The Enterovirus D68 Outbreak: A Public Health Concern

Tammie Lee Demler, BS, PharmD, MBA, BCPP


US Pharmacist. 2015;40(5):22-26. 

In This Article


EV-D68 was first discovered in California in 1962 when it was isolated from samples obtained from children with pneumonia.[1] The higher rate of severe cases in children when compared to adults is likely due to the physiological difference of smaller airways and less previously established immunity. The CDC has confirmed a total of 1,153 people in 49 states and the District of Columbia with respiratory illness caused by EV-D68 from mid-August 2014 to January 15, 2015, with 14 deaths among the cases.[1] According to Susan Gerber, MD, team lead of the Respiratory Viruses and Picornavirus Team, Division of Viral Diseases, at the CDC, "Most people who contract EV-D68 will get better, but for those with an underlying comorbid respiratory illness there can be risk of severe respiratory illness. Children who have asthma or a history of wheezing are at increased risk of severe respiratory illness."[2]

Enteroviruses come from the Picornaviridae family and Enterovirus genus and are nonenveloped, "positive sense," single-stranded RNA (ssRNA) viruses.[3] EV-D68 is epidemiologically and biologically similar to the human rhinovirus.[3] Roughly 100 serotypes of nonpolio enteroviruses have been recognized, but EV-D68 has been one of the less commonly reported. Due to the fact that humans are the only known host, these enteroviruses are described as human and are further classified as echoviruses, polioviruses, and coxsackieviruses group A and B. Although there are now more species recognized, the original division of the human enteroviruses (HEVs) placed the viral characteristics into four species: HEV types A, B, C, and D. HEV-68 has now been renamed EV-D68, reflecting the recent revision in taxonomy that removed the "human" host description from both enterovirus and rhinovirus species and added the type number to the species designation.[3] Of the currently recognized species of HEVs, EV-D68 is most similar to the human rhinovirus with regard to its ability to cause respiratory illness.

Although it is not a new illness, EV-D68 has become an emerging pathogen responsible for causing outbreaks internationally. Tokarz et al studied the increased prevalence and/or recognition of this illness and reported that the EV-D68 genome experienced a mutation in the protein arrangement, which resulted in a protein deletion in all the strains that were examined.[3] In the 1990s, a further viral mutation and protein deletion occurred, which affected the viral replication, virulence, fitness, and persistence. These changes are thought to have improved the viral translation/replication efficiency and may be correlated with the recent increases in EV-D68 cases internationally.[3]

The CDC obtained one complete genomic sequence and six nearly complete genomic sequences from viruses representing the three known strains of EV-D68 responsible for infections during the current outbreak. These sequences are genetically related to previous strains. These samples have been submitted to GenBank to make the sequences available for further testing. GenBank is the genetic sequence database of the National Institutes of Health, storing a collection of all publicly available DNA sequences.[4]

According to Dr. Gerber, "There are many different types of enteroviruses, and different types generally predominate seasonally in summer and fall. The CDC has identified smaller EV-D68 outbreaks in previous years. However, it is thought that increased surveillance and awareness has led to the larger number of recognized diagnoses of EV-D68 infection. It is possible, and most likely, that many cases and outbreaks of EV-D68 and other enterovirus-associated illnesses have occurred but have not undergone specific testing. Additionally, there could be a detection bias in certain outbreaks due to the observed severity of illness because testing is more likely with severe cases. It is expected that a high percentage of cases of EV-D68 would be identified among intensive care patients and those requiring the most intensive supportive care. There have been new reports of fatalities in the current outbreak."[2]

"This illness does not require Department of Health or CDC notification; therefore, it is difficult to track with any degree of accuracy," said Dr. Gerber.[2] "Not all labs have the ability to test to confirm this infection, making benchmarking difficult, so better information collection is needed for future comparisons. Enteroviruses can cause a wide variety of illnesses, including hand-foot-and-mouth disease with a rash as a distinguishing feature, aseptic meningitis, and conjunctivitis. Pharmacists should be aware of the potential for EV-D68 to cause respiratory illness, and there is no approved vaccination or antiviral for use. There continues to be interest in increasing more research in this area, so there is a wider base of knowledge to apply in practice." Please refer to the SIDEBAR for additional content from the interview with Dr. Gerber.[1–3,5,6]