Cost-effectiveness Analysis of Herpes Simplex Virus Testing and Treatment Strategies in Febrile Neonates

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Abstract
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.