Parechovirus Infections in Young Febrile Infants: Towards Routine Testing

Background: Human parechoviruses (HPeV) can cause severe illness in young children; however clinical and laboratory manifestations are not completely defined. At our institution, all febrile infants ≤60 days of age have blood, CSF, and mucosal site samples tested by PCR for HPeV and enteroviruses (EV). We sought to determine the local HPeV prevalence, clinical characteristics and viral correlates of disease severity.

Methods: Clinical and laboratory data of all infants 4-60 days of age with fever or rule out sepsis work-up hospitalized between July 2013 and March 2016 were reviewed. HPeV and EV were detected using an in-house developed real-time PCR.

Results: Of the 1,631 patients tested, HPeV was detected in 75 (4.6%) patients in at least one site. Mean age was 28.9 days. Median length of stay (LOS) was 1.8 days. There were no complications or deaths. 88% of patients were diagnosed between months of July and December. CSF testing was positive in 27, blood in 53, and mucosal sites in 51 patients. 17 patients had all 3 samples positive and 20 had both CSF and blood samples positive. 70 patients (93.3%) had fever, 31% had rash. CBC, electrolytes, transaminases were normal in most patients. 30 patients had co-infections (3 bacterial, 27 viral). Among CSF positive patients, median CSF WBC count was 5 (0-352 cells/µl); 5 patients had 0 WBCs in CSF. Median CSF glucose and protein were normal. 6 of the 7 PICU admissions had positive CSF HPeV. Median PCR cycle time (Ct) value in CSF was 36.5 (range: 17.5-42.3). CSF Ct values in PICU patients were significantly lower (p = 0.010). Median blood Ct value was 31.9 (range: 21.1-40.7). Median mucosal site Ct value was 34.5 (range: 26.4-44.2) with higher Ct values observed among viral co-infected patients. Adding blood HPeV PCR after CSF, detected 45% of HPeV positive patients. Patients with blood Ct values <29 had longer hospitalizations but this was not statistically significant (2.35 vs 1.77 days, p=0.4).

Conclusion: We documented HPeV infection in 4.6% of febrile infants ≤ 60 days. There were no serious complications or fatalities, but 10% of the patients (mostly with meningitis) required PICU admission. Majority of patients with meningitis had normal CSF parameters. Routine testing detected patients with meningitis and viremia.