Prevalence and characteristics of human parechovirus and enterovirus
infection in febrile infants
and Jun-ichi Takanashi
Neurology and Developmental Pediatrics, Tokyo Women’s Medical University Yachiyo
Medical Center, Yachiyo and
Division of Virology, Chiba Prefectural Institute of Public Health, Chuou, Chiba, Japan
Abstract Background: Human parechovirus (HPeV) and human non-polio enterovirus (EV) are important causes of fever
without source (FWS) in young infants. Their prevalence and clinical characteristics are largely unknown in Asian
countries. This study was conducted to elucidate the epidemiology and clinical characteristics of HPeV and EV
infection in febrile young infants in Japan.
Methods: During February 2010–August 2015, we obtained 53 stool, 44 throat swab, and 20 cerebrospinal ﬂuid
samples from 56 infants (<3 months) with FWS at a single hospital. To each sample, we applied reverse transcrip-
tion–polymerase chain reaction for HPeV and EV. We compared the clinical characteristics of HPeV and EV
Results: HPeV was detected in 11 and EV in 17 patients. HPeV was detected during July–September. HPeV
patients, compared with EV patients, had lower age (32 vs 47 days; P = n.s.), higher prevalence of exclusive
breast-feeding (81.8 vs 29.4%; P = 0.024), and lower prevalence of sick contacts (36.4 vs 88.2%; P = 0.010). More
HPeV than EV patients met the systemic inﬂammatory response syndrome criteria (90.9 vs 52.9%; P = 0.049). In
the HPeV group, leukopenia, thrombopenia, and elevated deviation enzyme were observed, although the prevalence
of abnormal cerebrospinal ﬂuid was signiﬁcantly lower than in the EV group. HPeV patients had longer hospital
stay (7 vs 5 days; P = 0.025).
Conclusion: HPeV and EV are important causal viruses of FWS. Characteristic clinical pictures exist in these virus
infections, but further research is needed to accumulate more cases to produce a comprehensive picture of these
Key words enterovirus, fever, human parechovirus, infant, neonate.
Fever without source (FWS) in neonates–young infants up to
3 months of age is a potentially life-threatening illness
because the risk of severe bacterial infection (SBI) at this age
is higher than that in older children.
Today, the epidemiology
of FWS during early infancy has changed because of intra-
partum antibiotic prophylaxis for group B streptococcus and
the introduction of Haemophilus inﬂuenzae type b and pneu-
During the past decade, detection of
various viruses has improved by virtue of the development of
new molecular techniques and the availability of monoclonal
antibodies for many viral species. Furthermore, the FWS etiol-
ogy during early infancy is being gradually elucidated.
Human parechovirus (HPeV) and human non-polio entero-
virus (EV) are important causes of viral infection and
meningitis in neonates and young infants. The clinical spec-
trum of HPeV and EV infections varies from fever to severe
systemic disease, including sepsis and meningoencephalitis,
which might engender severe neuropsychological sequelae.
Several studies have speciﬁcally examined HPeV and EV
prevalence in European countries and the USA,
prevalence and clinical characteristics remain largely unknown
in Asian countries.
This study was conducted to investigate the prevalence of
HPeV- and EV-associated infection in a cohort of unselected
pediatric patients aged <3 months old admitted with suspicion
of infection to a single hospital in Japan. Cases of HPeV and
EV infection were identiﬁed in non-SBI febrile infants and the
clinical features compared.
From February 2010 to August 2015, we conducted a prospec-
tive study of febrile children aged <3 months with suspected
Correspondence: Hiromichi Hamada, MD PhD, Department of
Pediatrics, Tokyo Women’s University Yachiyo Medical Center,
Tokyo Women’s Medical University, 477-96, Owada-shinden,
Yachiyo, Chiba 2760046, Japan.
Received 23 February 2017; revised 12 October 2017; accepted
30 November 2017.
© 2017 Japan Pediatric Society
Pediatrics International (2018) 60, 142–147 doi: 10.1111/ped.13467