Congenital Herpes Simplex Virus Infection
description
Transcript of Congenital Herpes Simplex Virus Infection
Congenital Herpes Congenital Herpes Simplex Virus Simplex Virus
Infection Infection
Ashley S. Ross, M.D.Ashley S. Ross, M.D.Neonatology FellowNeonatology Fellow
University of Arkansas for Medical SciencesUniversity of Arkansas for Medical Sciences
Arkansas Children’s HospitalArkansas Children’s Hospital
ObjectivesObjectives
1.1. Recognize the clinical presentation Recognize the clinical presentation of congenital (neonatal) herpes of congenital (neonatal) herpes simplex virus (HSV) infectionsimplex virus (HSV) infection
2.2. Discuss current treatment modalities Discuss current treatment modalities for neonatal herpes infectionfor neonatal herpes infection
3.3. Discuss long term sequelae of Discuss long term sequelae of neonatal herpes infectionneonatal herpes infection
Transmission to the Transmission to the NeonateNeonate
1.1. IntrauterineIntrauterine
2.2. Intra-partumIntra-partum
3.3. Post-partumPost-partum
5% of cases5% of cases Ascending infection Ascending infection
cervix or vulvacervix or vulva TransplacentalTransplacental
First 20 weeksFirst 20 weeks Spontaneous abortionSpontaneous abortion StillbirthStillbirth Congenital Congenital
malformationsmalformations HydranencephalyHydranencephaly ChorioretinitisChorioretinitis ControversialControversial
Transmission to the Transmission to the NeonateNeonate
1.1. IntrauterineIntrauterine
2.2. Intra-partumIntra-partum
3.3. Post-partumPost-partum
Represents 85% of Represents 85% of casescases
Infected maternal Infected maternal secretions in birth secretions in birth canalcanal
Lesions at delivery, Lesions at delivery, C-section C-section preferred route of preferred route of deliverydelivery
Transmission to the Transmission to the NeonateNeonate
1.1. IntrauterineIntrauterine
2.2. Intra-partumIntra-partum
3.3. Post-partumPost-partum
10% of all cases of 10% of all cases of neonatal herpesneonatal herpes
Environmental Environmental sourcessources Oral lesionsOral lesions Herpetic whitlowHerpetic whitlow Other sites, such as Other sites, such as
breastbreast
Neonatal HSVNeonatal HSV
In USA, incidence 1 per 3,000 to In USA, incidence 1 per 3,000 to 20,000 live births20,000 live births
HSV-2 poorer prognosisHSV-2 poorer prognosis 75% of neonatal herpes75% of neonatal herpes HSV-1 infection more common in JapanHSV-1 infection more common in Japan
Incubation 2-14 daysIncubation 2-14 days
Transmission of HSV to Transmission of HSV to the Neonatethe Neonate
Primary infection, symptomatic vs. Primary infection, symptomatic vs. asymptomatic reactivationasymptomatic reactivation Delivered vaginally, with primary infectionDelivered vaginally, with primary infection
33%-50% risk of transmission33%-50% risk of transmission Reactivation risk of transmission 0-5%Reactivation risk of transmission 0-5% Primary vs. recurrent often impossible to distinguishPrimary vs. recurrent often impossible to distinguish >75% of infants with HSV born w/o maternal >75% of infants with HSV born w/o maternal
symptomssymptoms Quantity and quality of maternal antibodiesQuantity and quality of maternal antibodies Duration of ruptured membranes (>4-6 hours)Duration of ruptured membranes (>4-6 hours) Use of fetal scalp monitor during laborUse of fetal scalp monitor during labor
Clinical ManifestationsClinical Manifestations
1.1. Disseminated Disseminated disease disease
2.2. Localized central Localized central nervous systemnervous system
3.3. Skin, eyes, and Skin, eyes, and mouth (SEM) mouth (SEM)
Presentation birth to Presentation birth to 4 weeks4 weeks
Divided equallyDivided equally Overlap between Overlap between
groupsgroups Skin lesions not Skin lesions not
always presentalways present Makes diagnosis Makes diagnosis
difficultdifficult May appear late in May appear late in
disseminated diseasedisseminated disease
Disseminated DiseaseDisseminated Disease
Presentation earliestPresentation earliest 11stst week week
25% of neonatal cases25% of neonatal cases Sepsis syndrome with negative Sepsis syndrome with negative
bacterial culturesbacterial cultures Severe liver dysfunctionSevere liver dysfunction PneumoniaPneumonia
Overlap with other typesOverlap with other types
Disseminated DiseaseDisseminated Disease
Disseminated DiseaseDisseminated Disease
Encephalitis in 75% of disseminated Encephalitis in 75% of disseminated infectionsinfections Blood-borne route as opposed to neuronal Blood-borne route as opposed to neuronal
spreadspread MRI with panencephalitis possibleMRI with panencephalitis possible
High morbidity and mortalityHigh morbidity and mortality 50% permanent neurological sequelae50% permanent neurological sequelae 85% mortality if untreated85% mortality if untreated If treated, 30% mortalityIf treated, 30% mortality
Still 15% with permanent neurological impairmentStill 15% with permanent neurological impairment
CNS DiseaseCNS Disease
35% of neonatal 35% of neonatal diseasedisease
Presents later (2Presents later (2ndnd to 3to 3rdrd week) week) SeizuresSeizures LethargyLethargy TremorsTremors Poor feedingPoor feeding Temperature Temperature
instabilityinstability
Mortality 50% when Mortality 50% when untreateduntreated
2/3 will have 2/3 will have permanent permanent neurological sequelaeneurological sequelae
Temporal focus Temporal focus initiallyinitially Focality on MRI or Focality on MRI or
EEGEEG Panencephalitis can Panencephalitis can
developdevelop
CNS DiseaseCNS Disease
Coren ME, et al.J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):243-5.
CNS DiseaseCNS Disease
Burke JW, et al. AJNR Am J Neuroradiol. 1996 Apr;17(4):773-6.
CNS DiseaseCNS Disease
CNS disease:CNS disease: HSV CSF culture rarely positiveHSV CSF culture rarely positive Need HSV polymerase chain reaction Need HSV polymerase chain reaction
(PCR)(PCR) Elevated CSF proteinElevated CSF protein
Evidence of RBC’sEvidence of RBC’s Cutaneous lesion usually absentCutaneous lesion usually absent
CNS DiseaseCNS Disease
Predictors of poor outcomePredictors of poor outcome At time of treatmentAt time of treatment
Comatose at initiation of therapyComatose at initiation of therapy PrematurePremature SeizuresSeizures
HSV-2HSV-2 Persistently positive CSF HSV PCRPersistently positive CSF HSV PCR
SEM DiseaseSEM Disease 40% of neonatal HSV cases Presents at 40% of neonatal HSV cases Presents at
10-11 days of age10-11 days of age Discrete vesicles and conjunctivitisDiscrete vesicles and conjunctivitis Untreated diseaseUntreated disease
75% will progress to CNS or disseminated 75% will progress to CNS or disseminated diseasedisease
30-40% develop neurological impairment30-40% develop neurological impairment Spastic quadriplegia, microcephaly, blindnessSpastic quadriplegia, microcephaly, blindness Usually becomes apparent at 6-12 monthsUsually becomes apparent at 6-12 months
Treat as aggressively as Treat as aggressively as disseminate/CNSdisseminate/CNS
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DiagnosisDiagnosis
Average time from onset of symptoms Average time from onset of symptoms to treatment is 6 days!to treatment is 6 days! Time has not shortenedTime has not shortened
Early treatment, improved Early treatment, improved mortality/morbiditymortality/morbidity
Absent skin lesions does NOT exclude Absent skin lesions does NOT exclude diagnosisdiagnosis
Absent maternal history does NOT Absent maternal history does NOT exclude diagnosisexclude diagnosis
DiagnosisDiagnosis
Readily grows in cell cultureReadily grows in cell culture Cytopathogenic effects seen in 1-3 Cytopathogenic effects seen in 1-3
daysdays Special mediaSpecial media
For delayed inoculationFor delayed inoculation Cultures negative at 15 days likely Cultures negative at 15 days likely
negativenegative Obtain cultures after 48 hoursObtain cultures after 48 hours
DiagnosisDiagnosis Viral cultures can be obtained Viral cultures can be obtained
fromfrom Unroofed lesionsUnroofed lesions UrineUrine Nasopharynx or mouthNasopharynx or mouth RectumRectum BloodBlood
Readily grows in cell cultureReadily grows in cell culture Cytopathogenic effects seen Cytopathogenic effects seen
in 1-3 daysin 1-3 days Special mediaSpecial media
For delayed inoculationFor delayed inoculation Cultures negative at 15 days Cultures negative at 15 days
likely negativelikely negative Obtain cultures after 48 hoursObtain cultures after 48 hours
Surface contaminationSurface contamination
CSF for HSV PCRCSF for HSV PCR Attempt to seek Attempt to seek
evidence of evidence of disseminated disease disseminated disease with:with: Liver function testsLiver function tests CBCCBC CSF analysisCSF analysis Chest x-rayChest x-ray
IV acyclovir should be IV acyclovir should be administered at time of administered at time of lab evaluationlab evaluation Do not wait for lab Do not wait for lab
results!!!!!results!!!!!
DiagnosisDiagnosis
CSF cultures not useful (need PCR)CSF cultures not useful (need PCR) Serology not useful acutelySerology not useful acutely Direct fluorescent antibody (DFA) Direct fluorescent antibody (DFA)
and Enzyme Immunoassay (ELISA)and Enzyme Immunoassay (ELISA) Typing of culture aspiratesTyping of culture aspirates
Supportive diagnosisSupportive diagnosis EEGEEG MRIMRI
Neonatal HSV: Neonatal HSV: TreatmentTreatment
Treat all infections with IV acyclovirTreat all infections with IV acyclovir Acyclovir of 60 mg/kg/day IV divided Q8 Acyclovir of 60 mg/kg/day IV divided Q8
hourshours 14 days for SEM disease 14 days for SEM disease 21 days for disseminated or CNS disease21 days for disseminated or CNS disease
Repeat CSF analysis prior to end of therapyRepeat CSF analysis prior to end of therapy Consider tertiary referral, Consider tertiary referral,
neonatologist/infectious disease referralneonatologist/infectious disease referral Monitor renal function and neutropeniaMonitor renal function and neutropenia
Keep well hydratedKeep well hydrated Twice weekly labsTwice weekly labs
TreatmentTreatment Lumbar puncture at end of therapy for Lumbar puncture at end of therapy for
HSV PCRHSV PCR Continue treatment until CSF sterileContinue treatment until CSF sterile
Many will have recurrenceMany will have recurrence May need long-term suppressive treatmentMay need long-term suppressive treatment May need intermittent acyclovir therapyMay need intermittent acyclovir therapy Recurrent SEM under investigationRecurrent SEM under investigation
Ocular involvementOcular involvement Pediatric ophthalmologistPediatric ophthalmologist Topical treatment with IV acyclovirTopical treatment with IV acyclovir
TreatmentTreatment
Maternal history of HSV without Maternal history of HSV without lesionslesions Observation of infantObservation of infant Appropriate evaluation is evidence of Appropriate evaluation is evidence of
infectioninfection
TreatmentTreatment
Primary infection and Primary infection and exposed infantexposed infant At least 50% risk of At least 50% risk of
infectioninfection Controversy over Controversy over
approachapproach Surface cultures 24-48 Surface cultures 24-48
hours after deliveryhours after delivery Empiric therapy vs. Empiric therapy vs.
treating only positive treating only positive surface culturessurface cultures
Signs of infection/rash, Signs of infection/rash, immediate treatment immediate treatment and culturesand cultures
Recurrent infection Recurrent infection and exposed infantand exposed infant Surface culturesSurface cultures ObservationObservation
Vesicular lesionsVesicular lesions JaundiceJaundice Respiratory distressRespiratory distress SeizuresSeizures
Careful observation if Careful observation if cultures negativecultures negative
Treat positive culturesTreat positive cultures
Any symptomatic infant is Any symptomatic infant is treatedtreated
Neonatal HSV: Neonatal HSV: PreventionPrevention
All mothers screened prenatally and All mothers screened prenatally and at deliverat deliver
Delivery by C-sectionDelivery by C-section Clinically apparent lesionsClinically apparent lesions
No invasive fetal monitoringNo invasive fetal monitoring Risk of infection 50%-5%Risk of infection 50%-5% Within 4-6 hours of ROMWithin 4-6 hours of ROM
Maternal history of HSV without lesionsMaternal history of HSV without lesions May deliver vaginallyMay deliver vaginally
ConclusionConclusion >75% of infants are born to mom’s >75% of infants are born to mom’s
without a history of lesionswithout a history of lesions A lack of skin lesions does not eliminate A lack of skin lesions does not eliminate
the diagnosis of HSVthe diagnosis of HSV Think about HSV early and start therapy Think about HSV early and start therapy
even if you only have a suspicion of HSVeven if you only have a suspicion of HSV Remember your surface culturesRemember your surface cultures Remember liver function testRemember liver function test
ReferencesReferences 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
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
Waggoner-Fountain LA, Grossman LB. Herpes Simplex Virus. Pediatrics in Review. 2004;25:86-93