INFECTIOUS DISEASE

 

VIROLOGY - CHAPTER SEVENTEEN

Appendix

Acute Flaccid Myelitis (AFM): Update on Disease Symptoms and Potential Etiologic Agent(s)

December 2018

 

J. David Gangemi, Ph.D.
Professor Emeritus
Department of Microbiology and Molecular Medicine
Clemson University, and
Clinical Professor Pathology, Microbiology, and Immunology
USC School Medicine
 

AFM is a syndrome characterized by rapid onset of flaccid weakness in one or more limbs, and can include a mild respiratory illness followed by difficulty moving the eyes or drooping eyelids; facial droop or weakness; and difficulty with swallowing or slurred speech.  CDC has used these physical manifestations along with distinct abnormalities in the grey matter of the spinal cord (as revealed by magnetic resonance imaging) to confirm AFM cases.  Since 2014 CDC has reported that cases are sporadic occurring in children during late summer/early fall periods with symptoms similar to complications following infection with certain viruses including poliovirus, non-polio enteroviruses, adenoviruses, and West Nile virus. 

Enteroviruses are often associated with a mild or asymptomatic illness (especially in late summer/early fall), but can also cause neurologic illness such as meningitis, encephalitis, and AFM, but these are rare complications.  Infections with enteroviruses are usually silent, but even in the case of symptomatic disease (meningitis or encephalitis) these viruses are often cleared from the spinal cord by the time symptoms appear. All of the AFM cases have tested negative for poliovirus. During the summer/fall of 2014, 120 confirmed cases of AFM were reported to CDC. Most patients were less than 19 with an average age of 4, and reported a respiratory or febrile illness in the days prior to onset of neurologic symptoms.  In 2015, only 22 confirmed cases from 17 states were reported; however, in 2016, the number of confirmed cases again rose to that observed in 2014 with 149 cases in 39 states. As of October of 2018, 72 confirmed cases of AFM in 22 states have been reported to CDC.

Despite extensive pathogen-specific testing, no common agent or etiology has been identified; however, AFM outbreaks coincide with seasonal respiratory outbreaks of enterovirus D68.  In 2014, D68 was reported by health departments in several states to be the likely cause of sporadic AFM outbreaks, but CDC has not yet validated this etiology since consistent serologic conversion is not always apparent.  Because of this, CDC has broadened its search to include other viruses (adeno and encephalitic arboviruses) and environmental toxins as presumptive causes. It is not known why some people are at a greater risk for developing AFM, and the long term effects are not clear. Some patients recover quickly, and some with extensive nerve damage, continue to have paralysis and require ongoing care. Rehabilitative therapy may restore muscle function in less severe paralytic disease. There are no treatments for AFM and good hygiene with thorough washing of hands (as with most enteroviruses and rhinoviruses) may be the best preventative measure. While the true etiology of AFM has not yet been identified, enteroviruses are likely suspects. EV D68 is antigenically related to viruses in the enterovirus genus, but has biological properties similar to rhinoviruses, and, as such, may be the proverbial “wolf in sheep’s clothing”. If EV D68 is the causative agent, future research will focus on vaccine development and the mechanism by which this virus is able to infect the respiratory tract and cross the blood brain barrier.

Why does the number of AFM cases rise every other year?

As yet, we do not know enough about AFM to understand whether the apparent multiyear periodicity is a reproducible phenomenon, or what the cause of it is. However, there are ways that such a phenomenon might occur.

Some viruses may show a pattern in which there is not only a seasonal cycle in infections but also annual cycles where there may be a high level of clinical illness in one year followed by much lower level in the next year and then a higher level again. This pattern of intervening year(s) with low rates of clinical infections was commonly observed in many childhood diseases before the advent of effective vaccinations. There are many possible explanations (changes in the populations of vectors in vector-borne diseases, for example). However, in some cases this pattern may be due to the lack of a sufficiently large population of susceptible individuals in the intervening years.

For example, if a disease is common and if one infection confers life-long immunity so that most people are infected as children and are then protected from subsequent disease, adults will no longer act as a susceptible population. Children who have not yet been exposed to the disease will form the susceptible population. The virus will only spread rapidly if the susceptible population is large enough; thus, if person A has a viral infection and passes the virus to no-one (e.g. due to isolation, hygiene precautions, etc.,  or because everyone they meet is already protected from a prior infection or vaccination), person A will not cause or contribute to an outbreak. If person A only passes it to one other person while A is infectious, this will probably not cause an outbreak because person B is likely also only pass it to one other person. However if person A passes the infection to four people (the B’s), then if each of these pass it to four people, there are sixteen C people. The sixteen C people can now infect sixty four D people and the virus spreads more rapidly with every round of infection. It is possible that if an outbreak one year gives enough people protection from infection the following year, then the susceptible population may not be large enough to prevent the occurrence of a major outbreak. Remember that since subclinical infection with a particular virus may be common, many people may be protected from reinfection even if they have never been aware of having been infected. However, in succeeding years children borne since the prior outbreak will cause an increase in the size of the susceptible population until it is large enough for the virus to spread rapidly again. Hence the variation in the size of the susceptible population can lead to changes in the annual incidence.

This is a very simplistic overview – epidemiology is much more complicated than this, and there are many other possible explanations for apparent multiyear periodicity in viral outbreaks. However, observing periodicity and investigating the cause can give vital clues to understanding the natural history of a disease.

For further reading see:

CDC Acute Flaccid Myelitis (AFM) Update - Oct 22nd afludiary.blogspot.com/2018/10/cdc-acute-flaccid-myelitis-afm-update.html

Polio-like disease AFM now confirmed in 22 states, CDC says the disease seems to affect children more than other age groups

www.wafb.com/2018/10/17/polio-like-disease-afm-now-confirmed-states-cdc-says/

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