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Enterovirus D68 (EV-D68): Unraveling the Mystery

1 Contact Hour - 1 Pharmacology Hour
This course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP), Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Nursing Student, Registered Nurse (RN)
This course will be updated or discontinued on or before Monday, December 20, 2021
Course Description
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.
CEUFast Inc. did not endorse any product, or receive any commercial support or sponsorship for this course. The Planning Committee and Authors do not have any conflict of interest.

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To earn of certificate of completion you have one of two options:
  1. Take test and pass with a score of at least 80%
  2. Reflect on practice impact by completing self-reflection, self-assessment and course evaluation.
    (NOTE: Some approval agencies and organizations require you to take a test and self reflection is NOT an option.)
Author:    Pamela Downey (MSN, ARNP)

Outcomes

≥90% of participants will identify and react to patients with symptoms of EV-D68.

Objectives

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

  1. Describe infection control measures recommended to prevent the spread of EV-D68 infections in healthcare and non-healthcare settings.
  2. Relate the risk factors identified during the health history, which predispose individuals to enteroviral/EV-D68 infections.
  3. Describe the signs and symptoms of EV-D68 infection.
  4. Relate the treatment regimen for individuals experiencing EV-D68 infection.
  5. Describe acute flaccid myelitis, including signs and symptoms, testing, diagnosis, treatments, outcomes, and possible causations.

Introduction to Enterovirus

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.1

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.1 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 get tested.2

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.1

The pain and suffering caused by the enteroviruses and the upsurge specifically in EV-D68 infections have caused the world to pause, back up and investigate retrospectively why there has been an 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.

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 five 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 based on antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes based on reduced or nonreciprocal cross-neutralization between variant strains.

Based on their pathogenesis in humans and animals, the enteroviruses were initially 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: ENTEROVIRUSES3
Virus classification
Group: Group IV ((+)ssRNA)
Order: Picornavirales
Family: Picornaviridae
Species 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 species3:

  • 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-A1, CV-A11, CV-A13, CV-A17, CV-A19, CV-A20, CV-A21, CV-A22, and CV-A24 (found under the species: Enterovirus C).
    • Serotypes CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, CV-B6, and CV-A9 (found under the species: Enterovirus B).
    • 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).
  • 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 lower optimum growth temperature, both characteristic features of the human rhinoviruses. It was previously called human rhinovirus 87 by some researchers.

Table 2: ENTEROVIRUS 683
Virus classification
Group: Group IV ((+)ssRNA)
Family: Picornaviridae
Genus: Enterovirus
Species Enterovirus D
Subtype Enterovirus 68

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 typical during the warm months, from summer to autumn (August and September in the Northern hemisphere).

Transmission

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 five 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 resemble those of the common cold including4:

  • 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 including4:

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

Like all enteroviruses, EV-D68 may also cause4:

  • 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 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 providers5:

  • Consider EV-D68 as a possible cause of acute, unexplained severe respiratory illness, even if the patient does not have a 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 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.5

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.

Before sending specimens for diagnostic and molecular typing:

Treatment

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-D68.5

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 needed. 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 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-D686:

  • 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 before 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.6 (Table 3)

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
Table 3: Clorox Products Eligible for Limited EV-D68 Usage
EPA Reg. No.Product Names
5813-21 Clorox® Clean-Up Cleaner with Bleach Clorox® Clean-Up Cleaner + Bleach1
5813-40 Clorox® Disinfecting Bathroom Cleaner Tilex® Bathroom Cleaner
5813-40-67619 Clorox® Commercial Solutions Clorox Disinfecting Bathroom Cleaner Clorox® Commercial Solutions Tilex Soap Scum Remover & Disinfectant
5813-58 Clorox® Disinfecting Wipes
5813-79* Clorox® Disinfecting Wipes1 Clorox® Disinfecting Wipes3 Clorox® Disinfecting Wipes4
5813-89 Clorox® Toilet Bowl Cleaner with Bleach Clorox® Toilet Bowl Cleaner – Clinging Bleach Gel
5813-100 Clorox® Regular-Bleach1
5813-100-67619 Clorox® Commercial Solutions Clorox Germicidal Bleach1
5813-102 Clorox® Germicidal Bleach 1
5813-105 Clorox® Kitchen Cleaner + Bleach1 Clorox® CareConcepts Germicidal Bleach Spray
56392-7 Clorox® Healthcare Bleach Germicidal Cleaner
56392-8 Dispatch® Hospital Cleaner Disinfectant Towels with Bleach Clorox® CareConcepts Germicidal Bleach Wipes
67619-9 Clorox® Commercial Solutions Clorox Disinfecting Wipes Clorox® CareConcepts Germicidal Non-Bleach Wipes
67619-12 Clorox® Healthcare Bleach Germicidal Wipes
67619-16 Clorox® Commercial Solutions Clorox Toilet Bowl Cleaner with Bleach1
67619-17 Clorox® Commercial Solutions Clorox Clean-Up Disinfectant Cleaner with Bleach1
67619-20 Clorox® Broad Spectrum Quaternary Disinfectant Cleaner Clorox® CareConcepts Germicidal Non-Bleach Spray1
67619-21 Clorox® Commercial Solutions Clorox Disinfecting Spray
67619-24 Clorox® Commercial Solutions Clorox® Hydrogen Peroxide Disinfecting Cleaner Clorox® Healthcare Hydrogen Peroxide Cleaner Disinfectant
67619-25 Clorox® Commercial Solutions Clorox Hydrogen Peroxide Disinfecting Wipes Clorox® Healthcare Hydrogen Peroxide Cleaner Disinfectant Wipes
67619-26 Clorox® CareConcepts Germicidal Bleach
67619-29 Clorox® Commercial Solutions Clorox 4-in-1 Disinfectant & Sanitizer Clorox® Healthcare Citrace Hospital Disinfectant & Deodorizer Clorox® CareConcepts Disinfecting & Deodorizing Spray
67619-29-5813 Clorox® 4 in One Disinfecting Spray
1839-166-67619 Clorox® Pro Quaternary All-Purpose Disinfectant Cleaner1

Prevention/Education

Although there are no vaccines to prevent EV-D68 infections, healthcare providers should encourage all patients to follow these prevention steps6:

  • 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 providers7:

  • 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 six 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 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 systems1:

  • 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 to1:

  • Collect information from states to assess the situation to understand better:
    • 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.8"

As of October 2014, the CDC was investigating 10 cases of paralysis and 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 ten 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”
        • the sensation is usually intact. There might be slightly decreased sensation on 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. 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.8

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.8

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 the 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 the 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. Plasmapheresis, 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.

Conclusion

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.

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References

  1. Center for Disease Control and Prevention. Enterovirus D68. Updated November 14, 2018 Retrieved November 16, 2019. Visit Source.
  2. The transverse myelitis association. An update on Outbreak of Paralysis in US: Acute Flaccid Myelitis. Published 2014-10-16. Accessed 2019-11-14. Visit Source.
  3. Lauinger, I. L.; Bible, J. M.; Halligan, E. P.; Aarons, E. J.; MacMahon, E.; Tong, C. Y. W. (2012). "Lineages, Sub-Lineages and Variants of Enterovirus 68 in Recent Outbreaks". PLoS ONE 7 (4): e36005.
  4. AAP News (The American Academy of Pediatrics).  CDC continues investigation of neruologic illness; will issue guidelines. Published October 3, 2014. Retrieved October 6, 2014. Visit Source.
  5. Modlin, J. Enterovirus and parechoviruse infections: Clinical features, laboratory diagnosis, treatment, and prevention. UpToDate. Published. 10/25/18. Accessed 11/16/19.
  6. CDC. "Guidelines for Environmental Infection Control in Health-Care Facilities". 10/2/19. Retrieved 11/16/19. Visit Source.
  7. UpToDate. Patient education: Enterovirus D68 (The Basics). UpToDate. Updated 11/8/19. Retrieved 11/16/19. Visit Source.
  8. Migita, R. Etiology and evaluation of the child with weakness. UpToDate. Update: 10/8/19. Accessed11/16/19. Visit Source