H ERPES S IMPLEX V IRUS IN THE N EWBORN Sonya Mary Palathumpat, MD

I NTRODUCTION Discovery of neonatal Herpes Simplex virus (HSV) in the 1930s Neonatal infection with HSV occurs in 1/3200 to 1/10,000 live births HSV infection accounts for 0.6 percent of in-hospital neonatal deaths in the United States Estimated 1500 cases of neonatal HSV infection annually in the United States

V IROLOGY HSV enters human host through inoculation of oral, genital, or conjunctival mucosa or break in skin HSV infects the sensory nerve endings  transports via retrograde axonal flow to the dorsal root ganglia (where it remains for the life of the host)

T RANSMISSION 1. Intrauterine (Congenital HSV) Maternal viremia Ascending infection Usually after prolonged rupture of membranes 2. Perinatal HSV infection is present in the genital tract of pregnant woman at time of delivery Most common mode (85%) of neonatal HSV infection transmission 3. Postnatal When active HSV infection has close contact with the newborn

C LINICAL M ANIFESTATIONS Intrauterine HSV Placental Infarcts Necrotizing, calcifying funisitis (inflammation of the umbilical cord) Hydrops fetalis Fetal in utero demise Surviving babies: 1. Skin vesicles, ulcerations, or scarring 2. Eye damage 3. Severe CNS manifestations Microcephaly Hydranencephaly

C LINICAL MANIFESTATIONS Hypopigmented, scaling, and crusted erosions of the trunk and extremities in a neonate with intrauterine herpes simplex virus infection.

C LINICAL M ANIFESTATIONS Neonatal HSV Seen in infection with both HSV-1 and HSV-2 HSV-2 associated with poorer outcome 1. Skin, Eye, Mouth 2. Central Nervous System 3. Disseminated Disease

C LINICAL MANIFESTATIONS Skin, Eyes, & Mouth Usually presents in the first two weeks of life Associated with high risk of progression to CNS or disseminated disease Skin Coalescing or clustering vesicular lesions with an erythematous base Eyes Excessive watering of the eye Crying from apparent eye pain Conjunctival erythema Periorbital skin vesicles Can progress to cataracts and chorioretinitis  permanent vision loss Mouth Localized ulcerative lesions of the mouth, palate, and tongue

C LINICAL M ANIFESTATIONS

C LINICAL MANIFESTATION CNS Disease 1/3 of neonatal HSV disease involves the CNS Occurs because Localized retrograde spread from nasopharynx and olfactory nerves to brain Hematogenous spread in neonates with disseminates disease Presents in second-third week of life Seizures (focal or generalized) Lethargy Irritability Tremors Poor feeding Temperature instability Full anterior fontanelle

C LINICAL MANIFESTATION Disseminated Disease: ¼ of HSV disease is in the disseminated form Present in the first week of life Affects: liver, lungs, adrenals, CNS, skin, eyes, and mouth Presenting with nonspecific signs and symptoms: Temperature dysregulation Apnea Irritability Lethargy Reparatory distress Abdominal distention Ascites

C LINICAL MANIFESTATIONS Disseminated Disease: Hepatitis with elevated liver transaminases Ascites Direct hyperbilirubinemia Neutropenia Thrombocytopenia DIC (disseminated intravascular coagulation) Hemorrhagic pneumonitis Necrotizing Enterocolitis Meningoencephalitis with seizures Repiratory failure and shock Advanced disseminated neonatal HSV disease

E VALUATION & D IAGNOSIS If neonate presents with mucocutaneous lesions, CNS abnormalities, or sepsis-like picture and Pt born to an HSV +, or HSV unknown mother, consider a work-up CBC with manual differential Liver Transaminases, total and direct bilirubin, ammonia To assess liver function BUN, Creatinine, UA To assess renal function HSV DNA PCR of blood CSF count, glucose, protein, and HSV DNA PCR Mononuclear pleocytosis, elevated protein, normal or elevated glucose Swabs/ scrapings of skin or mucous membrane lesions for HSV direct immunofluorescence assay and viral culture

E VALUATION & D IAGNOSIS EEG Should be considered in all neonates suspected to have CNS involvement Brain Imaging MRI or CT to determine the location and extent of brain involvement Chest Radiograph May demonstrate bilateral, diffuse pneumonitis Abdominal US May demonstrate ascites and/or enlarged liver in neonates with HSV hepatitis and acute liver failure

T REATMENT Acyclovir Dose: 60 mg/kg per day IV every 8 hours Duration: Localized skin, & eye, mouth (If localized CNS infection as been excluded: 14-day course Disseminated and/or CNS infection 21-day course Adverse effects: Renal Failure Due to crystallization in the renal tubules More likely in the dehydrated patient Ensure Pt has adequate PO, otherwise place Pt on IVF!

S OURCES Neonatal Herpes Simplex Virus Infection: Clinical Features and Diagnosis. UptoDate. Demmier-Harrison, Gail MD Neonatal Herpes Simplex Virus Infection: Management and Prevention. UptoDate. Demmier-Harrison, Gail MD Neonatal Herpes Simplex Virus Infections. American Family Physician. Rudnick, Caroline MD, Hoekzema, Grant MD. 03/15/2002,