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A Primary Neuron Culture System for the Study of Herpes Simplex Virus Latency and Reactivation

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Herpes Simplex Virus Type 1 Encephalitis: A Prospective Population-Based Cohort Study.

Lærke Storgaard Duerlund^1,2,3,4, Lykke Larsen⁵, Merete Storgaard⁶

¹Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America

|February 23, 2026

Summary

Early recognition of herpes simplex type 1 (HSV-1) encephalitis is crucial. Delayed acyclovir treatment, particularly after lumbar puncture, significantly increases mortality risk in patients with HSV-1 encephalitis.

Keywords:

acyclovir encephalitis herpes simplex virus outcome population-based

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Area of Science:

Neurology
Infectious Diseases
Epidemiology

Background:

Herpes simplex type 1 (HSV-1) encephalitis presents diagnostic challenges.
The clinical characteristics and outcomes of HSV-1 encephalitis require further investigation.

Purpose of the Study:

To investigate the clinical characteristics and outcomes of patients diagnosed with HSV-1 encephalitis.
To assess the impact of treatment timing on mortality in HSV-1 encephalitis patients.

Main Methods:

A nationwide, prospective, population-based cohort study was conducted in Denmark from 2015-2023.
Modified Poisson regression analyzed the association between time to acyclovir treatment and 6-month mortality, adjusting for relevant factors.
Data were sourced from the Danish Study Group for Infections of the Brain database for microbiologically confirmed cases.

Main Results:

The study included 154 patients with HSV-1 encephalitis, with a mean annual incidence of 0.36/100,000.
Median times to lumbar puncture and acyclovir treatment were 21 and 24 hours, respectively.
Delayed acyclovir treatment (>6 hours post-lumbar puncture) was associated with a significantly increased risk of 6-month mortality (RR 1.85, 95% CI: 1.01-3.45).

Conclusions:

HSV-1 encephalitis is associated with high mortality, and early diagnosis remains difficult.
Timely initiation of acyclovir treatment is critical for improving patient outcomes.
Delays in acyclovir administration, especially after lumbar puncture, are linked to increased fatal outcomes.