Received: 23 October 2017
Accepted: 2 January 2018
Species differences in circulation and inflammatory responses
in children with common respiratory adenovirus infections
Department of Pediatrics, Mie National
Hospital, Tsu, Mie, Japan
Biwako Gakuen Yasu Medical and Welfare
Center, Yasu, Shiga, Japan
Ochiai Pediatric Clinic, Kameyama, Mie,
National Institute of Infectious Diseases,
Takao Fujisawa, MD, PhD, Department of
Pediatrics, Mie National Hospital, 357 Osato-
kubota, Tsu, Mie 514–0125, Japan,
Japan Agency for Medical Research and
Development; The Association of
Pediatricians in Mie, Grant number: Medical
Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but
previous epidemiological studies lacked analysis of the characteristics of the
inflammation. Consecutive patients <13 years old with acute febrile illness during a
2-year period were tested. HAdV strains were isolated from nasopharyngeal swabs,
and molecular identification was performed by hexon, fiber, and species-specific PCR
methods. Blood inflammatory markers, including the white blood cell (WBC) count,
CRP, and 29 cytokines, were measured. A total of 187 patients were enrolled, and
HAdV types were identified from 175 patients (93.5%). Species C (types 2, 1, 5, and 6, in
order of frequency) was most common at 37.1%, followed by B (type 3) at 30.9% and E
(type 4) at 26.9%. Species C was detected predominantly in 1-year-old, whereas B and
E were in older ages. Species C and B had seasonal circulation patterns, but E was found
in only one season during the 2-year study period. The WBC count was highest in
patients with species C. Eleven of the 29 tested serum cytokines were detected. Seven
kinds, including G-CSF, IL-6, and TNF-α, were elevated in species C infections, whereas
IL-10 was lowest in species C. Species differences in inflammatory responses,
especially regarding serum cytokines were described in common pediatric HAdV
infections. Species C causes the strongest inflammatory responses in young children.
adenovirus, cytokine/chemokine, epidemiology, inflammation, seasonal incidence
Family Adenoviridae, genus Adenovirus, human adenovirus types
(HAdVs) are known to cause strong inflammatory responses, such as
elevation of the white blood cell (WBC) count and C-reactive protein
(CRP), which sometimes leads to overuse of antibiotics.
in the immune responses to the various species of HAdV have
not been well studied. Links between epidemiology and immune
responses may provide clues to understanding the mechanisms
underlying HAdVs' circulation patterns.
Although HAdVs are one of the most common pathogens in young
children, accounting for 10-29% of upper respiratory infections,
diseases they cause are believed to be mild and self-limiting.
However, HAdVs sometimes cause outbreaks of severe disease not
only in children,
but also in adults.
Understanding the circulation
patterns of and inflammatory responses to HAdV in healthy children
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© 2018 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.
J Med Virol. 2018;90:873–880. wileyonlinelibrary.com/journal/jmv