Toxoplasmosis in pregnancy

Clinical Manifestations

• Often no history of illness during pregnancy
• Symptoms, if present, tend to be mild with low-grade fever, malaise, and lymphadenopathy
• Only half of women can identify a significant risk factor1
• Risk of transmission to fetus is with parasitemia associated with primary infection, so women who are seropositive are not at risk of having a child with congenital infection

Diagnosis

• Molecular
  • Definitive diagnosis is based on PCR of amniotic fluid around 18 months, usually done after maternal serology to confirm intrauterine infection
    • Sensitivity is 64 to 92% and specificity 100% (NPR around 88 to 98%)
    • Earlier than 18 weeks has unknown sensitivity and specificity, and has a higher risk of spontaneous abortion
  • Can also be done on fetal blood
• Serology
  • Can check maternal IgM and IgG, both of which appear within the first week after infection
  • IgM is not specific to recent infection, however, as it can be present for more than a year
  • IgG avidity testing is used to determine recency of infection
    • Low avidity is 35-50% and high is >60%
    • Low avidity is unhelpful, as avidity can remain low for more than a year
    • High avidity, on the other hand, suggests infected at least 3-4 months prior
  • Therefore, if infection is suspected in the first 16 weeks of gestation, high avidity effectively rules out infection acquired during pregnancy
• Needs serial head ultrasound to monitor for hydrocephalus and intraparenchymal brain calcifications
  • May also see hepatic calcifications, splenomegaly, and ascites

Management

IgM	IgG	Interpretation	Management
+	–	acute primary infection or false positive	repeat serology in 2 to 3 weeks; if unchanged, then was false positive
+	+	recent or prior infection	high IgG avidity: infection was >4 months ago so unlikely to be acute
			low IgG avidity: cannot determine when infection occurred
–	+	remote infection	no risk of transmission except rare cases of immunocompromise
–	–	no prior infection; at risk	counsel on prevention of primary infection

• In general, for highly suspected or confirmed infection, it is reasonable to start spiramycin while confirming the infection
• If acute infection, such as IgM + / IgG – that converts to IgG +, or IgM + / low IgG avidity with compatible clinical picture, then rule out fetal infection with an amniocentesis after week 18
• If infected < 14 weeks gestation, spiramycin 3 g/day until delivery
  • However, it doesn't cross the placenta and it's unclear whether it affects outcomes in the baby
  • Likely most effective if given within 8 weeks of maternal infection
  • Pyramethamine is contraindicated in pregnancy before 14 weeks gestation
  • Second-line would be monotherapy with sulfadiazine or clindamycin
• If age ≥ 14 weeks gestation and documented fetal infection by amniocentesis, or if suspected infection was ≥14 weeks gestation, use standard therapy
  • Standard therapy is: pyrimethamine 50 mg q12h for 2 days followed by 50 mg daily (plus folinic acid 10-20 mg daily until 1 week after stopping pyrimethamine), and sulfadiazine 75 mg/kg load followed by 50 mg/kg q12h (maximum 4 g/day)
  • This treatment crosses the placenta, which is why it is used in cases of documented or suspected fetal infection, as well as in later-term infections when the risk of fetal infection is higher
  • Therefore, if initially started on spiramycin, then switch to standard therapy if amniotic fluid PCR is positive or ultrasound is abnormal
  • However, it is teratogenic until 14 weeks gestation so spiramycin is used until then
• If age ≥33 weeks gestation, then continue spiramycin and await a postnatal diagnosis

Prevention

• Prevention mostly focusses on counselling around risk reduction:
  • Wash hands after changing cat litter
  • Wear gloves in the garden and when changing cat litter
  • Cook meat thoroughly
  • Avoid raw eggs and unpasteurized dairy
  • Wash fruits and vegetables
  • Do not obtain a new cat while pregnant