Congenital/Neonatal Herpes Simplex Infections Infectious and Tropical Pediatric Division Department of Child Health Medical Faculty University of Sumatera Utara

Herpes Infections “Herpes” – from the Greek “to creep, crawl” “Herpetic eruptions” described as early as 100 AD 1960’s – HSV1 and HSV2 differentiated HHV1 – HSV1 HHV2 – HSV2 HHV3 – VZV HHV4 – EBV HHV5 – CMV HHV6 – Causes? HHV7 – HHV8 -

Neonatal HSV 1 in 2,500-5,000 deliveries / 500-1500 per yr. Birth to 7 weeks of life HSV2 = 70-75%, HSV1 = 25-30% 3 Main Types Skin, Eye, Mouth (SEM) CNS Disseminated Disease (DISSEM) At Risk: Premature, ROM >6hr, Fetal scalp monitoring Can be acquired congenitally, during the birth process, and in the post-partum period

Routes of Transmission 85% via infected maternal genital tract Ascending infection? En route 10% postpartum 5% (or less) – intrauterine/congenital infection

Congenital HSV Rare, most devastating Only 50 cases described Skin vesicles Chorioretinitis Microcephaly Micro-ophthalmia IUGR

Skin, Eye, Mouth (SEM) Approximately ½ of all HSV infections 1st-2nd week presentation Limited to skin, eye, mouth/mucous membranes 60-70% of untreated patients progress to CNS/disseminated disease

SEM (cont) Long term neurologic sequelae seen in 30% of cases – even if treated Ophthalmology involvement

“Presenting Part” (SEM)

Scalp Monitors

HSV - CNS Disease Encephalitis without visceral involvement, mainly involving the temporal lobes Early to 3rd week of life presentation Skin lesions may appear late, if at all 35% of all cases, only 2-5% untreated survive normally

Radiographic Findings

Disseminated Disease Approximately 20% of all infections Hepatitis Pneumonitis DIC Infant may be ill on first day of life Skin lesions appear late, or not at all

Signs

Postnatal acquisition Most commonly HSV1 Moms with HSV Mask Breastfeeding – O.K. if without lesions The Mohel and the Mezizah

Contacts “Personnel with an active herpetic whitlow should not have direct patient care of neonates”. Family transmission has been described

Morbidity and Mortality

Stretch Break

Take Home Message Infection is most common when a mother develops a genital infection late in pregnancy ( her primary HSV1 or HSV2 infection) – then delivers before the development of protective maternal antibodies

Herpes Simplex Approximately 5% of the general population has been diagnosed with genital herpes – but approximately 20-30% of women may be infected with HSV-2 Viral shedding occurs without identifiable lesions on 1-3% of days

Maternal Testing? Identify discordant couples to avoid transmission in the third trimester If mom is HSV1/HSV2 negative If mom is HSV2 negative If mom is HSV2 positive – risk is low for a vaginal delivery? Is testing after delivery going to be helpful? Will blood tests of the baby be helpful, or just reflect mom’s status? Psychosocial ramifications?

Herpes during Pregnancy As many as 2% of pregnant women are infected with HSV2 during pregnancy 25% of women with a history of genital herpes have an outbreak at some time during their pregnancy, 11-14% at time of delivery 36% at delivery for those with first infection! Virus is recovered from 1% of asymptomatic women at delivery

What is the risk? Vaginal delivery when mom has presence of first symptomatic lesions – 50% Vaginal delivery when mom is asymptomatic, but is newly infected – 33% Vaginal delivery when mom has recurrent lesions – 4% Vaginal delivery when mom has a history of herpes lesions in past, none presently – 0.04%

OB Management 70’s-80’s – weekly HSV cultures 1988 – patient examined at delivery, Cesarean delivery if: (no data) Identifiable genital lesions Patient describes prodromal symptoms Vaginal delivery for those with hx only Primary infection diagnosed - treat Estimated $2-4 million to prevent each case 20-30% of infants who are diagnosed with neonatal herpes are delivered by Cesarean delivery

Diagnostics HSV Cx – positive in 1-2 days (cytopathic effect) DFA – sensitivity/specificity in the 75%-85% range

PCR Testing Detects minute amounts of DNA, RNA DISSEM – 93% CNS – 76% SEM – 24% False negative may occur if CSF is obtained “too early” Order through IVF!

Diagnostics (cont) Surface cultures Cultures Mouth (40-50%) Eyes (25%) Rectum Skin Cultures Stool Urine CSF >100 WBC/Inc. Pro Tzanck – neither sensitive nor specific

Treatment - Acyclovir SEM infections DISSEM and CNS HSV infections 60mg/kg/day divided q8h for 14 days May be lengthened to 21 days in the near future Oral Acyclovir needed later in life? DISSEM and CNS HSV infections 60mg/kg/day divided q8h for 21 days Re-tap if CNS disease exists prior to d/c Watch for neutropenia – 2x week ANCs

Take Home Messages Most neonates with HSV infection are born to mothers with asymptomatic genital shedding at delivery, with no history of genital herpetic lesions No one test is 100% sensitive / specific Keep HSV in mind How would you manage our case?