCREENING in:
-High-risk persons
Who eat undercooked meat (pork, lamb)
Who clean litter boxes.
Who garden without glove.
Who have had a recent mononucleosis-type like illness
-U/S findings suggestive of toxoplasmosis:
hydrocephalus
intracranial calcifications
Microcephaly
fetal growth retardation
Ascites
Hepatosplenomegaly [C]
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29. •Indications of screening during pregnancy
(Bader et al,1997)
1. Symptoms suggestive of acute infection
2. Exposure to the organism during pregnancy
3. Residence or migration to high prevalence
areas e.g. France
4. Infection with HIV
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30. Preconceptional:
IgG +ve No further tests
-ve IgG/ 4-8 W during pregnancy
First antenatal visit:
IgG -ve IgG/4-8 w +ve Acute infection
+ve IgM titer high Acute infection
-ve or low Past infection
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31. TREATMENT
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32. Indications:
•Pregnancy
•Immunocompromised or immunodeficient
•Severe persistent symptoms
•Serious damage of vital organs
•Infection acquired via blood transfusion
Mode of action:
Non of the drugs is effective against the encysted
form
slowing down multiplication of tachozites
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33. Aim during pregnancy:
1. Prevention of localization in the placenta
2. Prevention or modification of neonatal infection
By 60% (Holfeld et al, 1994)
No effect on intracranial or occular lesions (Gras
et al, 2001)
Effectiveness is less
if infection acquired in late pregnancy or
tt is delayed.
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34. Pyrimethamine & S. diazine combination
Pyrimethamine
• Mode of action:
inhibit production of dihydrofolate reductase &
synthesis of DNA,RNA & proteins
•Side effects:
teratogenic in first trimester
bone marrow depression
•How to avoid side effects:
not used in 1st trimester
CBC/4d
folonic ac (yeast tab 8 tab/4d)Aboubakr Elnashar

35. S. diazine
•Other types of sulpha:
S. pyrimidine, S. pyrazine, S. methazine.
• Side effects:
crystalluria
haematuria
rash
neonatal hyper bilirubinemia at term
• How to avoid side effects:
Maintain high urinary flow
not used at term.
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36. •Dose & duration
Non pregnant
Pyrim: loading dose: 2 mg/ k/d x 2 d
Maintenance dose: 1 mg/ k/d x 4 - 6 w
S. diazine: Loading dose: 50 mg /k
then 100 mg / k /d 4 divided doses
Pregnant
1 st trimester: S. diazine (50 - 100 mg /k /d)
2nd & 3rd trimester: S. diazine + Pyrim.(0.5 -1 mg /k /d)X4 w
At term: Pyrim.
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37. Spiramycin
• Mode of action:
macrolide cross placental barrier poorly.
intracellular toxoplasmicidal
•Side effects:
n. & vomiting, diarrhea, allergic skin reaction
•Dose: (T= 1.5 million iu= 0.5 gm)
# 3 gm in 4 divided doses X 3 w on & 2 w off till
term
# If f. infection is confirmed:
Pyrim. & S. diazine X 3 w then spiramycin x 3 w
& so on till delivery
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38. •Therapeutic abortion is not recommended
1. Risk of transmission to the f. is low
2. Treatment can prevent f. infection as the
parasite takes 4-8 w to cross placenta
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39. Aboubakr Elnashar

40. Prevention of maternal infection (primary prevention)
•Kill tissue cysts in the meat :
heat 60c
freeze at -20 or -6 for 24 h
•Avoidance of oocytes from cats :
Hand wash,
Wear gloves,
Wash fruits & vegetables
Dry heat or boiling water
Avoid contamination with cats
Prevent infection of cats
• Avoid blood or blood products with toxoplasmosis
Aboubakr Elnashar

41. Prevention of congenital infection (secondary
prevention)
•Preconceptional screening
•Diagnosis & treatment of acute infection during
pregnancy
•Avoid infection during pregnancy
Tertiary Prevention:
Early detection and treatment of neonatal
disease
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42. Aboubakr Elnashar

43. •Toxoplasmosis is not a cause of habitual
abortion.
•Routine screening should consider the cost
benefit ratio.
•If IgG is +ve before pregnancy: No need for
retesting or treatment. No fear of congenital
infection.
•Only primary acute infection can lead to fetal
infection which occurs in 33%.
•Acute infection is diagnosed if IgM is high or IgG
avidity is low.
•+ve IgG or +ve IgM is not diagnostic of acute
infection.
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44. Thanks
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