Enterovirus A71 Neurologic Disease Detected in 34 Children in Colorado

September 18, 2018
Michaela Fleming

Children’s Hospital Colorado reported an increase of pediatric cases of meningitis and encephalitis in which patients tested positive for enterovirus.

Enterovirus-A71 (EV-A71) is 1 of more than 100 non-polio enteroviruses. It was first identified in the United States in 1969 as a common cause of hand, foot, and mouth disease. In rare circumstances, EV-A71 can also cause severe neurologic diseases such as meningitis, encephalitis, and acute flaccid myelitis (AFM).

On May 10, 2018, the Colorado Department of Public Health and Environment (CDPHE) was notified of an influx of cases of meningitis and encephalitis in infants who also tested positive for EV-A71 at the Children’s Hospital Colorado (CHCO).

Surveillance data for the month of May showed a 2.75-fold increase in encephalitis as well as a 3-fold increase in enterovirus/rhinovirus compared with the 5-year average.

By August 26, 2018, EV-A71 was identified in 34 children with neurological disease, and in a recent Morbidity and Mortality Weekly Report, clinical findings were reported for 13 of the 34 children.

The 13 patients ranged in age from 10 days to 35 months with a median age of 13 months; eleven of the patients were male. All of the patients were hospitalized for neurologic diseases—meningitis (12), encephalitis (9), and acute flaccid myelitis (3). All 13 children demonstrated irritability and 3 developed lesions typical of hand, foot, and mouth disease.

Neurologic signs included encephalopathy (7), ataxia (7), myoclonus (6), limb weakness (4), cranial nerve deficits (2) and seizures (1), according to the report.

Specimens from the children with neurologic diseases were tested by EV reverse transcription-polymerase chain reaction (RT-PCR). Additionally, 10 children had a cerebrospinal fluid (CSF) specimen analyzed. Nine of the 10 children analyzed had a pleocytosis (median white blood cell count = 106 cells/ML range = 17 — 698 [normal= 0=5]).

All 13 children had EV-A71 identified in nasopharyngeal, pharyngeal, or rectal specimens but only 2 of the patients had a specimen positive for enterovirus by pan-EV RT-PCR.

Eight children underwent brain imaging and abnormalities were observed in 6 of the children—5 in the brain stem, 3 in the cerebellum, and 3 in the spinal cord.

The onset of the infections occurred between March 10 and June 5, 2018. All 13 patients were hospitalized for a range of 1 to 23 days with a median hospitalization period of 5 days. Four patients were admitted to the intensive care unit. All patients survived.

Severe central nervous system EV-A71 infections can cause brainstem encephalitis which can lead to cardiopulmonary collapse and polio-like AFM. According to the Centers for Disease Control and Prevention, infants and children are most likely to become infected with enteroviruses and fall ill because they have not built up immunity yet.

Due to the fact that different mixes of enteroviruses circulate each year, it can be difficult to predict when EV-A71 outbreaks will occur.

Furthermore, there is no vaccine available in the United States to prevent EV-A71 and no specific treatments or antiviral medications currently available for individuals who become infected with the disease.

EV-A71 epidemics have occurred in the Asian-Pacific region since the late 1990s. Since the 1980s, the National Enterovirus Surveillance System has detected EV-A71 activity in the United States, which has accounted for <1% of enteroviruses.

Colorado previously experienced EV-A71 outbreaks in 2003 and 2005. There have been no other clusters of the virus reported in 2018 at this time.

The investigation indicates a need for testing non-sterile sites when central nervous system disease associated with EV is suspected and CSF is negative, according to the authors of the report. Additionally, health care providers should consider EV-A71 as an etiology when febrile patients display symptoms such as myoclonus, ataxia, or limb weakness.