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Neonatal Herpes Simplex Infections. MAJ Mark Burnett Pediatric ID Fellow MAR 2003. Neonatal Herpes. Background A Case Study Types of Infections Risks of Infection Diagnostics Treatment Summary. “Herpes” – from the Greek “to creep, crawl”

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neonatal herpes simplex infections

Neonatal Herpes Simplex Infections

MAJ Mark Burnett

Pediatric ID Fellow

MAR 2003

neonatal herpes
Neonatal Herpes
  • Background
  • A Case Study
  • Types of Infections
  • Risks of Infection
  • Diagnostics
  • Treatment
  • Summary
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 -

Herpes Infections
a case study a b
A Case Study – A.B.
  • Term infant born to a 22 y/o GBS+ mother with no Pmhx of HSV-2
  • 4 doses of IV PCN given PTD
  • ROM <18 hours PTD, no maternal fevers
  • Forceps delivery
  • APGARS of 9/9
  • Well until fever to 101.7 at 30 hrs of life
  • Fever work-up initiated
slide5
A.B.
  • WBC 23K (50S 2B 38L)
  • AST 98 ALT 92
  • CSF 48 WBC 2650 RBC Pro 93/Glu 53
  • HSV PCR, Enteroviral PCR, HSV Surface cx – sent
  • Exam unremarkable
  • Amp/Gent/Acyclovir initiated
  • Fevers persisted over next 13 hours, again spiking to 101.5
  • AST 147 / ALT 93 two days later
a b additional info
A.B. – additional info
  • No history of HSV reported in mother, father
  • Mother without febrile illness
  • Niece with a “cold sore” visited prior to delivery, and “held the baby” after he was born
  • LP repeated two days after initial study with normalization of cell count
questions
Questions?
  • What diagnostic tests could we perform, and how reliable are they really?
  • Would it be worthwhile to run tests on mom?
  • Is the niece’s “cold sore” a “red herring” – what are the risks?
  • Bottom line – how worried should we be about HSV, and how would we treat it?
neonatal hsv
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
Routes of Transmission
  • 85% via infected maternal genital tract
    • Ascending infection?
    • En route
  • 10% postpartum
  • 5% (or less) – intrauterine/congenital infection
congenital hsv
Congenital HSV
  • Rare, most devastating
  • Only 50 cases described
  • Skin vesicles
  • Chorioretinitis
  • Microcephaly
  • Micro-ophthalmia
  • IUGR
skin eye mouth sem
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
SEM (cont)
  • Long term neurologic sequelae seen in 30% of cases – even if treated
  • Ophthalmology involvement
hsv cns disease
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
disseminated disease
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
postnatal acquisition
Postnatal acquisition
  • Most commonly HSV1
  • Moms with HSV
    • Mask
    • Breastfeeding – O.K. if without lesions
  • The Mohel and the Mezizah
contacts
Contacts
  • “Personnel with an active herpetic whitlow should not have direct patient care of neonates”.
  • Family transmission has been described
take home message
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
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
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
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
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
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
Diagnostics
  • HSV Cx – positive in 1-2 days (cytopathic effect)
  • DFA – sensitivity/specificity in the 75%-85% range
pcr testing
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
Diagnostics (cont)
  • Surface cultures
    • Mouth (40-50%)
    • Eyes (25%)
    • Rectum
    • Skin
  • Cultures
    • Stool
    • Urine
    • CSF >100 WBC/Inc. Pro
  • Tzanck – neither sensitive nor specific
treatment acyclovir
Treatment - Acyclovir
  • SEM 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
questions controversies
Questions / Controversies
  • Would maternal “pre-treatment” change the time /clinical presentation of HSV?
  • Should an infant delivered vaginally to a mother with active lesions be treated?
  • Can HSV be resistant to Acyclovir?
take home messages
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?