PEDIATRICS Vol. 108 No. 2 August 2001, pp. 223-229
Natural History of Neonatal Herpes Simplex Virus Infections in the Acyclovir Era
Received Sep 1, 2000; accepted Dec 11, 2000.
,
,,,
From the * Department of Pediatrics, University of
Alabama at Birmingham, Birmingham, Alabama; Objective. During the 2 decades in
which effective antiviral therapies have been available for neonatal
herpes simplex virus (HSV) disease, changes have been documented not
only in the outcomes of infected infants, but also in the natural
history of the disease itself. Numerous studies previously have
reported that early institution of antiviral therapy is beneficial to
the outcome of the disease. The objective of this study was to provide
an update of neonatal HSV disease to identify means by which future
improvements in the management of HSV-infected neonates can be made.
Design/Methods. Neonates enrolled in 2 studies of
parenteral acyclovir for the treatment of neonatal HSV
disease provided the data source. The National Institute of Allergy and
Infectious Diseases Collaborative Antiviral Study Group conducted the
studies between 1981 and 1997. A total of 186 patients are summarized,
all of whom were treated with acyclovir. Demographic and
clinical characteristics of these patients are reported.
Results. Comparisons between patients treated in the
periods between 1981-1988 and 1989-1997 according to extent of
disease revealed that the mean time between the onset of disease
symptoms and initiation of therapy has not changed significantly from
the early 1980s to the late 1990s. Of all patients evaluated, 40% had
fetal scalp monitors during the delivery process. A significant
minority of patients did not have skin vesicles at the time of their
presentation and did not develop them during the acute HSV disease
(39% of patients with disseminated disease; 32% of patients with
central nervous system [CNS] disease; and 17% of patients with skin,
eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV
disease treated with acyclovir at 30 mg/kg/d, mortality
was associated with aspartate transaminase elevations of Conclusion. Data presented in the current comparison of
neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997)
demonstrate that no progress has been made in decreasing the interval
between onset of HSV symptoms and initiation of antiviral therapy.
Additional strides in the improvement of disease outcome may occur only
if the interval between onset of symptoms and initiation of therapy is
shortened. The means by which this will be accomplished lie in
increased consideration of neonatal HSV infections in acutely ill
infants. Specific data and recommendations to facilitate this goal are
contained within.
Department of
Pediatrics, University of Arkansas, Little Rock, Arkansas; § Department
of Pediatrics, Ohio State University, Columbus, Ohio; Department of
Pediatrics, University of Washington, Seattle, Washington; ¶ Department
of Pediatrics, Vanderbilt University, Nashville, Tennessee; # Department
of Pediatrics, University of Florida Health Science Center,
Jacksonville, Florida; ** Department of Pediatrics, University of
California San Diego, San Diego, California; Chicago Department
of Public Health, Chicago, Illinois; §§ Department of Pediatrics, Case
Western Reserve, Cleveland, Ohio; || Department of Pediatrics,
Stanford University, Stanford, California; ¶¶ Cook Children's Medical
Center, Fort Worth, Texas; ## Department of Medicine, State University
of New York, Syracuse, New York; *** Department of Pediatrics,
University of Florida, Gainesville, Florida; and Hospital
Infantil de Mexico, Mexico City, Mexico.
10 times the
upper limit of normal at the time of initiation of
acyclovir therapy. Mortality was also associated with
lethargy at initiation of antiviral therapy for patients with
disseminated disease. Patients' morbidity status was associated with
the extent of disease (skin, eye, and/or mouth disease vs CNS vs
disseminated). For those patients with CNS disease, morbidity was also
associated with seizures at initiation of antiviral therapy.
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