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Enterovirus D68 (EV-D68): Unraveling the Mystery

2.00 Contact Hours:
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A score of 80% correct answers on a test is required to successfully complete any course and attain a certificate of completion.
Author:    Pamela Downey (MSN, ARNP)


Enteroviruses alone, excluding the poliovirus, cause about 10 to 15 million infections in the United States each year. Tens of thousands of individuals are hospitalized each year for illnesses caused by enteroviruses. Enterovirus D68 (EV-D68, EV68, HEV68) is a member of the Picornaviridae family, an enterovirus. First isolated in California in 1962 and once considered rare, EV-D68 has been on a worldwide upswing in the 21st century.

In 2014, the United States experienced a nationwide outbreak of EV-D68 associated with severe respiratory illness. From mid-August 2014 to January 15, 2015, the CDC or state public health laboratories confirmed 1,153 total cases of respiratory illness caused by EV-D68 in 49 states and the District of Columbia. Almost all of the confirmed cases were among children, many of whom had asthma or a history of wheezing. Additionally, there were likely millions of mild EV-D68 infections for which individuals did not seek medical treatment and/or get tested.

The CDC received about 2,600 specimens for enterovirus laboratory testing during 2014, which is substantially more than usual. About 36% of those tested positive for EV-D68. About 33% tested positive for an enterovirus or rhinovirus other than EV-D68. EV-D68 was detected in specimens from 14 patients who died and had samples submitted for testing. State and local officials have the authority to determine and release information about the cause of these deaths.

The pain and suffering caused by the enteroviruses and the upsurge specifically in EV-D68 infections has caused the world to pause, backup and investigate retrospectively why this upsurge in activity and how better can we as healthcare providers prevent EV-D68 infections in the future before EV-D68 raises its ugly head again.


After completing this course, the learner will be able to meet the following objectives:

  1. State the modes of transmission of EV-D68.

  2. Describe infection control measures recommended to prevent the spread of EV-D68 infections in healthcare and non-healthcare settings

  3. Relate the risk factors identified during the health history which predispose individuals to enteroviral/EV-D68 infections.

  4. Describe the signs and symptoms of EV-D68 infection.

  5. Describe healthcare provider’s responsibility to report clusters of severe respiratory illness to local and state health departments.

  6. Relate the treatment regimen for individuals experiencing EV-D68 infection.

  7. Relate educational strategies healthcare providers can utilize to teach individuals how to prevent EV-D68 infection.

  8. Describe acute flaccid myelitis including signs and symptoms, testing, diagnosis, treatments, outcomes and possible causations.

Introduction to Enterovirus

Enteroviruses affect millions of people worldwide each year. They are often found in the respiratory secretions (e.g., saliva, sputum, or nasal mucus) and stool of an infected individual. Historically, poliomyelitis was the most significant disease caused by an enterovirus i.e. the poliovirus.

There are 64 non-polio enteroviruses that can cause disease in humans: 23 Coxsackie A viruses, 6 Coxsackie B viruses, 28 echoviruses, and 5 other enteroviruses. Poliovirus, as well as, coxsackie and echovirus are spread through the fecal-oral route. Infection can result in a wide variety of symptoms ranging from mild respiratory illness i.e. the common cold, hand, foot and mouth disease, acute hemorrhagic conjunctivitis, aseptic meningitis, myocarditis, severe neonatal sepsis-like disease, and acute flaccid myelitis.

Species and Genetics: Enteroviruses

Enteroviruses are members of the Picornaviridae family (Table 1), a large and diverse group of small RNA viruses characterized by a positive-sense single-stranded RNA (ssRNA) associated with several human and mammalian diseases. All enteroviruses contain a genome of approximately 7,500 bases and are known to have a high mutation rate due to low-fidelity replication and frequent recombination. After infection of the host cell, the genome is translated in a cap-independent manner into a single polyprotein, which is subsequently processed by virus-encoded proteases into the structural capsid proteins and the nonstructural proteins, which are mainly involved in the replication of the virus.

Serologic studies have distinguished 71 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the basis of reduced or nonreciprocal cross-neutralization between variant strains.

On the basis of their pathogenesis in humans and animals, the enteroviruses were originally classified into four groups: Polioviruses, Coxsackie A viruses (CA), Coxsackie B viruses (CB), and Echoviruses. It was quickly realized that there were significant overlaps in the biological properties of viruses in the different groups. Enteroviruses isolated more recently are named with a system of species designation and consecutive numbers: EV-D68, EV-B69, EV-D70, EV-A71, etc.

Table 1: Enteroviruses
Virus classification
Group: Group IV ((+)ssRNA)
Order: Picornavirales
Family: Picornaviridae
Genus: Enterovirus
Enterovirus A
Enterovirus B
Enterovirus C
Enterovirus D
Enterovirus E
Enterovirus F
Enterovirus G
Enterovirus H
Enterovirus J
Rhinovirus A
Rhinovirus B
Rhinovirus C

The enterovirus genus includes the following twelve species:

  • Enterovirus A (formerly Human enterovirus A)
  • Enterovirus B (formerly Human enterovirus B)
  • Enterovirus C (formerly Human enterovirus C)
  • Enterovirus D (formerly Human enterovirus D)
  • Enterovirus E (formerly Bovine enterovirus group A)
  • Enterovirus F (formerly Bovine enterovirus group B)
  • Enterovirus G (formerly Porcine enterovirus B)
  • Enterovirus H (formerly Simian enterovirus A)
  • Enterovirus J
  • Rhinovirus A (formerly Human rhinovirus A)
  • Rhinovirus B (formerly Human rhinovirus B)
  • Rhinovirus C (formerly Human rhinovirus C)

Within these twelve species are the serotypes:

  • Coxsackievirus:

    Coxsackieviruses are a non-phylogenetic group. Coxsackie A viruses (CV-A) tend to infect the skin and mucous membranes causing herpangina, acute hemorrhagic conjunctivitis and hand, foot and mouth (HFM) disease. Coxsackie B viruses (CV-B) tend to infect the heart, pleura, pancreas and liver causing pleurodynia, myocarditis, pericarditis, hepatitis and pancreatitis. Both Coxsackie A and B can cause nonspecific febrile illnesses, rashes, upper respiratory tract disease and aseptic meningitis.

    Serotypes CV-A2, CV-A3, CV-A4, CV-A5, CV-A6, CV-A7, CV-A8, CV-A10, CV-A12, CV-A14 and CV-A16 (found under the species: Enterovirus A).

    Serotypes CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, CV-B6 and CV-A9 (found under the species: Enterovirus B).

    Serotypes CV-A1, CV-A11, CV-A13, CV-A17, CV-A19, CV-A20, CV-A21, CV-A22 and CV-A24 (found under the species: Enterovirus C).

    Echovirus (E) 

    Echoviruses are a cause of many of the nonspecific viral infections. It is highly infectious and its primary target is children. The echovirus is among the leading causes of acute febrile illness in infants and young children and is the most common cause of aseptic meningitis. Infection of an infant with this virus following birth may cause severe systemic diseases and is associated with high infant mortality rates. Echoviruses are found in the gastrointestinal tract and can cause nervous disorders. The usual symptoms of echoviruses are fever, mild rash, and mild upper respiratory tract (URT) illness.

    Serotypes E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-9, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-24, E-25, E-26, E-27, E-29, E-30, E-31, E-32, and E-33 (found under the species: Enterovirus B).
  • Enterovirus (EV)

    Serotypes EV-A71, EV-A76, EV-A89, EV-A90, EV-A91, EV-A92, EV-A114, EV-A119, SV19, SV43, SV46 and BA13 (found under the species: Enterovirus A).

    Serotypes EV-B69, EV-B73, EV-B74, EV-B75, EV-B77, EV-B78, EV-B79, EV-B80, EV-B81, EV-B82, EV-B83, EV-B84, EV-B85, EV-B86, EV-B87, EV-B88, EV-B93, EV-B97, EV-B98, EV-B100, EV-B101, EV-B106, EV-B107, EV-B110 and SA5 (found under the species: Enterovirus B).

    Serotypes EV-C95, EV-C96, EV-C99, EV-C102, EV-C104, EV-C105, EV-C109, EV-C116, EV-C117 and EV-C118 (found under the species: Enterovirus C).

    Serotypes EV-D68, EV-D70, EV-D94, EV-D111 and EV-D120 (found under the species: Enterovirus D).

    Serotypes EV-H1 (found under the species: Enterovirus H).

    Serotypes SV6, EV-J103, EV-J108, EV-J112, EV-J115 and EV-J121 (found under the species: Enterovirus J).
  • Human rhinovirus (HRV)

    There are three species of Rhinoviruses: Human Rhinovirus A, Human Rhinovirus B, and Human Rhinovirus C which contain over 100 serotypes. Rhinoviruses are the most suspected causative agents of the common cold. This makes it difficult to develop a single vaccine against so many serotypes.

    serotypes HRV-A1, HRV-A2, HRV-A7, HRV-A8, HRV-A9, HRV-A10, HRV-A11, HRV-A12, HRV-A13, HRV-A15, HRV-A16, HRV-A18, HRV-A19, HRV-A20, HRV-A21, HRV-A22, HRV-A23, HRV-A24, HRV-A25, HRV-A28, HRV-A29, HRV-A30, HRV-A31, HRV-A32, HRV-A33, HRV-A34, HRV-A36, HRV-A38, HRV-A39, HRV-A40, HRV-A41, HRV-A43, HRV-A44, HRV-A45, HRV-A46, HRV-A47, HRV-A49, HRV-A50, HRV-A51, HRV-A53, HRV-A54, HRV-A55, HRV-A56, HRV-A57, HRV-A58, HRV-A59, HRV-A60, HRV-A61, HRV-A62, HRV-A63, HRV-A64, HRV-A65, HRV-A66, HRV-A67, HRV-A68, HRV-A71, HRV-A73, HRV-A74, HRV-A75, HRV-A76, HRV-A77, HRV-A78, HRV-A80, HRV-A81, HRV-A82, HRV-A85, HRV-A88, HRV-A89, HRV-A90, HRV-A94, HRV-A95, HRV-A96, HRV-A98, HRV-A100, HRV-A101, HRV-A102 and HRV-A103 (found under the species: Rhinovirus A).

    serotypes HRV-B3, HRV-B4, HRV-B5, HRV-B6, HRV-B14, HRV-B17, HRV-B26, HRV-B27, HRV-B35, HRV-B37, HRV-B42, HRV-B48, HRV-B52, HRV-B69, HRV-B70, HRV-B72, HRV-B79, HRV-B83, HRV-B84, HRV-B86, HRV-B91, HRV-B92, HRV-B93, HRV-B97, and HRV-B99 (found under the species: Rhinovirus B).

    serotypes HRV-C1, HRV-C2, HRV-C3, HRV-C4, HRV-C5, HRV-C6, HRV-C7, HRV-C8, HRV-C9, HRV-C10, HRV-C11, HRV-C12, HRV-C13, HRV-C14, HRV-C15, HRV-C16, HRV-C17, HRV-C18, HRV-C19, HRV-C20, HRV-C21, HRV-C22, HRV-C23, HRV-C24, HRV-C25, HRV-C26, HRV-C27, HRV-C28, HRV-C29, HRV-C30, HRV-C31, HRV-C32, HRV-C33, HRV-C34, HRV-C35, HRV-C36, HRV-C37, HRV-C38, HRV-C39, HRV-C40, HRV-C41, HRV-C42, HRV-C43, HRV-C44, HRV-C45, HRV-C46, HRV-C47, HRV-C48, HRV-C49, HRV-C50 and HRV-C51 (found under the species: Rhinovirus C.)
  • Poliovirus (PV)

    There are three serotypes of poliovirus, PV1, PV2, and PV3. Each has a slightly different capsid protein. Capsid proteins define cellular receptor specificity and virus antigenicity. PV1 is the most common form encountered in nature; however, all three forms are extremely infectious. Poliovirus can affect the spinal cord and cause poliomyelitis.

    Serotypes PV-1, PV-2, & PV-3 found under the species: Enterovirus C

Enterovirus 68 (EV-D68)

EV-D68 (Table 2) is one of more than one hundred types of enteroviruses (Table 1), as discussed previously. It is unenveloped. Unlike all other enteroviruses, EV-D68 displays acid lability and a lower optimum growth temperature, both characteristic features of the human rhinoviruses. It was previously called human rhinovirus 87 by some researchers. 

Virus classification


Group IV ((+)ssRNA)





Enterovirus D
Enterovirus 68

History Of EV-D68

Enterovirus 68 (EV-D68, HEV68, EV68) was first isolated in California in 1962 from four children diagnosed with bronchiolitis and pneumonia. EV-D68 has been rarely reported since that time. As such, the full spectrum of illness that it can cause is unknown.

1962 – 2005
Since EV-D68 was discovered through 2005, there were only 26 confirmed reports of the virus to the CDC.

2008 - 2010
Six clusters (equal to or more than 10 cases) or outbreaks between 2008 - 2010 associated with EV-D68 occurred in the Philippines, Japan, the Netherlands, and the states of Georgia, Pennsylvania and Arizona in the United States. EV-D68 infection presented with symptoms of respiratory illness ranging from relatively mild illness that did not require hospitalization to severe illness requiring intensive care and mechanical ventilation.


  • During October 2008 - March 2009, an outbreak of EV-D68 was detected in the Eastern Visayas region of the Philippines among pediatric patients hospitalized with pneumonia.
  • Clinical samples from 816 patients hospitalized with pneumonia during May 2008 - May 2009 were screened retrospectively for EV-D68 by molecular methods (RT-PCR and partial sequencing).
  • 21 (2.6%) were found to be positive for EV-D68.
  • The virus was first detected in late October 2008, and cases peaked in early December. No cases of EV-D68 related illness were found after March 2009.
  • Among the 21 patients with EV-D68 infection, 17 (81%) were aged 0-4 years.
  • Common signs and symptoms included: cough, difficulty breathing, wheezing, and retractions.
  • Two cases were fatal. 


  • Japan's Infectious Agent Surveillance Report (IASR) system first began to receive sporadic reports of EV-D68 in 2005, with =10 cases identified each year until 2010.
  • During 2010, an increase in EV-D68 cases was observed, with more than 120 cases reported.
  • Most EV-D68 infections occurred during July - October 2010, with detections throughout Japan during this time.
  • Clinical and demographic information was available on only a subset of 11 pediatric patients who were positive for EV-D68. Of these 11 EV-D68 cases, 10 were patients diagnosed with acute respiratory illnesses, such as asthmatic bronchitis or pneumonia, and one in a patient with febrile convulsions.
  • Of the 11 patients, 10 were aged 0-4 years.
  • One fatal case occurred, involving a boy age 4 years in whom EV-D68 was detected by nucleic acid amplification from a pharyngeal swab. The boy, who had been healthy with no underlying disease, arrived at the emergency department in cardiopulmonary arrest and could not be resuscitated.


  • During August - November 2010, EV-D68 was detected within a prospective, hospital-based study of respiratory infections in the northern part of the Netherlands. All rhinovirus-positive samples obtained during September 2009 - January 2011 were sequenced as part of a validation study.
  • Specimens from 24 patients with acute respiratory illness, including pneumonia, asthma exacerbation, and wheezing, were positive for EV-D68. Among the 24 patients, 23 were hospitalized during their illness, and five required intensive care. Three of the infections were acquired while in the hospital. Half of the 24 patients with EV-D68 infection were aged =20 years.
  • Chronic underlying illness was present in approximately 80% of patients.
  • No deaths were reported. 

United States 

  •  Georgia
    • In September 2009, a hospital in Atlanta started using a new, multipathogen testing system (Luminex xTAG Respiratory Viral Panel [RVP], Luminex Corporation, Austin, Texas) for respiratory viral testing in its laboratory. The system can detect several respiratory viruses, including Human Rhinoviruses (HRVs) and enteroviruses. These were identified by the system only as "entero-rhinovirus."
    • During the next respiratory illness season, September 2009 - April 2010, adult patients at the Atlanta hospital facility who were diagnosed with "entero-rhinovirus" appeared to be more ill than those diagnosed with HRV in previous seasons.
    • Nucleic acid sequencing of 68 specimens from the 2009 - 2010 season revealed that 62 (91.2%) contained HRV and six (8.8%) contained EV-D68.
    • Among the six patients with EV-D68, three were aged >50 years and two were immunocompromised. Five patients had fever and four had cough. One patient had abnormal findings on chest radiography that were attributed to cryptococcosis. No other cases were associated with coinfections. Three patients were hospitalized for a median of 4 days. None of the patients required admission to an intensive-care unit (ICU), and none died. 
  • Pennsylvania
    • In mid-September 2009, a pediatric hospital in Philadelphia observed more than twice the proportion of respiratory specimens testing positive for HRV by RT-PCR compared with those seen during previous fall HRV seasons.
    • An investigation identified 390 children treated at the hospital during August - October 2009 from whom at least one respiratory specimen was positive for HRV. Respiratory specimens from 66 of these children were sent to the CDC for further molecular characterization. EV-D68 was identified in 28 (42%) of the specimens. Among the 28 patients with EV-D68 infection, 15 (54%) were aged 0 - 4 years, and 15 were admitted to the ICU. The median duration of hospitalization was 5 days. None of the patients died. 
  • Arizona 
    • During August - September 2010, hospital officials at an isolated community hospital in rural Arizona noted an increase in pediatric admissions for lower respiratory tract illness. During this time, 43% of pediatric admissions were for respiratory illness, compared with a mean of 17% during the same period in the previous three years, a statistically significant difference.
    • Similar illness, characterized by cough and tachypnea or hypoxemia, occurred in 18 patients. Abnormal lung examination results and wheezing, particularly new-onset wheezing, were noted. At least half of children with available chest radiographs had infiltrates.
    • Hospitalization lasted a median of 1.5 days, and no deaths were reported.
    • Despite viral testing and blood cultures performed at the Arizona Department of Health Services on patients with specimens available, no pathogen was detected.
    • Nasopharyngeal specimens of seven patients were sent to the CDC for further testing, and EV-D68 was identified in five of the patients, one of whom also was positive by RT-PCR testing for Streptococcus pneumonia. 

The Centers for Disease Control and Prevention (CDC) learned of these clusters of EV-D68 from public health agencies requesting consultation or diagnostic assistance and from reports presented at scientific conferences. In each cluster, EV-D68 was diagnosed by reverse transcription-polymerase chain reaction (RT-PCR) testing targeting the 5'-nontranslated region, followed by partial sequencing of the structural protein genes, VP4-VP2, VP1, or both, to give definitive, enterovirus type-specific information.

2009 – 2013
EV-D68 has rarely been reported in the United States. The National Enterovirus Surveillance System only received 79 EV-D68 reports during 2009–2013. 

2012 - 2013
EV-D68 was found in 2 of 5 children during a 2012/13 cluster of polio-like disease in California. 

In August 2014, EV-D68 caused clusters of respiratory disease in the United States. According to the Division of Viral Diseases at the National Center for Immunization and Respiratory Diseases EV-D68 "is one of the most rarely reported serotypes, with only 26 reports throughout the 36-year study period (1970 through 2006)."

The outbreak began in 11, mostly Midwestern, states and was first confirmed in Kansas City, Missouri, and Chicago, Illinois.

  • Missouri
    • On August 19, 2014, the CDC was notified by Children's Mercy Hospital in Kansas City, Missouri, of an increase (relative to the same period in previous years) in patients examined and hospitalized with severe respiratory illness, including some admitted to the pediatric intensive care unit. An increase also was noted in detections of rhinovirus/enterovirus by a multiplex polymerase chain reaction assay in nasopharyngeal specimens obtained during August 5 - 19.
    • Nasopharyngeal specimens from most of the patients with recent onset of severe symptoms were sequenced by the CDC Picornavirus Laboratory. EV-D68 was identified in 19 of 22 specimens from Kansas City.
    • Of the 19 patients from Kansas City in whom EV-D68 was confirmed, 10 (53%) were male, and ages ranged from 6 weeks to 16 years (median = 4 years). Thirteen patients (68%) had a previous history of asthma or wheezing, and six patients (32%) had no underlying respiratory illness. All patients had difficulty breathing and hypoxemia, and four (21%) also had wheezing. Notably, only five patients (26%) were febrile. All patients were admitted to the pediatric intensive care unit, and four required bilevel positive airway pressure ventilation. Chest radiographs showed perihilar infiltrates, often with atelectasis. Neither chest radiographs nor blood cultures were consistent with bacterial coinfection. 
  • Illinois
    • On August 23, the CDC was notified by the University of Chicago Medicine Comer Children's Hospital in Illinois of an increase in patients similar to those seen in Kansas City.
    • Nasopharyngeal specimens from most of the patients with recent onset of severe symptoms were sequenced by the CDC Picornavirus Laboratory. EV-D68 was identified in 11 of 14 specimens from Chicago. 
    • Of the 11 patients from Chicago in whom EV-D68 was confirmed, nine patients were female, and ages ranged from 20 months to 15 years (median = 5 years). Eight patients (73%) had a previous history of asthma or wheezing. Notably, only two patients (18%) were febrile. Ten patients were admitted to the pediatric intensive care unit for respiratory distress; two required mechanical ventilation (one of whom also received extracorporeal membrane oxygenation), and two required bilevel positive airway pressure ventilation.

By mid-September 2014 there were 145 suspected cases, including Colorado, Louisiana, Alabama, New York, New Jersey, North Carolina, Michigan, Missouri, Iowa, Illinois, Montana, Kentucky, Kansas, Oklahoma, Indiana, Connecticut, Massachusetts, Rhode Island, and Wisconsin. One case involved a previously asthmatic non-immunocompromised adult. In Canada in September 2014, 49 cases of the virus were confirmed in Alberta, three in British Columbia, and over 100 in Ontario. Health officials reported Los Angeles County's first case of EV-D68 on October 1, 2014. By October 2, 6 more cases had been reported in California: four in San Diego County, and one each in Ventura and Alameda counties.

From mid-August to December 18, 2014, the CDC or state public health laboratories had confirmed a total of 1,152 people in 49 states and the District of Columbia with respiratory illness caused by EV-D68. Five children died.

States with lab-confirmed cases of Enterovirus D68

Seasonal Factors

In the United States, people are more likely to get infected with enteroviruses in the summer and fall. EV-D68 cases have been described to occur late in the enterovirus season, which is typically during the warm months, from summer to autumn (August and September in the Northern hemisphere).


EV-D68 can shed from an infected person's respiratory secretions, such as saliva, nasal mucus, or sputum for 1 to 3 weeks or less. Infected people can shed the virus even if they are asymptomatic.

The virus likely spreads from person to person when an infected person coughs, sneezes, or touches objects or surfaces that have the virus on them and then touches their own eyes, mouth or nose.

Health History: Risk Factors

  • Age

    Infants, children (especially less than 5 years old) and teenagers are more likely to become infected and become sick. They simply have not yet acquired immunity from previous exposures to the enteroviruses. This is also believed to be true for EV-D68. 

    Adults can also become infected with enteroviruses, but they are more likely to have no symptoms or mild symptoms. EV-D68, similar to other enteroviruses, is known to cause infections primarily in children but has been known to infect adults. According to the CDC, approximately a quarter of all EV-D68 cases before 2005 were adults.
  • Children/adults suffering from reactive airway disease
  • Children/adults with asthma or a history of wheezing
  • Children/adults who have weakened immune systems or who are immunosuppressed

Signs And Symptoms

EV-D68 almost exclusively causes respiratory illness which may vary from mild to severe. Respiratory symptoms are more acute among children than adults. Infants, children and teenagers, especially if they have a history of asthma or reactive airway disease can require a trip to the emergency department for treatment and possible admission.

In adults, the symptoms may not be as severe, but in the confirmed cases of EV-D68 from 2008 to 2010, the median length of time adults were hospitalized ranged from 1.5 to five days.
Healthcare providers should consider EV-D68 as a possible cause of acute, unexplained severe respiratory illness.

Initial symptoms are resemble those of the common cold including:

  • a runny nose
  • sore throat
  • cough
  • sneezing
  • fever (some but not all)
  • body and muscle aches

Progression of the disease may lead to more serious symptoms including:

  • difficulty breathing as in pneumonia
  • wheezing
  • hypoxemia
  • reduced alertness
  • reduction in urine production
  • dehydration
  • respiratory failure

Like all enteroviruses, EV-D68 may also cause:

  • variable skin rashes
  • abdominal pain
  • soft stools
  • muscle weakness or paralysis of one or more limbs

Clinical Evaluation And Reporting

When seeing patients, especially children, with respiratory illness, healthcare providers should be aware of EV-D68 as a potential cause. They should consider laboratory testing of respiratory specimens for enteroviruses when the cause of infection in severely ill patients is unclear.

Many hospitals and/or clinics can test suspected patients for enteroviruses, but most are not able to do the testing needed to determine the type of enterovirus. Healthcare providers can approach their state health department for such testing. Healthcare providers should report clusters of severe respiratory illness to state and local health departments.

The CDC recommends that healthcare providers:

  • Consider EV-D68 as a possible cause of acute, unexplained severe respiratory illness, even if the patient does not have fever. For these patients, they should: 
    • Consider laboratory testing of respiratory specimens for enteroviruses.
    • Consider EV-D68 testing of specimens that test positive for enterovirus or rhinovirus. State health departments can be approached for diagnostic and molecular typing for enteroviruses. However, state or local health departments should be contacted before sending the specimens.
  • Report suspected clusters of severe respiratory illness to local and state health departments. EV-D68 is not nationally notifiable, but state and local health departments may have additional guidance on reporting.

Laboratory Testing

EV-D68 can only be diagnosed by doing specific laboratory tests on specimens from a patient’s nose and throat.

Many hospitals and some physicians’ offices can test ill patients to see if they have an enterovirus infection. However, most cannot do specific testing to determine the type of enterovirus, like EV-D68. The CDC and some state health departments can do this sort of testing.

On October 14, 2014, the CDC started using a new, faster laboratory test for detecting EV-D68, allowing the CDC to test and report results within a few days of receiving specimens. The CDC’s new laboratory test is a “real-time” reverse transcription polymerase chain reaction, or rRT-PCR, and it identifies all strains of EV-D68 that were seen this past summer and fall. The new test has fewer and shorter steps than the test that the CDC and some states were using for the EV-D68 2014 outbreak. Also, the new test allows more specimens to be tested at the same time.

Since the outbreak of EV-D68 began in August, the CDC has tested 1163 specimens submitted from around the country. Of the specimens tested by the CDC laboratory from August 1 to October 10, about half have tested positive for EV-D68. About one third have tested positive for a rhinovirus or an enterovirus other than EV-D68. The new laboratory test will allow the CDC to process the approximately one-thousand remaining specimens at a much faster rate.

The CDC Picornavirus Laboratory from mid-September to mid-October 2014 developed and evaluated the EV-D68-specific rRT-PCR assay. The assay and protocol are primarily focused on evaluating respiratory disease due to EV-D68. 

For protocols about using the EV-D68 Real-Time RT-PCR assay, please see:

Before sending specimens for diagnostic and molecular typing:

  • Contact your state or local health department.
  • Submit specimens (nasopharyngeal and oropharyngeal swabs are preferred or any other type of respiratory specimens) using:

and complete specimen submission form 50.34

  • Complete a patient summary form for each patient for whom specimens are being submitted. Please send a printed copy of the form at the same time as the specimen submission.


There is no specific treatment and no vaccine, so EV-D68 has to run its course. There are no antiviral medications currently available for people who become infected with EV-D68. The antiviral drugs pleconaril, pocapavir, and vapendavir have significant activity against a wide range of enteroviruses and rhinoviruses. The CDC has tested these drugs for activity against currently circulating strains of EV-D68, and none of them has activity against EV-D68 at clinically relevant concentrations. A 2015 study suggested the antiviral drug pleconaril may be useful for the treatment of EV-D68.

Clinical care is directed against symptoms (symptomatic treatment): bronchodilators, oxygen therapy up to and including mechanical ventilation, antibiotics for coinfections where appropriate, pain control if necessary, fever control if necessary. Most people recover completely. However, some need to be hospitalized, and some have died as a result of the virus.

Five EV-D68 paralysis cases were unsuccessfully treated with steroids, intravenous immunoglobulin and/or plasma exchange. The treatments had no apparent benefit as no recovery of motor function was seen.

Infection Control Recommendations

Healthcare providers in healthcare settings should strive to prevent the spread of EV-D68:

Infection control precautions should include Standard, Contact, and Droplet Precautions.

Although non-enveloped viruses such as EV-D68 may be less susceptible to alcohol than enveloped viruses or vegetative bacteria, alcohol-based hand rub (ABHR) offers benefits in skin tolerance, compliance, and, especially when combined with glove use, overall effectiveness for a wide variety of healthcare pathogens. Therefore, upon removal and prior to donning gloves, perform hand hygiene using either ABHR or soap and water.

As EV-D68 is a non-enveloped virus, environmental disinfection of surfaces in healthcare settings should be performed using a hospital-grade disinfectant with an EPA label claim for any of several non-enveloped viruses (e.g. norovirus, poliovirus, rhinovirus). Disinfectant products should be used in accordance with the manufacturer’s instructions for the specific label claim and in a manner consistent with environmental infection control recommendations.

Infection control recommendations for other than health care settings such as home, office, schools etc. include Clorox products. Clorox has a broad portfolio of EPA-registered surface disinfectants that can be used to clean and disinfect frequently touched surfaces. Although currently Clorox does not have any products that have been tested against EV-D68, the following products meet the criteria established by the CDC. (Table 3)

Table 3: Clorox Products Eligible for Limited EV-D68 Usage
Criteria established by the CDC: Must be an EPA-registered disinfectant with claims against:
  • Pseudomonas aeruginosa
  • At least one non-enveloped virus (Norovirus, Adenovirus, Rotavirus, Rhinovirus, Poliovirus, Hepatitis A Virus
EPA Reg. No. Product Names


Clorox Clean-Up Cleaner with Bleach

Clorox Clean-Up Cleaner + Bleach1


Clorox Disinfecting Bathroom Cleaner

Tilex Bathroom Cleaner


Clorox Commercial Solutions Clorox Disinfecting Bathroom Cleaner

Clorox Commercial Solutions Tilex Soap Scum Remover & Disinfectant


Clorox Disinfecting Wipes


Clorox Disinfecting Wipes1

Clorox Disinfecting Wipes3

Clorox Disinfecting Wipes4


Clorox Toilet Bowl Cleaner with Bleach

Clorox Toilet Bowl Cleaner – Clinging Bleach Gel


Clorox Regular-Bleach1


Clorox Commercial Solutions Clorox Germicidal Bleach1


Clorox Germicidal Bleach 1


Clorox Kitchen Cleaner + Bleach1

Clorox CareConcepts Germicidal Bleach Spray


Clorox Healthcare Bleach Germicidal Cleaner


Dispatch Hospital Cleaner Disinfectant Towels with Bleach

Clorox CareConcepts Germicidal Bleach Wipes


Clorox Commercial Solutions Clorox Disinfecting Wipes

Clorox CareConcepts Germicidal Non-Bleach Wipes


Clorox Healthcare Bleach Germicidal Wipes


Clorox Commercial Solutions Clorox Toilet Bowl Cleaner with Bleach1


Clorox Commercial Solutions Clorox Clean-Up Disinfectant Cleaner with Bleach1


Clorox Broad Spectrum Quaternary Disinfectant Cleaner

Clorox CareConcepts Germicidal Non-Bleach Spray1


Clorox Commercial Solutions Clorox Disinfecting Spray


Clorox Commercial Solutions Clorox Hydrogen Peroxide Disinfecting Cleaner

Clorox Healthcare Hydrogen Peroxide Cleaner Disinfectant


Clorox Commercial Solutions Clorox Hydrogen Peroxide Disinfecting Wipes

Clorox Healthcare Hydrogen Peroxide Cleaner Disinfectant Wipes


Clorox CareConcepts Germicidal Bleach


Clorox Commercial Solutions Clorox 4-in-1 Disinfectant & Sanitizer

Clorox Healthcare Citrace Hospital Disinfectant & Deodorizer

Clorox CareConcepts Disinfecting & Deodorizing Spray


Clorox 4 in One Disinfecting Spray


Clorox Pro Quaternary All-Purpose Disinfectant Cleaner1


Although there are no vaccines to prevent EV-D68 infections, healthcare providers should encourage all patients to follow these prevention steps:

  • Avoid those who are sick
  • Wash hands often with soap and water for 20 seconds
  • Cover the nose and mouth when sneezing or coughing
  • Avoid touching eyes, nose, and mouth with unwashed hands
  • Avoid kissing, hugging, and sharing cups or eating utensils with people who are sick
  • Disinfect frequently touched surfaces, such as toys and doorknobs, especially if someone is sick
  • Stay home when you are sick

Children/adults with asthma or suffering from reactive airway disease are at greater risk for severe symptoms from EV-D68 and other respiratory illnesses. The CDC recommends that healthcare providers:

  • Discuss and update the patient’s asthma action plan.
  • Encourage the patient to take their prescribed asthma medications as directed, especially long term control medication(s).
  • Encourage the patient to keep their reliever medication with them.
  • Encourage the patient to get the influenza vaccine when available. The CDC recommends everyone age 6 months and older get an annual influenza vaccination.
  • Stress that if the patient develops new or worsening symptoms, they should be encouraged to follow the steps of their asthma action plan. If their symptoms do not resolve, they should call their primary care provider as soon as possible or go to their nearest emergency department.
  • Encourage parents to educate their child’s caregiver and/or teacher about their child’s condition. Parents should make sure that they know how to help if the child experiences any symptoms related to asthma.


Surveillance Systems

Information on cases and outbreaks of enterovirus infection is collected in the United States using two surveillance systems:

  • National Respiratory and Enteric Virus Surveillance System (NREVSS) is a voluntary, laboratory-based surveillance system that has included enterovirus reporting since July 2007. This system is used to track the number of enterovirus tests that are done and the proportion that are positive, by specimen type, location, and when they were collected. Serotyping, demographic data, and clinical data are not reported.
  • National Enterovirus Surveillance System (NESS) is a passive, voluntary, laboratory-based system that collects basic data on specimens that are positive for enterovirus, including serotype.

The CDC's Role In EV-D68

The CDC continues to:

  • collect information from states to assess the situation to better understand:
    • EV-D68 and the illness caused by the virus
    • how widespread EV-D68 infections may be within each state and the populations affected
  • help states with diagnostic and molecular typing for EV-D68
  • work with state and local health departments and clinical and state laboratories to:
    • enhance their capacity to identify outbreaks
    • perform diagnostic and molecular typing tests to improve detection of enteroviruses and enhance surveillance
  • provide information to healthcare professionals, policymakers, general public, and partners in numerous formats, including Morbidity and Mortality Weekly Reports (MMWRs), health alerts, websites, social media, podcasts, infographics, and presentations

The CDC obtained one complete genomic sequence and six nearly complete genomic sequences from viruses representing the three known strains of EV-D68 that are causing infection at this time. Comparison of these sequences to sequences from previous years shows they are genetically related to strains of EV-D68 that were detected in previous years in the United States, Europe, and Asia. The CDC has submitted the sequences to GenBank to make them available to the scientific community for further testing and analysis.

On October 14, 2014 the CDC started using a new, faster laboratory test for detecting EV-D68, allowing the CDC to test and report results within a few days of receiving specimens. The CDC’s laboratory test is a “real-time” reverse transcription polymerase chain reaction, or rRT-PCR, and it identifies all strains of EV-D68 that circulated during summer and fall 2014. It has fewer and shorter steps than the test that the CDC and some states were using previously during this EV-D68 outbreak.

The CDC has made the protocols publicly available on its EV-D68 for Health Care Professionals web page and is exploring options for providing test kits to state public health labs.

A "Fly In The Ointment": Acute Flaccid Myelitis

Acute flaccid myelitis has been formerly described as “acute flaccid paralysis with anterior myelitis” or “polio-like syndrome”. It is an acute neurologic illness with focal limb weakness which occurs in children. Its etiology is unknown.

EV-D68 has been suspected as the leading candidate for the cause of this rare polio-like syndrome since two California children who tested positive for the virus had  muscle weakness or paralysis of one or more limbs reaching peak severity within 48 hours of onset. "Recovery of motor function was poor at 6-month follow-up."

As of October 2014 the CDC was investigating 10 cases of paralysis and/or cranial dysfunction in Colorado and other reports around the country, coinciding with the increase in EV-D68 activity. As of October 23, 2014 it was believed that the actual number of cases might be 100 or more.

Clinical Description of Acute Flaccid Myelitis

A summary of the condition was issued by the United States Centers for Disease Control as part of a September 26, 2014 health advisory:

August 9 – September 17, 2014

  • Nine cases of acute neurologic illness among pediatric patients were investigated by the CDPHE, Children's Hospital Colorado, and CDC:
    • children aged 1–18 years (median age 10 years)
    • most of the children were from the Denver metropolitan area.
    • all were hospitalized
    • Common features included acute focal limb weakness with specific findings on magnetic resonance imaging (MRI) of the spinal cord consisting of non-enhancing lesions largely restricted to the gray matter. In most cases, these lesions spanned more than one level of the spinal cord
    • some also had acute cranial nerve dysfunction with correlating non-enhancing brainstem lesions on MRI
    • none had any cortical, subcortical, basal ganglia, or thalamic lesions on MRI.
    • most children reported a febrile respiratory illness in the two weeks preceding development of neurologic symptoms
    • in most cases, cerebrospinal fluid (CSF) analyses demonstrated mild-moderate pleocytosis (increased cell count in the CSF) consistent with an inflammatory or infectious process
    • none of the children experienced altered mental status or seizures

October 13, 2014

  • a report in AAFP News, citing a CDC Morbidity and Mortality Weekly Report and a CDC Clinician Outreach and Communication Activity (COCA) conference call, noted that many cases had neck, back, or extremity pain, but otherwise those affected generally had normal sensation in their limbs. A few participants in the conference call discussed whether pain, later abating, might precede the onset of paralysis.

October 21, 2014

  • a report in Neurology News described outbreaks in California and Colorado, suggesting that the number of cases might be 100 or more nationwide
  • diagnosis included:
    • a good medical history
    • MRI imaging
    • elimination of transverse myelitis or Guillain-Barré syndrome as potential causes
  • the largest known cluster of cases was in Colorado, with 29 total, 12 of which were reported since August 2014
  • the report quoted Jayne M. Ness, an associate professor at the University of Alabama at Birmingham, speaking of four cases treated at Children's of Alabama, three of which involved a complete inability to move one arm, reminiscent of peripheral nerve injury
    • shared symptoms included:
      • severe arm flaccidity, “if the arm is lifted up and let go, it literally drops”
      • sensation is usually intact. There might be slightly decreased sensation in the other arm
      • no mental status changes
      • spine MRIs showed gray matter involvement.
  • The report quoted Jean-Baptiste Le Pichon, a child neurologist at Children’s Mercy Hospital, where three or possibly four cases had occurred since August
    • shared symptoms included:
      • sudden onset of flaccid paralysis in single or multiple limbs with sensation remaining intact
      • MRIs all showed uniformly a signal increase in the ventral horns of the spinal cord — this is exactly the same region of the spinal cord affected in polio
      • almost all of the patients had an increase in their white blood cells in the cerebrospinal fluid
      • some of the patients had brainstem findings and cranial-nerve findings reminiscent of polio

October 23, 2014

  • A report by Jean-Baptiste Le Pichon for The Atlantic covered a special session at an annual meeting of the Child Neurology Society, where a show of hands suggested that the 250 participants had collectively treated more than 100 cases.
  • Though a third of the participants raised their hands when asked if they had seen a recent case, only two hands were raised when they were asked if they had seen a complete recovery.
  • Children's Hospital of Philadelphia chief of neurology Brenda Banwell indicated that her hospital had seen at least 10 cases. At that time the nationwide CDC count was given as 51.
  • Child neurologist Keith Van Haren of the Stanford University School of Medicine suggested an even higher number: "I was on a conference call a few weeks ago with about 50 doctors from medical centers across North America. Every center had seen cases. That puts the numbers real high, real fast."

Of 64 patients meeting the CDC criteria before October 29, 2014, 80% had had a preceding respiratory illness and 75% reported fever in the days leading up to limb weakness, the onset of which was generally abrupt. By November 20, 2014 the number of confirmed cases stood at 88 from 29 states.

Possible Causes of Acute Flaccid Myelitis

The suspected cause of the 2014 cases is a strain of enterovirus D. Most enteroviruses and rhinoviruses cause only common cold symptoms. The September 26, 2014 the CDC health advisory that described the cases continued with the identification of EV-D68, a member of the enterovirus D species, as a suspected cause.

Cerebral spinal fluid (CSF) testing to date had been negative for West Nile virus and other enteroviruses, including poliovirus. Nasopharyngeal specimens were positive for rhinovirus/enterovirus in six out of eight patients that were tested. Of the six positive specimens, four were typed as EV-D68, and the other two were pending typing results. Testing of other specimens continued. Eight out of nine children had been confirmed to be up to date on polio vaccinations. Epidemiologic and laboratory investigations of these cases are ongoing.

The Morbidity and Mortality Weekly Report (MMWR) noted the difficulty of establishing causation by EV-D68:

  • “This cluster of acute neurologic illnesses occurred against a backdrop of detection of EV-D68 causing severe respiratory disease in many parts of the United States, including Colorado. There are two case reports in the literature of EV-D68 causing neurologic illness (acute flaccid paralysis and encephalomyelitis) as evidenced by detection of EV-D68 in the CSF. However, given the current suspected widespread circulation of EV-D68 respiratory infections in Colorado, and the antecedent respiratory illness in most of these children, the detection of EV-D68 in nonsterile upper respiratory tract specimens in those with neurologic illness might be coincidental. Epidemiologic and laboratory investigations of these cases are ongoing”.

Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke and president of the International Society for NeuroVirology, compared the situation to the prolonged investigations that led to confirmation of HIV as the cause of AIDS. In response to the suggestion that the enterovirus might be taking over the role of polio, Nath said that enterovirus 68 was far less virulent and spread much more slowly than polio, and that, unlike in polio, only a few cases of paralysis were seen per thousand children infected. He also suggested that adults with respiratory diseases should also be evaluated for neurologic deficits, and that infectious disease should be considered as a cause when patients presented with neurologic symptoms.

Treatment of Acute Flaccid Myelitis

There is no known treatment for acute flaccid myelitis. It has not been established whether steroids are helpful or harmful.  Plasmaphoresis, intravenous immunoglobulin, and experimental antiviral drugs have been attempted on a trial basis, but have not been reported to be effective.

On November 7, 2014 the CDC issued "Interim Considerations for Clinical Management of Patients with Acute Flaccid Myelitis", based on "consensus guidance drawn from experts in infectious diseases, neurology, pediatrics, critical care medicine, public health epidemiology and virology." Mark Sawyer of the American Academy of Pediatrics, who contributed to the guidance, was quoted by the organization's newsletter:

  • “The most important issue summarized in the document is that there is no clear evidence that therapies intended to modify the immune system (e.g., corticosteroids, immune globulin, plasmapheresis) have a beneficial effect in this condition. Plasmapheresis is specifically not recommended because the potential for harm is significant in the absence of any evidence of benefit.” 

Outcomes: Acute Flaccid Myelitis

Six of ten children in Denver were sent home for outpatient treatment. Some with mild symptoms have recovered from temporary limb weakness, while the fate of those more severely affected remains unclear. Intensive physical therapy and occupational therapy may be beneficial for recovery.


In summary, the Enterovirus genus includes twelve species within which are the serotypes for each species. The serotypes are astounding in number. EV-D68 is only one of the total of known serotypes and during the 2014 EV-D68 outbreak at least three strains of EV-D68 have been discovered. Years of research and development will ensue before a vaccine will be discovered to stop the enteroviruses in their tracts. Until then treatment for EV-D68 infection will remain symptomatic. So with the coming of the enterovirus season, summer and fall 2015, remember EV-D68 usually rears its ugly head in August and September. So, PREVENTION, PREVENTION, PREVENTION proactively.



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This course is applicable for the following professions:

Advanced Registered Nurse Practitioner (ARNP), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Registered Nurse (RN)


Advance Practice Nurse Pharmacology Credit, CPD: Practice Effectively, Infection Control/Disease, Medical Surgical

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