Enterovirus Associated with "Polio-like Syndrome" in Pediatric Patients

Following an outbreak of acute flaccid myelitis (AFM) identified at Children’s Hospital Colorado in Aurora over thee months in 2014, a potential association has been found between enterovirus D68 (EV-D68) infection and AFM in pediatric patients, according to the results of a study published recently in Emerging Infectious Diseases.¹

The study was presented by first author Negar Aliabadi, MD, from the Epidemic Intelligence Service and Division of Viral Diseases at the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC) in Atlanta, and his colleagues. In describing the rationale for the study, Dr. Aliabadi told Contagion, "Since August 2014, when CDC began receiving an increase in reports of acute flaccid myelitis (AFM), we have been investigating cases and clusters of this illness to better understand potential causes and how often the illness occurs. The increase in reported AFM cases occurred around the same time as a national outbreak of severe respiratory illness caused by EV-D68, a type of enterovirus. The CDC has tested many different specimens collected from children with AFM for a wide range of pathogens that can result in AFM, including enteroviruses, some of which are known to cause neurologic illness. However, to date, we have not found a definitive link to EV-D68. The CDC conducted this study of the Colorado AFM cases to better understand this illness, and to determine if there was any epidemiologic association between EV-D68 infection and AFM."

To further investigate a possible epidemiologic association between EV-D68 and AFM, Dr. Aliabadi and his colleagues conducted a retrospective case—control study of children who had nasopharyngeal specimens collected for the detection of respiratory pathogens in Colorado during the epidemiologic weeks when confirmed AFM cases were identified. The presence of EV-D68 in these specimens was assessed and compared between the 11 case-patients and two groups of control children.

"As described above, the CDC conducted this study with the expectation of learning more about AFM and the possible causes. The case-control study showed an epidemiologic association between EV-D68 and AFM. Between August 8, 2014, and October 14, 2014, 11 children were identified at Children’s Hospital Colorado as having characteristic symptoms of acute flaccid myelitis (AFM): acute limb weakness with abnormal clinical and radiologic findings. Ten of the eleven children had a respiratory illness preceding AFM and four had nasal specimens test positive for EV-D68. We found that children with AFM were 10 times more likely to have EV-D68 infection in the nasal cavity as compared to control groups of children tested for a respiratory illness who were seen in the emergency department," Dr. Aliabadi said.

Regarding the broader implications of his team's study results, Dr. Aliabadi told Contagion, "This is only one study, and this was the first epidemiologic study of the 2014 AFM cases. The study showed an epidemiological association between EV-D68 and AFM. However, an association does not prove that EV-D68 caused AFM in this cluster of cases in Colorado given the limitations of the study. AFM is rare, and there were only 11 cases available to be enrolled in this study. Although EV-D68 was detected in the nasal cavity of 4 children with AFM, it was not detected in cerebrospinal fluid (CSF). Detection of EV-D68 in the nasal cavity does not prove causation of AFM. Virus detected in the CSF would have been the most definitive evidence to link AFM to EV-D68. These data suggest a possible causal link, but there is still a gap in epidemiologic data and data from extensive lab testing. Continued surveillance and additional targeted epidemiologic studies are needed. CDC will continue to investigate AFM cases, risk factors, and possible causes of this illness. We understand that Americans may be concerned about these illnesses. Severe illness is always a concern to us, especially when children are affected. We will continue to share information as soon as we have it, and post updates on our website. We encourage clinicians to continue to be vigilant and immediately report any patients who meet the clinical case definition for AFM to their state or local health department."

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.

References

1. Aliabadi N, Messacar K, Pastula DM, et al. Enterovirus D68 infection in children with acute flaccid myelitis, Colorado, USA, 2014. Emerg Infect Dis. 2016 Aug. DOI: 10.3201/eid2208.151949. [Epub ahead of print].