What are the symptoms and treatment options for enterovirus (EV) infection in children?

Enterovirus Infection in Children: Symptoms and Treatment

Clinical Presentation

Enterovirus infections in children typically begin with fever (often low-grade but can exceed 39°C), accompanied by respiratory symptoms (cough, rhinitis, sore throat), gastrointestinal symptoms (nausea, vomiting, diarrhea, poor feeding), and rash in approximately 37% of cases, presenting as small pink macules evolving to vesicular lesions characteristic of hand, foot, and mouth disease. 1

Common Symptoms

• Fever is typically the first symptom, accompanied by malaise, general discomfort, and irritability 1
• Respiratory manifestations including cough, rhinitis, and sore throat occur frequently 1
• Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and poor feeding are common 1
• Rash appears in 37% of cases with characteristic distribution on palms, soles, and oral mucosa 1
• Peak incidence occurs in late summer and early fall 1

Severe Complications and Warning Signs

Aseptic meningitis is more common than encephalitis in enterovirus infections, but severe neurological complications can occur and require urgent recognition. 1

• Meningoencephalitis presents with disturbances in consciousness and seizures 1
• Enterovirus 71 rhombencephalitis manifests with myoclonus, tremors, ataxia, and cranial nerve defects 1
• Acute flaccid myelitis (AFM) causes rapid limb weakness with low muscle tone, particularly associated with Enterovirus-D68 and Enterovirus-71 1
• Neurogenic pulmonary edema can occur with Enterovirus-71 rhombencephalitis, potentially leading to fatal cardiorespiratory collapse 1

Neonatal Presentation

In neonates, enterovirus infections present differently and more severely than in older children 2:

• Clinical manifestations are difficult to differentiate from bacterial sepsis: fever, poor feeding, lethargy, respiratory distress, and cardiovascular collapse 2
• Severe life-threatening complications include hepatic necrosis with coagulopathy, meningoencephalitis, and myocarditis, usually presenting during the first week of life 2
• In 70.5% of severe neonatal cases, symptom onset occurs before 7 days of age 3
• The lethality rate in neonates with severe infection is 30.4%, with the highest rate (38.6%) in those with myocarditis 3

Treatment Approach

Standard Management

No specific antiviral treatment is recommended for enterovirus encephalitis in most cases; supportive care remains the mainstay of treatment, though pleconaril (if available) or intravenous immunoglobulin may be considered in patients with severe disease. 4

Supportive Care

• Supportive care is the primary treatment for most enterovirus infections 4
• Patients with falling level of consciousness require urgent assessment by pediatric Intensive Care Unit staff for airway protection, ventilatory support, management of raised intracranial pressure, and correction of electrolyte imbalances 4
• Transfer to a specialist pediatric neuroscience unit should occur within 24 hours if diagnosis is unclear or patient fails to improve 4, 5

Intravenous Immunoglobulin (IVIG)

IVIG may be useful in patients with severe enterovirus 71 infection and chronic enterovirus meningitis, though no randomized trials have been conducted. 4

• Standard dosing is 2 g/kg divided over 2-5 days 5
• Alternative approach: 1-2 g/kg in 2-4 divided doses 5
• Treatment may need to be repeated at monthly intervals for sustained effect 5
• In severe neonatal cases, early IVIG treatment (particularly high-dose 2 g/kg) may help reduce morbidity and mortality 2, 3
• High-dose IVIG was associated with early negative viral load in children with malignancy, though mortality remained significant 6

Pleconaril

Pleconaril is an antiviral drug that binds within the viral capsid protein of enteroviruses, inhibiting viral binding to cellular receptors 4:

• Has broad activity against most enteroviruses at low concentrations 4
• In phase III trials, reduced symptoms of aseptic meningitis by approximately two days compared to placebo 4
• Has been used in chronic enterovirus infection due to agammaglobulinemia, enterovirus myocarditis, and neonatal infection 4
• No trials have assessed its role in enterovirus encephalitis, and it is often not available 4
• Used in only 5.9% of severe neonatal cases in systematic review 3

Special Populations

Children with agammaglobulinemia who develop chronic enteroviral meningoencephalitis may require intravenous immunoglobulin or intraventricular gamma-globulin for chronic and/or severe disease. 1

• Chronic enteroviral meningoencephalitis occurs in children with agammaglobulinemia (rare) 1
• These patients require IVIG with target IgG levels ≥400 mg/dL 5

Diagnostic Approach

All patients with suspected encephalitis should have CSF PCR testing for HSV (1 and 2), VZV, and enteroviruses, as this will identify 90% of known viral cases. 4

• Throat and rectal swabs for enterovirus investigations should be considered in all patients with suspected viral encephalitis 4
• Diagnosis of enterovirus radiculoneuropathy relies on CSF PCR for enterovirus detection, not serum antibody testing, with results available within 24-48 hours 5
• Rapid reverse-transcriptase PCR test for viral load may help physicians diagnose severe cases in a timely manner 2

Critical Pitfalls to Avoid

• Failing to recognize severe complications early: Temperature abnormalities, rash, and poor feeding are the most common symptoms in severe neonatal infection, but progression to hepatitis, myocarditis, or meningoencephalitis can be rapid 3
• Delaying ICU assessment: Patients with declining consciousness require urgent pediatric ICU evaluation 4
• Missing the diagnosis in immunocompromised patients: Children with lymphoid malignancy have 87% incidence of enteroviral infections and higher rates of severe manifestations 6
• Inadequate monitoring in neonates: Echoviruses and coxsackievirus B are most commonly associated with neonatal sepsis, and severe complications usually present during the first week of life 2