Congenital toxoplasmosis: Difference between revisions

Revision as of 17:11, 30 July 2020

Background

Can be acquired during maternal parasitemia associated with primary infection
- However, it is possible to acquire from reactivation of latent toxoplasmosis in an HIV-infected mother
Risk of transplacental infection of fetus is lowest in first trimester and highest in third
See also toxoplasmosis in pregnancy

Clinical Manifestations

At birth, 85% of infected babies are asymptomatic and only 15% are symptomatic
- Risk of infection is related to trimester of infection: 6% in first, 40% in second, and 72% in third
- Risk of signs of congenital infection is inversely related to trimester of infection: 61% in first, 25% in second, and 9% in third
Classic triad of chorioretinitis (most common), intraparenchymal cerebral calcifications, and hydrocephalus
Others: thrombocytopenia, hepatitis, hepatosplenomegaly, cataracts, strabismus, microphthalmia

Diagnosis

Standard workup starts with serology, then adds PCR and other investigations if clinical suspicion is high
Serology: in neonates, IgG serology reflects maternal status, so use IgM and IgA instead
Molecular testing: if clinical suspicion is high, add PCR of the peripheral blood, urine, and CSF to the serology
If clinical suspicion is high, also get ophthalmologic evaluation, hearing assessment, ultrasound or CT of the brain, and lumbar puncture

Management

Postnatal treatment of neonates is with standard therapy for at least 12 months
- Sulfadiazine 50 mg/kg q12h
- Pyrimethamine 1 mg/kg q12h for 2 days (load), followed by 1 mg/kg for 2 to 6 months, followed by 1 mg/kg qMWF
- Folinic acid 10 mg PO thrice weekly until 1 week after pyrimethamine is stopped
Treatment of congenital infection in older children is standard therapy until 1 to 2 weeks after resolution of signs or symptoms
- Pyrimethamine 1 mg/kg q12h (max 50 mg) for 2 days, followed by 1 mg/kg/day (max 25 mg)
- Sulfadiazine 75 mg/kg load, followed by 50 mg/kg q12h (max 4 g/day)
- Folinic acid 10-20 mg po thrice weekly
- Can add prednisone for severe chorioretinits at 1 mg/kg/day divided bid (max 40 mg/day), followed by a rapid taper
Serial evaluations with a clinical assessment, neuroradiology, ophthalmology, and CSF analysis
For prevention, refer to the management of toxoplasmosis in pregnancy

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-== Background ==
+==Background==
-* Can be acquired during maternal parasitemia associated with primary infection
-** However, it is possible to acquire from reactivation of latent toxoplasmosis in an HIV-infected mother
-* Risk of transplacental infection of fetus is lowest in first trimester and highest in third
+*Can be acquired during maternal parasitemia associated with primary infection
-== Clinical Manifestations ==
+**However, it is possible to acquire from reactivation of latent toxoplasmosis in an HIV-infected mother
-* Often no history of illness during pregnancy
+*Risk of transplacental infection of fetus is lowest in first trimester and highest in third
-** Symptoms, if present, tend to be mild with low-grade fever, malaise, and lymphadenopathy
+*See also [[toxoplasmosis in pregnancy]]
-* At birth, 85% of infected babies are asymptomatic and only 15% are symptomatic
-** Risk of infection is related to trimester of infection: 6% in first, 40% in second, and 72% in third
-** Risk of signs of congenital infection is inversely related to trimester of infection: 61% in first, 25% in second, and 9% in third
-* Classic triad of [[Causes::chorioretinitis]] (most common), [[Causes::intraparenchymal cerebral calcifications]], and [[Causes::hydrocephalus]]
-* Others: [[Causes::thrombocytopenia]], [[Causes::hepatitis]], [[Causes::hepatosplenomegaly]], [[Causes::cataracts]], [[Causes::strabismus]], [[Causes::microphthalmia]]
+==Clinical Manifestations==
-== Diagnosis ==
-=== In pregnancy ===
-* 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
-** 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, avidity testing may be able to rule out infection during pregnancy
-* Needs serial head ultrasound to monitor for hydrocephalus and intraparenchymal brain calcifications
-** May also see hepatic calcifications, splenomegaly, and ascites
+*At birth, 85% of infected babies are asymptomatic and only 15% are symptomatic
-=== In children ===
+**Risk of infection is related to trimester of infection: 6% in first, 40% in second, and 72% in third
-* Standard workup starts with serology, then adds PCR and other investigations if clinical suspicion is high
+**Risk of signs of congenital infection is inversely related to trimester of infection: 61% in first, 25% in second, and 9% in third
-* Serology
+*Classic triad of [[Causes::chorioretinitis]] (most common), [[Causes::intraparenchymal cerebral calcifications]], and [[Causes::hydrocephalus]]
-** In neonates, IgG serology reflects maternal status, so use IgM and IgA instead
+*Others: [[Causes::thrombocytopenia]], [[Causes::hepatitis]], [[Causes::hepatosplenomegaly]], [[Causes::cataracts]], [[Causes::strabismus]], [[Causes::microphthalmia]]
-* Molecular testing
-** If clinical suspicion is high, add PCR of the peripheral blood, urine, and CSF to the serology
-* Other
-** If clinical suspicion is high, also get ophthalmologic evaluation, hearing assessment, ultrasound or CT of the brain, and lumbar puncture
-== Management ==
+==Diagnosis==
-=== In pregnancy ===
-* If infected < 14 weeks gestation, [[Is treated by::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
-** Second-line would be monotherapy with [[Is treated by::sulfadiazine]] or [[Is treated by::clindamycin]]
-* If age ≥ 14 weeks gestation and documented fetal infection, or if suspected infection was ≥14 weeks gestation, use standard therapy
-** Standard therapy is: [[Is treated by::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 [[Is treated by::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
+*Standard workup starts with serology, then adds PCR and other investigations if clinical suspicion is high
-=== In children ===
+*Serology: in neonates, IgG serology reflects maternal status, so use IgM and IgA instead
-* Postnatal treatment of neonates is with standard therapy for at least 12 months
+*Molecular testing: if clinical suspicion is high, add PCR of the peripheral blood, urine, and CSF to the serology
-** [[Is treated by::Sulfadiazine]] 50 mg/kg q12h
+*If clinical suspicion is high, also get ophthalmologic evaluation, hearing assessment, ultrasound or CT of the brain, and lumbar puncture
-** [[Is treated by::Pyrimethamine]] 1 mg/kg q12h for 2 days (load), followed by 1 mg/kg for 2 to 6 months, followed by 1 mg/kg qMWF
-** [[Folinic acid]] 10 mg PO thrice weekly until 1 week after [[pyrimethamine]] is stopped
+==Management==
-* Treatment of congenital infection in older children is standard therapy until 1 to 2 weeks after resolution of signs or symptoms
-** [[Is treated by::Pyrimethamine]] 1 mg/kg q12h (max 50 mg) for 2 days, followed by 1 mg/kg/day (max 25 mg)
+*Postnatal treatment of neonates is with standard therapy for at least 12 months
-** [[Is treated by::Sulfadiazine]] 75 mg/kg load, followed by 50 mg/kg q12h (max 4 g/day)
+**[[Is treated by::Sulfadiazine]] 50 mg/kg q12h
-** [[Folinic acid]] 10-20 mg po thrice weekly
-** Can add [[prednisone]] for severe chorioretinits at 1 mg/kg/day divided bid (max 40 mg/day), followed by a rapid taper
+**[[Is treated by::Pyrimethamine]] 1 mg/kg q12h for 2 days (load), followed by 1 mg/kg for 2 to 6 months, followed by 1 mg/kg qMWF
+**[[Folinic acid]] 10 mg PO thrice weekly until 1 week after [[pyrimethamine]] is stopped
-* Serial evaluations with a clinical assessment, neuroradiology, ophthalmology, and CSF analysis
+*Treatment of congenital infection in older children is standard therapy until 1 to 2 weeks after resolution of signs or symptoms
+**[[Is treated by::Pyrimethamine]] 1 mg/kg q12h (max 50 mg) for 2 days, followed by 1 mg/kg/day (max 25 mg)
+**[[Is treated by::Sulfadiazine]] 75 mg/kg load, followed by 50 mg/kg q12h (max 4 g/day)
+**[[Folinic acid]] 10-20 mg po thrice weekly
+**Can add [[prednisone]] for severe chorioretinits at 1 mg/kg/day divided bid (max 40 mg/day), followed by a rapid taper
+*Serial evaluations with a clinical assessment, neuroradiology, ophthalmology, and CSF analysis
+*For prevention, refer to [[Toxoplasmosis in pregnancy#Management|the management of toxoplasmosis in pregnancy]]
 [[Category:Obstetrical infections‏‎]]