Title : Congenital HHV-6 infection and the clinical significance of HHV6 positivity on the film array meningitis/encephalitis panel
Abstract:
Introduction:
HHV6 is a herpesvirus ubiquitous in children known to cause Roseola Infantum. Congenital HHV6 infection is possible through germline passage of the chromosomally integrated HHV-6 DNA from a parent (ciHHV6). Less commonly, it occurs through transplacental transmission during acute infection or viral re-activation during the pregnancy. In this case study, we examine an infant found to have a positive HHV-6 (variant B) CSF PCR at birth while evaluating for neonatal sepsis. The infant’s blood and placenta HHV6 PCRs were also positive and undetectable in the mother. The presence of HHV-6 in the infant’s blood, CSF, and placenta raises the question the etiology of the viral congenital transmission: transplacental or a ciHHV6.
Case Report:
The patient is a newborn female born at 32 weeks and 5 days GA from a 33-year-old mother via urgent C-section due to complete breech presentation with difficult extraction resulting in right head contusion with depressed skull fracture and underlying subdural hematoma at birth head CT. Pregnancy was complicated by maternal grade III heart failure and T2DM; mother tested negative for HIV with no h/o STI’s or infections during pregnancy. The patient was admitted to the NICU for respiratory failure and to rule out sepsis. She was positive for HHV-6 on CSF and blood PCRs. CBC showed no cytopenia and LFTs remained WNL; CSF study revealed a bloody tap: total nucleated cells: 12, RBC: 575, glucose: 59 (40-70 mg/dl), TP: 244 mg/dl (15-45 mg/dl). IV Ampicillin and Gentamicin were discontinued at 36 hours due to negative sepsis on work up and resolved respiratory distress. No HHV-6-specific anti-viral therapy was given. Patient and maternal serum IgG were positive, and IgM was negative; infant’s blood HHV-6 PCR was 2,600,000 DNA copies/ml and undetectable in maternal blood. A CUS at DOL # 23 showed grade I IVH resolved on follow-up CUS at DOL # 65. Patient was asymptomatic with adequate growth and development at 6-month follow-up.
Discussion:
The ciHHV6 should be suspected when HHV6-DNA real-time PCR detects viral loads > 6.0 log 10 copies/ml in whole-blood as seen here. Transplacental HHV6 transmission usually results in viral loads ≤ 5.0 log 10 copies/ml. The definitive diagnosis of ciHHV6 is achieved by PCR HHV-DNA detection on newborn nail and hair follicle samples, which was not possible in this case.
The positive CSF HHV6 PCR, clinical presentation, laboratory and imaging results, and rapid clinical improvement without anti-viral therapy suggested asymptomatic HHV6 replication. Clinical judgment is paramount in determining the clinical significance of HHV6 positivity in CSF to avoid unnecessary anti-viral therapy and side-effects.
The patient and maternal HHV-6 IgM were negative indicating non-acute infection. The newborn’s positive HHV6 IgG antibodies may have provided further protection through placental transfer.
The clinical consequences of congenital HHV6 is not well understood and previously had unknown clinical significance. However, recent studies suggest congenital HHV-6 infection may have a detrimental effect on neurodevelopment at 12 months of age (3). The long-term neurodevelopment of children with congenital HHV-6 infection is currently unknown.
