What are the symptoms of enterovirus in children?

Symptoms of Enterovirus Infection in Children

Enterovirus infections in children present with a wide spectrum of symptoms ranging from mild, self-limited illness to severe, life-threatening complications, with clinical manifestations varying significantly by age and specific viral serotype.

General Clinical Presentation

Common Mild Symptoms

• Fever is typically the first symptom, usually low-grade but can exceed 102.2°F (39°C), often accompanied by malaise, general discomfort, and irritability 1
• Respiratory symptoms including cough, rhinitis, and sore throat are frequently present 1
• Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and poor feeding occur commonly 1, 2, 3
• Rash appears in approximately 37% of cases, presenting as small pink macules that evolve to vesicular lesions with characteristic distribution on palms, soles, and oral mucosa in hand, foot, and mouth disease 1, 3

Timing and Epidemiology

• Peak incidence occurs in late summer and early fall 4, 5
• Most cases present during May through July in temperate climates 5
• The disease is worldwide in distribution 4

Age-Specific Presentations

Neonates (First Month of Life)

Neonates are at particularly high risk for severe, life-threatening disease that is difficult to differentiate from bacterial sepsis 2, 3

• Temperature abnormalities (present in 53.6% of severe cases) 3
• Poor feeding and lethargy (24.5% of severe cases) 2, 3
• Respiratory distress (21.9% of severe cases) 3
• Cardiovascular collapse may occur 2
• Rash (37.1% of severe cases) 3

Critical timing: In 70.5% of neonates with severe infection, symptoms begin within the first 7 days of life 3

Infants and Young Children (6 months to 2 years)

• Children in this age group are at significantly higher risk for severe neurological involvement 6
• Appearance of neurological symptoms within the first 12 hours from infection onset, especially when associated with skin rash, is a significant risk factor for severe disease 6

Older Children

• Headache (97% of cases) and vomiting (80% of cases) are the most frequent symptoms 5
• Fever is present in only 56% of older children with meningitis 5
• Positive meningeal signs on examination in 78% 5

Severe Complications and Warning Signs

Neurological Manifestations

Aseptic meningitis is more common than encephalitis in enterovirus infections 4

• Meningoencephalitis (11.0% of severe neonatal cases) with disturbances in consciousness and seizures 4, 3
• Seizures are a significant risk factor for severe disease 7
• Drowsiness/lethargy is significantly associated with severe infection 7
• Enterovirus 71 rhombencephalitis in children presents with myoclonus, tremors, ataxia, and cranial nerve defects 4
• Acute flaccid myelitis (AFM) causes rapid limb weakness with low muscle tone, particularly associated with Enterovirus-D68 and Enterovirus-71 8

Cardiac Manifestations

• Myocarditis occurs in 37.1% of severe neonatal cases and carries the highest lethality rate of 38.6% 3

Hepatic Manifestations

• Hepatitis or coagulopathy develops in 46.0% of severe neonatal cases, typically presenting during the first week of life 2, 3
• Hepatic necrosis with coagulopathy is a life-threatening complication 2

Respiratory Manifestations

• Pneumonia is a common severe complication 7
• Neurogenic pulmonary edema can occur with Enterovirus-71 rhombencephalitis, potentially leading to fatal cardiorespiratory collapse 8
• Dyspnea is associated with severe disease 7

Other Severe Complications

• Hemophagocytic lymphohistiocytosis (5.9% of severe cases) 3
• Pulmonary hemorrhage (5.9% of severe cases) 3
• Hyperglycemia is significantly related to severe infection 7

High-Risk Features for Severe Disease

Clinical Red Flags

• Age less than 1 year 7
• Highest body temperature greater than 39.0°C 7
• Duration of fever greater than 3 days 7
• Absence of oral lesions (paradoxically associated with more severe disease) 7
• Absence of skin lesions 7
• Seizures 7
• Drowsiness/lethargy 7

Serotype-Specific Risks

• Enterovirus-71 (EV-A71) is most commonly associated with the most severe neurological conditions 6
• Coxsackievirus B viruses are most common serotypes associated with neonatal sepsis and severe disease (52.3% of severe neonatal cases) 2, 3
• Echoviruses are also commonly associated with neonatal sepsis 2
• Echovirus-30 is mostly associated with aseptic meningitis 6

Special Populations

Immunocompromised Children

• Chronic enteroviral meningoencephalitis occurs in children with agammaglobulinemia (rare) 4
• These patients may require intravenous immunoglobulin or intraventricular gamma-globulin for chronic and/or severe disease 4

Important Clinical Caveats

• Half of patients are diagnosed within the first 6 hours of illness, and 20% within the first 2 hours, emphasizing the rapid progression that can occur 5
• Fever is an inconstant finding, particularly in older children with meningitis (present in only 56%) 5
• CSF pleocytosis may be absent in some cases of confirmed enteroviral meningitis 5
• Polymorphonuclear cell predominance in CSF occurs in 45% of cases, which can mimic bacterial meningitis 5
• Clinical manifestations are difficult to differentiate from bacterial sepsis in neonates, requiring a high index of suspicion 2
• Overall lethality rate for severe neonatal enterovirus infection is 30.4% 3