Approach

Enterovirus D68 (EV-D68) is an important cause of acute respiratory illness, especially in children.[1][2][3]​​​​ In 2014, the US experienced an outbreak of EV-D68, with numerous children requiring hospital admission due to severe lower respiratory illness and asthma. This outbreak coincided with an increase in acute flaccid myelitis (AFM) cases in the US, and there has been increasing evidence for causality of EV-D68 for this serious neurologic complication.​​[9][10][11][12][23][24]

Respiratory illness

Most individuals infected have mild symptoms including runny nose, cough, sneezing, shortness of breath, or muscle aches; some patients have fever. Often patients with more severe disease have a history of asthma or chronic lung disease. These patients typically present with wheezing in EV-D68 infection.[36][37]

Most patients with EV-D68 will have a mild self-limited upper respiratory tract infection for which specific diagnostic testing is not indicated. The illness may be suspected based on epidemiologic considerations. Often EV-D68 occurs as a seasonal outbreak in the late summer or fall. During outbreaks, emergency departments and hospitals may see an increase in the number of children requiring treatment for asthma or respiratory symptoms. In the hospital setting, respiratory viral testing may be indicated for epidemiologic purposes or for specific diagnosis in critically ill patients. Specific testing for EV-D68 should be considered in children with severe unexplained respiratory illness, even in the absence of fever.[35]​ 

Because most patients have respiratory symptoms, the virus is generally tested for in respiratory samples, such as nasopharyngeal or oropharyngeal specimens. The standard method for detection is real-time reverse transcription polymerase chain reaction (rRT-PCR), and EV-D68 might be examined for using specific assays or as part of a multiplex respiratory viral panel. Many laboratories use methods that do not distinguish between different enteroviruses or between enteroviruses and rhinoviruses. For these assays, further testing with specific EV-D68 rRT-PCR or molecular sequencing is necessary if specific identification of EV-D68 is required. In the US, specific testing can be performed on a case-by-case basis through state or local health departments, or the Centers for Disease Control and Prevention (CDC).[38]

Acute flaccid myelitis

Mounting evidence suggests a causal relationship between EV-D68 infection and polio-like AFM.[5][6][7][8][9]​​​[10][11][12]​​​​​ In 2014, an increase in AFM cases coincided with an outbreak of EV-D68-related severe respiratory illness in the US.[23][24]​​ In 2022, several US health systems reported increases in severe respiratory illness in children who tested positive for rhinovirus or enterovirus, with a higher proportion of EV-D68 positivity than in previous years. The CDC published an advisory urging healthcare providers to consider EV-D68 as a possible cause of acute severe respiratory illness, with or without fever in children, and to advise of the potential for an increase in AFM cases.[25]

The cardinal symptom of AFM is acute, flaccid weakness of one or more limbs.[39] The majority of patients have prodromal fever, respiratory illness, or both, beginning a median of 6 days before the onset of weakness.[40] Thirty-five percent of patients have fever at the time of evaluation for weakness. Patients may also experience gait difficulty, back, neck or limb pain, or acute cranial nerve dysfunction.[40][41] Other symptoms include difficulty holding up the head, decreased appetite, difficulty swallowing, and bladder or bowel changes, especially constipation.​

Young children and their carers may not describe impaired limb function as weakness. If a child has new difficulty in feeding or dressing themselves, is limping, falling frequently, has difficulty throwing a ball overhead or getting out of a bathtub, or is suddenly using one limb less, he or she may have limb weakness.

Patients should have a comprehensive neurologic examination, evaluation for respiratory insufficiency and evaluation for autonomic manifestations (e.g., temperature instability, blood pressure lability). Sensory examination is often normal in patients with AFM.

Initial investigations include magnetic resonance imaging of the spine and brain, and analysis of cerebrospinal fluid, nasopharyngeal or oropharyngeal specimens, stool or rectal swab, and serum.[42]​ Nerve conduction studies may also be useful in diagnosing AFM.[43]​ Paralysis may be prolonged and recovery is often incomplete.

When a child presents with paralysis, the differential diagnoses include Guillain-Barre syndrome, traumatic neuritis, acute transverse myelitis, and toxin-mediated diseases such as botulism and tick paralysis. AFM may be caused by infection with several viruses in addition to EV-D68, such as other nonpolio enteroviruses, poliovirus, West Nile virus, and Japanese encephalitis virus.[44] Given the clinical similarity between AFM and acute flaccid limb paralysis caused by poliovirus, patients suspected of having AFM should also be tested for poliovirus infection.[45] The World Health Organization routinely lists countries where endemic or vaccine-derived poliomyelitis is currently circulating: Global polio eradication initiative Opens in new window See Poliovirus infection.

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