Journal of Clinical Virology 51 (2011) 126–131
Contents lists available at ScienceDirect
Journal of Clinical Virology
journal homepage: www.elsevier.com/locate/jcv
Molecular epidemiology and clinical presentation of human adenovirus
infections in Kansas City children
Suresh B. Selvaraju
a
, Michelle Kovac
b
, Laura M. Dickson
c
, Adriana E. Kajon
c
, Rangaraj Selvarangan
a,∗
a
Children’s Mercy Hospitals and Clinics, and University of Missouri Kansas City-School of Medicine, Kansas City, MO 64108, United States
b
University of Kansas, Kansas City, KS 66160, United States
c
Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, United States
article info
Article history:
Received 10 September 2010
Received in revised form 16 February 2011
Accepted 22 February 2011
Keywords:
Human adenoviruses
Hexon gene sequencing
Restriction enzyme analysis
Genomic variants
Children
abstract
Background: A significant increase in adenovirus detection among patients at the Children’s Mercy Hos-
pital, Kansas City was observed between June 2007 and January 2008.
Objective: To molecularly characterize the human adenoviruses and describe their association with clin-
ical illness in children.
Study design: One hundred adenovirus-positive specimens from 79 children were typed by hexon gene
sequence typing method. Restriction enzyme analysis (REA) was performed on isolates of HAdV-3, -7
and -14 to identify genomic variants. Medical records were reviewed to understand the clinical illnesses
associated with adenovirus serotypes and genome types.
Results: The most prevalent HAdV serotypes were HAdV-3 (37%), HAdV-7 (25%), HAdV-1 (16%), HAdV-
2 (8%). HAdV infection was common in children ≤3 years of age (71%) versus children >3 years (29%).
Majority of the HAdV-infected children were hospitalized (78%); 22/79 (28%) stayed >3 days and 8/79
(10%) required intensive care unit stay. Hospitalization rates for HAdV-3 (36%) and HAdV-7 (25%) were
comparable. REA data indicated that HAdV-3a2 was the predominant HAdV-3 genome type. Two novel
genomic variants of HAdV-3 exhibiting unique BglII or BstEII profiles were identified in isolates from
patients with bronchiolitis. All HAdV-7 and -14 isolates were identified as corresponding to genome
types 7d2 and 14p1, respectively.
Conclusions: In Kansas City, we noticed an increase in the incidence of HAdV-7 (25%; n = 24/98) infections
compared to the previous two years (6%; n = 6/107). Two new genomic variants of HAdV-3 appear to have
emerged in our area and seem to be associated with lower respiratory tract infections in children.
© 2011 Elsevier B.V. All rights reserved.
1. Background
Human adenoviruses are members of the family Adenoviridae
that cause a wide spectrum of acute and chronic diseases. Ade-
novirus infections occur primarily in infants and children under 5
years of age, accounting for 2–5% of respiratory illnesses, and 4–10%
of pneumonias.
1
To date, 52 different adenovirus serotypes have
been reported and are grouped into 7 species, A–G.
2
It is becoming
increasingly clear that specific serotypes are associated with cer-
Abbreviations: HAdV, human adenovirus; ARD, acute respiratory disease;
NP, nasopharyngeal aspirate/swab; BAL, bronchoalveolar lavage; REA, restric-
tion enzyme analysis; CPE, cytopathic effect; LRRI, Lovelace Respiratory Research
Institute; CDC, centers for disease control and prevention; WHO, World Health
Organization.
∗
Corresponding author at: Department of Pathology and Laboratory Medicine,
Children
′
s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108,
United States. Tel.: +1 816 234 3031; fax: +1 816 802 1492.
E-mail address: rselvarangan@cmh.edu (R. Selvarangan).
tain clinical manifestations and severity of disease.
3
Recently, two
emergent virulent strains, HAdV-7d2 and -14p1, were reported to
cause severe illness and death in children and adults in the USA.
4–7
In China, an outbreak of acute respiratory tract infection and one
death among school children due to HAdV-11a serotype infection
was reported.
8
A study on autopsied lung tissues from patients who
died of severe pneumonia indicated HAdV association in 9.14% of
the cases. Three HAdV serotypes, 3, 4 and 41, were identified by
sequencing a region of the hexon gene.
9
Recently, a sudden death
of a child from myocarditis was reported due to an uncontrolled
inflammatory response to a disseminated adenovirus serotype 3
infection in the UK.
10
Sequences of hypervariable regions of hexon gene provide
excellent correlation for identification of adenoviruses at the
serotype level.
11–14
Each adenovirus serotype can be further dis-
criminated into genome types on the basis of distinct DNA fragment
patterns generated with restriction enzymes, and this type of anal-
ysis has been widely used in molecular epidemiologic studies.
6,15,16
Data from several studies suggest that certain genome types might
1386-6532/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jcv.2011.02.014