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Neonatal HSV . Morning Report July 1 st , 2013. EPIDEMIOLOGY & TRANSMISSION. Neonatal infection with HSV occurs in 1 out of every 3,200-10,000 live births Approximately 1500 cases annually in US (incidence is increasing) Can be HSV-1 or HSV-2, HSV-2 associated with poorer outcome
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Neonatal HSV Morning Report July 1st, 2013
EPIDEMIOLOGY & TRANSMISSION • Neonatal infection with HSV occurs in 1 out of every 3,200-10,000 live births • Approximately 1500 cases annually in US (incidence is increasing) • Can be HSV-1 or HSV-2, HSV-2 associated with poorer outcome • Transmission • Intrauterine: rare • Perinatal: majority of cases (85%); occurs when HSV infection is present in genital tract at time of delivery; mom’s infection can be asymptomatic • MOST NEONATES WITH HSV ARE BORN TO MOTHERS WITHOUT HISTORY OF HSV INFECTION • Postnatal: 10% of cases; when caretaker with active HSV infection has close contact with newborn (ex: herpes labialis)
CLINICAL MANIFESTATIONS • Skin, Eye, Mouth (SEM) Disease • Makes up 45% of neonatal HSV • Usually presents within first 2 wks of life • Skin: • Coalescing or clustering vesicular lesions with erythematous base • Eye: • May initially be asymptomatic • Excessive watering, conjunctival erythema, periorbital skin vesicles • Mouth: • Localized ulcerative lesions of mouth, palate and tongue
CLINICAL MANIFESTATIONS • CNS Disease (HSV Meningoencephalitis) • Approx 30% of neonatal HSV involves CNS • Occurs from retrograde spread from nasopharynx and olfactory nerves to brain or via hematogenous spread in disseminated disease • Usually presents in 2nd or 3rd week of life • Can occur +/- SEM and +/- Disseminated disease, but 70% have skin vesicles at some point in their course • Seizures, lethargy, irritability, tremors, poor feeding, temperature instability • CSF can be normal early in course; classic: mononuclear pleocytosis, normal or low glucose, mildly elevated protein • RBCs in CSF are NOT significantly associated with HSV • EEG: focal or multifocal periodic epileptiform discharges • CT and MRI of brain: edema, hemorrhage, destructive lesions involving temporal, frontal, parietal or brainstem regions
CLINICAL MANIFESTATIONS • Disseminated Disease • Makes up 25% of neonatal HSV; CNS involved in 75% of cases • Present in 1st week of life • Fever, apnea, irritability, lethargy, respiratory distress, abdominal distention, ascites (rarely present with fever alone) • Diagnosis is OFTEN delayed until 2ndwk of life (awaiting results of bacterial sepsis evaluation) • Progression: hepatitis w/ elevated transaminases, ascites, direct hyperbilirubinemia, neutropenia, thrombocytopenia, DIC, NEC, meningoencephalitis + seizures; eventually leads to respiratory failure and shock • Skin vesicles may appear late in course, 20% will never have them • Acute liver failure • Dx is often made after extensive organ damage has occurred
EVALUATION AND DIAGNOSIS • Suspect Neonatal HSV in all infants < 6 wks WITH: • Vesicles • Sepsis-like illness • CSF pleocytosis • Seizures • Focal neurologic signs • Respiratory distress, apnea or progressive pneumonitis • Thrombocytopenia • Elevated liver transaminases, viral hepatitis or acute liver failure • Conjunctivitis • Early in course, can present with persistent fever and negative bacterial cultures***
EVALUATION AND DIAGNOSIS • Comprehensive lab evaluation (even in infants with SEM) • CBC • LFTs + ammonia (to exclude liver failure) • BMP • HSV DNA PCR of blood • CSF cell count, glucose, protein and HSV DNA PCR • Skin scrapings of vesicles for HSV DFA + culture • Surface cultures of conjunctivae, mouth, nose, rectum (single swab)
TREATMENT • Indications for empiric treatment are not standardized • Clinical features suggestive of HSV (vesicles, seizures, lethargy, thrombocytopenia, coagulopathy, hepatomegaly, ascites, transaminitis) • Unclear situations: CSF pleocytosis in well appearing infant, erythema/crusting at scalp electrode site, fever without localizing signs in infant < 21 days old • Acyclovir • Administer at time neonatal HSV is SUSPECTED • Dose is same for all forms of neonatal HSV • 60mg/kg/d divided q8h • Duration of therapy • SEM: minimum 14 days if CNS and disseminated disease is r/o • CNS or Disseminated: minimum 21 days • Repeat LP near end of therapy for HSV PCR; continue acyclovir until PCR is negative
OUTCOME • HSV infection is lifelong; recurrent disease may occur • Disseminated disease • 1 year mortality: 29%; risk increased with severe hepatitis, acute liver failure, DIC • Mortality > 80% in untreated disease • Acute liver failure can be fatal; liver transplantation has been successful in a few reported cases • CNS disease • 1 year mortality: 4%; risk increased with prematurity, seizures, coma • 30% of survivors will have normal neurologic development • SEM disease • Mortality and developmental delay is rare