Significant Morbidity and Mortality Associated With Enterovirus 71 in Children

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EV71 has been associated with significant morbidity and mortality in children.
EV71 has been associated with significant morbidity and mortality in children.

Initial presentation of enterovirus (EV) 71 may be suggestive of the disease course and outcomes, reported investigators of a prospective study of the 2013 outbreak of EV71 at the Sydney Children's Hospital Network in Sydney, Australia, in an online edition of JAMA Neurology.

The outbreak affected 61 children (ages 0.3 to 5.2 years) over a 30-day period in January of 2013 and resulted in 4 deaths. A prospective study conducted across the 2 hospitals involved identified a range of different presentations including combinations of myoclonic jerks (86%), ataxia (54%), vomiting (54%), limb weakness (40%), truncal weakness (39%), urinary retention (29%), seizures (22%), and cranial nerve dysfunction (7%), all appearing to originate in the brainstem and spinal cord. All of the children in the study experienced fever. Additionally, 9 of the 57 survivors (16%) showed signs of autonomic dysregulation including shock, tachycardia/bradycardia, hypertension or hypotension, and respiratory distress.

Severe brain involvement was evident in the majority of patients; 23 (40%) were identified as having encephalomyelitis, 20 (35%) with brainstem encephalitis, 6 (11%) with encephalitis, 4 (7%) with acute flaccid paralysis, and 4 (7%) with autonomic dysfunction and pulmonary edema.

Viral Distribution

Viral infection was distributed across a range of sites, consistent with the many clinical manifestations reported, and the investigators determined that clinical progression was often indicative of multisite involvement.

Magnetic resonance imaging (MRI) studies of the brain obtained for 38 of the 57 survivors, based on clinical discretion according to symptomatology, showed abnormalities in 24 patients (63%) in the dorsal brainstem region, including the central mid-brain, the posterior medulla oblongata and pons, as well as in the dentate nuclei portion of the cerebellum. Abnormalities were also identified in 27 of 34 patients (79%) who underwent spinal MRI.

The investigators examined samples taken from blood, feces, and cerebrospinal fluid (CSF); rectal and throat swabs; and collection of nasal fluid. Although diagnostic yields were lower in CSF in general (14%), 100% of children with encephalitis who had CSF samples taken (5) tested positive for EV71 in CSF.  Diagnostic yields were higher for other patients on fecal samples (95%), rectal swabs (95%), and throat swabs (85%).

Treatment Effect and Outcomes

Of the 57 children who survived, 29 (51%) received immunomodulatory treatment, and 44 (77%) had favorable outcomes at 2 months, which improved to 51 patients (89%) at 12 months' follow-up.  Type of treatment varied, with 10 (18%) patients receiving intravenous immunoglobulin, 7 (12%) given high-dose corticosteroids and 12 (21%) given both.

Four children who presented with fulminant disease and did not receive immunotherapy died within hours of hospitalization from cardiopulmonary collapse despite attempts at resuscitation. Postmortem examination of 2 of these patients indicated severe inflammation of the medulla, corresponding to signal abnormalities found on brain MRI related to pulmonary edema.

The investigators concluded that EV71 should be considered “the new polio,” due to long-term consequences of the initial infection including permanent functional disability. They cite the need for randomized trials to comparatively evaluate treatments, as well as the development of treatment algorithms for the management of individual patients with EV71.

Reference

  1. Teoh H-L, Mohammad SS, Britton PN, et al. Clinical characteristics and functional motor outcomes of enterovirus 71 neurological disease in children. JAMA Neurol. 2016; Jan 19.
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