Cost-effectiveness analysis of herpes simplex virus testing and treatment strategies in febrile neonates

Arch Pediatr Adolesc Med. 2008 Jul;162(7):665-74. doi: 10.1001/archpedi.162.7.665.


Objective: To determine the clinical effectiveness and cost-effectiveness of testing for and empirically treating herpes simplex virus (HSV) infection in neonates with fever aged from birth to 28 days.

Design: Cost-effectiveness analysis.

Setting: Decision model.

Patients: Neonates with fever with no other symptoms and neonates with fever with cerebrospinal fluid (CSF) pleocytosis.

Interventions: Four clinical strategies: (1) HSV testing and empirical treatment while awaiting test results; (2) HSV testing and treatment if test results were positive for HSV or the patient had symptoms of HSV; (3) treatment alone without testing; or (4) no HSV testing or treatment unless the patient exhibited symptoms. The 2 HSV testing methods used were CSF HSV polymerase chain reaction (PCR) and comprehensive evaluation with blood HSV PCR, CSF HSV PCR, and multiple viral cultures.

Main outcome measures: Twelve-month survival and quality-adjusted life expectancy with a cost-effectiveness threshold of $100,000 per quality-adjusted life year (QALY) gained.

Results: Clinical strategy 1, when applied in febrile neonates with CSF pleocytosis, saved 17 lives per 10,000 neonates and was cost-effective using CSF HSV PCR testing ($55,652/QALY gained). The cost-effectiveness of applying clinical strategy 1 in all febrile neonates depended on the cost of the CSF HSV PCR, prevalence of disease, and parental preferences for neurodevelopmental outcomes. Clinical strategies using comprehensive HSV testing were not cost-effective in febrile neonates ($368,411/QALY gained) or febrile neonates with CSF pleocytosis ($110,190/QALY gained).

Conclusions: Testing with CSF HSV PCR and empirically treating with acyclovir sodium saves lives and is cost-effective in febrile neonates with CSF pleocytosis. It is not a cost-effective use of health care resources in all febrile neonates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / economics
  • Acyclovir / therapeutic use*
  • Antiviral Agents / economics
  • Antiviral Agents / therapeutic use*
  • Cost-Benefit Analysis
  • Decision Support Techniques
  • Disease Progression
  • Female
  • Fever
  • Herpes Simplex / diagnosis*
  • Herpes Simplex / drug therapy*
  • Herpes Simplex / economics
  • Humans
  • Infant, Newborn
  • Leukocytosis / cerebrospinal fluid
  • Male
  • Probability
  • Quality-Adjusted Life Years
  • Treatment Outcome


  • Antiviral Agents
  • Acyclovir