How to rule out neonatal herpes (Herpes Simplex Virus) infection?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 20, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

To rule out neonatal herpes infection, obtain viral cultures from multiple sites and perform HSV PCR testing on blood and cerebrospinal fluid (CSF), and start empiric acyclovir treatment immediately at 20 mg/kg body weight/dose three times daily intravenously while awaiting results. This approach is based on the recommendations from the CDC, the National Institutes of Health, and the Infectious Diseases Society of America 1. The diagnosis of neonatal HSV infection should be based on clinical signs, including skin vesicles, fever or hypothermia, lethargy, irritability, seizures, respiratory distress, or poor feeding, as well as risk factors such as maternal history of genital herpes, prolonged rupture of membranes, and use of fetal scalp electrodes.

Key Diagnostic Steps

  • Obtain viral cultures from multiple sites, including skin vesicles, mouth, nasopharynx, conjunctivae, and rectum, as positive cultures from any of these sites >48 hours after birth indicate viral replication rather than contamination after intrapartum exposure 1
  • Perform HSV PCR testing on blood and CSF, as CSF should be tested for HSV nucleic acid by amplifying an HSV DNA sequence common to both HSV-1 and HSV-2 using PCR assays 1
  • Conduct a lumbar puncture for CSF analysis to rule out central nervous system (CNS) involvement

Treatment and Management

  • Start empiric acyclovir treatment immediately at 20 mg/kg body weight/dose three times daily intravenously while awaiting results, as delayed treatment significantly increases mortality 1
  • Complete blood count, liver function tests, and brain imaging (MRI preferred over CT) should be performed to assess the extent of the disease and monitor for potential complications
  • Acyclovir therapy should not be discontinued in neonates with CNS disease unless a repeat CSF HSV DNA PCR assay is negative at day 19--21 of treatment 1

From the FDA Drug Label

Neonatal Herpes Simplex Virus Infection Two hundred and two infants with neonatal herpes simplex infections were randomized to receive either acyclovir 10 mg/kg every 8 hours (n = 107) or vidarabine 30 mg/kg/day (n = 95) for 10 days.

To rule out neonatal herpes (Herpes Simplex Virus) infection, diagnostic testing is necessary, but the provided drug labels do not directly address the diagnostic process. The labels discuss treatment options for neonatal herpes simplex virus infection, such as acyclovir dosage, but do not provide information on how to diagnose or rule out the infection.

From the Research

Ruling Out Neonatal Herpes Simplex Virus Infection

To rule out neonatal herpes simplex virus (HSV) infection, the following steps can be taken:

  • Consider the epidemiology and risk factors of neonatal HSV, which has an estimated global incidence of 10 per 100,000 live births 2
  • Be aware of the often vague signs and symptoms of neonatal HSV, which can make diagnosis challenging 2
  • Use empiric antiviral therapy before the results of definitive testing to improve outcomes for infants with HSV 2
  • Perform diagnostic tests, such as viral cultures, immunoperoxidase stains, and antibody determination by enzyme-linked immunosorbent assay, to confirm the presence of HSV 3
  • Consider the clinical and laboratory findings to determine the timing of the herpetic infection, which can help guide treatment decisions 3

Treatment and Management

Treatment for neonatal HSV typically consists of:

  • Intravenous (IV) administration of acyclovir, which is the gold standard antiviral drug for the prevention and treatment of HSV infections 4, 5
  • Supportive care for patients with life-threatening disease, which is an integral component of patient management 4
  • Consideration of alternative therapeutic interventions, such as cidofovir and foscarnet, in cases of acyclovir resistance 5

Important Considerations

  • Neonatal HSV can have severe consequences if left untreated, with mortality rates exceeding 80% in some cases 2
  • Overtesting and overtreatment can result in prolonged hospitalizations and expose neonates to medication toxicity 2
  • Prompt evaluation and use of empiric antiviral therapy can improve outcomes for infants with HSV 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Congenital herpes simplex retinitis.

American journal of ophthalmology, 1986

Research

Herpes Simplex Virus in Children.

Current treatment options in neurology, 2002

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.