Neonatal HSV

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Background

Epidemiology

  • Risk of transmission is determined by maternal serostatus at time of maternal genital infection
    • Newly acquired
      • First-episode primary infection (mother has no serum antibodies to HSV-1 or -2 at onset): risk of transmission is about 60%
      • First-episode nonprimary infection (mother has a new infection with one HSV type in the presence of antibodies to the other type): risk of transmission is less than 30%
    • Recurrent (mother has pre-existing antibodies to the HSV type that is isolated from the genital tract): risk of transmission is less than 2%

Pathophysiology

  • Generally acquired at time of delivery, though 5-8% may be congenital
  • Localized CNS infection is thought to occur by retrograde axonal transmission

Clinical Presentation

  • Incubation period 7 to 21 days post-partum, with range from birth to 6 weeks
  • Spectrum of disease from cutaneous to disseminated

Disseminated disease

  • 25% of cases
  • Sepsis syndrome that predominantly affects the liver, lungs, and CNS
    • May not have skin findings (25%)
    • CNS involved in 60-75%, causing meningoencephalitis
    • Can also affect larynx, trachea, esophagus, stomach, lower gastrointestinal tract, spleen, kidneys, pancreas, and heart
  • Later in the course of the disease, may develop elevated ALT/AST and direct bilirubin, as well as coagulopathy and thrombocytopenia
  • Usually presents in the first or second week of life
  • Should be considered in sepsis without bacterial cause and with liver dysfunction or coagulopathy

Localized CNS disease

  • 30% of cases
  • Usually presents in the second or third week of life
  • May not have cutaneous manifestations
  • Can cause seizures

Skin, eye, and mouth disease

  • 45% of cases
  • Localized to skin, eyes, and/or mouth
  • Usually presents in the first or second week of life

Diagnosis

  • Most commonly diagnosed with PCR of lesions or CSF
    • Do not send superficial swabs for PCR during the first 24 hours of life, since this can generate false positive from superficial contamination from the birthing process
    • Early CSF PCR may be falsely negative; consider continuing acyclovir and repeating at 72 hours if high clinical suspicion

Management

  • Disseminated disease: high-dose acyclovir 60 mg/kg/day IV divided q8h for at least 21 days
    • If CNS disease, repeat lumbar puncture at the end of therapy to document resolution of CSF parameters and ensure that PCR is negative
  • Localized CNS disease: same as for disseminated
  • Localized skin, eye, and mouth disease: high-dose acyclovir 60 mg/kg/day IV divided q8h for at least 14 days
    • For eye involvement, consult and ophthalmologist to add topical trifluridine, idoxuridine, or vidarabine

Prognosis

  • Disseminated disease has 65% mortality if untreated, improves to 30% with treatment
  • With CNS disease, 80% have developmental problems
  • Prognosis much better with isolated cutaneous disease