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Predictors of Invasive Herpes Simplex Virus Infection in Young Infants
Andrea T Cruz1, Lise E Nigrovic2, Jianling Xie3
1Baylor College of Medicine, Houston, Texas acruz@bcm.edu.
Insights
A new risk score helps identify infants with a very low risk of invasive herpes simplex virus (HSV) infection, potentially reducing the need for routine testing and treatment.
Area of Science:
- Neonatal infectious diseases
- Virology
- Pediatric emergency medicine
Background:
- Invasive herpes simplex virus (HSV) infection in infants can lead to severe complications.
- Accurate risk stratification is crucial for appropriate management of suspected HSV cases in neonates.
Purpose of the Study:
- To identify independent predictors of invasive HSV infection in infants.
- To develop and validate a risk score for invasive HSV in infants.
Main Methods:
- A nested case-control study involving 149 infants with HSV and 1340 controls (≤60 days old).
- Cerebrospinal fluid (CSF) analysis and clinical data were collected within 24 hours of presentation.
- Logistic regression was used to identify independent predictors, which were then used to derive a risk score.
Main Results:
- Key predictors of invasive HSV included younger age, prematurity, seizure at home, ill appearance, abnormal temperature, vesicular rash, thrombocytopenia, and CSF pleocytosis.
- The derived HSV risk score ranged from 0-17, with higher scores associated with invasive disease (median 6 vs. 3).
- The risk score demonstrated good discriminatory ability (AUC 0.85) and high sensitivity (95.6%) at a cut-point of ≥3 for identifying invasive HSV.
Conclusions:
- A novel HSV risk score effectively identifies infants at extremely low risk for invasive HSV.
- This score may help clinicians avoid routine testing and empirical treatment in low-risk infants.
- The validated risk score aids in optimizing the management of neonatal HSV infections.
Objectives:
To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection.
Methods:
In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively.
Results:
Of all infants included, 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] <14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with >28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43).
Conclusions:
A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.
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