Skip to main content

Evaluate for HSV

Fever in infants less than 29 days of age


Suspicion of Herpes Simplex Virus (HSV) infection


Epidemiology

  • The incidence of HSV among infants less than 29 days is low: ranging from 0.2 – 0.6% of infants tested (Caviness, Demmler et al. 2008; Caviness, Demmler et al. 2008) or 5.1 – 5.9 cases per 100,000 live births. (Kropp, Wong et al. 2006; Mahnert, Roberts et al. 2007)

  • Mortality (15-20%) and morbidity (25% with neurologic sequellae) for untreated neonatal HSV disease is high.

  • HSV is manifest clinically as: (Kropp, Wong et al. 2006; Mahnert, Roberts et al. 2007; Caviness, Demmler et al. 2008)

    • Skin, eye, and mouth infection (25-60% of cases)

    • Meningoencephalitis (25 - 37.5% of cases)

    • Disseminated infection (18 - 37.5% of cases)

HSV risk Factors, diagnostic workup, and medical decision making

  • Infants less than 29 days of life are recommended for HSV testing when they present with any of the following:

    • An ill or septic appearance including hypothermia (rectal temperature less than 36 degrees Celsius) and severe respiratory distress

    • Seizures (or the history of seizure)

    • Obvious herpetic lesions/vesicles on physical exam

    • CSF pleocytosis for age (white blood cell count greater than 20 per microliter)

    • Elevated AST and/or ALT of previous labs obtained

  • Additional risk factors as identified by Kropp et al in a prevalance study and Caviness et al in a case control study include the following. Each may increase the risk of HSV over the general population, but should be taken in the context of the entire clinical scenario. We recommend that clinicians speak with families about this risk and determine, along with the input from the family, whether or not to pursue further testing and empiric treatment with acyclovir.

    • Known maternal HSV (we recognize that primary infection places the infant at much higher risk than recurrent infection, however there appears to be a 1-2% risk of transmission with recurrent infection and this places the infant at a higher risk than the general population) (Kropp, Wong et al. 2006; Mahnert, Roberts et al. 2007; Caviness, Demmler et al. 2008)

    • Thrombocytopenia (exclusively associated with disseminated HSV)

    • Maternal fever at labor and delivery (OR: 5.8, 95% CI: 2.3–14.5) (Caviness, Demmler et al. 2008)

  • Required testing, in addition to the full diagnostic workup for febrile infants above, includes:

    • Cerebral Spinal Fluid HSV polymerease chain reaction (PCR)

    • Nasopharyngeal, eye, and rectal viral cultures

    • Liver function tests, specifically evaluating AST and ALT

Inpatient management

  • Empiric administration of intravenous ampicillin and cefotaxime (see dosing guidelines above) is required.

  • Empiric treatment of suspected HSV is required: acyclovir 20 mg/kg/dose intravenously every 8 hours.

  • Treatment of confirmed HSV is acyclovir 20 mg/kg/dose intravenously every 8 hours for the general duration indicated by the clinical manifestation. (Kimberlin 2001 Pediatrics. 2001 Aug;108(2):230-8. )

    • Patients with disseminated disease or skin, eye, and mouth disease without central nervous system involvement are generally treated intravenously for 21 days.

    • Patients with meningoencephalitis are treated intravenously for 21 days

    • Infants with confirmed HSV disease require Infectious Diseases consultation specific recommendation of therapy duration and for follow-up.

Rationale and evidence base

Infants less than 29 days of life are at risk of neonatal HSV. In the second week of life, the risk of neonatal HSV approaches that of bacterial meningitis. However, there is no consensus recommendation for the empiric treatment of HSV with acyclovir in infants less than 29 days of life. While some experts recommend acyclovir routinely in all febrile infants less than 29 days of life, others risk stratify based on known risk factors. This lack of consistency may lead to the lack of recognition and delayed treatment of neonatal HSV. (Caviness, Demmler et al. 2008)

We have adopted a conservative approach, including known risk factors in a check list to help clinicians identify the infant at risk for neonatal HSV disease. The data that support our recommendation come from descriptive and case control studies on the epidemiology and risk factors of neonatal HSV disease. (Kropp, Wong et al. 2006; Mahnert, Roberts et al. 2007; Caviness, Demmler et al. 2008) It is also important to recognize that red blood cells in the CSF are not a risk factor of HSV meningitis.

GRADE:

We RECOMMEND based on low quality evidence that empiric treatment with acyclovir and a thorough HSV evaluation (see # 1 above) be completed if any item of the HSV checklist is present (Figure 1 – Algorithm).

Additional risk factors as identified by Kropp et al in a prevalance study and Caviness et al in a case control study are listed in # 2 above. Each may increase the risk of HSV over the general population, but should be taken in the context of the entire clinical scenario. We RECOMMEND based on low quality evidence that clinicians speak with families about this risk and determine, along with the input from the family, whether or not to pursue further testing and empiric treatment with acyclovir.

We STRONGLY RECOMMEND based on low-quality of evidence to use the dose of 20mg/kg every 8 hours of acyclovir when treating possible neonatal HSV disease. The strong recommendation is based on weighing the benefits versus risk of side effects of the suggested dose compared with the risks of using a smaller dose when treating a potentially fatal disease.

There are no randomized controlled trials regarding the treatment of HSV infection in neonates. Data on dosing of acyclovir and length of treatment is taken from Lexi-Comp and the American Academy of Pediatrics Red Book and is based on a prospective, open label cohort study. (Kimberlin, Lin et al. 2001)

These guidelines do not establish a standard of care to be followed in every case. It is recognized that each case is different and those individuals involved in providing health care are expected to use their judgment in determining what is in the best interests of the patient based on the circumstances existing at the time. It is impossible to anticipate all possible situations that may exist and to prepare guidelines for each. Accordingly these guidelines should guide care with the understanding that departures from them may be required at times.