By Kelly A. Reynolds, MSPH, PhD
Enterovirus 68 has been linked to a cluster of 25 cases of flaccid paralysis in California children. Without a vaccine or a cure, concern is mounting relative to where this virus came from and why it is possibly emerging as a new cause of neurological disease. Typically associated with cold-like illness, this new polio-like illness raises many questions as to how likely this virus is to spread and what environmental routes play a role in transmission.
HEV68 is a member of the Enterovirus genus, a group of human pathogens that includes the now rare poliovirus. Humans are commonly infected with enteroviruses as evidenced by their high concentration in sewage (7,000 viruses per liter). Typically spread via the fecal-oral route, enteroviruses cause a variety of illnesses, such as polio, meningitis and hand-foot-and-mouth disease. Enterovirus 71 is a major causative agent of hand-foot-and-mouth disease and sometimes associated with severe central nervous system (i.e., polio-like) diseases. Most infections, however, are thought to elicit no or mild symptoms in infected individuals.
Genetic tools have been utilized to study HEV68 and revealed characteristics of other enteroviruses (known to cause respiratory illnesses) and rhinovirus (known to cause the common cold). The rhinovirus, in particular, is known to have a high rate of genetic variability, which is one of the reasons a vaccine for the common cold has eluded medical science. Currently there are hundreds of known strains of human entero- and rhinoviruses.
Is HEV68 a new virus?
In November 2011, On Tap first warned of An Emerging and Deadly Waterborne Virus: Human Enterovirus 68. In late November, human enterovirus 68 (HEV68) was making headlines as the cause of a flu-like illness potentially transmitted by drinking water. Previously (dating back to the 1960s), the virus had been linked to respiratory infections and was specifically identified as a causative agent of pneumonia—which was first identified in another California cohort of children. In 2011, we reported that there seemed to be a change in HEV68, with clusters of respiratory disease cases being reported around the globe (US, Asia and Europe). Health outcomes ranged from mild to severe respiratory illness and even death. Only enterovirus 70 was previously thought to cause respiratory illnesses.
Via the National Enterovirus Surveillance System, which has collected information on enterovirus isolates in the United States since 1961, an increase in HEV68 incidence was identified in 2003. Instead of the usual sporadic cases reported over a 15-year period, a cluster of 11 cases was reported in a single year. Eight years later, the CDC published a report on HEV68 clusters worldwide, from 2008-2010. There were six identified clusters and hundreds of cases reported, along with three deaths in the Philippines and Japan. Physicians were now alerted to HEV as an increasing cause of potentially fatal respiratory illness. During this time frame, respiratory disease cases doubled in Pennsylvania, where over 40 percent (28/66) of the patients tested were positive for HEV68. Half of those (15/28) were under the age of four. Although no one died in this outbreak, 15 people were hospitalized in the intensive care unit. In an Arizona cohort, hospital admissions from respiratory infections were 26 percent above normal, where out of seven patients tested for HEV68, five were positive.
Most recently, a cluster of polio-like syndrome has been identified in California. This time, HEV68 appears to be at work, causing injury to the spine. In a report published by the American Academy of Neurology, five new cases identified between August 2012 and July 2013 in California signaled “the possibility of an emerging infectious polio-like syndrome.” All five cases were in children and marked by paralysis in one or more arms or legs with a sudden onset of symptoms. Three of the children were actively ill with a respiratory infection prior to the paralysis event and all were previously vaccinated for poliovirus. Six months later, the children were still experiencing poor limb function, despite active treatment. While only two of the children tested positive for HEV68, the causative agent was not identified in the other three. The California Department of Public Health has since received 20 additional reports of similar polio-like cases of paralysis, but a common cause continues to elude officials, which makes it difficult to link the cases or declare an outbreak situation. (Outbreaks are defined as two or more cases of illness from a common cause). A vaccine for poliovirus was widely available in the 1950s. Since then, polio has been largely eliminated from the US with only a few, random imported cases reported since then—one in 1979 and 1993. (The last case associated with use of the vaccine was reported in 1999, following a switch from the live attenuated oral vaccine to an inactivated version.)
A cause for concern?
Other enteroviruses, including echoviruses and adenoviruses, in addition to West Nile virus, can cause rare paralysis events. CDC officials caution that the recent paralysis events in California are likely not a cause for concern. Paralysis has always occurred in a segment of the population relative to virus infection and these new cases may not be over the expected values relative to the historical record. Recently, researchers in the Philippines collected nasal-fluid samples from 5,240 patients and found 12 positive for HEV68 infection. Conversely, HEV68 may indeed be a new, emerging pathogen with exposure, infection and the possibility for more adverse health outcomes on the rise. Perhaps it is time we look for the virus more diligently. There is much still to learn about this virus and its transmission patterns.
Best prevention practices
Although few waterborne outbreaks of enteroviruses have been reported, enteroviruses are frequently found in finished tap-water sources. They are able to survive well in water but are generally susceptible to chlorination, ozone and ultraviolet light treatment. While conventional water treatment is effective, failures in treatment or post-treatment contamination events (i.e., in the water distribution channel) are frequent sources of waterborne pathogens. There is currently no vaccine or cure for HEV68. Thus exposure prevention, as with other enteroviruses, is the best defense. Given the possible waterborne transmission route of HEV68 (particularly via aerosols), POU/POE systems are recommended as a back-up treatment step to municipal treatment works. Such interventions at the tap provide the best practice for protecting individuals from both indigenous and emerging pathogens.
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- Tadatsugu, I.; Roy, C.N.; Lupisan, S., et al. Molecular Evolution of Enterovirus 68 Detected in the Philippines, 20 September 2013. [Online]. Available: www.plosone.org/article/info percent3Adoi percent2F10.1371 percent2Fjournal.pone.0074221 [Accessed 14 March 2014].
About the author
Dr. Kelly A. Reynolds is an Associate Professor at the University of Arizona College of Public Health. She holds a Master of Science Degree in public health (MSPH) from the University of South Florida and a doctorate in microbiology from the University of Arizona. Reynolds is WC&P’s Public Health Editor and a former member of the Technical Review Committee. She can be reached via email at firstname.lastname@example.org