Herpes simplex infection in children — branching viva

Opening question

Examiner: Take me through this infant. What is the diagnosis, and what is your frame for managing him? [2]

Candidate: The leading diagnosis is neonatal herpes simplex virus disease. A 12-day-old with fever, poor feeding and lethargy has bacterial sepsis on the differential, but this infant has the highest-risk HSV exposure: a maternal primary genital HSV at 38 weeks with vaginal delivery through active lesions, because a primary infection means the mother has not yet made antibody to transfer to the baby. The scalp vesicle clinches it. My frame is to treat this as neonatal HSV from the first minute — start high-dose intravenous aciclovir, run the full HSV workup, and treat empirically because outcome worsens with every hour of delay. [2] [7]

Examiner: Why is a primary maternal infection so much more dangerous than a recurrent one? [1]

Candidate: Because neonatal HSV transmission is far higher from a primary genital infection — around forty-four percent — than from a recurrent one, which is only a few percent. In a primary infection the mother lacks antibody, so the neonate receives neither transplacental antibody nor the cell-mediated advantage of maternal immunity. The baby meets a large viral inoculum unprotected, and the immature neonatal immune system cannot contain it. [1] [7]

Branch 1 — pathophysiology and disease classes

Examiner: Explain the pathophysiology of HSV, and how neonatal disease differs from the childhood sore mouth. [8]

Candidate: Herpes simplex virus is a neurotropic herpesvirus. It enters through mucosa or broken skin, replicates in epithelium to form vesicles, and travels up sensory nerves to a ganglion where it establishes lifelong latency held by cell-mediated immunity. In the healthy child that produces a primary gingivostomatitis and, later, recurrent cold sores when the virus reactivates down the same nerve. In the neonate the immature immune system fails to contain the virus, so it disseminates to the liver, lungs and brain. [8] [1]

Examiner: How do you classify neonatal HSV disease, and why does it matter? [3]

Candidate: Into three classes. Skin-eye-mouth disease — vesicles, keratitis, mouth ulcers — has the best prognosis. Central nervous system disease presents with lethargy, poor feeding and seizures, with a CSF pleocytosis. Disseminated disease is a sepsis-like illness with hepatitis, pneumonitis and coagulopathy, and has the worst prognosis. The classification matters because it sets the duration of aciclovir — 14 days for skin-eye-mouth, 21 days for CNS or disseminated — and the decision to give six months of post-treatment suppression after CNS or disseminated disease. [2] [8]

Branch 2 — investigations and confirmation

Examiner: How will you confirm the diagnosis here? [2]

Candidate: I would send the full neonatal HSV workup: surface PCR swabs from the conjunctiva, oropharynx, rectum and the scalp vesicle, blood PCR, and CSF for cell count, protein, glucose and HSV PCR. I would add liver function tests and a coagulation screen to detect hepatitis and disseminated intravascular coagulation, a full blood count, and a chest X-ray for pneumonitis. I would run the bacterial septic workup in parallel — blood, urine and CSF cultures — because bacterial sepsis stays on the differential. Critically, I would not delay high-dose aciclovir while waiting for results. [2] [8]

Examiner: When is HSV PCR falsely negative, and what do you do? [8]

Candidate: A CSF PCR drawn very early in the illness can be falsely negative because viral load in the CSF has not yet risen. If the clinical picture persists and the first PCR is negative, I would repeat the lumbar puncture after a few days rather than dismiss the diagnosis. The point is that a single early negative PCR does not exclude neonatal HSV or encephalitis when the clinical picture fits, and empirical aciclovir is continued. [8] [2]

Branch 3 — treatment and the suppression question

Examiner: What treatment will you give this infant, and for how long? [8]

Candidate: High-dose intravenous aciclovir, 20 mg per kilogram per dose every eight hours. The duration depends on the disease class — 14 days for skin-eye-mouth disease, and 21 days for CNS or disseminated disease. I would maintain hydration carefully because aciclovir is nephrotoxic, and I would monitor liver function, coagulation and the full blood count throughout. After CNS or disseminated disease I would give six months of oral aciclovir suppression. [8] [5]

Examiner: Why six months of suppression? [5]

Candidate: Because the Kimberlin et al. New England Journal trial showed that six months of oral acyclovir suppression after neonatal CNS or disseminated HSV disease improves neurodevelopmental outcome at twelve months, with better Bayley mental-development scores than placebo. The trade-off is neutropenia, which needs blood-count monitoring, but the neurodevelopmental benefit makes suppression the standard of care. [5] [2]

Branch 4 — herpes simplex encephalitis in the older child

Examiner: Move on. A six-year-old presents with fever, confusion and a focal seizure. How does HSV encephalitis differ from neonatal HSV, and what is your management? [8]

Candidate: Herpes simplex encephalitis is the destructive temporal-lobe disease of the older child and is most often HSV-1. The virus reaches the temporal lobe and produces a haemorrhagic, necrotising, focal encephalitis — fever, altered consciousness, behavioural change and focal or generalised seizures. My management is empirical high-dose intravenous aciclovir, 20 mg per kilogram every eight hours for 21 days, before the PCR returns. I would send CSF for HSV PCR, request an MRI for temporal-lobe signal change and an EEG for periodic lateralised epileptiform discharges, control seizures, and admit to PICU if the child is encephalopathic. [8] [2]

Examiner: What determines the outcome? [8]

Candidate: The level of consciousness at presentation and the delay to aciclovir. Early treatment dramatically improves survival and neurological outcome; delay leaves a legacy of cognitive, behavioural and seizure burden. That is exactly why I treat empirically — the cost of aciclovir is low, the cost of a missed or delayed diagnosis is permanent neurological injury. [8]

Branch 5 — eczema herpeticum and prevention

Examiner: Tell me about eczema herpeticum, and how you would manage it. [12]

Candidate: Eczema herpeticum is dissemination of HSV across the barrier-deficient skin of atopic dermatitis, producing rapidly spreading, painful, monomorphic punched-out erosions with fever, malaise and lymphadenopathy. It is a dermatological emergency. I would give systemic aciclovir — oral if the child is well and the disease mild, intravenous if extensive, unwell or immunocompromised — confirm with a viral swab PCR, send a bacterial swab for co-infection, treat the underlying eczema, and avoid topical steroid or calcineurin monotherapy because they worsen the HSV. [12] [1]

Examiner: Finally, how do you prevent neonatal HSV? [7]

Candidate: Through the maternal-neonatal pathway. Maternal suppressive aciclovir from 36 weeks reduces shedding and the risk of a lesion at delivery. Caesarean delivery is recommended when active genital lesions are present. The asymptomatic neonate exposed at delivery is managed by the structured Kimberlin-Baley pathway of the American Academy of Pediatrics, which sets the surveillance, sampling and empirical-treatment thresholds. And pre-conception counselling — suppressing genital HSV and disclosing status — is the durable prevention, because a primary maternal infection near delivery is the scenario that transmits. [7] [1]

Wrap

Examiner: Summarise the HSV stance in one sentence. [1]

Candidate: Recognise the syndrome — gingivostomatitis, eczema herpeticum, ocular HSV, neonatal HSV or encephalitis — and set the host-risk tier, because together they fix the strength of aciclovir, from supportive care for the healthy child to high-dose intravenous aciclovir for the neonate and the brain, never delaying treatment when neonatal HSV or encephalitis is plausible, giving six months of suppression after neonatal CNS or disseminated disease, and running the maternal-neonatal prevention pathway that protects the next neonate. [1] [8]