Neonatal HSV

Background

• See also Herpes simplex virus

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 Manifestations

• 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, CSF, or mucosal membranes (conjunctivae, mouth, nasopharynx)
  • 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

Diagnosed neonates

• Obtain CSF (± blood PCR), and transaminases to determine if the disease involves CSF and is disseminated
• 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

Exposed neonates

• First-episode genital HSV at delivery
  • Rupture of membranes before vaginal or cesarean delivery
    • Swab mucous membranes for PCR either at birth or at 24 hours
    • Start empiric acyclovir IV for 10 days
    • If swabs confirm HSV infection, follow management above for diagnosed neonates
    • If swabs are negative, complete the 10-day course regardless
  • Cesarean delivery prior to rupture of membranes
    • Swab mucous membranes or blood PCR at 24 hours
    • Counsel caregiver on signs and symptoms, and discharge
    • If swabs confirm HSV infection, readmit to complete investigations and manage as above for diagnosed neonates
• Recurrent genital HSV at delivery
  • Swab mucous membranes for PCR at 24 hours
  • Counsel caregiver on signs and symptoms, and discharge
  • If swabs confirm HSV infection, readmit to complete investigations and manage as above for diagnosed neonates

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