Who Made Who? Enterovirus & Paralysis

Since enterovirus-D68  (EV-D68) emerged on the scene there has been increased attention focused on cases of acute flaccid myelitis (AFM)—the limb weakness that was once the hallmark of the almost eradicated poliovirus. 

The focus on AFM-associated EV-D68 stems from the fact that that polio itself is an enterovirus and viruses within the same family often produce similar symptoms. Thus far 112 cases have been found with many patients experiencing antecedent illnesses compatible with EV-D68 and only one recovering. There have now been several reports and at least one major paper linking EV-D68 to cases of paralysis but all have fallen short of definitively proving causation. This is not surprising since microbiological causation can be hard to definitively establish with a fleeting infection and when the paralysis could be caused by immunologic phenomenon rather than direct viral infection, explaining the inability to recover EV-D68 RNA from the CSF of paralyzed individuals. 

It may be some time before EV-D68’s role in the pathophysiology of paralysis is definitely determined but I believe, ultimately, EV-D68 and possibly some related enteroviruses will be found to be behind these cases, even if only as an immunologic trigger, for several reasons that include:

·      Antecedent upper respiratory infections, some of which were due to EV-D68

·      The emergence of EV-D68 and its widespread dissemination throughout the population

·      The ability of enteroviruses to cause flaccid paralysis

·       The seasonality of paralysis matching that of enteroviruses

However, I wouldn't exactly label these cases with the ominous-sounding adjective “mysterious," as some have done, despite the lack of finding EV-D68 in the spinal fluid of paralyzed cases, and invoke memories of fear-inducing polio, which--through direct viral effects--paralyzes at a rate of 0.5% and is easily demonstrable in spinal fluid, just yet. What remains to be done is to look at cases of AFM and compare them with non-cases in a case-control study that may point clues to the etiology. Also, since the genetic signature of EV-D68 was note found, are antibodies present in cases? Scouring the country for more AFM cases, which isn't nationally reportable, will also be needed to understand the baseline and account for increased case finding in the wake of widespread awareness of EV-D68.

It will be interesting to see how EV-D68, now the dominant enterovirus, behaves during this year's enteroviral season because the 1100+ confirmed cases with 14 deaths did not represent the full reach of this virus.

A Back to School Victim-Finding Spree for Enterovirus 68

There are multiple reports today of a large outbreak of respiratory illness in the Midwest and, no, it's not Ebola or MERS.

It's Enterovirus D68. You might recall a few months earlier a big scare with this virus causing a polio-like paralytic disease in California, but this virus (which bears Jaromir Jagr's number, for Pittsburghers) is well known as a cause of respiratory illness.

A few points about this outbreak:

  • Seems very large: 300 kids in Kansas City, MO (other states are reporting too) but this is likely not the full extent of infection as most cases are likely asymptomatic
  • High degree of ICU admission: 15%
  • Hospitals are limiting visitation of the hospitalized children

Enteroviruses, in general, are a ubiquitous group of viruses that number over 100 and cause a wide variety of illnesses from meningitis to upper respiratory tract infection. Each year over 10 million cases of infection with this group of viruses occur. However, the vast majority of these infections are without symptoms (but are still contagious). 

This new outbreak could reflect a number of things.

1. Better diagnostics: Many hospitals are moving to PCR-based testing of respiratory illness and what may have been an undifferentiated cluster of illness is now able to be named.

2. The start of school: It is widely known that schools function as viral exchange centers and this virus is likely benefiting from the school year (a sort of back to school victim finding spree for the virus).

The next steps will be to determine the true burden of this virus, understand it's full spectrum of illness, given its now proven ability to cause severe infection, and assess whether a vaccine against it (like is being developed against Enterovirus 71) is warranted.