Epidemiology of respiratory viruses in children admitted to an infant/toddler unit
Aaron M. Milstone MD, MHSa,b,*, Trish M. Perl MD, MScb,c, Alexandra Valsamakis MDd
aDepartment of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD
bDepartment of Hospital Epidemiology and Infection Control, The Johns Hopkins Hospital, Baltimore, MD
cDepartment of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD
dDepartment of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, MD
This study examined the prevalence of common respiratory viruses in an infant/toddler cohort tested as
part of a comprehensive strategy to prevent nosocomial respiratory virus transmission and measured the
unrecognized reservoir of viruses in children without common respiratory virus symptoms.
Copyright ? 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc.
Published by Elsevier Inc. All rights reserved.
Preventing nosocomial transmission of respiratory viruses is
challenging.1,2Viral diagnostic studies can identify contagious and
threatening virusesinchildren hospitalizedwitha respiratory illness
to facilitate appropriate patient placement and cohorting.3Increas-
ingly, respiratory viruses are identified in children with and without
symptoms of a respiratory viral infection.4,5The objectives of the
present study were to determine the prevalence of common respi-
ratory viruses in a large cohort of infant and toddlers tested as part
of a comprehensive strategy to prevent nosocomial respiratory
virus transmission and to measure the unrecognized reservoir of
viruses inchildrenwithout a symptomaticrespiratory viralinfection.
MATERIALS AND METHODS
Study population and setting
Eligible patients were admitted to a 14-room, 34-bed infant/
toddler ward between October 15, 2007, and March 15, 2008. The
Johns Hopkins Hospital has a comprehensive program to identify
and isolate children with contagious respiratory viruses.6Beginning
in 2007, all patients admitted to the infant and toddler ward were to
have a nasopharyngeal aspirate collected within 24 hours of
admission. Specimens were tested as described in Table 1.
Data collection and definitions
For all patients, primary admission diagnoses were ascertained
by querying administrative databases (ICD-9 codes) and categorized
as the presence or absence of common manifestations of respiratory
viral illness (RVI), including bronchiolitis, apnea, croup, tracheitis,
pneumonia, acute asthma exacerbation, and unexplained fever.
For patients with a laboratory-identified respiratory virus, complete
medical records were reviewed to characterize the presenting
symptoms in this cohort of children who underwent testing regard-
lessofsymptoms. Inpatients withalaboratory-identifiedrespiratory
virus, “obvious RVI symptoms” were defined as repeated reports
or observations of upper/lower respiratory tract symptoms (eg,
rhinorrhea, congestion, cough, apnea, wheezing, increased work of
breathing, tachypnea, hypoxia) or unexplained fever, and “subtle RVI
symptoms” were defined as a single report or observation of upper/
lower respiratory tract symptoms within 48 hours before or after
admission that did not persist during the hospitalization. The
hospital’s Institutional Review Board approved this study.
During the study period, a total of 1,103 patients were admitted
to the study unit. The median patient age was 1 year (range,16 days
to 9 years), and the median hospital length of stay was 2 days. Of
the 1,103 patients admitted, 309 (28%) had a primary diagnosis of
a common complication of a respiratory viral illness, and 281 (91%)
had nasopharyngeal aspirates. Of the remaining 794 patients, 615
(77%) had nasophayngeal aspirates.
* Address correspondence to Aaron M. Milstone, MD, MHS, JHU Departments of
Pediatrics and Epidemiology, 200 North Wolfe Street, Rubenstein 3141, Baltimore,
E-mail address: firstname.lastname@example.org (A.M. Milstone).
The data from this study were presented in part at the 19th Annual Scientific
Meeting of the Society for Healthcare Epidemiology of America, San Diego, March
NCRR 1KL2RR025006-01, to A.M.M.) and the R Baby Foundation.
Conflict of interest: A.M.M. and T.M.P. report no disclosures. A.V. was on an
advisory board for and has received research support in the form of reagents from
Diagnostic Hybrids, Inc.
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American Journal of Infection Control xxx (2011) 1-3
A respiratory virus was identified in 167 of 896 tested children
(18.6%) (Table 1). Of those 167 patients,138 (83%) wereadmitted for
treatment of an RVI and had obvious RVI symptoms. A respiratory
virus was detected in 29 patients admitted for a nonrespiratory
viral illness (eg, an elective surgical procedure). Ten of these
patients (34%) had obvious RVI symptoms, 6 (21%) had subtle RVI
symptoms, and 13 (45%) had no RVI symptoms. Adenovirus (ADV)
was most commonly virus identified in asymptomatic children
(n ¼ 6); other viruses included respiratory syncytial virus (RSV;
n ¼ 2), influenza virus A (Flu A; n ¼ 2), parainfluenza virus (PIV) 1
(n ¼ 2), PIV2 (n ¼ 1), and PIV3 (n ¼ 1). Viruses were detected
by culture in 10/13 (77%) asymptomatic children (RSV, n ¼ 1; Flu A,
n ¼ 1; ADV, n ¼ 6; PIV1, n ¼ 2; PIV3, n ¼ 1), 2 were positive by
immunochromatography (RSV, n ¼ 1; Flu A, n ¼ 1), and 1 (PIV2)
was positive only by DFA. One patient had sample that was positive
for ADV and PIV1 by culture.
Infants and toddlers admitted to the hospital for nonrespiratory
illness can harbor respiratory viruses. In our cohort, 8% of children
who tested positive for a respiratory virus had no reported or
observed symptoms of a respiratory viral infection.
Nosocomial respiratory virus transmissions can occur, and
subsequent health careeassociated infections can have significant
morbidity in pediatric hospitals.7Our study confirms previous
observations that live virus can be isolated from the respiratory
tract of asymptomatic children.8Although these children likely
pose little risk to others, their presence highlights the importance
of hand hygiene and standard precautions to reduce nosocomial
transmission of all organisms. To the best of our knowledge, this is
the first description of the epidemiology of respiratory viruses in
a large cohort of hospitalized children that included children
admitted for reasons other than an acute respiratory viral illness.
These asymptomatic children may serve as a reservoir for trans-
mission of viruses in the hospital; however, syndromic screening
remains a very effective approach to identifying most children who
are shedding live virus.
Detecting a respiratory virus in an asymptomatic child can reflect
asymptomatic infection, prolonged shedding after a previous infec-
of asymptomatic childrenwith a positive test had avirus detected by
viral culture, making a false-positive result less likely. During the
study period, our clinical virology laboratory used conventional
respiratory virus detection tests, including immunochromatography,
direct fluorescent antibody, and viral culture. New molecular diag-
nostic tests have increased the detection of respiratory viruses in
children9; however, a positive molecular test results does not prove
a causal association between a virus and an illness.5Identifying live
replicating virus from hospitalized children has implications for
treatment and infection control measures, but the implications of
molecular testing results on treatment and infection prevention
strategies require further study.
The use of retrospective data to identify clinical symptoms in
patients was a limitation of this study, given that some patients
who tested positive for a respiratory virus might have had unre-
ported and unrecorded symptoms. Our laboratory used conven-
tional testing methods that may be less sensitive for detecting
certain viruses, but this approach is consistent with those being
used by many hospital-based laboratories.
Overall, asymptomatic children may harbor contagious respi-
ratory viruses and serve as a silent source of transmission in
pediatric wards. Standard precautions, including handwashing, are
essential to prevent transmissions of viruses to patients and
subsequent health careeassociated respiratory viral infections.
More research is needed to assess the potential benefits and risks of
detecting viruses in children without common symptoms of
a respiratory viral infection, especially as rapid molecular diag-
nostics for respiratory viruses become widely available.
We thank Kathleen Speck, Sharon Strobel, Dr George Dover,
Dr Arnab Sengupta, Andrew Lee, Mirinda Gillespie, members of The
Johns Hopkins Hospital Department of Hospital Epidemiology and
Infection Control and Clinical Virology Laboratory, and the nurses
on The Johns Hopkins Hospital Infant/Toddler Floor.
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Viruses detected in infant/toddlers hospitalized with and without symptomatic RVI
Patients admitted for reasons other than RVI
Total Obvious RVI symptomsz
Subtle RVI symptomsx
No RVI symptoms
ADV and PIV1
*RSV, Flu A, Flu B, PIV1, PIV2, PIV3, ADV, and human metapneumovirus (hMPV) were detected with the following tests. During the high-prevalence period,
immunochromatography was performed for RSV (BinaxNOW RSV; Inverness Medical, Princeton, NJ) and for Flu A and Flu B (BinaxNOW Influenza A & B; Inverness
Medical). All specimens during low-prevalence periods and all negative specimens during high-prevalence periods were further tested by direct fluorescent antibody
stain (D3 Ultra and D3 metapneumovirus; Diagnostic Hybrids, Athens, OH), vial culture (R-Mix Too; Diagnostic Hybrids), and tube culture.
yPatients with a primary admission diagnosis of a common manifestation of an RVI, such bronchiolitis, apnea, croup, tracheitis, pneumonia, acute asthma exacerbation, or
zObvious RVI symptoms included repeated report of upper or lower respiratory tract symptoms or unexplained fever.
xSubtle RVI symptoms included inconsistent or a single report of upper or lower respiratory symptoms.
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