Epidemiology

Enterovirus D68 (EV-D68) was originally isolated in 1962 in Berkeley, California from four children with lower respiratory tract symptoms.[15] After this, EV-D68 was infrequently reported as a cause of human disease. In a large survey of enteroviruses conducted by the US Centers for Disease Control and Prevention (CDC) from 1970 to 2005, EV-D68 was isolated only 26 times.[16] More recently, however, EV-D68 has emerged as a respiratory pathogen of significant importance worldwide.

Seasonal outbreaks have been described throughout the world, typically occurring during the late summer and autumn and causing severe lower respiratory illness, primarily in children.[17][18][19]​​​​​ Several studies have observed a biennial outbreak pattern that aligns with spikes in acute flaccid myelitis (AFM) cases.[20][21]​​ Seroepidemiological studies suggest that most adults have immunity.[22]

A large outbreak occurred in the US Midwest starting in August 2014. The outbreak involved children primarily, many of whom required admission to hospital for severe respiratory disease.[1][2] In that outbreak, the CDC and state public health laboratories confirmed EV-D68 infection in at least 1153 people throughout the US. Many more children with similar symptoms were hospitalised during the outbreak, but were not tested for EV-D68 because the test was not widely available. It is likely that cases of EV-D68 infection giving rise to mild symptoms, which did not require in-hospital treatment or respiratory viral testing, far exceeded confirmed or suspected cases of EV-D68-related severe respiratory illness.

Few data are available from the outbreak on the prevalence of EV-D68 in adult populations as rigorous testing was not performed in adults. The clinical impression, however, is that the EV-D68 was much more prevalent in children.

Following the 2014 outbreak in the US, surveillance in Europe, including the UK, was enhanced, and 55 sporadic cases were detected.[23] Cases have been detected in children and adults. The majority seem to have presented with respiratory symptoms resulting in hospital admission, with two children presenting with neurological signs and symptoms. In 2018, 68 samples in England and Wales.[24]

Although EV-D68 primarily causes respiratory illness, systemic disease may occur, and there is increasing evidence that EV-D68 infection can cause the serious neurological complication AFM.[9][12]​​​ In 2014, an increase in AFM cases coincided with an outbreak of EV-D68-related severe respiratory illness in the US.[25][26]​​ The US Centers for Disease Control and Prevention (CDC) verified 120 AFM case reports between August and December 2014.[25] Most patients were children; the median age was 7.1 years and 59% were male. The CDC did not consistently detect EV-D68 in every confirmed AFM case.[25][26]

There have been 756 confirmed cases of AFM reported to the CDC between August 2014 and July 2024.[26] Most patients develop AFM between August and November, and there have been peaks in case numbers in 2014, 2016 and 2018.[26] 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.[27]

Sporadic cases of AFM associated with EV-D68 infection have also been reported in Australia, Canada, Norway, Sweden, France, Spain, Scotland, and the UK.[10][28][29][30][31][32][33]​​

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