ID Consult

Enterovirus D68 – An emerging threat to child health


In August 2014, we first heard of increased pediatric cases of severe respiratory tract disease, many requiring management in the ICU, and of acute flaccid myelitis/paralysis (AFM) of unknown etiology from many states across the United States. Concurrently with this outbreak in the United States, similar clinical cases were reported in Canada and Europe. Subsequently, enterovirus D68 was confirmed in some, but not all, of the paralyzed children. Although new to many of us, enterovirus D68 was already known as an atypical enterovirus sharing many of its structural and chemical properties with rhinovirus. For example, it most often was reported from respiratory samples and less common from stool samples. It also had been associated with clusters of respiratory disease since 2000 and a 2008 case of fatal AFM.

Dr. Stephen I. Pelton

Dr. Stephen I. Pelton

The 2014 outbreak in the United States was associated with a broad range of respiratory illnesses. Selection bias likely overdetected severe illness, but an increase in hospitalizations and admissions to the pediatric ICU among children was observed. Coughing (38%), fever (24%), wheezing (approximately 21%), and pneumonia (13%) were the most common symptoms of D68 infection. Children at highest risk were those with underlying comorbidity, especially those with underlying asthma, chronic lung disease, or immunocompromising conditions.

There were 120 cases of AFM, coinciding with the nationwide outbreak of enteroviral D68 disease, reported in 2014. The Centers for Disease Control and Prevention has evaluated the cerebrospinal fluid in many of these cases, and no pathogen has consistently been detected. The children were mostly school age, aged 7-11 years, presented with acute, febrile respiratory illness followed by acute onset of cranial nerve dysfunction or flaccid paralysis of one or more limbs. The CSF revealed mild pleocytosis, most often with mild elevation of protein and a normal glucose. However, the MRI was distinctly abnormal with focal lesion in the cranial nerve nuclei (in those with bulbar dysfunction) and/or in the anterior horn or spinal cord gray matter. Long-term prognosis is unknown, although most patients have persistent weakness, despite some improvement, to date.

In 2016, the CDC has reported an increase in cases after a decline in 2015 despite the absence of epidemic respiratory tract disease in the United States from enterovirus D68. In the Netherlands, an increase in respiratory disease from enterovirus D68 in children and adults also has been reported since June 2016. Respiratory disease has been observed in children as young as 3 months of age, and most of the children have underlying comorbidity, many with asthma or other pulmonary conditions. Thirteen of 17 (77%) cases in children have required ICU admission, while most of the adult cases were mild and influenzalike. One child developed bulbar dysfunction and limb weakness.

AFM cases by year of illness onset, 2014-2016
Current management relies on supportive care including mechanical ventilation, feeding support, and rehabilitation therapies to prevent muscle atrophy and contractures. None of the current antivirals in clinical development for enteroviral or rhinovirus infections (pleconaril, vapendavir, or pocapavir) have been found to have significant in vitro activity against the circulating (2014) strains of enterovirus D68. Fluoxetine, which is currently FDA licensed for depression, demonstrates in vitro activity against circulating strains of enterovirus D68 through an unknown mechanism, although no clinical data about use in enteroviral D68 infection is reported. Intravenous immunoglobulin has neutralizing antibodies to the 2014 outbreak strains of enterovirus D68, but no clinical evidence is available to suggest a dramatic effect on disease course. Intravenous immunoglobulin has been used in immunocompromised newborns with severe and prolonged enteroviral infection and could have a potential role in immunocompromised patients with D68 infection.

Enterovirus D68 infection should be suspected in children with moderate to severe respiratory tract infection or acute onset bulbar or flaccid paralysis of unknown etiology, especially in summer and fall. In such cases, respiratory specimens (nasopharyngeal or oral swabs or wash, tracheal secretions or bronchoalveolar lavage) should be obtained. Increasingly, hospitals and laboratories can perform multiplex polymerase chain reaction testing for enterovirus/rhinovirus. However, most do not determine the specific enterovirus. CDC and some state health departments use real-time reverse transcription polymerase chain reaction (rRT-PCR), which enables reporting of specific enterovirus species within days. CDC recommends that clinicians consider enterovirus D68 testing for children with unknown, severe respiratory illness or AFM. Details for sending specimens should be available from your state’s Department of Public Health website or the CDC.

Prevention strategies may be critical for limiting the spread of enterovirus D68 in the community. The CDC recommends:

  • Wash your hands often with soap and water for 20 seconds.
  • Avoid touching your eyes, nose and mouth with unwashed hands.
  • Avoid close contact such as kissing, hugging, and sharing cups with people who are ill.
  • Cover your coughs and sneezes with a tissue or shirt sleeve, not your hands.
  • Clean and disinfect frequently touched surfaces, such as toys and doorknobs, especially if someone is sick.
  • Stay home when you are ill.

In 2014, it was speculated that the epidemic might have been a one-time event. It now appears more likely that enterovirus D68 activity has been increasing since 2000, and that children and immunocompromised hosts will be at greatest risk because of a lack of neutralizing antibody. Ongoing enterovirus surveillance will be critical to understand the potential for severe respiratory disease as will the development of new and effective antivirals. A vaccine for enterovirus 71 recently demonstrated efficacy against hand, foot, and mouth disease in children and may provide insights into the development of vaccines against enterovirus D68.


Lancet Infect Dis. 2016 May;16(5):e64-75

Emerg Infect Dis. 2017 Jan;23(1):140-3.

J Med Virol. 2016 May;88(5):739-45

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. Email him at

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