June 2000
MARINA DEL REY, Calif. - Herpes simplex virus (HSV) infections are extremely common, with 40% to 90% of the U.S. population infected with HSV-1 and 15% to 30% infected with HSV-2. While many people, especially adults, are asymptomatic, herpes infections may be particularly dangerous for infants.
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"Neonatal herpes is the most feared consequence of herpes genitalis," said Charles G. Prober, MD, department of pediatrics and the division of infectious diseases at Stanford University in Stanford, Calif. Neonatal herpes is generally contracted during birth, and the risk for infection is greatest if the mother is experiencing a primary HSV-2 outbreak at that time.
In this situation, "the mom has no antibody to pass on to the baby to provide some degree of passive protection," Prober said.
The greatest risk to infants from perinatally acquired HSV infection is during the first four weeks of life. "It appears that after the baby gets up to the ripe old age of 5 or 6 weeks, herpes is not nearly as much of a problem," Prober said.
Neonatal herpes can be divided into three categories: skin, eye and mouth (SEM) disease; disseminated disease and central nervous system (CNS) disease. SEM disease is the most common form of neonatal herpes, representing 40% of all infections. The typical onset of symptoms is between 1 and 2 weeks of age. However, it may appear at birth or as late as 3-4 weeks of age. Conjunctivitis, as well as skin lesions, may be present.
Culturing the lesions is important for accurate diagnosis, and prompt treatment is vital, Prober said. "If you do not recognize and/or treat neonatal skin disease, it will progress to more severe forms of the disease with higher morbidity and mortality rates."
Disseminated disease represents 25% of neonatal herpes infections. Infants may present with the disease between 2 and 5 days of age and may appear to have bacterial sepsis.
"However, they have a marked amount of liver dysfunction, similar to the liver dysfunction with enteroviruses," said Prober, who spoke here at the Infectious Diseases in Children Symposium West. "The liver dysfunction results in coagulopathy, and the baby may bleed to death, or there may be severe respiratory distress."
Lesions may not always be present; therefore, diagnosing this potentially deadly disease may be difficult.
Disseminated disease may involve the CNS, or the CNS may be the only site affected by the disease (35% of cases). Neonates generally present between 2 and 3 weeks of age with nonspecific symptoms such as lethargy, irritability, fever and seizures. An electroencephalogram is helpful in confirming the diagnosis because it shows focal abnormalities. Magnetic resonance imaging or polymerase chain reaction may be helpful as well.
As for treatment, Prober said both acyclovir and vidarabine (Vira-A, Monarch) may be used to treat neonatal herpes. Results from a study published in The New England Journal of Medicine in 1991 showed that all 85 infants with SEM disease treated with either drug survived, with 94% surviving intact. Eighty-six percent of 71 infants with CNS disease treated with either drug survived, but only 36% survived intact. Only 54% of 46 infants with disseminated disease treated with either drug survived, and of those, only 59% survived intact.
HSV-1 is the usual cause of oral herpes and herpes encephalitis. Primary gingivostomatitis, caused by HSV, occurs primarily in children between 1 and 3 years of age. Symptoms include vesicular lesions, tender submandibular adenopathy and a high fever. Children with gingivostomatitis often will refuse to eat or drink.
Systemic acyclovir is the drug of choice against primary HSV-1 infections, Prober said. The drug has been shown to reduce duration of primary gingivostomatitis by approximately four days. However, it has little effect on subsequent infections.
The most severe infection caused by HSV-1 is herpes encephalitis. It has an untreated mortality rate of 70%. Acyclovir reduces mortality to about 40%.
HSV-2 is responsible for most cases of genital herpes infections. Complete healing of primary infections may take as long as one month. Systemic acyclovir is the treatment of choice for primary infections. The course of recurrent genital infections is less dramatically affected by antiviral therapy, "simply because recurrent disease is so mild and so short in duration that it's hard to demonstrate much effectiveness," said Prober, who added that acyclovir may have a role in suppressive therapy as well.
"If you were to have patients with frequently recurrent disease (six or more times per year), there are good data that show if you put them on chronic suppressive acyclovir therapy, titrating the dose to the individual patient, that you can reduce their activation, their symptomatic disease, by 70% to 80%," Prober said. "There are some patients who have been on therapy for up to 15 years, continuing to have benefit."
Human herpes virus-6, which generally occurs in children between the ages of 6 months and 3 years, is the primary cause of roseola exanthem. A child will have a high fever for three to five days, followed by a maculopapular rash that generally lasts one to two days. Respiratory symptoms, swollen eyelids, lymphadenopathy and bulging fontanel may be present, as well as nonspecific febrile illness without rash, irritability and febrile seizures.
For more information:
- Prober CG. Herpes infections. Presented at the Infectious Diseases in Children Symposium West. Feb. 26-27, 2000. Marina del Rey, Calif.
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