Source: Caviness AC, Demmler GJ, Selwyn BJ. Clinical and laboratory features of neonatal herpes simplex virus infection. A case-control study. Pediatr Infect Dis J. 2008;25(5):425–430; doi:10.1097/INF.0b013e3181646d95In this retrospective, case-controlled study, researchers from Texas Children’s Hospital (TCH) compared the clinical and laboratory features of neonates with HSV infection to similar patients without HSV infection.Neonates hospitalized between July 1991 and December 2005 at TCH who underwent testing to identify HSV infection were eligible for inclusion. Neonates were classified as having HSV infection if they had both 1) virologic confirmation of HSV infection and 2) HSV infection confirmed in the review of their medical record. HSV infection was characterized as disseminated, central nervous system (CNS), or skin, eye, and mouth disease (SEM). The comparison group was made up of four neonates without HSV infection admitted within four weeks of each study case.There were 6,559 neonates with at least one test that could have identified HSV infection, of which 40 neonates had at least one positive HSV test. Patients were diagnosed with disseminated (37.5%), CNS (37.5%), or SEM (25%) disease. Neonates with HSV infection were six times more likely to have mothers with fever at delivery (OR 5.8; 95% CI, 2.3–14.5), and maternal fever was more likely to be present in infants with disseminated disease (60% vs 7% and 20% in CNS and SEM disease, respectively). Severe respiratory distress (73%), hypothermia (27%), jaundice (23%), thrombocytopenia (53%), and elevated hepatic enzymes (AST 73% and ALT 47%) were exclusively associated with disseminated, rather than CNS or SEM disease. The only feature associated exclusively with CNS disease was seizures (36%).Red blood cells in the CSF were not associated with HSV infection. In patients without vesicular rash, three features, although not highly sensitive, had high specificity for HSV infection: maternal fever (95.2%; 95% CI, 88.3–98.7), respiratory distress requiring mechanical ventilation (97.6%; 95% CI, 91.7–99.7), and cerebrospinal fluid pleocytosis (82.8%; 95% CI, 70.6–91).The authors conclude that neonatal HSV infection is associated with well-known findings such as maternal primary HSV infection, vaginal delivery, prematurity, cutaneous vesicles, seizures, hypothermia, elevated hepatic enzymes, and cerebrospinal fluid (CSF) pleocytosis as well as the newly appreciated findings of maternal fever, respiratory distress, and thrombocytopenia.Dr. Pate has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The spectrum of neonatal HSV infection includes three presentations: sepsis-like disseminated disease, infection limited to the skin and mucosal surfaces (SEM), and CNS infection. Appropriate initial therapy until infection is excluded or confirmed is acyclovir, 60mg/kg/day in three divided doses.1The evaluation and diagnosis of neonatal HSV infection presents a unique challenge for practitioners. Not wanting to “miss” a potentially devastating and treatable infection, physicians inconsistently evaluate and empirically treat for HSV infection, leading to potentially inappropriate testing, prolonged hospital stays, and unnecessary treatment with acyclovir.2,3More importantly, the current study provides evidence that appropriate treatment may be significantly delayed for patients with disseminated HSV infection, which carries the worst prognosis and may be the most difficult to diagnose at presentation.Individual practitioners and hospital systems can utilize this study to “fine tune” the initial assessment of the ill neonate and apply a more consistent and evidence-based approach to the evaluation and empiric treatment of possible HSV infection. Histories should query for maternal fever, primary HSV infection, and the infant’s gestational age. Evaluation of the ill-appearing, febrile, or hypothermic infant under four weeks of age should include CSF examination for pleocytosis and hepatic function tests. Even in the absence of cutaneous vesicles or seizures, the patient with a concerning history and/or laboratory features and a sepsis-like presentation with respiratory distress should be treated empirically with acyclovir after appropriate diagnostic studies, including PCR and viral mucosal surface cultures, have been obtained.There is no consensus among infectious disease experts on the criteria which should trigger empiric therapy for HSV in neonates: “experts vary in th[eir] tipping point.”4 The three studies relating to HSV summarized in this issue, their accompanying commentaries, and the editorials by Long4 and Kimberlin5 define the conscientious clinician’s current conundrum and outline the approach of some knowledgeable, experienced, and wise physicians. We hope these contributions will assist AAP Grand Rounds readers in reconsidering their own approach to this problem and provide some assistance in deciding whether that approach is valid or needs to be revised.