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Benha University Hospital, EGYPT
E mail: elnashar53@hotmail. com
TOXOPLASMOSIS
IN PREGNANCY
Aboubakr Elnashar
DEFINE
Disease caused by an obligate intracellular
parasite;T. gondii
HISTORY
•Wolf & Cowen (1937): congenital Toxoplasmosis
•Sabin & Feldman (1948): dye test
Aboubakr Elnashar
PREVALENCE
• Depend on:
1. Age: seroconversion increases by 1% /y
2. Eating habits
3. Exposure
Aboubakr Elnashar
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
Aboubakr Elnashar
Aboubakr Elnashar
Bradyzoite Bradyzoite
Tachyzoite
Bradyzoite
Sporozoite
Tachyzoite
Bradyzoite
Aboubakr Elnashar
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
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
Aboubakr Elnashar
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)
Aboubakr Elnashar
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
Aboubakr Elnashar
CLINICAL PICTURE
Aboubakr Elnashar
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
Aboubakr Elnashar
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%
Aboubakr Elnashar
•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
Aboubakr Elnashar
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
Aboubakr Elnashar
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)
Aboubakr Elnashar
INVESTIGATIONS
Aboubakr Elnashar
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
Aboubakr Elnashar
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
Aboubakr Elnashar
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
Aboubakr Elnashar
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.
Aboubakr Elnashar
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
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.
Aboubakr Elnashar
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
Aboubakr Elnashar
2. Amniocentesis or cordocentesis
. IgM
. High eosinophil count, LFT & low platelet count
. PCR: sensitive & specific
. Inoculation to mice or tissue culture
Aboubakr Elnashar
Aboubakr Elnashar
•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]
Aboubakr Elnashar
•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]
Aboubakr Elnashar
•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
Aboubakr Elnashar
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
Aboubakr Elnashar
TREATMENT
Aboubakr Elnashar
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
Aboubakr Elnashar
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.
Aboubakr Elnashar
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
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.
Aboubakr Elnashar
•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.
Aboubakr Elnashar
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
Aboubakr Elnashar
•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
Aboubakr Elnashar
Aboubakr Elnashar
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
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
Aboubakr Elnashar
Aboubakr Elnashar
•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.
Aboubakr Elnashar
Thanks
Aboubakr Elnashar

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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 Aboubakr Elnashar
  • 3. PREVALENCE • Depend on: 1. Age: seroconversion increases by 1% /y 2. Eating habits 3. Exposure Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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) Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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% Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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) Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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. Aboubakr Elnashar
  • 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. Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 25. 2. Amniocentesis or cordocentesis . IgM . High eosinophil count, LFT & low platelet count . PCR: sensitive & specific . Inoculation to mice or tissue culture 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] Aboubakr Elnashar
  • 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] Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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. Aboubakr Elnashar
  • 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. Aboubakr Elnashar
  • 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. Aboubakr Elnashar
  • 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 Aboubakr Elnashar
  • 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 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 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. Aboubakr Elnashar