Enterovirus and Human Parechovirus: A Closer Look at Childhood Pathogens

In July 2022, the CDC issued a health alert for human parechovirus (HPeV), a pathogen that has been shown to cause severe illness in infants as young as one month.¹ HPeVs along with enteroviruses (EVs) are part of the Picornaviridae family and are common causes of mild respiratory and gastrointestinal infection in children, though more serious illness can occur. The recent increased diagnosis of sepsis-like illness, meningitis, and encephalitis attributable to HPeV type 3 (HPeV-A3), in particular, has raised the alarm.¹

Given that meningitis and neonatal sepsis are the second biggest infectious killers of children under five worldwide, clinicians and ID specialists are encouraged to consider testing for HPeV as well as EV when pediatric patients present with symptoms of neurological infection.²Below is an overview of the two viruses and how the BIOFIRE^®FILMARRAY^® Meningitis/Encephalitis (ME) Panel can help quickly identify them to support optimal therapy for neonates and young children.

Symptoms, Epidemiology, and More

Clinical manifestations of EV and HPeV vary in scope, ranging from asymptomatic and mild symptoms—commonly associated with HPeV type 1 (HPeV-A1)— to severe illness.¹ Infected patients may develop^1,3:

- Fever
- Rashes
- Respiratory symptoms
- Gastrointestinal symptoms
- Hand-foot-and-mouth disease
- Pleurodynia
- Hepatitis
- Myopericarditis
- Pancreatitis
- Meningitis
- Encephalitis
- Paralysis
- Sepsis (especially in neonates)

Both EV and HPeV are frequent causes of viral meningitis. The CDC has drawn a focus around HPeV-A3, which is the most dangerous of all observed HPeV types and is associated with seizures, paralysis, meningitis, meningoencephalitis, sepsis-like illness, and even sudden death.^1,3

EV and HPeV infections are most common in children under the age of one, but cases have been recorded across all age groups.³ Looking at EV on its own, children under one year of age account for 44% of all enterovirus cases in the United States, with similar numbers seen in Europe.⁴ Another study reported over 90% of children under the age of two have been infected with at least one type of HPeV.³ It’s important to note that children under three months, whose immune systems are still developing, are the most vulnerable to severe forms of EV and HPeV infection.⁵

The seasonality of EVs and HPeVs (types 1 and 3) is notably not uniform. HPeV-A3 infections peak in the spring and summer months on a biennial basis, with the cycle’s zenith falling on even-numbered years.⁴ EV infections have seasonal peaks in summer and fall, whereas HPeV-A1 cases have been recorded year-round with a low incidence in the summer months.^3,6

Few studies have been conducted to determine the long-term outcomes of EV and HPeV infections in pediatric patients, but it has been shown that infected children, especially those under one year of age, are at risk of developmental and neurological impairments, including smaller head circumference, lower IQ, and impaired language skills.³

Challenges to Treatment

Despite the incidence of both EV and HPeV among children every year, there are no antiviral therapies that target these pathogens specifically. As such, the CDC recommends the use of multiplex meningitis and encephalitis panels to quickly detect EV and HPeV in neonates and young children.¹ Rapid detection can help clinicians determine supportive therapies more effectively, thereby increasing the chances of recovery and survival.

Beyond identifying EV and HPeV infections, it is vital to also rule out bacterial meningitis in patients presenting symptoms. Bacterial meningitis may be fatal within 24-48 hours of infection, so rapid diagnosis can allow clinicians to determine the correct course of treatment, without having to resort to unnecessary antimicrobial therapy.

Catching EV and PHeV With the Syndromic Approach

A multiplex PCR test that targets multiple pathogens associated with meningitis can help deliver a fast and accurate diagnosis of EV and HPeV infections. The BIOFIRE^®FILMARRAY^® Meningitis/Encephalitis (ME) Panel leverages the syndromic approach by simultaneously testing 14 of the most common bacterial, viral, and fungal pathogens that attack the nervous system, including EV and HPeV.

The BIOFIRE ME Panel goes from sample to results in about one hour and can shorten time to diagnosis for pediatric patients by four days.⁷ This rapid turnaround time coupled with the comprehensive nature of the testing empowers clinicians to help children recover more quickly so that they can keep on being kids.

References:

Recent Reports of Human Parechovirus (PeV) in the United States—2022. Accessed 8 February 2023. Retrieved from: https://emergency.cdc.gov/han/2022/han00469.asp
World Meningitis Day 2022 Fact Sheet. Accessed on 8 February 2023. Retrieved from: https://f37f9f4d-dea8-4f37-b461-7719570767ff.usrfiles.com/ugd/f37f9f_11e6bc2e5a3840ce889ad9f8febde050.pdf
de Crom S, et al. Enterovirus and parechovirus infection in children: a brief overview. Eur J Pediatr. 2016;175:1023-1029.
Harvala H, et al. Comparison of human parechovirus and enterovirus detection frequencies in cerebrospinal fluid samples collected over a 5-year period in Edinburgh: HPeV type 3 identified as the most common picornavirus type. Journal of Medicial Virology. March 2011;83(5):889-896.
Tao L, et al. Cluster of Parechovirus Central Nervous System Infection in Young Infants — Tennessee, 2022. MMWR. 2022 July;71(30)
van der Sanden S, et al. Prevalence of Human Parechovirus in The Netherlands in 2000 to 2007. Journal of Clinical Microbiology. 2008 September;46(9).
O’Brien MP, et al. Impact of Cerebrospinal Fluid Multiplex Assay on Diagnosis and Outcomes of Central nervous System Infection in Children: A Before and After Cohort Study. Pediatr Infect Dis J. 2018 Sep;37(9)868-871.

Enterovirus and Human Parechovirus: A Closer Look at Childhood Pathogens

Symptoms, Epidemiology, and More

Challenges to Treatment

Catching EV and PHeV With the Syndromic Approach

Share this entry