PEDBASE.org - The Pediatric Database - Detailed information of CONGENITAL HSV

CONGENITAL HSV

DEFINITION:

A contagious infectious disease caused by a DNA herpesviruses Herpes Simplex I and II with localized, disseminated, and intrauterine manifestations.

EPIDEMIOLOGY:

incidence: 1/2500 - 1/20,000 live births
age of onset:
- newborn
risk factors:
- exposure to HSV

PATHOGENESIS:

1. Routes of Transmission

1. Neonatal

1. Antenatal (in utero)

1. Primary Maternal Infection

50% vertical transplacental transmission rate due to high viral titres in the genital tract, involvement of the cervix, and lack of antibodies to HSV

2. Recurrent Maternal Infection

less than 5% transmission rate
reactivation of a latent virus

2. Perinatal

accounts for 80-90% of neonatal HSV infections
acquired during passage of the fetus through the birth canal

3. Postnatal

horizontal transmission via human-infant contact
with perinatal route accounts for the majority of neonatal HSV infections

2. Background

HSV-II is the agent responsible for 75-85% of neonatal HSV infections
prevalence of genital HSV is 1-2% during pregnancy and 0.1-0.4% at parturition
incubation period is 2-14 days
establishes latency in the sacral root ganglia
low risk (1-2%) of asymptomatic shedding at delivery in women with recurrent genital HSV

CLINICAL FEATURES:

1. Localized (77%)

1. Central Nervous System (Encephalitis) - 35%

onset of symptoms: 2nd to 3rd week
caused by HSV-II
symptoms:
- fever, poor feeding, irritability or lethargy
- apnea
- loss of rudimentary reflexes
- skin rash in 67% of cases
- liver may also be affected
often have 1 to 2 days of fever and lethargy followed by the sudden onset of seizures (usually focal & unilateral) with facial and upper extremity involvement initially -> generalized seizures which are very difficult to treat

2. SEM (Skin, Eyes, Mucous Membranes) - 42%

onset of symptoms: 1st to 2nd week (mean onset= 11.2 days)
symptoms:
- skin
  - vesicular or bulbous skin lesions
  - observed initially over sites of trauma i.e., fetal electrode, presenting body part
- eyes
  - conjuctivitis but not ocular lesions
- mucous membranes
  - quite uncommon but may involve eyes or mouth

2. Disseminated (23%)

onset of symptoms: 1st to 2nd week (mean onset = 10.5 days)
caused by HSV-I or HSV-II
multiorgan involvement:
- brain - meningoencephalitis with unremitting often fatal focal seizures ending in coma
- lung - pneumonitis, pneumonia, respiratory distress
- heart - shock (hypotension) with metabolic acidosis
- liver - hepatomegaly, jaundice, coagulopathy, hepatic dysfunction -> severe hepatitis
- skin - lesions usually absent at onset but 66% will eventually have lesions
- others - bone marrow - DIC - fever
  - adrenal gland
rapid progression with death in 80% of untreated patients

3. Intrauterine HSV (5%)

most caused by HSV-II, primary or recurrent genital HSV
symptoms:
- prematurity with RDS, IUGR, stillborn
- neuro - microcephaly or hydranencephaly, intracranial calcifications
eye - chorioretinitis or microophthalmia, blindness
skin - widespread cutaneous lesions present at birth with
CNS findings

INVESTIGATIONS:

1. Diagnostic

1. Virology

gold standard
isolate virus from oro- or nasopharynx, CSF, skin lesions, conjunctiva, rectum, brain biopsy, blood (buffy coat)
cytopathic effect in 2-3 days

2. Others

immunocytochemistry - immunoperoxidase staining of cells taken from a lesion
fluorescein-conjugated monoclonal antibody to samples taken from skin lesions
Tzanck preparation - multinucleated giant cells
PCR

2. Serum

CBC - anemia, thrombocytopenia
conjugated hyperbilirubinemia, unconjugated hyperbilirubinemia
elevated hepatic transaminases
DIC - elevated PT, decreased fibrinogen

3. CSF

1. CNS Variant

mixed or lymphocytic pleocytosis; WBC between 50-100
RBC's
elevated protein which dramatically increases with time

4. EEG

abnormal background rhythms
multifocal or quasiperiodic pattern of slow or sharp waves

5. Imaging Studies

1. CT (Head)

cerebral swelling
focal hypodensities
intracranial calcifications or severe cystic encephalomalacia (intrauterine HSV)
classic temporal lobe lesion is unusual at this age

MANAGEMENT:

1. Medical

1. Acyclovir

30 mg/kg/day IV tid for 10-14 days
low toxicity

2. Supportive

DIC - FFP
seizures - anticonvulsants

2. Prognosis

1. Localized

1. CNS

mortality - 15% treated, 50% untreated
morbidity - 70% rate of neurologic sequelae (see below)

2. SEM

mortality - 0% treated
morbidity - low rate of long-term sequelae but if left untreated 75% will progress to the disseminated or CNS types

2. Disseminated

mortality - >50% treated, 80% untreated
morbility - high rate of neurologic sequelae - mental retardation, seizures, visual or motor deficits

3. Intrauterine

mortality - high
morbidity - severe neurodevelopmental sequelae

Pediatric Database - CONGENITAL HSV

Pediatric Organization - Pedbase [at] Gmail.com