TORCH Infections - Microbiology

What is TORCH?

• Sherris & Ryan's Medical Microbiology, 8th Ed.
• Tietz Textbook of Laboratory Medicine, 7th Ed.

Routes of Transmission

T - Toxoplasma gondii

• Type: Obligate intracellular protozoan parasite
• Source: Ingestion of oocysts from undercooked meat or cat feces (maternal primary infection)
• Transmission: Transplacental; rate increases from ~30% at 6 months' gestation approaching 100% at term
• Incidence: ~0.01-0.1% of live births (about 1/10th the rate of congenital CMV)
• Classic triad: Chorioretinitis + Hydrocephalus + Intracranial calcifications (the complete triad is rare)
• Other features: 70-90% asymptomatic at birth; anemia, thrombocytopenia, jaundice, hepatosplenomegaly, seizures
• Imaging: Parenchymal calcifications similar to CMV; ventriculomegaly from obstructive hydrocephalus (ependymitis); notably NO cerebellar hypoplasia or polymicrogyria
• Treatment: Pyrimethamine + sulfadiazine + folinic acid

O - "Other" Agents

Treponema pallidum (Syphilis)

• Type: Gram-negative spirochete bacterium
• Transmission: Transplacental at any stage of pregnancy
• Early features: Snuffles (nasal discharge), mucous membrane lesions, hepatosplenomegaly, maculopapular rash, osteochondritis, anemia, thrombocytopenia
• Late features (months-years later): Hutchinson's teeth, keratitis, saddle nose, saber shins, CNS syphilis
• Prevention/Treatment: Maternal screening + penicillin G

Varicella-Zoster Virus (VZV)

• Type: Herpesvirus (DNA)
• Transmission: Transplacental
• Features: Skin scarring, limb hypoplasia, neurological defects, chorioretinitis
• Prevention: VZV vaccination before pregnancy

Parvovirus B19

• Type: Single-stranded DNA virus (Erythrovirus)
• Transmission: Transplacental
• Key effect: Hydrops fetalis from aplastic crisis (infects erythroid precursors)

Zika Virus

• Type: Flavivirus (RNA), transmitted by Aedes mosquitoes (unique among TORCH)
• Features: Microcephaly, hypertonia, ocular abnormalities, hearing loss, seizures ("congenital Zika syndrome")
• Note: No specific treatment; first recognized clinically in 2015 (Brazil outbreak)

R - Rubella Virus

• Type: Togavirus (single-stranded positive-sense RNA), genus Rubivirus
• Transmission: Transplacental (respiratory droplet-acquired in mother, then crosses placenta)
• Timing matters: First 8 weeks - cataracts, glaucoma, cardiac defects; severity decreases as pregnancy progresses; third trimester infection may be asymptomatic
• Classic triad (Congenital Rubella Syndrome - CRS): Sensorineural hearing loss + Cataracts + Cardiac defects (PDA, pulmonary artery stenosis) - in a small-for-gestational-age infant
• Other features: Microphthalmia, chorioretinitis, "blueberry muffin rash" (purpura/petechiae from thrombocytopenia), hepatosplenomegaly
• Epidemiology: Eliminated in the US since 2004 after MMR vaccination; still >100,000 cases/year worldwide; immigrant populations remain at risk
• Prevention: MMR vaccination (live-attenuated) before pregnancy

C - Cytomegalovirus (CMV)

• Type: Herpesviridae (double-stranded DNA); Human Herpesvirus 5 (HHV-5)
• Transmission: Transplacental (primary or reactivation), intrapartum (cervix), breast milk
• Most common serious congenital viral infection in developed countries: 0.5-1% of all births (~40,000 infants/year in the US)
• ~90% are asymptomatic at birth
• Symptomatic features: Small for gestational age, petechiae/purpura, thrombocytopenia, jaundice/hepatitis, chorioretinitis, microcephaly, periventricular intracranial calcifications (most characteristic), sensorineural hearing loss (can develop up to 2 years post-birth)
• Imaging signature: Periventricular calcifications (vs. scattered calcifications in toxoplasmosis); lenticulostriate vasculopathy on cranial US; timing of infection determines pattern:
  • 2nd trimester: lissencephaly, thin cortex, cerebellar hypoplasia, ventriculomegaly
  • Later: polymicrogyria, parenchymal damage, temporal pole cysts
• Pathogenesis: Direct viral insult to germinal matrix cells (periventricular); vascular insult; vertical transmission risk much higher with primary vs. recurrent CMV
• Treatment: Valganciclovir (reduces hearing loss and improves neurodevelopmental outcomes)

H - Herpes Simplex Virus (HSV)

• Type: Herpesviridae (double-stranded DNA); HSV-1 and HSV-2
• Transmission: Primarily perinatally - direct contact with maternal genital lesions during vaginal delivery (HSV-2 most common); congenital (transplacental) infection is quite rare
• Three clinical presentations of neonatal HSV:
  1. SEM disease - Skin, Eyes, Mucous membranes (visible vesicular lesions; best prognosis)
  2. CNS disease - encephalitis (rapidly disseminating, diffuse - unlike adult pattern of temporal lobe involvement)
  3. Disseminated - liver and lungs most commonly; highest mortality
• Imaging (CNS): Widespread asymmetrical regions of T2 hyperintensity in white matter; progressive cortical swelling; cerebral atrophy and cystic encephalomalacia develop rapidly (as early as week 2)
• Treatment: IV acyclovir (high doses; limits neurologic complications)

Summary Comparison Table

CT Scan of Congenital TORCH Infection

Key Diagnostic Points

• TORCH titers have limited utility alone - serology cannot precisely determine timing of infection; can lead to unnecessary invasive procedures
• CMV is the most common cause - always include in workup for congenital infection
• The "O" category now includes VZV, enteroviruses, parvovirus B19, Zika virus, syphilis, HIV, HBV, HCV
• Gestational timing determines severity: infections before 16-18 weeks (neuronal migration phase) cause the most severe CNS malformations (lissencephaly); later infections cause gliosis, cystic change, calcification