Pediatric Case: CMV

October 20, 2014

Passive Maternal Antibody Transfer
- Begins to cross placenta approximately 28 weeks
gestation
- Achieves maternal IgG level by 38 weeks gestation
- Only IgG crosses, not IgA or IgM
- Presence in neonate of IgG cannot define infection,
but IgM can
Fetal/Neonatal Immune System is Nave
- In response to pathogen, develops specific
responses
o T cells, B cell priming, antibody
production
Case 1: 37 week gestation infant with a rash
- PE: normocephalic, tachypnea, pallor
- Hepatosplenomegaly
- Rash: non-blanchable, round, palpable, blush from lesions
o Non-blanchable suggests leakage out of vessels
o Blueberry muffin rash signifies areas of extramedullary hematopoiesis (not enough blood so
making somewhere else)
- Clinical findings
o Thrombocytopenia, anemia
o Hepatitis
o Rash
Differential CMV, enterovirus, rubella
Diagnosis of Neonatal CMV Infection
- Clinical symptoms
o IUGR
o Microcephaly
o Hearing loss (sensory-neuronal)
o Periventricular calcifications
o Hepatosplenomegaly
o Thrombocytopenia
- Viral diagnostic tests
o Urine spin-enhanced (shell vial) or standard culture
o Plasma or CSF PCR
o Blood viremia
o IgM reasonable
Consequences of Transplacental Fetal Infection with CMV
- Prematurity
- Growth retardation
- Anomalies
- Persistent postnatal infection (CMV is a DNA virus)
CMV: Clinical Findings
- Early manifestations: Petechiae, HSM, jaundice, microcephaly, IUGR, prematurity, chorioretinitis,
hearing loss small baby, small head
- Later manifestations: microcephaly, psychomotor retardation, hearing loss

CMV infection in people 40-60%

Management and Outcome
- 3 PRBC transfusions
- 8 platelet transfusions
- Received ganciclovir at 5mg/kg/dose q12 for 6 weeks
- Cranial CT: unilateral calcification
- At 21yo, unilaterally deaf but developmentally normal
Case 2: 39 week gestation with microcephaly
- HC<<5%
- Axillary adenopathy, HSM, asymmetric moro, prominent head lag
Transmission
- 40k infants are born with CMV each year
- Present in urine, oropharyngeal secretions, cervical and vaginal secretions, breast milk, semen, tears
o Breast milk (oral route) baby will get infected but does well
o Blood route worse
Primary Maternal CMV infection
- Owl Eye = CMV inclusion which clogs up the endoplasmic reticulum
- ??
Clinical manifestations in asymptomatic infants at birth
- 90% asymptomatic
- 5% develop microcephaly, neuromuscular defects
- 2% develop chorioretinitis
- 10% develop sensory-neuronal hearing loss progressive/delayed onset, bilateral
Key points
- CMV is common (1%)
- Small baby, small head, hearing loss
o Failed hearing screen, rash, HSM, low platelets
- Sensory neuronal hearing loss
- Primary maternal infection >>>> recurrent (high viral titers in primary)
- Diagnosis: urine CMV culture
- Treatment: ganciclovir?
o Works but has risk of toxicity
- Prevention: vaccine?, maternal testing
Why dont we have a CMV vaccine?
CMV is a DNA virus
The need for a vaccine
- Childhood vaccine could reduce congenital CMV disease
- Vaccine administered to adolescents or adult women could also reduce congenital CMV
Factors that preclude anti viral vaccine development
- high mutation rate
- antigenic variation
- immune evasion e.g. latency, immune evasion genes
- immune status of target population
CMV immune evasion
- inhibition of MHC class I antigen presentation

expression of viral class I homologues

viral cyotkines
viral chemokine rceptors
immunoglobulin binding proteins
apoptosis