Perinatal Herpes Simplex Virus (HSV) Infections
Introduction to Perinatal Herpes Simplex Virus (HSV) Infections
Perinatal Herpes Simplex Virus (HSV) infection is a serious condition that can occur when newborns are exposed to HSV before, during, or shortly after birth. It can lead to significant morbidity and mortality if not recognized and treated promptly. HSV infections in newborns can range from localized skin, eye, and mouth disease to severe disseminated infection involving multiple organs, including the central nervous system. Understanding the etiology, epidemiology, clinical presentation, and management of perinatal HSV infections is crucial for healthcare providers to ensure optimal outcomes for affected infants.
Etiology of Perinatal HSV Infections
Perinatal HSV infections are caused by Herpes Simplex Virus, primarily of two types:
- HSV-1: Traditionally associated with oral herpes but increasingly causing genital infections
- HSV-2: Primarily associated with genital herpes
Transmission to the newborn can occur through three main routes:
- Intrauterine (in utero): Rare, accounting for about 5% of cases
- Peripartum (during delivery): Most common, accounting for 85% of cases
- Postnatal: Accounts for about 10% of cases, usually due to contact with infected caregivers
Risk factors for transmission include:
- Primary maternal HSV infection during late pregnancy
- Asymptomatic viral shedding at the time of delivery
- Prolonged rupture of membranes
- Use of fetal scalp monitors
- Maternal HSV-1 or HSV-2 seronegative status
Epidemiology of Perinatal HSV Infections
Perinatal HSV infection is relatively rare but can have severe consequences:
- Incidence: Approximately 1 in 3,000 to 1 in 20,000 live births in the United States
- Global variation: Incidence varies by geographic region and population
- Maternal seroprevalence: HSV-2 seroprevalence in women of childbearing age ranges from 10% to 30% in developed countries
Key epidemiological points:
- Transmission risk:
- 30-50% risk of neonatal infection if mother has primary HSV infection near term
- 1-3% risk if mother has recurrent HSV infection
- Increasing proportion of cases due to HSV-1, particularly in developed countries
- Higher risk in areas with high HSV-2 seroprevalence in the general population
- Racial and socioeconomic disparities in HSV seroprevalence and neonatal HSV incidence
Pathophysiology of Perinatal HSV Infections
The pathophysiology of perinatal HSV infections involves several stages:
- Viral entry: HSV enters through mucosal surfaces or breaks in the skin
- Local replication: The virus replicates at the site of entry
- Spread to sensory nerves: HSV travels to sensory nerve ganglia
- Latency establishment: The virus establishes latency in sensory ganglia
- Reactivation and spread: Periodic reactivation leads to viral shedding and potential spread
Specific pathophysiological features in neonates:
- Immature immune system: Neonates have limited ability to contain HSV infection
- Skin barrier: Neonatal skin is more permeable and susceptible to viral entry
- CNS involvement: HSV has a predilection for the central nervous system in neonates
- Dissemination: Rapid viral replication can lead to multi-organ involvement
The clinical manifestations and severity of infection depend on the route of transmission, viral type, maternal antibody status, and the infant's immune response.
Clinical Presentation of Perinatal HSV Infections
Perinatal HSV infections can present in three main forms:
1. Skin, Eye, and Mouth (SEM) Disease (45% of cases):
- Vesicular skin lesions
- Conjunctivitis
- Oral mucosa lesions
2. Central Nervous System (CNS) Disease (30% of cases):
- Lethargy
- Poor feeding
- Seizures
- Bulging fontanelle
- Temperature instability
3. Disseminated Disease (25% of cases):
- Multi-organ involvement (liver, lungs, adrenal glands, CNS)
- Shock
- Disseminated intravascular coagulation (DIC)
- Respiratory distress
- Hepatitis
Key points about clinical presentation:
- Symptoms typically appear within the first 4 weeks of life
- SEM disease usually presents earlier (7-10 days) than CNS or disseminated disease (10-21 days)
- Absence of skin lesions does not rule out HSV infection
- Fever may be absent in up to 50% of cases
- Clinical presentation can be nonspecific, mimicking bacterial sepsis
Diagnosis of Perinatal HSV Infections
Prompt diagnosis of perinatal HSV infection is crucial for timely treatment. Diagnostic approaches include:
1. Laboratory Tests:
- PCR (Polymerase Chain Reaction):
- CSF PCR for HSV DNA (gold standard for CNS disease)
- Blood PCR for HSV DNA
- Surface swab PCR from skin, eye, or mouth lesions
- Viral culture: Less sensitive than PCR but can type the virus
- Serology: Limited utility in neonates due to maternal antibodies
2. Imaging Studies:
- Brain MRI: To assess for CNS involvement
- CT scan: May show characteristic findings in CNS disease
3. Other Investigations:
- Lumbar puncture: For CSF analysis and PCR
- Liver function tests
- Coagulation studies
- Complete blood count
4. Maternal History and Testing:
- Review of maternal HSV history and serostatus
- Genital examination of mother for active lesions
A high index of suspicion is crucial, as early symptoms can be nonspecific. Empiric treatment should be initiated while awaiting test results in suspected cases.
Treatment of Perinatal HSV Infections
Treatment of perinatal HSV infections involves antiviral therapy and supportive care:
1. Antiviral Therapy:
- Drug of choice: Intravenous (IV) Acyclovir
- Dosage: 60 mg/kg/day divided every 8 hours
- Duration:
- SEM disease: 14 days
- CNS or disseminated disease: 21 days
2. Supportive Care:
- Fluid and electrolyte management
- Respiratory support if needed
- Management of seizures if present
- Treatment of secondary bacterial infections
3. Long-term Management:
- Oral acyclovir suppression (300 mg/m2/dose, three times daily) for 6 months after acute treatment
- Regular neurodevelopmental follow-up
- Ophthalmological evaluations
4. Monitoring:
- Repeat CSF PCR at the end of IV treatment for CNS disease
- Monitor for acyclovir-related neutropenia
- Follow-up PCR testing to ensure viral clearance
Early initiation of antiviral therapy is crucial for improving outcomes, especially in CNS and disseminated disease.
Prevention of Perinatal HSV Infections
Prevention strategies for perinatal HSV infections focus on reducing the risk of transmission:
1. Maternal Management:
- Antiviral suppression from 36 weeks gestation for women with known genital herpes
- Cesarean delivery for women with active genital lesions or prodromal symptoms at the time of labor
- Avoid invasive procedures during labor (e.g., fetal scalp electrodes) if mother has active HSV infection
2. Neonatal Management:
- Surface cultures and PCR for exposed infants
- Consider empiric acyclovir for high-risk infants pending test results
3. Education and Counseling:
- Educate pregnant women about HSV and risks of perinatal transmission
- Counsel partners of HSV-negative pregnant women to avoid transmission during pregnancy
4. Screening:
- Consider type-specific HSV serologic testing for pregnant women with unknown HSV status
- Screen partners of HSV-negative women
5. Postnatal Precautions:
- Proper hand hygiene for all caregivers
- Avoid contact between infants and individuals with active herpes lesions
Prevention strategies should be tailored based on maternal HSV status, history, and presence of active lesions.
Prognosis of Perinatal HSV Infections
The prognosis of perinatal HSV infections varies depending on the extent of disease and timing of treatment:
Outcomes by Disease Classification:
- SEM Disease:
- Generally good prognosis with timely treatment
- Risk of recurrence without suppressive therapy
- CNS Disease:
- Higher risk of neurological sequelae
- 29-40% mortality without treatment; improved with early antiviral therapy
- 50-60% of survivors may have long-term neurological impairment
- Disseminated Disease:
- Highest mortality rate (up to 29% even with treatment)
- Survivors at risk for multi-organ complications
Factors Affecting Prognosis:
- Timing of diagnosis and treatment initiation
- Extent of disease at presentation
- Viral type (HSV-1 vs HSV-2)
- Presence of maternal antibodies
- Gestational age and birth weight of the infant
Long-term Follow-up:
- Regular neurodevelopmental assessments
- Monitoring for ocular complications
- Assessment of hearing and speech development
- Evaluation for recurrences and need for continued suppressive therapy
Early diagnosis and prompt initiation of antiviral therapy are crucial for improving outcomes in perinatal HSV infections. Long-term follow-up is essential to address potential sequelae and optimize developmental outcomes.
Perinatal Herpes Simplex Virus (HSV) Infections
- What is the primary mode of transmission for perinatal HSV infections?
Mother-to-infant transmission during delivery - Which type of HSV is more commonly associated with neonatal infections?
HSV-2 - What percentage of neonatal HSV infections are acquired during delivery?
Approximately 85% - What are the three main categories of neonatal HSV disease?
Skin, eye, and mouth (SEM) disease; central nervous system (CNS) disease; and disseminated disease - How long after birth do symptoms of neonatal HSV typically appear?
Within the first 4 weeks of life - What is the recommended antiviral treatment for neonatal HSV infections?
Intravenous acyclovir - How long should antiviral treatment be administered for CNS or disseminated HSV disease?
21 days - What is the mortality rate for untreated disseminated neonatal HSV infection?
Up to 85% - Which diagnostic test is considered the gold standard for confirming neonatal HSV infection?
PCR (Polymerase Chain Reaction) of CSF or blood - What is the recommended mode of delivery for pregnant women with active genital HSV lesions?
Cesarean section - How effective is cesarean delivery in preventing neonatal HSV infection?
It reduces the risk by approximately 87% - What percentage of infants born to mothers with a history of genital HSV will become infected?
Less than 1% - Which maternal antibody type provides the most protection against neonatal HSV infection?
Transplacentally acquired type-specific neutralizing antibodies - What is the recommended antiviral prophylaxis for pregnant women with recurrent genital HSV infections?
Oral acyclovir or valacyclovir starting at 36 weeks gestation - How long should suppressive antiviral therapy be continued in infants following treatment for HSV infection?
6 months - What is the most common presentation of neonatal HSV infection?
Skin, eye, and mouth (SEM) disease - Which form of neonatal HSV infection has the highest mortality rate?
Disseminated disease - What percentage of neonatal HSV infections are caused by HSV-1?
Approximately 30% - How soon after birth should empiric acyclovir treatment be initiated in suspected cases of neonatal HSV?
As soon as possible, ideally within 24 hours of symptom onset - What is the primary risk factor for neonatal HSV infection?
First-episode maternal genital HSV infection near term - How often should infants treated for neonatal HSV receive follow-up PCR testing of CSF?
At the end of treatment (21 days) and, if positive, every 7-14 days until negative - What is the recommended dosage of intravenous acyclovir for neonatal HSV treatment?
60 mg/kg/day divided into three doses - Which specialized test can help differentiate between primary and recurrent maternal HSV infections?
Type-specific serologic testing - What is the approximate incidence of neonatal HSV infection in the United States?
1 in 3,000 to 1 in 20,000 live births - How does the risk of transmission differ between primary and recurrent maternal HSV infections?
Primary infections have a 30-50% transmission risk, while recurrent infections have less than 1% risk - What neurological complication is commonly associated with neonatal HSV CNS disease?
Seizures - How long can viral shedding persist in neonates following HSV infection?
Up to 6 weeks after the completion of antiviral therapy - What is the recommended management for asymptomatic infants born to mothers with active genital HSV lesions?
Close observation, HSV surface cultures at 24 hours of life, and consideration of empiric acyclovir if signs of infection develop - Which laboratory finding is characteristic of neonatal HSV CNS disease?
Elevated CSF protein levels - What is the long-term neurological prognosis for survivors of neonatal HSV CNS disease?
Approximately 70% have moderate to severe neurological impairment
