Herpes simplex neonatorum

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Lakshmi Gopalakrishnan, M.B.B.S.

Overview

Neonatal HSV disease is a rare but serious condition, usually as a consequence of vertical transmission of the virus from the mother to the newborn child, although an estimated 10% of cases may be acquired postnatally from a parent, caretaker, or sibling. Between 1 in 3,000 and 1 in 20,000 live births are infected with neonatal herpes. Approximately 22% of pregnant women have had a previous exposure HSV-2, and a further 2% or more women acquire the virus during pregnancy. Particularly among young adults, genital herpes infections are increasing caused by HSV-1.

Pathophysiology

Risk of Transmission

The risk of transmission is 30-57% in cases of primary infection acquisition by the mother in the third trimester of pregnancy. Risk of transmission by a mother with existing antibodies for both HSV-1 and HSV-2 has a much lower (1-3%) transmission rate. This in part is due to the presence of significant titer of protective maternal antibodies in the fetus from about the seventh month of pregnancy. However, shedding of HSV-1 from both primary genital infection and reactivation is associated with high transmission from mother to infant.

Epidemiology and Demographics

Developing Countries

HSV-1 neonatal herpes is extremely rare in developing countries because primary exposure to HSV-1 (and therefore development of HSV-1 specific antibodies) usually occurs in childhood or adolescence, precluding a genital HSV-1 infection; HSV-2 infections are much more common in these countries.

Developed Countries

• In industrialized nations the adolescent HSV-1 seroprevalance has been dropping steadily for the last 5 decades as a result of better hygiene, less over-crowding, and smaller family size. The resulting increase in the number of young women entering the sexually active/child bearing years as HSV-1 seronegative, has been a harbinger of increased HSV-1 genital herpes, and as a result, increased HSV-1 neonatal herpes in developed nations.

• A recent three year study in Canada revealed neonatal HSV infections in 5.9 per 100,000 live births. HSV-1 was the cause of 62.5% of cases of neonatal herpes, and 98.7% of transmission was asymptomatic.

• Asymptomatic genital HSV-1 has been shown to be more infectious to the neonate and is more likely to produce neonatal herpes than HSV-2.

Complications

• Untreated, SEM herpes may spread to the internal organs and cause DIS or CNS herpes, resulting in increased mortality and morbidity.

• Death from neonatal HSV disease in the United States is currently decreasing; as many as 85% of HSV-infected neonates died a few decades ago, whereas the current death rate is about 25%. Reduction in mortality is due to the use of antiviral treatments such as vidarabine and acyclovir.

• However, morbidity and mortality still remain high, as the diagnosis of DIS and CNS herpes often comes too late for effective antiviral administration. Early diagnosis is difficult because 20-40% of infected neonates that have no visible lesions.

Diagnosis

History and Symptoms

• Neonatal herpes manifests itself in three forms: skin, eyes and mouth (SEM) herpes, disseminated (DIS) herpes, and central nervous system (CNS) herpes.

• SEM herpes is characterized by external lesions but no internal organ involvement, and has the best prognosis. Lesions are likely to appear on trauma sites such as the attachment site of fetal scalp electrodes, forceps or vacuum extractors that are used during delivery; in the margin of the eyes; the nasopharynx; and in areas associated with trauma or surgery (including circumcision).

• DIS herpes affects internal organs, especially the liver.

• CNS herpes is an infection of the nervous system and the brain that can lead to encephalitis. Infants with CNS herpes present with seizures, tremors, lethargy, and irritability. They feed poorly, have unstable temperatures, and their fontanelle (soft spot of the skull) may bulge. CNS herpes is associated with highest morbidity, and DIS herpes has a higher mortality rate.

Treatment

Medical Therapy

• Infants exposed to HSV during birth, as documented by maternal virologic testing or presumed by observation of maternal lesions, should be followed carefully in consultation with a pediatric infectious disease specialist.
• Surveillance cultures of mucosal surfaces to detect HSV infection might be considered before the development of clinical signs of neonatal herpes.
• In addition, administration of acyclovir might be considered for infants born to women who acquired HSV near term because the risk for neonatal herpes is high for these infants.
• All infants who have neonatal herpes should be promptly evaluated and treated with systemic acyclovir. The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg IV every 8 hours for 21 days for disseminated and CNS disease or for 14 days for disease limited to the skin and mucous membranes.

Prevention

• Herpes simplex virus infection in the newborn "carries high mortality and morbidity rates from central nervous system involvement," according to Harrison's Principles of Internal Medicine, which recommends that pregnant women with active genital herpes lesions at the time of labor be delivered by cesarean section.

• Women whose herpes is not active can be managed with acyclovir.