Neonatal Herpes Simplex Virus: The Long Road to Improved Outcomes

Herpes simplex virus (HSV) acquired during delivery places the neonate at risk for mortality or long-term neurodevelopmental disability. Exposure generally occurs from recurrent genital herpes infection, although primary infections result in the highest risk of neonatal disease. Neonates generally present in the second or third week of life with lesions. Encephalitis with seizures indicates the presence of central nervous system involvement, and other end organs may also be impacted. Clinical suspicion for neonatal HSV infection warrants immediate initiation of appropriate antiviral therapy. In the last 50 years, antiviral therapy has progressed from agents with prohibitive toxicity or cumbersome administration to herpes virus-specific agents that dramatically improve clinical outcomes with manageable toxicity. Multicenter clinical trials have demonstrated the superiority of high-dose intravenous acyclovir for acute therapy, followed by long-term oral suppressive therapy. This work has dramatically reduced morbidity and mortality from neonatal HSV, representing the benchmark for future clinical trials in neonatal pharmacotherapy.