Congenital toxoplasmosis: Difference between revisions

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== Background ==
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==Background==
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* Can be acquired during maternal parasitemia associated with primary infection
  
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** However, it is possible to acquire from reactivation of latent toxoplasmosis in an HIV-infected mother
  
βˆ’
* Risk of transplacental infection of fetus is lowest in first trimester and highest in third
  
   
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*Can be acquired during maternal parasitemia associated with primary infection
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== Clinical Presentation ==
  
  +
**However, it is possible to acquire from reactivation of latent toxoplasmosis in an HIV-infected mother
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* Often no history of illness during pregnancy
  
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*Risk of transplacental infection of fetus is lowest in first trimester and highest in third, but the risk of severe disease is highest if infected in first trimester and lowest in third trimester[[CiteRef::2007ef]]
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** Symptoms, if present, tend to be mild with low-grade fever, malaise, and lymphadenopathy
  
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*See also [[toxoplasmosis in pregnancy]]
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* At birth, 85% of infected babies are asymptomatic and only 15% are symptomatic
  
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** Risk of infection is related to trimester of infection: 6% in first, 40% in second, and 72% in third
  
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** Risk of signs of congenital infection is inversely related to trimester of infection: 61% in first, 25% in second, and 9% in third
  
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* Classic triad of [[Causes::chorioretinitis]] (most common), [[Causes::intraparenchymal cerebral calcifications]], and [[Causes::hydrocephalus]]
  
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* Others: [[Causes::thrombocytopenia]], [[Causes::hepatitis]], [[Causes::hepatosplenomegaly]], [[Causes::cataracts]], [[Causes::strabismus]], [[Causes::microphthalmia]]
  
   
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{| class="wikitable"
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== Diagnosis ==
  
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! rowspan="2" |Trimester
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=== In pregnancy ===
  
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! rowspan="2" |Transmission to Fetus
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* Molecular
  
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! colspan="4" |Severity of Disease
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** Definitive diagnosis is based on PCR of amniotic fluid around 18 months, usually done after maternal serology to confirm intrauterine infection
  
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! rowspan="2" |Overall Probability of Any Symptomatic Disease
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*** Sensitivity is 64 to 92% and specificity 100% (NPR around 88 to 98%)
  
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|-
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*** Earlier than 18 weeks has unknown sensitivity and specificity, and has a higher risk of spontaneous abortion
  
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!Asymptomatic
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** Can also be done on fetal blood
  
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!Mild
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* Serology
  
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!Severe
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** Can check maternal IgM and IgG
  
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!Fetal Death
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** IgM is not specific to recent infection, however, as it can be present for more than a year
  
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|-
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** IgG avidity testing is used to determine recency of infection
  
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|first
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*** Low avidity is 35-50% and high is >60%
  
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|15%
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*** Low avidity is unhelpful, as avidity can remain low for more than a year
  
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|18%
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*** High avidity, on the other hand, suggests infected at least 3-4 months prior
  
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|6%
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** Therefore, if infection is suspected in the first 16 weeks of gestation, avidity testing may be able to rule out infection during pregnancy
  
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|41%
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* Needs serial head ultrasound to monitor for hydrocephalus and intraparenchymal brain calcifications
  
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|35%
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** May also see hepatic calcifications, splenomegaly, and ascites
  
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|11%
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|-
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|second
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|30%
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|67%
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|18%
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|8%
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|7%
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|10%
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|-
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|third
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|60%
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|89%
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|11%
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|0%
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|0%
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|6%
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|-
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|overall
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|33%
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|72%
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|13%
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|8%
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|7%
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|8%
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|}
   
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==Clinical Manifestations==
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=== In children ===
  
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* Standard workup starts with serology, then adds PCR and other investigations if clinical suspicion is high
  
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* Serology
  
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** In neonates, IgG serology reflects maternal status, so use IgM and IgA instead
  
βˆ’
* Molecular testing
  
βˆ’
** If clinical suspicion is high, add PCR of the peripheral blood, urine, and CSF to the serology
  
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* Other
  
βˆ’
** If clinical suspicion is high, also get ophthalmologic evaluation, hearing assessment, ultrasound or CT of the brain, and lumbar puncture
  
   
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*At birth, 85% of infected babies are asymptomatic and only 15% are symptomatic
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== Management ==
  
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**Risk of infection is related to trimester of infection: 6-15% in first, 30-40% in second, and 60-72% in third
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=== In pregnancy ===
  
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**Risk of signs of congenital infection is inversely related to trimester of infection: 61% in first, 25% in second, and 9% in third
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* If infected < 14 weeks gestation, [[Is treated by::spiramycin]] 3 g/day until delivery
  
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*Classic triad of [[Causes::chorioretinitis]] (most common), [[Causes::intraparenchymal cerebral calcifications]], and [[Causes::hydrocephalus]]
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** However, it doesn't cross the placenta and it's unclear whether it affects outcomes in the baby
  
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*Others: [[Causes::thrombocytopenia]], [[Causes::hepatitis]], [[Causes::hepatosplenomegaly]], [[Causes::cataracts]], [[Causes::strabismus]], [[Causes::microphthalmia]]
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** Likely most effective if given within 8 weeks of maternal infection
  
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*Somewhere between 24 and 85% of children who are asymptomatic at birth will later develop [[chorioretinitis]], [[strabismus]], [[blindness]], [[hydrocephalus]], [[microcephaly]], [[cerebral calcifications]], [[developmental delay]], [[epilepsy]], [[deafness]] in the months to years following birth
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** Second-line would be monotherapy with [[Is treated by::sulfadiazine]] or [[Is treated by::clindamycin]]
  
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* If age β‰₯ 14 weeks gestation and documented fetal infection, or if suspected infection was β‰₯14 weeks gestation, use standard therapy
  
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** 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)
  
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** 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
  
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** Therefore, if initially started on [[spiramycin]], then switch to standard therapy if amniotic fluid PCR is positive or ultrasound is abnormal
  
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** However, it is teratogenic until 14 weeks gestation so [[spiramycin]] is used until then
  
   
βˆ’
=== In children ===
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==Diagnosis==
βˆ’
* Postnatal treatment is with standard therapy for at least 12 months
  
βˆ’
** [[Is treated by::Sulfadiazine]] 50 mg/kg q12h
  
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** [[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
  
βˆ’
** [[Folinic acid]] 10 mg PO thrice weekly until 1 week after [[pyrimethamine]] is stopped
  
βˆ’
* Serial evaluations with a clinical assessment, neuroradiology, ophthalmology, and CSF analysis
  
   
  +
*Standard workup starts with serology, then adds PCR and other investigations if clinical suspicion is high
βˆ’
[[Category:Obstetrical infectionsβ€β€Ž]]
  
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*Serology: in neonates, IgG serology reflects maternal status, so use IgM and IgA instead
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[[Category:Pediatrics]]
  
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*Molecular testing: if clinical suspicion is high, add PCR of the peripheral blood, urine, and CSF to the serology
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[[Category:Parasites]]
  
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*If clinical suspicion is high, also get ophthalmologic evaluation, hearing assessment, ultrasound or CT of the brain, and lumbar puncture
  +
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==Management==
  +
  +
*Postnatal treatment of neonates is with standard therapy for at least 12 months
  +
**[[Is treated by::Sulfadiazine]] 50 mg/kg q12h
  +
**[[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
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*Treatment of congenital infection in older children is standard therapy until 1 to 2 weeks after resolution of signs or symptoms
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**[[Is treated by::Pyrimethamine]] 1 mg/kg q12h (max 50 mg) for 2 days, followed by 1 mg/kg/day (max 25 mg)
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**[[Is treated by::Sulfadiazine]] 75 mg/kg load, followed by 50 mg/kg q12h (max 4 g/day)
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**[[Folinic acid]] 10-20 mg po thrice weekly
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**Can add [[prednisone]] for severe chorioretinits at 1 mg/kg/day divided bid (max 40 mg/day), followed by a rapid taper
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*Serial evaluations with a clinical assessment, neuroradiology, ophthalmology, and CSF analysis
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*For prevention, refer to [[Toxoplasmosis in pregnancy#Management|the management of toxoplasmosis in pregnancy]]
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  +
[[Category:Congenital infectionsβ€β€Ž]]

Latest revision as of 12:22, 20 September 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, but the risk of severe disease is highest if infected in first trimester and lowest in third trimester1
  • See also toxoplasmosis in pregnancy
Trimester Transmission to Fetus Severity of Disease Overall Probability of Any Symptomatic Disease
Asymptomatic Mild Severe Fetal Death
first 15% 18% 6% 41% 35% 11%
second 30% 67% 18% 8% 7% 10%
third 60% 89% 11% 0% 0% 6%
overall 33% 72% 13% 8% 7% 8%

Clinical Manifestations

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
  • 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

References

  1. ^   Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data. The Lancet. 2007;369(9556):115-122. doi:10.1016/s0140-6736(07)60072-5.

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