In many infectious disease outbreaks, including measles and influenza, as the number of cases rises, so too does the chance complications may arise. Such appears to be the situation with the current epidemic of Enterovirus D species, serotype 68 (EV-D68) in North America. The virus has now spread to most of the continental United States and associated sequelae, which include acute flaccid paralysis (AFP), neurological dysfunction and death, have begun to emerge.

Last week, a CDC report revealed some 23 cases of AFP over the last two years. The majority of cases have been documented as having no known infectious cause except a possible association with EV-D68. Even with this single isolation, the spotlight was given to a different member of the picornavirus family, Enterovirus C species, poliovirus serotype.

Poliovirus might be the most obvious culprit due to its long standing association with paralysis. However over the last few decades; searches for an etiological association with AFP have revealed a rather large number of potential enterovirus culprits. They include but are not limited to:

  • Enterovirus A species, serotypes coxsackievirus A13, A17, A24
  • Enterovirus A species, serotypes enterovirus 71, 76
  • Enterovirus B species, serotypes coxsackievirus B3, B5, B6
  • Enterovirus B species, serotypes echovirus 3, 6, 7, 11, 12, 13, 14, 19, 20, 21, 24, 27, 29, 30, 33
  • Enterovirus B species, serotypes enterovirus 69, 73, 77, 93, 100
  • Enterovirus C species, serotype poliovirus
  • Enterovirus D species, serotypes enterovirus 68, 94

Though the viral association with the onset of AFP may appear to be a mystery, there is a possible explanation in which the pathogen initiates or exacerbates a known medical condition. From research done over the last 40 years, a particular immunological abnormality found primarily in asthma sufferers could be the possible cause of symptoms while viral infection could either initiate or exacerbate it.

Acute postasthmatic amyotrophy or Hopkins’ Syndrome (based on the discoverer of the condition, Ian Hopkins in 1974), is a poliomyelitis-like illness associated with severe bouts of asthma. Further investigations have revealed many factors are involved including increased serum antibody levels, particularly Immunoglobulin M (IgM) and possibly low levels of T-cells, which are responsible for the management of an immune response. In some cases, the antibody associated with an allergic response, Immunoglobulin E (IgE) was also high. In all cases, there was no indication of poliovirus infection.

Despite no viral involvement, the physiological target of Hopkins’ Syndrome appears to be similar to poliovirus: the anterior horn of the spinal cord. However, most work has been in response to novel and unusual clinical cases. As a result, few cases are documented. In one such report, an enterovirus – coxsackievirus A24 – was isolated and found to be associated with the onset of postasthmatic paralytic symptoms. But this singular case did not warrant an actual conclusive link between infection and the syndrome.

Regardless of the cause, there are few options for treatment of the resultant AFP. Based on the mechanism of action, controlling the autoimmune function might be a valid basis for treatment. In this case, the use of intravenous immunoglobulin (IVIG) offers benefit. It has been used in the past to resolve Hopkins’ Syndrome as well as various other causes of AFP including onset associated with enterovirus B71, echovirus 19, and non-enterovirus virial infections.

In terms of the current EV-D68 epidemic, a postulate may be made. As the major risk factor for onset of severe illness including respiratory distress is asthma, virus infection may initiate a hyperimmue status or exacerbate an already present one (Hopkins’ Syndrome). Moreover, depending on the biology of the virus, the potential for epitope mimicry exists allowing for a Hopkins’ Syndrome–like illness.

In regards to treatment, based on the information from AFP and Hopkins’ Syndrome, IVIG may be considered as a treatment for those suffering. Though resolution is not entirely guaranteed, based on the amount of clinical information available – sparse and mostly not open access – this option may lead to successful outcomes and the restoration of proper neurological and muscular function. In addition, the treatment is widely used and is generally safe for children.

There is little doubt the EV-D68 epidemic will eventually wind down and disappear however the toll currently felt is leaving much of the population understandably worried. There is therefore every reason to explore all options to identify a cause and treatment. This postulate may not incorporate the entire picture of viral infection as details continue to be evasive; but public health officials may wish to explore this avenue at least in regards to treatment. Ultimately, such an effort may be worthwhile if only to find a means to bring calm to the hearts and minds of children and parents.