Congenital toxoplasmosis

• A protozoa that causes a self-limiting (usually asymptomatic) infection in healthy people, resulting in lifelong immunity to further infection (i.e. can only get it once).
• There is a risk of fetal infection if maternal infection occurs during pregnancy.
• Unlike CMV, fetal infection due to maternal reactivation/reinfection is not a risk in immune-competent women.
• Overall, around 10% of congenitally infected infants will develop long-term sequelae.
• The incidence of congenital infection varies internationally, based on hygiene practises (i.e. level of exposure to cat faeces), and culinary practises (i.e. level of exposure to undercooked meat).

• If maternal infection occurs, the risk of fetal infection increases with fetal age (due to increasing placental size).
• However, if fetal infection does occur, the risk of sequelae decreases with fetal age.

• Routine screening in pregnant women in NZ not recommended, including if they have a cat.
• Test in pregnant women with possible acute infection e.g. fever, cervical lymphadenopathy.
• Test in pregnant women with fetal USS findings that may suggest congenital infection.
  • Commonest are intracranial hyperechoic foci/calcifications or ventricular dilation.
  • A number of other USS findings may be seen, including other CNS abnormalities, hyperechoic bowel, IUGR, ascites/pleural/pericardial effusion, hepatosplenomegaly.

Request “Toxoplasma serology”

• Toxoplasma IgG indicates infection at some point in time (can be acute or past infection). Usually appears within 2 weeks of symptoms and persists life-long.
  • Excellent sensitivity – a negative result excludes toxoplasma infection, unless within 2 weeks of infection
  • Excellent specificity – a positive result confirms infection at some stage
• Toxoplasma IgM is a marker of primary (acute) infection and usually appears within 1 week of symptoms. May persist for months or years.
  • Good sensitivity – a negative resultmakes the diagnosis very unlikely if >1 week of symptoms.
  • Moderate specificity – a positive result in someone with compatible symptoms is supportive, but cannot confirm toxoplasmosis.
  • Because of the importance of diagnosing acute toxoplasmosis in pregnancy, further investigations should be undertaken in women with a positive IgM. This should be discussed with a clinical microbiologist.
    • If the antenatal booking blood sample predates symptoms, then this can be retrieved for serology testing.
      • Conversion from IgG negative to positive confirms acute toxoplasmosis.
      • IgG positivity on the booking sample if prior to symptoms excludes acute toxoplasmosis.
  • IgG avidity testing can also be performed on either the current sample or booking sample if necessary (discuss with microbiologist):
    • High avidity suggests acute infection >4 months prior
    • Low avidity is less specific and can mean recent or old infection.

Request “Toxoplasma serology”

• Toxoplasma IgG indicates infection at some point in time (can be acute or past infection)
  • Excellent sensitivity – negative result excludes congenital toxoplasmosis as cause of USS findings
  • Poor specificity – positive result indicates maternal infection at some point in time, but gives no indication as to whether infection may have passed to fetus
• If the Toxoplasma IgG is positive then these points should be considered (in conjunction with a clinical microbiologist):
  • Has acute maternal infection occurred during pregnancy?
  • If maternal infection during pregnancy may have occurred, has fetal infection occurred?
    • The decision on whether to pursue further investigations is based on the likelihood of acute maternal infection, and how suspicious the USS findings are. This should be in conjunction with a maternal fetal medicine specialist.
• If antenatal diagnosis is pursued, then amniocentesis for Toxoplasma PCR is the test of choice:
  • Sensitivity is high if performed between 18-21 weeks gestation and >4 weeks after possible maternal infection. Otherwise sensitivity is lower.

• This is complicated, and it is often not possible to definitively exclude infection at birth.
• If the maternal toxoplasma IgG is negative, then congenital toxoplasmosis can be excluded without the need for any infant testing. Otherwise:
• Workup usually involves a combination of testing of infant and placenta
  • Paired infant and maternal toxoplasma serology 
    • Suggestive, but not confirmatory of congenital infection:
      • infant IgM positive, or;
      • IgG value significantly higher than mother’s
  • Toxoplasma PCR on infant blood or CSF
    • Moderate sensitivity – negative result doesn’t exclude congenital infection
    • Excellent specificity – positive result confirms congenital infection
  • Histology and toxoplasma PCR on placenta
    • Moderate sensitivity – negative result doesn’t exclude congenital infection
    • Good specificity – positive result makes congenital infection likely
• If the diagnosis cannot be excluded at birth (common), then infant serology should be monitored periodically
  • At 12-18 months of age:
    • Positive infant toxoplasma IgG – confirms congenital infection
    • Negative infant toxoplasma IgG: – excludes congenital infection

Toxoplasma IgA serology

• This is often considered a better marker of acute infection than IgM because levels decline sooner, whereas IgM may remain positive for months.
• However, most laboratories do not have IgA testing available.

Confirmation of congenital infection in a fetus or neonate only tells you congenital infection has occurred, it does not tell you whether the infection will cause sequelae or not.