Enterovirus D68: the unexpected guest

Abstract

Reports of increasing numbers of children admitted to hospital with severe respiratory illness and associated muscle weakness and paralysis in the USA and Canada have caused alarm. Enterovirus D68—a member of the enterovirus genus that also includes rhinoviruses, coxsackieviruses, and polioviruses—is believed to be the most likely cause of this outbreak. Infections caused by this virus are rarely reported (only 79 cases were recorded between 2009 and 2013 in the USA) and they normally involve mild respiratory symptoms similar to a cold, but these can become severe in children with underlying problems such as asthma. However, two previous case reports of paralysis caused by enterovirus D68 as a complication of respiratory illness have raised concerns that in this recent outbreak the virus might be responsible for the unexpected high number of children with respiratory symptoms and neurological complications. Between Aug 8 and Oct 8, 2014, 30 cases of respiratory illness with neurological complications in children were reported in nine US states and 13 other cases were reported in three Canadian provinces. During the same period, 628 children who had developed severe respiratory symptoms that needed admission to hospital or paediatric intensive care units tested positive for the virus both in the USA (44 states) and Canada (three provinces). Two of these children subsequently died in Rhode Island and New Jersey but the role of enterovirus D68 in their deaths is still unclear. The US Centers for Disease Control and Prevention (CDC) asked hospitals across North America to report patients aged 21 years or younger who have developed limb weakness and who had an MRI examination that showed abnormalities in spinal cord nerve tissue. Hospitals in both the USA and Canada have responded by reporting cases of neurological symptoms in children that appeared after respiratory illness. These cases are being treated with physical therapy but the long-term prognosis is uncertain because most children have not shown relevant improvements so far. Few laboratories in North America have the capacity to specifically identify enterovirus D68, therefore the CDC is also collecting and analysing nasopharyngeal swabs from all children admitted to hospital with severe respiratory illness. Seven of 43 children with muscle weakness or paralysis tested positive for enterovirus D68. The detection of the virus in respiratory specimens from these children with neurological symptoms does not prove causality, especially because no virus was detected in the cerebrospinal fluid. However, available laboratory tests such as virus isolation in cell culture often fail to detect the virus in the cerebrospinal fluid, so better diagnostic methods are needed to obtain definitive results. Although the detection of enterovirus D68 during recent weeks is not surprising because infections are usually reported in summer and autumn, the unusually high number of admissions to hospital and the reported cases of neurological complications with uncertain prognosis are a serious cause for concern. However, until the presence of enterovirus D68 in cerebrospinal fluid is shown, a causal link with the neurological symptoms is speculative. In the absence of a specific diagnosis, and since a vaccine or specific antiviral drugs for enterovirus D68 are not available, the CDC recommends following the basic rules for prophylaxis from seasonal respiratory illnesses, such as frequent handwashing, avoidance of close contact with ill people, disinfection of contaminated surfaces, and remaining at home if unwell. No similar cases of respiratory syndrome with neurological complications have been reported in other continents, but the outbreak in North America means that the international community should be alert. The reports of high numbers of cases of severe respiratory syndromes with possible neurological complications linked to enterovirus D68 suggest that this virus might be more virulent than previously thought. More information about possible changes in antigenicity and genome evolution in enterovirus D68 is needed. Concern also exists that as a consequence of the eradication of poliovirus, relatively rare enteroviruses such as enterovirus D68 might emerge and occupy the vacant ecological niche and cause polio-like syndromes. What clearly emerges from this outbreak is that the development of specific devices for the diagnosis and surveillance of these viruses is essential to clearly understand their role in the recent cases and guarantee timely and efficient responses in the future. For more on non-polio enterovirus outbreaks in the USA see http://www.cdc.gov/non-polio-enterovirus/outbreaks/EV-D68-outbreaks.html For more on non-polio enterovirus outbreaks in the USA see http://www.cdc.gov/non-polio-enterovirus/outbreaks/EV-D68-outbreaks.html For more on enterovirus D68 in Europe see http://www.ecdc.europa.eu/en/publications/_layouts/forms/Publication_DispForm.aspx?List=4f55ad51-4aed-4d32-b960-af70113dbb90&ID=1175 For more on enterovirus D68 in Europe see http://www.ecdc.europa.eu/en/publications/_layouts/forms/Publication_DispForm.aspx?List=4f55ad51-4aed-4d32-b960-af70113dbb90&ID=1175 Rare enterovirus continues to circulate in North AmericaD68, an uncommon strain of enterovirus, has caused an unexpectedly high number of respiratory illnesses across the USA and has now appeared in Canada. Brian Owens reports. Full-Text PDF