Causes of 2014 EV-D68 outbreak still unknown

Researchers are still searching for the reasons behind a 2014 outbreak of enterovirus D68, or EV-D68, which affected more than 1,100 people nationwide.

Christopher J. Harrison, MD, professor of pediatrics at the University of Missouri-Kansas City School of Medicine and director of the Infectious Disease Research Laboratory at Children’s Mercy Hospital, and colleagues wrote that in the last 50 years, the United States has seen fewer than 100 sporadic cases and periodic outbreaks caused by EV-D68. However, in 2014, an outbreak affected 1,153 people in 49 states and Washington, D.C. Nationwide, EV-D68 patients mostly had respiratory symptoms consistent with those seen in previous outbreaks, and severe disease occurred primarily in children.

“Instead of having a few scattered cases here and there, there were hundreds,” Harrison told Infectious Diseases in Children. “When that clinical outbreak occurred, the question came up of ‘why now?’ And, ‘why in these kids?’”

The outbreak prompted researchers to look back and assess the local seroprevalence of EV-D68 before 2014. They examined serum samples that were collected from Kansas City residents during a polio prevalence study, which were banked up to 2 years before the outbreak occurred. The samples were analyzed for neutralizing antibody against four phylogenetically distinct EV-D68 isolates, including Fermon, the first EV-D68 isolate that was identified in the U.S. in 1968; the dominant 2014 Missouri isolate, 14-18949; and two related but non-Missouri isolates — 14-18952 and 14-18953.

All 436 serum samples had neutralizing antibody against Fermon and 14-18949. Most children also had antibody against 14-18952 (89%) and 14-18953 (97%).

According to the researchers, the introduction of EV-D68 to an epidemiologically “naive” population might not explain the 2014 outbreak.

“Why this large outbreak was able to occur in a population with a high prevalence of neutralizing antibody against the outbreak isolates remains unclear,” Harrison and colleagues wrote. “One possibility is that respiratory tract mucosal antibody” — probably in the form of secretory immunoglobulin A — “is more relevant than serum antibody for protection against respiratory disease. Also, certain persons could be more susceptible to severe disease because of genetic factors, pre-existing atopy or asthma, or differences in other parts of the immune response, including immunopathologic responses.”

Harrison said EV-D68 is a virus that generally appears when most respiratory disease is not occurring.

“If you start seeing very severe asthma that is difficult to control and respiratory symptoms in late summer or early fall, pediatricians might want to think about EV-D68. If pediatricians have patients with severe asthma and may be more symptomatic, pediatricians might want to consider being proactive, watch them carefully and give parents extra advice on what danger signs to look for because it can accelerate pretty quickly,” he said.

EV-D68 is one of the pathogens suspected of causing acute flaccid myelitis, a rare condition that affects the nervous system and may cause sudden onset of arm or leg weakness, facial droop or weakness, difficulty swallowing or slurred speech. Harrison said that these findings highlight the possibility that AFM may be a reaction caused by a genetic shift in the virus that has become more prominent that triggers an unusual host response. – by Katherine Bortz

References:

CDC: Acute flaccid myelitis - about acute flaccid myelitis. https://www.cdc.gov/acute-flaccid-myelitis/about-afm.html. Accessed February 12, 2019.

Harrison CJ, et al. Emerg Infect Dis. 2019;10.3201/eid2503.180960.

Disclosure: Harrison reports no relevant financial disclosures.

Researchers are still searching for the reasons behind a 2014 outbreak of enterovirus D68, or EV-D68, which affected more than 1,100 people nationwide.

Christopher J. Harrison, MD, professor of pediatrics at the University of Missouri-Kansas City School of Medicine and director of the Infectious Disease Research Laboratory at Children’s Mercy Hospital, and colleagues wrote that in the last 50 years, the United States has seen fewer than 100 sporadic cases and periodic outbreaks caused by EV-D68. However, in 2014, an outbreak affected 1,153 people in 49 states and Washington, D.C. Nationwide, EV-D68 patients mostly had respiratory symptoms consistent with those seen in previous outbreaks, and severe disease occurred primarily in children.

“Instead of having a few scattered cases here and there, there were hundreds,” Harrison told Infectious Diseases in Children. “When that clinical outbreak occurred, the question came up of ‘why now?’ And, ‘why in these kids?’”

The outbreak prompted researchers to look back and assess the local seroprevalence of EV-D68 before 2014. They examined serum samples that were collected from Kansas City residents during a polio prevalence study, which were banked up to 2 years before the outbreak occurred. The samples were analyzed for neutralizing antibody against four phylogenetically distinct EV-D68 isolates, including Fermon, the first EV-D68 isolate that was identified in the U.S. in 1968; the dominant 2014 Missouri isolate, 14-18949; and two related but non-Missouri isolates — 14-18952 and 14-18953.

All 436 serum samples had neutralizing antibody against Fermon and 14-18949. Most children also had antibody against 14-18952 (89%) and 14-18953 (97%).

According to the researchers, the introduction of EV-D68 to an epidemiologically “naive” population might not explain the 2014 outbreak.

“Why this large outbreak was able to occur in a population with a high prevalence of neutralizing antibody against the outbreak isolates remains unclear,” Harrison and colleagues wrote. “One possibility is that respiratory tract mucosal antibody” — probably in the form of secretory immunoglobulin A — “is more relevant than serum antibody for protection against respiratory disease. Also, certain persons could be more susceptible to severe disease because of genetic factors, pre-existing atopy or asthma, or differences in other parts of the immune response, including immunopathologic responses.”

Harrison said EV-D68 is a virus that generally appears when most respiratory disease is not occurring.

“If you start seeing very severe asthma that is difficult to control and respiratory symptoms in late summer or early fall, pediatricians might want to think about EV-D68. If pediatricians have patients with severe asthma and may be more symptomatic, pediatricians might want to consider being proactive, watch them carefully and give parents extra advice on what danger signs to look for because it can accelerate pretty quickly,” he said.

EV-D68 is one of the pathogens suspected of causing acute flaccid myelitis, a rare condition that affects the nervous system and may cause sudden onset of arm or leg weakness, facial droop or weakness, difficulty swallowing or slurred speech. Harrison said that these findings highlight the possibility that AFM may be a reaction caused by a genetic shift in the virus that has become more prominent that triggers an unusual host response. – by Katherine Bortz

References:

CDC: Acute flaccid myelitis - about acute flaccid myelitis. https://www.cdc.gov/acute-flaccid-myelitis/about-afm.html. Accessed February 12, 2019.

Harrison CJ, et al. Emerg Infect Dis. 2019;10.3201/eid2503.180960.

Disclosure: Harrison reports no relevant financial disclosures.