Pediatric Herpes Simplex Virus Infection
- Author: Swetha G Pinninti, MD; Chief Editor: Russell W Steele, MD more...
Herpes simplex virus (HSV) infections are ubiquitous and have a wide range of clinical manifestations (see the images below). Beyond the neonatal period, most primary HSV-1 infections occur in infancy and childhood and are transmitted primarily by contact with infected saliva. Primary HSV-2 infections are acquired after onset of sexual activity, and genital herpes infections are among the most common sexually transmitted infections.
See 13 Common-to-Rare Infant Skin Conditions, a Critical Images slideshow, to help identify rashes, birthmarks, and other skin conditions encountered in infants.
Also, see the Herpes Simplex Viruses: Test Your Knowledge slideshow for more information on clinical, histologic, and radiographic imaging findings in HSV-1 and HSV-2.
Essential update: AAP clinical practice guidelines
In January 2013, the American Academy of Pediatrics issued new guidelines for the evaluation of asymptomatic neonates exposed to HSV during delivery.[1, 2, 3] The guidelines assume laboratory access to polymerase chain reaction (PCR) assays for HSV DNA or type-specific serologic tests and may not be applicable in clinical settings without rapid testing turnaround times. Recommendations include the following:
Women in labor with visible genital lesions should be swabbed for HSV PCR and culture, and positive test results should be further analyzed to distinguish HSV-1 from HSV-2
A history of genital herpes should be obtained before the pregnancy
In women with a recurrent maternal herpes outbreak, skin and mucosal specimens should be obtained from the neonate for culture and PCR assay about 24 hours after delivery, and blood should be sent for HSV DNA PCR assay; preemptive treatment with acyclovir need not be started if the infant remains asymptomatic; if results become positive within 5 days, confirming neonatal HSV infection, the infant should undergo a complete evaluation to determine the extent of disease, and intravenous acyclovir should be initiated as soon as possible
In women without a history of genital herpes who have genital lesions at delivery, serologic testing should be done on maternal samples swabbed during delivery to determine the type of infection present; the infant should undergo a complete evaluation, and IV acyclovir should be initiated; if the mother has a first-episode infection and the neonate’s results are normal, the infant should be treated with IV acyclovir for 10 days; if the neonate’s results are positive, the infant should be treated with IV acyclovir for 14-21 days (depending on the extent of disease) and reevaluated to ensure clearance of the virus; after completion of IV acyclovir treatment, infants should receive suppressive therapy with oral acyclovir for 6 months
Signs and symptoms
HSV causes myriad clinical presentations, as follows:
Intrauterine and perinatal infection (herpes neonatorum)
Central nervous system infection
Infection in immunocompromised hosts
Other infections: Herpetic whitlow, herpes gladiatorum, keratoconjunctivitis, Mollaret meningitis, erythema multiforme
Clinical features of orolabial HSV infection include the following :
Abrupt onset of illness
Listlessness or irritability
Inability to eat and/or drink
Gingivitis (with markedly swollen, erythematous, and occasionally bleeding gums)
Increased drooling in infants due to pain on swallowing
Vesicular lesions on the tongue, buccal mucosa, and palate with extension, at times, to the lips and face (these may rupture and coalesce to form large, ulcerated areas)
Tender submandibular or cervical adenopathy
In recurrent cases, a prodrome of pain, burning, tingling, and itching
Clinical features of genital HSV infection may include the following:
In first episodes, severe constitutional symptoms (eg, fever, malaise, myalgias  )
Initial itching and pain, followed by more troublesome signs and symptoms
Lesions that evolve from vesicles to pustules to wet ulcers and heal by crusting
Painful inguinal lymphadenopathy, dysuria, and vaginal discharge
Paresthesias of the legs and perineum
Herpes neonatorum may be categorized as follows[6, 7, 8, 9, 10] :
Skin, eye, and mucous membrane (SEM) disease
Clinical features of HSV CNS infection may include the following:
Insidious or abrupt onset
Headache, altered consciousness, and focal neurologic abnormalities at presentation
Symptoms of aseptic meningitis (headache, fever, stiff neck, photophobia)
Symptoms of autonomic nervous system dysfunction and transverse myelitis (eg, hyperesthesia or anesthesia of the lower back, perineum, or sacral region)
See Clin ical Presentation for more detail.
Measures for diagnosing HSV infection in children include the following:
Isolation of the virus in tissue cultures (most common confirmation method)
Histologic analysis of scrapings or punch biopsy specimens
Cytologic evaluation via a Tzanck preparation
Serologic testing (only for determining past HSV exposure)
PCR assay (preferred for CNS infection [11, 12, 13] and possibly valuable for disseminated disease)
Lumbar puncture and cerebrospinal fluid analysis
Imaging studies: Computed tomography, magnetic resonance imaging
See Workup for more detail.
Specific medical therapy for pediatric HSV infection involves antiviral medications. Antiviral agents used include the following:
Oral acyclovir (most common)
Oral famciclovir (a prodrug that is converted to penciclovir)
Oral valacyclovir (a prodrug that is converted to acyclovir)
IV acyclovir (for encephalitis, neonatal disease, severe infection in immunocompromised patients, occasional cases of severe orolabial or genital disease, [14, 15, 16, 17] , and recurrent genital HSV infections)
Inpatient management is often indicated for pediatric patients with HSV infections. Suggested criteria include the following:
Many children with severe HSV gingivostomatitis who are dehydrated
Neonates with disseminated or CNS disease
Older patients with encephalitis who may be very ill at presentation
HSV infection in immunocompromised patients
Measures to prevent or minimize transmission of genital HSV infection include the following:
Avoid contact with individuals excreting the virus (difficult, because they are often asymptomatic)
Start oral antiviral therapy at the first symptom or sign of genital HSV disease
Promote condom use
Provide appropriate evaluation, counseling, and education
Measures to prevent transmission of HSV to newborns include the following:
Reassure women with recurrent disease that risk of neonatal infection is low
Perform cesarean delivery if a mother has active lesions during delivery 
Observe infants delivered vaginally by mothers with active genital herpes; follow up neonates carefully, and immediately institute antiviral therapy if symptoms occur 
In pregnant women with symptomatic genital herpes, consider antiviral suppressive treatment initiated at 36 weeks’ gestation
Herpes simplex virus (HSV) is a double-stranded, enveloped, DNA virus. Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) belong to the family Herpesviridae, subfamily Alphaherpesvirinae. Following initial infection, the herpes viruses become latent in the sensory neural ganglia (the trigeminal ganglion in HSV-1 infection and the sacral ganglion in HSV-2 infection). Herpes simplex virus infections are ubiquitous and cause a wide range of infections from isolated mucocutaneous lesions to disseminated infection in all age groups. Neonatal herpes simplex virus disease is associated with high morbidity and mortality. Herpes simplex virus infections are among the few non-HIV viral infections amenable to antiviral therapy. Available antiviral chemotherapy can be used to treat infection, shorten the clinical course, and, in certain circumstances, prevent infection with herpes simplex virus.
Infection occurs in a susceptible host following exposure of abraded skin or mucosal surfaces to the virus. After inoculation, the virus travels to the sensory ganglion, where it replicates and establishes latency. Recurrence occurs when the virus subsequently migrates along the peripheral sensory nerve, replicates, and produces a typical local lesion.[21, 22] Lifelong latency and periodic recurrences are hallmarks of herpes simplex virus infection. These reactivations can follow exposure to ultraviolet light, stress, hormonal changes, immunosuppression, and other infection.[23, 24] Histology of skin lesions shows cellular balloon degeneration, condensation of nuclear chromatin, and formation of multinucleated giant cells.
Disseminated infection occurs when the host is unable to control viral replication leading to viremia and multiorgan involvement. It is usually seen in neonates and immunocompromised individuals (and very rarely in immunocompetent hosts). Specific immunologic factors responsible for immunity to herpes simplex virus are not completely understood. Both antibody and cell-mediated immunity influence the severity and frequency of recurrences. Herpes simplex virus is also believed to suppress innate immunity by suppressing the production of interferon-alfa and interferon-beta. Additionally, titers of antibodies that mediate antibody-dependent cellular cytotoxicity inversely correlate with severity of neonatal infection.
Herpes simplex virus infections occur throughout the world, with humans serving as the only reservoir. The infection is acquired by intimate mucocutaneous contact between a susceptible host and a symptomatic or asymptomatic host shedding virus during primary infection or reactivation. Because the infection results in lifelong latency, the prevalence in any population is cumulative.
Beyond the neonatal period, most primary HSV-1 infections occur in infancy and childhood and are transmitted primarily by contact with infected saliva. Primary HSV-2 infections are acquired after onset of sexual activity and genital herpes infections are among the most common sexually transmitted infections (STIs).
The prevalence of herpes simplex virus infections depends on socioeconomic status, age, race, and geographic location. For example, approximately 33% of children from lower socioeconomic populations have serologic evidence of herpes simplex virus disease by age 5 years compared with 20% of middle-class individuals. Greater person-to-person contact in crowded living conditions is believed to account for the role of socioeconomic status in prevalence. The importance of daycare attendance is likely, but not well studied.
In the United States, HSV-2 seroprevalence increases from about 20-30% in patients aged 15-29 years to 35-60% in patients aged 60 years. This change represents a 30% increase compared with data from 1976-1980. Factors that increase the frequency of HSV-2 infection in older adolescents and adults include gender (more women than men), race (more blacks than whites), marital status (more divorced individuals than single or married individuals), and place of residence (more city residents than suburban residents).[27, 28]
The seroprevalence rate of HSV-2 in pregnant women ranges from 15-30%. Approximately 10% of pregnant women who are HSV-2 seronegative have a sexual partner who is HSV-2 seropositive and are, therefore, at risk of contracting a primary HSV-2 infection during pregnancy. Transmission typically results from contact with an asymptomatic sexual partner with a reported risk of acquisition of approximately 10%.[30, 31] Overall, approximately 2% of women acquire herpes simplex virus during pregnancy.
Herpes simplex virus has worldwide distribution. The prevalence of genital herpes in developing countries is 2-74% and varies among countries.[32, 33] In African countries that are experiencing HIV epidemics, HSV-2 infection is highly prevalent (≥70%). Evidence suggests that genital herpes simplex virus infection increases the risk of HIV infection and that persons infected with both viruses are more likely to transmit HIV.[35, 36, 37]
Most cases of infection with either HSV-1 or HSV-2 do not result in serious morbidity. Morbidity and mortality associated with herpes simplex virus are discussed in Complications. Mortality associated with herpes simplex virus is primarily related to perinatal infection, encephalitis, and infection in individuals who are immunocompromised.
At the time of vaginal delivery, the risk of herpes simplex virus transmission from a mother with true primary herpes simplex virus infection to her infant is approximately 50%. Women with primary infections at delivery are 10-30 times more likely than women with a recurrent infection to transmit the virus to their babies. Infants born to mothers with newly acquired infections who do not have primary infections in the presence of preexisting immunity caused by another viral infection (ie, first-episode nonprimary) have a transmission risk of 25-30%.
The neonatal herpes simplex virus infection rate is considered to be less than 2% when the mother has active infection caused by the shedding of herpes simplex virus acquired before pregnancy or during gestation before the onset of labor (recurrent infection). Approximately two thirds of women who acquire genital herpes during pregnancy have no symptoms.[30, 39] Of mothers who deliver an infant with herpes simplex virus infection, 60-80% have no evidence of genital herpes simplex virus infection at the time of delivery and have no history of previous genital infection and have sexual partners with no history. Of babies born to mothers with a primary infection near the time of delivery, 30-50% acquire the infection.
Neonatal herpes simplex virus infection is estimated to occur in approximately 1 per 3000 deliveries in the United States. In 2006, a lower incidence of 9.6 cases per 100,000 births was ascertained. Studies determined that herpes simplex virus infection in neonates and infants was associated with substantial morbidity, mortality, and resource use.
Although the risk of herpes simplex virus infection is not related to race, infection rates in the United States vary with race because of various factors, such as racial and ethnic differences in the prevalence of poverty and low socioeconomic status, access to health care, sexual and health-related behavior, and illicit drug use.
By age 5 years, more than 35% of black children are infected with HSV-1 compared with 18% of white children. Through adolescence, the prevalence of antibodies to HSV-1 in blacks is approximately twice the rate among whites. By age 40 years, HSV-1 seroprevalence is similar among blacks and whites. The prevalence of HSV-2 antibodies among blacks is 3-4 times higher than that among whites.
Seroprevalence among women of childbearing age in the late 1970s was estimated to be 50% for blacks and 20% for whites. By the late 1980s, rates of infection had increased to approximately 60% for blacks and 35% for whites. As shown in 2 nationwide surveys of HSV-2 seroprevalence in the last 2 decades, the cumulative lifetime incidence of HSV-2 reaches 25% in white women, 20% in white men, 80% in black women, and 60% in black men. Studies have indicated that the seroprevalence of HSV-2 among Hispanics ranges from 17-22.3%. Infants born to non-Hispanic white women may be at higher risk of herpes simplex virus infections. This is a result of a greater likelihood that these women are herpes simplex virus seronegative and at risk of acquiring a primary HSV-1 or HSV-2 infection in late pregnancy.
Infection rates with HSV-1 tend to be similar in both genders during early childhood. However, through adolescence, the prevalence of antibodies to HSV-1 is slightly higher among females than among males. Rates of HSV-2 infection are higher in women than in men. Nationwide surveys of HSV-2 seroprevalence over the last 2 decades have demonstrated cumulative lifetime incidences of 25% in white women and 80% in black women. This compares with rates of 20% in white men and 60% in black men.
Beyond the neonatal period, most childhood herpes simplex virus infections are caused by HSV-1. The seroprevalence of HSV-1 antibodies increases with age, and its rate is 20% by age 5 years. No increase occurs until 20-40 years of age, when 40-60% of individuals are HSV-1 seropositive. As a reflection of the association between infection and sexual activity, many HSV-2 infections occur around puberty and early adolescence. A progressive increase in HSV-2 infections occurs in all populations beginning in adolescence. In the United States, HSV-2 seroprevalence increases from approximately 20-30% in those aged 15-29 years to 35-60% in those aged 60 years. Most neonatal infections are caused by HSV-2, but increasing proportions are being caused by HSV-1.[19, 44]
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