July 1997
SAN FRANCISCO — Neonatal herpes simplex virus (HSV) infection typically occurs within the first six weeks of life. But about two-thirds of cases happen within the first week. "Even more remarkable is that about one-quarter occur on the first day of life," said Steve Kohl, MD, professor of pediatrics and chief of pediatric infectious diseases at the University of California-San Francisco.
From onset of signs to doctor presentation averages 24 hours. Three more days are lost in contemplating and procuring viral cultures. "Unfortunately, while one waits to obtain cultures, the virus does not wait," said Kohl, who spoke here at the annual meeting of the American Academy of Dermatology. "We've got to treat these babies very early because this makes a tremendous difference in their outcome."
Kohl noted that the incidence of neonatal HSV infection is approximately 1:3,000 to 1:6,000 live births in the U.S., with an estimated 1,000 cases per year. A Z study conducted in the Seattle, Wash. area showed a ten-fold increase from 1966 to 1982 — from 2.4 to 28.2 cases per 100,000 births. Furthermore, there is about a 33% attack rate among women with a first episode of herpes, compared with only 3% for reactivation.
Moreover, the disease is not limited to genital herpes. "You can acquire neonatal herpes from non-maternal sources, such as grandma with a fever blister or dad with the Whitlow in roughly 10% of cases," said Kohl. "Most of the time this is type 1, not type 2, as you would expect."
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Women with genital herpes tend to be young (on average 21 years old) and married. In addition, 20% have had a previous abortion. However, only about 10% have a history of sexual contact with an HSV-infected partner. Kohl stressed that patient history is often not very helpful. "Only about 13% to 15% will have had a history of genital herpes, and only about 10% give you a contact with a history of herpes," he said.
For those women with a reliable history, recurrence is most likely. "You can offer her a lot of reassurance because having a recurrence during pregnancy is not the same implication as having recent acquisition herpes," said Kohl.
Of five women with asymptomatic primary genital herpes acquired in the third trimester, four had premature births. Another study indicated that one-third of births to women with asymptomatic herpes were by cesarean section. "Even though there was this high rate of C-section, these babies still had neonatal herpes," said Kohl. "Although C-section is considered somewhat protective, it is not 100% protective. There has never been a controlled study with C-section."
The presentation of the neonate often is the most seriously involved, noted Kohl. "Thus, in a baby with breech presentation, those areas should be closely examined." Fetal scalp monitoring is one risk for HSV infection. "These lesions may be difficult to discern, especially in a child with dense hair. Careful inspection of the site, plus consideration of HSV and not merely bacterial infection is mandatory if a fetal scalp monitoring site becomes ulcerated or pustular."
Kohl showed a slide of a baby whose head had been shaved to reveal a small lesion. "As you can see, in the process of shaving, the virus was spread and inoculated in a fairly large area," he said. "So if you can make the diagnosis without lots of shaving, I think it may change the intensity of the infection."
For suspected cases of HSV, Kohl advocated starting therapy immediately, while waiting for culture results. "Acyclovir [Zovirax, Glaxo Wellcome] is a benign drug in the neonate," he said. "It's much better to start therapy and stop it in a few days if the culture is negative, rather than wait and sit tight for the culture while the virus disseminates."
Every case of neonatal herpes "is emotionally loaded," related Kohl. "There is tremendous anger which comes from the guilt of the parent. So if you can diffuse the guilt initially, you can sometimes decrease the anger. You may also be able to reduce the risk of medicolegal consequences, which are common in neonatal herpes cases."
Practitioners should always perform a simple Gram's stain and bacterial culture of the vesicular-pustular eruptions before telling the parents of suspected herpes because "the most common infectious cause confused with HSV is superficial bacterial infections, often from staph," said Kohl.
In the presence of skin lesions, scrapings of the base of the lesion with appropriate staining may prove beneficial. However, "the Tzanck smear is only about 50% sensitive and is plagued by false-positive results," Kohl said. In contrast, immunologic diagnosis either by enzyme-linked immunosorbent assay (ELISA) or fluorescent microscopy "is more specific and more sensitive, achieving 85% to 90% accuracy."
Many labs now offer accelerated cultures, said Kohl. "With rapid shell vial techniques combining viral culture with viral antigen detection methods a culture may be positive 18 to 24 hours after inoculation." Skin lesions, especially vesicular fluid, provide the highest yield. "Other sites that are worth culturing include the eyes, mouth, cerebrospinal fluid (CSF), rectum, urine and blood."
A recent major advance in detecting HSV DNA is the use of the polymerase chain reaction (PCR). It has been reported that in cases of herpes and encephalitis, PCR is almost always positive early on. "You don't get positive viral cultures in the CSF, but you can get positive DNA," said Kohl. Moreover, a recent study indicated that neonates with CSF disease will have a positive CSF reading about 75% of the time. However, "only about 5% of the time will these babies have a positive culture," Kohl said.
Many survivors of neonatal HSV continue to experience cutaneous recurrences. "Frequent recurrences in the first six months of life are associated with a higher rate of morbidity," said Kohl. Vidarabine (Vira-A, Parke Davis) and acyclovir are "basically the same and they markedly reduce the mortality rate." These drugs also limit the spread of the disorder. "If you've got a baby with skin, eye and mouth disease, he will typically not progress to other stages."
In addition, the rate of normalcy at 1 year by treating with vidarabine or acyclovir compared with placebo "is much higher," reported Kohl. "So you're treating not just to save lives, but you're treating to save good lives."
One future strategy for preventing neonatal infection is an HSV vaccine. Although there is data on a vaccine that successfully decreases the rate of recurrence in nonpregnant women, it has not yet been carefully evaluated.
It may also be possible to prophylactically treat neonates with recombinant human cytokines and interferons. "Similarly, the use of high titered anti-HSV serum or monoclonal antibodies may ameliorate infection in the high-risk neonate," predicted Kohl. In essence, "The hopes for control of neonatal HSV remain brighter than ever as our tools and basic understanding of the immunology, virology, epidemiology and sociology of HSV infection advances."
For more information:
- Kohl S. Neonatal herpes: diagnosis and management. Presented at the American Academy of Dermatology. Mar. 21-26. San Francisco.
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