What is the treatment approach for patients diagnosed with Enterovirus 71 (EV 71)?

Treatment Approach for Enterovirus 71 (EV71) Infection

For patients diagnosed with Enterovirus 71 (EV71), treatment is primarily supportive care as there is no specific antiviral therapy recommended, with intravenous immunoglobulin recommended for severe cases with neurological complications.

Clinical Manifestations of EV71 Infection

EV71 can cause a spectrum of clinical presentations:

• Hand, foot, and mouth disease (HFMD) - most common presentation
• Neurological complications:
  • Brainstem encephalitis (most critical manifestation)
  • Aseptic meningitis
  • Acute flaccid myelitis/paralysis
  • Encephalomyelitis
• Cardiopulmonary complications:
  • Pulmonary edema/hemorrhage
  • Cardiopulmonary failure

Diagnostic Approach

• Collection of appropriate specimens:

  • Respiratory specimens (nasal/throat swabs)
  • Stool samples
  • Cerebrospinal fluid (CSF)
  • Blood samples 1

• Diagnostic testing:

  • Reverse transcriptase PCR (RT-PCR) targeting the 5′non-coding region is the recommended method 1
  • VP1 capsid protein gene sequencing for typing 1
  • EV71 is more commonly identified in feces (95%), rectal swabs (95%), and throat swabs (85%) than in CSF (24%) 2

Treatment Algorithm

1. Mild Disease (Uncomplicated HFMD)

• Supportive care:
  • Antipyretics for fever control (acetaminophen or ibuprofen)
  • Adequate hydration
  • Pain management
  • Rest 3

2. Moderate Disease (Neurological Symptoms without Severe Complications)

• Close monitoring for progression
• Supportive care:
  • Antipyretics
  • Adequate hydration
  • Pain management
  • Anticonvulsants if seizures occur 1

3. Severe Disease (Neurological Complications)

• Intravenous immunoglobulin (IVIG) is recommended for severe cases, especially with brainstem encephalitis 1, 4
• For patients with pulmonary edema or cardiopulmonary failure:
  • Milrinone (phosphodiesterase inhibitor) is recommended 4, 5
  • Mechanical ventilation support
  • Fluid management
  • Vasopressors and inotropes as needed 5
• For patients with falling level of consciousness:
  • Urgent assessment for airway protection and ventilatory support
  • Management of raised intracranial pressure
  • Optimization of cerebral perfusion pressure
  • Correction of electrolyte imbalances 1

4. Critical Disease (Cardiopulmonary Failure)

• Intensive care management:
  • Mechanical ventilation
  • Hemodynamic support
  • Consider extracorporeal membrane oxygenation in refractory cases 5
• Early tracheostomy may be beneficial for patients with neurological pulmonary edema or hypotension 6

Important Clinical Considerations

1. Predictors of severe disease requiring tracheostomy or gastrostomy:

   • Age <2 years
   • Body weight <10th percentile
   • Pulmonary hemorrhage or edema
   • Hypotension
   • Positive MRI findings of upper spinal cord and brainstem 6

2. Neuroimaging findings:

   • Characteristic increased T2-weighted signal in the dorsal pons and spinal cord
   • Dorsal brainstem restricted diffusion is associated with severe disease 2

3. Prognosis and follow-up:

   • Most patients (77%) show resolution of brainstem or motor dysfunction by 2 months
   • By 12 months, 90% of patients show resolution 2
   • Focal paresis is the most common persisting problem at 12 months
   • Patients initially presenting with acute flaccid paralysis or pulmonary edema have significantly greater frequencies of motor dysfunction at follow-up 2

Experimental Therapies

• Pleconaril: Has broad activity against most enteroviruses but limited evidence for EV71 encephalitis and often not available 1, 7
• Corticosteroids: Some evidence suggests potential benefit in patients with EV71-related neurological complications, but data is limited 7

Prevention

• Hand hygiene is the most effective way to prevent transmission 3
• EV71 vaccines have completed phase III clinical trials in China but are not yet widely available globally 4

Key Pitfalls to Avoid

1. Failing to collect appropriate specimens (respiratory, stool, CSF) for diagnosis
2. Relying solely on CSF samples for diagnosis, as EV71 is more commonly detected in stool and respiratory specimens
3. Delaying transfer to specialized neurological care when patients fail to improve
4. Not recognizing early signs of cardiopulmonary involvement (tachycardia, hypertension)
5. Underestimating the need for long-term follow-up and rehabilitation for patients with neurological sequelae

Remember that patients with suspected acute encephalitis should have access to immediate neurological specialist opinion and should be managed in a setting where clinical neurological review can be obtained promptly 1.