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Department of Pediatrics : Academic Divisions : Emergency Medicine : Resident Manual : Pediatric ED Treatment Guidelines : Herpes Simplex Virus Treatment Guidelines

What the literature tells us:

  • Incidence is approximately 5.9/100,000 births with a fatality rate of 15%.
  • A significant number of infants with neonatal HSV are born to mothers with no history of genital HSV infections (40-100% in varying studies).
  • In this study, 92.7% were less than 28 days of age and 28% were premature.
  • 45-60% involved skin, eye and mucous membranes, with 94% of those only involving the skin. 23% are disseminated and 17-30% are CNS infections.1

Overall, 39% of infants with neonatal HSV infections present with fever. Those infants with CNS and disseminated disease often present with lethargy. Seizures occurred in 57% of those with CNS disease, and DIC and pneumonia occurred in over 35% of those with disseminated disease.2 17-39% with HSV infection do not have any skin lesions at presentation, nor later in their course.

CSF pleocytosis may be low or not evident in individuals with early HSV encephalitis; elevated neutrophils and protein may be early signs of CNS disease. CSF PCR for HSV has a sensitivity of approximately 70% early in infection and it can be negative in the first few days of infection. Testing of CSF shortly after onset of symptoms indicates that HSV DNA can be detected in nearly 100% of individuals with HSV encephalitis. Therefore, serial LPs may be indicated in some infants. Serum HSV PCR needs to be considered to aid in the diagnosis.3

Early initiation of antiviral therapy has been proven to favorably impact the outcome of neonatal HSV disease. Evaluation of blood by PCR may be beneficial but application is currently less advanced than CSF PCR. Liver transaminases should be obtained as their elevation could suggest disseminated disease.2

Enhanced appreciation of neonatal HSV infection, in conjunction with judicious utilization of diagnostic modalities, represent the most immediate manner in which additional improvements in the outcome of neonatal HSV disease can be accomplished.2

Suggestions for management:

Who to test:

  • All febrile or hypothermic neonates (less than or equal to 28 days of age).
  • All toxic appearing infants less than or equal to 60 days of age.
  • All infants less than or equal to 60 days of age with the following laboratory abnormalities:
    • CSF pleocytosis
    • Elevated liver transaminases
    • Thrombocytopenia

What to send (in addition to routine studies):

  • HSV CSF and blood PCR (see reference below for how and how much for CSF studies)
  • HSV culture of any concerning skin lesions
  • Febrile neonates less than 28 days with the following laboratory abnormalities
    • Also consider surface cultures of eye, mucous membranes and rectum in patients with vesicular lesions
  • LFTs
  • DIC panel for infants with thrombocytopenia

Treatment:

  • Treat who you test
  • Acyclovir 20mg/kg/dose q8hr IV

CSF Studies:

  • Glucose, Spinal Fluid: minimum: 0.5 ml / absolute minimum: 0.2 ml
  • Protein, Total, Spinal Fluid: minimum: 0.5 ml / absolute minimum: 0.3 ml
  • CSF Differential Cell Count: minimum: 0.5 ml / absolute minimum: 0.5 ml
  • Routine bacterial culture: minimum: 1 ml / absolute minimum: 3 drops (2 plates + unconcentrated Gram stain)
  • Herpes Simplex Virus Type 1 & 2 by PCR on CSF: minimum: 1 ml / absolute minimum: 0.25 ml
    • Transport: Refrigerate if specimen cannot be sent to lab immediately after collection.

    also...
  • Enterovirus on CSF by PCR: minimum: 1 ml / absolute minimum: 0.25 ml
    • Transport: Refrigerate if specimen cannot be sent to lab immediately after collection.

References

  1. Kroop RY et al. Neonatal Herpes Simplex Virus Infections in Canada: Results of a 3-Year National Prospective Study. Pediatrics 2006, 117:1955-1962.
  2. Kimberlin DW et al. Natural History of Neonatal Herpes Simplex Virus Infections in the Acyclovir Era. Pediatrics 2001, 108:223-229.
  3. Frenkel LM. Commentaries: Challenges in the Diagnosis and Management of Neonatal Herpes Simplex Virus Encephalitis. Pediatrics 2005, 115; 795-797

 

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