Incidence, Duration, and Risk Factors Associated With Missed Opportunities to Diagnose Herpes Simplex Encephalitis: A Population-Based Longitudinal Study

Open Forum Infect Dis. 2021 Jul 26;8(9):ofab400. doi: 10.1093/ofid/ofab400. eCollection 2021 Sep.


Background: Delays in diagnosing herpes simplex encephalitis (HSE) are associated with increased morbidity and mortality. The purpose of this paper is to determine the frequency and duration of diagnostic delays for HSE and risk factors for diagnostic delays.

Methods: Using data from the IBM Marketscan Databases, 2001-2017, we performed a retrospective cohort study of patients with HSE. We estimated the number of visits with HSE-related symptoms before diagnosis that would be expected to occur in the absence of delays and compared this estimate to the observed pattern of visits. Next, we used a simulation-based approach to compute the number of visits representing a delay, the number of missed diagnostic opportunities per case patient, and the duration of delays. We also investigated potential risk factors for delays.

Results: We identified 2667 patients diagnosed with HSE. We estimated 45.9% (95% confidence interval [CI], 43.6%-48.1%) of patients experienced at least 1 missed opportunity; 21.9% (95% CI, 17.3%-26.3%) of these patients had delays lasting >7 days. Risk factors for delays included being seen only in the emergency department, age <65, or a history of sinusitis or schizophrenia.

Conclusions: Many patients with HSE experience multiple missed diagnostic opportunities before diagnosis.

Keywords: HSE; delayed diagnosis; missed opportunities.