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Enterovirus D68

Enteroviruses (EV) are members of the Picornaviridae family. The genus Enterovirus includes four species, A through D, that are known to infect humans. Human enterovirus D68 (EV-D68) is a unique enterovirus that shares epidemiologic and biologic features with human rhinoviruses. EV-D68 causes acute respiratory illness in young children and adolescents. Typical signs and symptoms include cough, nasal congestion, wheezing, and dyspnea. EV-D68 infection can exacerbate asthma/reactive airway disease. Some cases have been severe enough to require hospitalization. 

EV D68 was first isolated in California in 1962 from children with bronchiolitis and pneumonia. EV-D68 infections have occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID19 mitigation measures such as wearing face masks, enhanced hand hygiene, and physical distancing.

EV-D68 is associated with acute flaccid myelitis (AFM). Providers should have a high index of clinical suspicion for AFM in children with a recent history of respiratory illness who develop acute flaccid limb weakness. Children with AFM can experience rapid progression of weakness and should be promptly hospitalized. These patients should also be tested for poliovirus because of the clinical similarity to acute flaccid paralysis caused by poliovirus infection.

More recent studies have confirmed that EV-D68 can directly infect spinal cord neurons. The photomicrograph shows neurons containing red-staining enterovirus D68 RNA.

Cytolytic CD8+ T cells proliferate to kill virus infected cells. Sometimes, a robust immune response also damages surrounding neurons that are not infected. Damaged neurons are not able to regenerate. 

Most hospital laboratories perform qualitative molecular tests for enterovirus that do not differentiate the type of enterovirus causing an infection. Real time PCR multi-pathogen detection systems such as the Luminex xTAG RVP and Idaho Technologies FilmArray Respiratory Panel incorporate broadly reactive primers that amplify RNA from human rhinoviruses and enteroviruses. Results are reported as "Entero-Rhinovirus" or "Human Rhinovirus/Enterovirus". CDC has developed a real-time reverse transcription–polymerase chain reaction for EV-D68. Partial sequencing of the HEV68 structural protein genes, VP4-VP2 or VP1 is considered to be the gold standard method of detection. 

EV-D68 is often detected in respiratory specimens of patients with AFM, but rarely detected in their cerebrospinal fluid. Enterovirus infections, including EV-D68, are not reportable in the United States, but providers should immediately report AFM cases to local and state health departments.

Specimen requirement is a nasopharyngeal swab transported in M6 viral media.


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