Transcript ANGELS HSV 2006 - University of Arkansas for Medical Sciences

Congenital Herpes
Simplex Virus Infection
Ashley S. Ross, M.D.
Neonatology Fellow
University of Arkansas for Medical Sciences
Arkansas Children’s Hospital
Objectives
1.
Recognize the clinical presentation of
congenital (neonatal) herpes simplex virus
(HSV) infection
2.
Discuss current treatment modalities for
neonatal herpes infection
3.
Discuss long term sequelae of neonatal herpes
infection
Transmission to the Neonate
1.
Intrauterine
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5% of cases
Ascending infection
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2.
Intra-partum
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First 20 weeks
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3.
Post-partum
cervix or vulva
Transplacental
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Spontaneous abortion
Stillbirth
Congenital malformations
Hydranencephaly
Chorioretinitis
Controversial
Transmission to the Neonate
1.
Intrauterine
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2.
Intra-partum
3.
Post-partum
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Represents 85% of cases
Infected maternal
secretions in birth canal
Lesions at delivery, Csection preferred route
of delivery
Transmission to the Neonate
1.
2.
Intrauterine
Intra-partum
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10% of all cases of
neonatal herpes
Environmental sources
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3.
Post-partum
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Oral lesions
Herpetic whitlow
Other sites, such as breast
Neonatal HSV
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In USA, incidence 1 per 3,000 to 20,000 live
births
HSV-2 poorer prognosis
75% of neonatal herpes
 HSV-1 infection more common in Japan
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Incubation 2-14 days
Transmission of HSV to the
Neonate
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Primary infection, symptomatic vs. asymptomatic
reactivation
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Delivered vaginally, with primary infection
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33%-50% risk of transmission
Reactivation risk of transmission 0-5%
Primary vs. recurrent often impossible to distinguish
>75% of infants with HSV born w/o maternal symptoms
Quantity and quality of maternal antibodies
Duration of ruptured membranes (>4-6 hours)
Use of fetal scalp monitor during labor
Clinical Manifestations
1.
Disseminated disease
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2.
Localized central
nervous system
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Presentation birth to 4
weeks
Divided equally
Overlap between groups
Skin lesions not always
present
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3.
Skin, eyes, and mouth
(SEM)
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Makes diagnosis difficult
May appear late in
disseminated disease
Disseminated Disease
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Presentation earliest
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1st week
25% of neonatal cases
Sepsis syndrome with negative bacterial cultures
Severe liver dysfunction
 Pneumonia
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Overlap with other types
Disseminated Disease
Disseminated Disease
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Encephalitis in 75% of disseminated infections
Blood-borne route as opposed to neuronal spread
 MRI with panencephalitis possible
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High morbidity and mortality
50% permanent neurological sequelae
 85% mortality if untreated
 If treated, 30% mortality
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Still 15% with permanent neurological impairment
CNS Disease
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35% of neonatal disease
Presents later (2nd to 3rd
week)
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Seizures
Lethargy
Tremors
Poor feeding
Temperature instability
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Mortality 50% when
untreated
2/3 will have permanent
neurological sequelae
Temporal focus initially
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Focality on MRI or EEG
Panencephalitis can
develop
CNS Disease
Coren ME, et al.J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):243-5.
CNS Disease
Burke JW, et al. AJNR Am J Neuroradiol. 1996 Apr;17(4):773-6.
CNS Disease
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CNS disease:
HSV CSF culture rarely positive
 Need HSV polymerase chain reaction (PCR)
 Elevated CSF protein
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Evidence of RBC’s
Cutaneous lesion usually absent
CNS Disease
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Predictors of poor outcome
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At time of treatment
Comatose at initiation of therapy
 Premature
 Seizures
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HSV-2
 Persistently positive CSF HSV PCR
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SEM Disease
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40% of neonatal HSV cases Presents at 10-11
days of age
Discrete vesicles and conjunctivitis
Untreated disease
75% will progress to CNS or disseminated disease
 30-40% develop neurological impairment
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Spastic quadriplegia, microcephaly, blindness
 Usually becomes apparent at 6-12 months
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Treat as aggressively as disseminate/CNS
www.dermatlas.org
Diagnosis
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Average time from onset of symptoms to
treatment is 6 days!
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Time has not shortened
Early treatment, improved mortality/morbidity
Absent skin lesions does NOT exclude diagnosis
Absent maternal history does NOT exclude
diagnosis
Diagnosis
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Readily grows in cell culture
Cytopathogenic effects seen in 1-3 days
Special media
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For delayed inoculation
Cultures negative at 15 days likely negative
Obtain cultures after 48 hours
Diagnosis
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Viral cultures can be obtained from
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Readily grows in cell culture
Cytopathogenic effects seen in 1-3
days
Special media
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Unroofed lesions
Urine
Nasopharynx or mouth
Rectum
Blood
For delayed inoculation
Cultures negative at 15 days likely
negative
Obtain cultures after 48 hours
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Surface contamination
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CSF for HSV PCR
Attempt to seek evidence of
disseminated disease with:
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Liver function tests
CBC
CSF analysis
Chest x-ray
IV acyclovir should be
administered at time of lab
evaluation
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Do not wait for lab results!!!!!
Diagnosis
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CSF cultures not useful (need PCR)
Serology not useful acutely
Direct fluorescent antibody (DFA) and Enzyme
Immunoassay (ELISA)
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Typing of culture aspirates
Supportive diagnosis
EEG
 MRI
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Neonatal HSV: Treatment
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Treat all infections with IV acyclovir
Acyclovir of 60 mg/kg/day IV divided Q8 hours
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14 days for SEM disease
21 days for disseminated or CNS disease
Repeat CSF analysis prior to end of therapy
Consider tertiary referral, neonatologist/infectious
disease referral
Monitor renal function and neutropenia
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Keep well hydrated
Twice weekly labs
Treatment
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Lumbar puncture at end of therapy for HSV
PCR
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Continue treatment until CSF sterile
Many will have recurrence
May need long-term suppressive treatment
 May need intermittent acyclovir therapy
 Recurrent SEM under investigation
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Ocular involvement
Pediatric ophthalmologist
 Topical treatment with IV acyclovir
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Treatment
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Maternal history of HSV without lesions
Observation of infant
 Appropriate evaluation is evidence of infection
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Treatment
Any symptomatic infant is treated
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Primary infection and
exposed infant
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At least 50% risk of infection
Controversy over approach
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Surface cultures 24-48 hours
after delivery
Empiric therapy vs. treating
only positive surface cultures
Signs of infection/rash,
immediate treatment and
cultures
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Recurrent infection and
exposed infant
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Surface cultures
Observation
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Vesicular lesions
Jaundice
Respiratory distress
Seizures
Careful observation if cultures
negative
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Treat positive cultures
Neonatal HSV: Prevention
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All mothers screened prenatally and at deliver
Delivery by C-section
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Clinically apparent lesions
No invasive fetal monitoring
 Risk of infection 50%-5%
 Within 4-6 hours of ROM
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Maternal history of HSV without lesions
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May deliver vaginally
Conclusion
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>75% of infants are born to mom’s without a history
of lesions
A lack of skin lesions does not eliminate the diagnosis
of HSV
Think about HSV early and start therapy even if you
only have a suspicion of HSV
Remember your surface cultures
Remember liver function test
References
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American Academy of Pediatrics. Herpes simplex. In: Pickering
LK, ed. 2003 Red Book: Report of the Committee on Infectious Diseases.
26th ed. Elk Grove Village, Ill: American Academy of Pediatrics;
2003:344–353
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Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Frenkel LM, the
NIAID Collaborative Antiviral Study Group. Natural history of
neonatal herpes simplex virus infections in the acyclovir era.
Pediatrics. 2001;108:223–229
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Waggoner-Fountain LA, Grossman LB. Herpes Simplex Virus.
Pediatrics in Review. 2004;25:86-93