Infection: Congenital toxoplasmosis; congenital Toxoplasma gondii infection

Also refer to: How do I diagnose – Toxoplasmosis

Brief description:
  • 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).
Did you know?
  • 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.
Diagnostic approach:
  • 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.
Antenatal diagnosis test of choice (if possible maternal acute infection):

RequestToxoplasma 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.

Antenatal diagnosis test of choice (if abnormal USS findings):

RequestToxoplasma 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.
Postnatal diagnosis:
  • 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 IgGconfirms congenital infection
      • Negative infant toxoplasma IgG: – excludes congenital infection

Tests to avoid/specialist tests:

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.
Other considerations:

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.