Neonatal And Postnatal Herpes Simplex Virus Diagnosis

Herpes simplex virus (HSV) is of two types, HSV-1 and HSV-2, both classified as alphaherpesviruses (a category of human herpesviruses) (1). HSV-1 and HSV-2 both have the potential to lead to a viral infection in not only adults, but also neonates through perinatal acquisition, the diagnosis of which can be problematic (1). Although congenital herpes simplex virus infection is rare (1:3200-1:15000 pregnancies), it can lead to varying clinical manifestations, and this variation has a profound effect on neonatal and postnatal diagnosis and treatment (2, 3). Neonatal HSV infections are associated with mortality and chronic morbidity, and negative outcomes are exacerbated with delayed treatment (4).

As of yet there is no systematic criteria of signs and symptoms to diagnose all neonates that have a HSV infection, although it is common practice that patients undergo HSV testing and empirical treatment initiation if clinical presentation is suggestive of HSV (3). It is in those neonates with non-specific complaints (such as fever) in which diagnostics and treatment is ambiguous. This leads to different nonstandardized approaches being used nationally, which is associated with longer lengths of stay and thus higher costs (3, 4).

There are a few different courses of diagnostics and treatments that can be taken. The first approach is universal testing and diagnosis. To minimize the risk of delayed treatment, it has been suggested to immediately test and treat all neonates under 21 days’ post birth that display any specific or non-specific symptoms (3, 4). This approach has the advantage of not allowing disease progression in affected neonates by indiscriminately applying antiviral therapy to all symptomatic neonates. However, one of the reasons that this method is not unilaterally beneficial is diagnostic testing is time consuming and costly. Because HSV is a rare infection, this will keep unaffected neonates in the hospital for longer unnecessarily, increasing risk for nosocomial infection. Also, the immediately applied antiviral therapy has known adverse side effects, including nephrotoxicity, and a reason as to why immediate treatment is unwanted (4).

A second methodology to HSV diagnostics and treatment is the targeted approach. This suggests instead testing and treatment be restricted to neonates that present with high risk features of HSV (such as seizures, vesicles or CSF pleocytosis) (4). This method is advantageous in the fact that it can exclude the unaffected neonates from the prolonged hospital stay, the increased cost, and adverse effects from antiviral therapy. However, as mentioned previously, clinical presentation is variable, and a subpopulation of HSV infected neonates may have non-specific symptom manifestation and thus this population may be delayed treatment (4).

A more novel protocol for HSV infection has been described in literature, which combines parts of the two aforementioned methods (4). This method will include testing of HSV alongside bacterial testing in symptomatic neonates younger than 21 days (4). However, only those with specific symptoms suggestive of HSV, or with abnormal CSF, will start immediate treatment with antiviral therapy. This method will exclude unnecessary treatment for those infants that do not have a HSV infection, but will still apply treatment to those that have highly suggestive symptoms of HSV.

The criteria of abnormal CSF parameters has been added to cover infants with non-specific symptoms, as CNS involvement is frequently linked to paucity of symptoms (4). A disadvantage to this approach is that neonates with non-specific symptoms may be tested for HSV infection, however treatment is delayed if CSF parameters are within range and laboratory evaluation return positive.

Determining the patients to test and treat constitutes one challenge, however the laboratory techniques used in perinatally acquired HSV infection diagnostics have associated disadvantages as well. The most common method employed in testing being HSV PCR (of CSF, surface swabs, vesicle scrapings and of serum) (3, 4). An associated disadvantage of the CSF HSV PCR technique is that it increases the length of hospital stay, dependent on if PCR is performed in-house or if HSV samples are sent out, and it will also increase cost (3). As well, CSF PCR can have false negative results when testing for HSV encephalitis within the first few days of infection, and maintains only a 70% sensitivity within that initial time period (5). This can be corrected by serial CSF PCR evaluation for HSV encephalitis, however this can also delay treatment (5). Viral culture has been proven to be specific and sensitive, although hospitals are relying more and more on this newer PCR approach in diagnosis due to its relative efficiency (3). With this increased reliance, the diagnostic issues prevalent with this methodology has to be reviewed and taken into account.

Although perinatally acquired HSV infection is rare, variability in testing can lead to patients being over tested or under tested, leading to an increased cost or increased risk of delayed treatment. Without standardized procedures between hospitals, and even within hospitals, measuring the efficacy of different diagnostic paths and treatments is increasingly more difficult.

Communication with other hospitals and professionals can be improved, to learn from one another’s successes and short comings to help plan a nationally standardized protocol for HSV testing and treatment. This would lead the ability to study the efficacy of a single approach that could be faulted and improved upon by the scientific community as a whole, rather than having varying faults in multiple different nonstandardized protocols that may or may not be studied upon in depth.