Neonatal Herpes Infection: A Review

Leslie A. Parker, MSN, RNC, NNP; Sheryl J. Montrowl, MSN, RNC, NNP


NAINR. 2004;4(1) 

In This Article


As with any clinical entity, the diagnostic procedure must begin with a thorough physical assessment. Findings of vesicular lesions, respiratory distress, hepatosplenomegaly, and/or CNS dysfunction may be indicative of herpes infection. Once a suspicion of a herpes infection arises, a full investigation for the presence of the virus and treatment with antiviral therapy is indicated ( Table 2 ). [39]

In the presence of vesicular lesions, the base of the lesion should be scraped and sent for both viral culture and polymerase chain reaction (PCR). The PCR is a rapid genetic amplification technique, which detects the presence of minute quantities of viral DNA.[29] It can be performed on blood, cerebrospinal fluid, and mucocutaneous lesions. The PCR test has been shown to be highly sensitive in the diagnosis of herpes infection and has also been shown to be even more reliable than viral culture for CNS and mucocutaneous infections.[22,40] Although the presence of a positive PCR is highly predictive of infection, a negative result does not eliminate the possibility of disease and thus, if herpes infection remains high on the differential diagnosis, antiviral therapy should be either initiated or continued.[31,41] Direct immunofluorescent antibody staining detects the presence of the HSV antigen and can also be performed on cutaneous lesions. Although this test is not as reliable as the PCR and both false negatives and false positives may occur, it may be necessary in those situations for which PCR testing is not available in a timely manner.

Besides culturing any cutaneous lesions, viral cultures of the oropharynx, nasopharynx, conjunctiva, and rectum as well as both the blood and urine should be performed.[2,29,30] Although it is possible to test for the presence of HSV-specific IgM in the blood through the use of enzyme-linked immunosorbent assay (ELISA) testing, this is not recommended during the newborn period due to a high rate of both false positive and negative results. Only 12% of infected infants will have a positive ELISA test at one week of age and, if one waits until two to six weeks or even 6 to 18 months, 25% of infants who had documented herpes infection will still not have detectable IgM levels. To make matters even more complicated, over 80% of infants whose mothers experienced a herpes infection in the perinatal period were uninfected, but had positive IgG levels due to transplacental delivery of maternal antibodies.[42]

Accurately diagnosing herpes meningitis and/or encephalitis can be very difficult. On CSF analysis, one can usually appreciate a pleocytosis with 20 to 100 white blood cells and an elevated protein in excess of 1 g/dL. However, these findings may not be present early in the disease process, and thus withholding antiviral treatment should not be based on a normal CSF profile.[43] Viral cultures are notoriously poor in their ability to successfully diagnose herpes meningitis, with less than 50% of CSF viral cultures being positive in infants with HSV meningitis.[2,9,33] Historically, the gold standard for the diagnosis of herpes meningitis was brain biopsy, however, due to the invasive nature of such a test, it is rarely performed except at autopsy. Recently, the use of PCR testing of CSF is replacing the brain biopsy as the gold standard for the identification of neonatal herpes meningitis. It has been shown to be extremely reliable with a sensitivity rate of 75 to 100% in the detection of HSV DNA and is considered far superior to viral culturing of CSF.[22] However, even PCR testing is negative in 24% of herpes meningitis and may not become positive until later in the disease process and therefore serial testing of PCR may be necessary.[41,44]

In infected infants presenting with seizures or other neurologic symptoms, it is recommended that an electroencephalogram (EEG) and either a CT or preferably magnetic resonance imaging is performed as part of the diagnostic procedure.[22] The EEG is likely to reveal either the presence of seizure activity or an abnormal background with a paroxysmal pattern, which is very suggestive of HSV encephalitis.[45] Neurologic scans may be normal initially in the disease but, after approximately five days,[46] typically begin to show focal abnormalities in the temporal lobes, insular cortex, and the gyrus rectus.[3,47]


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