Open Journal of Pediatrics, 2011, 1, 41-44
doi:10.4236/ojped.2011.14012 Published Online December 2011 ( OJPed
Published Online December 2011 in SciRes.
Impact of rotavirus vaccine on acute gastroenteritis
emergency department visits and hospitalizations in
a highly-vaccinated urban cohort
Sheila M. Nolan1, Priya Prasad1, Alexander G. Fiks2, Theoklis E. Zaoutis1, Thomas R. TenHave3,
Susan E. Coffin1
1Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, USA;
2Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, USA;
3Department of Biostatistics, School of Medicine, The University of Pennsylvania, Philadelphia, USA.
Received 7 October 2011; revised 14 November 2011; accepted 22 November 2011.
Background: Rotavirus vaccines (RVV) have signifi-
cantly reduced rotavirus disease in children over the
past 4 years in the United States. In this study, we
describe the impact of RVV in preventing acute gas-
troenteritis (AGE) hospital encounters in a highly-
vaccinated urban pediatric network during the 2007
and 2008 rotavirus seasons. Methods: We used 5 ur-
ban practices from a practice-based network to con-
duct a retrospective cohort study comparing the
numbers of AGE emergency department (ED) visits
and hospitalizations in RVV-immunized (exposed)
and non-immunized (unexposed) children during the
first 2 full seasons following RVV introduction. We
determined incident rate ratios (IRR), using Poisson
regression, and vaccine effectiveness for each out-
come. Results: The 2007 and 2008 cohorts were ana-
lyzed separately. 62% of the 2007 cohort was vacci-
nated and 88% of the 2008 cohort. AGE hospitaliza-
tions were significantly reduced among RVV-immu-
nized children from the 2007 cohort in the 2008 sea-
son with vaccine effectiveness of 67%. Sub-analysis of
this cohort by age revealed that RVV was most pro-
tective against hospitalizations in the youngest age
group (IRR = 0.21, 95% CI (0.06, 0.82). A trend to-
ward protection against hospitalization was detected
for both cohorts in the first season following immu-
nization that did not reach a statistically significant
level. For AGE ED visits, no significant difference
was seen between RVV-immunized and non-immu-
nized children in either cohort, although there was a
trend toward protection (IRR’s: 0.67 - 0.7). Conclu-
sions: RVV was highly effective in preventing AGE
hospitalizations for a subset of our cohort in 2008.
Given reports of RVV effectiveness, we hypothesize
that herd immunity is responsible for the inability to
detect a significant difference between RVV-immu-
nized and non-immunized children in our highly-
vaccinated cohort.
Keywords: Rotavirus; Pediatrics; Acute Gast roenteritis
Prior to the introduction of rotavirus vaccine (RVV) in
2006, rotavirus (RV) was the most common cause of
acute gastroent eritis (AGE) among children unde r 5 years
of age in the United States [1]. Recent surveillance data
and several post-licensure studies have shown sign ificant
reductions in RV disease activity and RV-related health-
care encounters [2,3]. In this report, we examine the ef-
fectiveness of RVV in preventing hospital-related AGE
outcomes in a highly vaccinated urban cohort of children
enrolled in a pediatric practice-based research network.
2.1. Study Design
A retrospective cohort study was performed evaluating
the effectiveness of RVV in preventing AGE emergency
department (ED) visits and hospitalizations during the
first two full RV seasons after RVV introduction.
2.2. Study Setting
The CHOP network includes 33 ambulatory pediatric
practices, of which 5 are located within 2 miles of
CHOP’s main hospital. These practices refer >90% of
children to CHOP’ s main hospital for emergency care and
hospitalization [4] and use the EpicCare (Verona, WI)
electronic health record (EHR). T he CHOP main hos pital
S. M. Nolan et al. / Open Journal of Pediatrics 1 (2011) 41-44
is a tertiary care pediatric hospital with over 24,000 in-
patient admissions and 70,000 ED visits annually. All
CHOP ED visits and hospitalizations are captured in the
2.3. Study Populations
The study population included any child born between
February 22, 2006 (RotaTeq® licensure date; RotaTeq®
was the only RVV available in the US during the study
period) and February 29, 2008, who had at least one visit
at one of the 5 selected sites prior to 2 months of age.
Children were divided into 2 distinct cohorts: 1) the 2007
cohort included children eligible for AGE outcomes in
both the 2007 and 2008 seasons and 2) the 2008 cohort
included child ren eligib le for AGE outcomes in the 200 8
season only.
2.4. Exposures and Outcomes
The exposure was recei pt of any number of dos es of RVV
(1, 2 or 3); unexposed patients received zero RVV doses.
The primary outcomes were AGE-related ED visits and
hospitalizations, defined as any ED or hospital encounter
with a diagnosis code for a diarrheal illness using the
AGE ICD-9-CM codes: 001 - 005, 006 - 007, 008 - 008.5,
008.6, 008.61, 008.8, 009 - 009.3, 558.9, 787 - 787.03,
787.91 [5]. Outcomes were not assessed until the child
was 6 week s of age (ear liest recommended age for RVV
2.5. Data Collection
The EHR was queried to identify total numbers of AGE
ED visits and hospitalizations, subject demographics,
other immunizations received, complex chronic condi-
tions (CCC) [6], and numbers of primary care sick and
preventativ e visits.
2.6. Statistical Methods
We characterized cohort subjects by all potential risk
factors. We compared demographic variables and health-
care utilization between RVV-immunized and non-im-
munized groups using chi-square analysis for categorical
variables a nd s tude nt’s t test f or cont in uous vari a bles. We
conducted univa riable analyses using Poisso n regression
to determine associations between potential risk factors
and outcomes.
For the multivariable analysis, we estimated the asso-
ciation between RVV exposure and the outcomes for each
season using Poisson regression. All potential confound -
ers and risk factors with a p value < 0.2 on univariable
analysis were included in the multivariable model. We
used a stratified analysis to assess effect modification.
Vaccine effectiveness (VE) in preventing AGE out-
comes was calculated using the formula: VE = (1-Inci-
dent Rate Ratio (IRR)) × 100, where IRR is the adjusted
ratio for each AGE outcome among vaccinated versus
unvaccinated subjects [7].
3.1. Characteristics of the Study Population
The study population included 2 cohorts: 3278 children in
the 2007 cohort and 2705 children in the 2008 cohort.
Among the 2007 cohort, 62% received at least 1 RVV
dose and 43% were fully vaccinated with 3 doses. For
the 2008 cohort, 88% received at least 1 dose and 63%
received 3 doses. Dem ographic characteristics of children
in the 2 cohorts were similar except non-vaccinated
children in the 2008 co hort were more likely to be black
(70.6% vs. 80%, p = 0.003). Non-vaccinated children had
lower rates of healthcare utilization than their vaccinated
peers; this disparity was more pronounced in the 2008
cohort. In 2007 and 2008, respectively 60% and 44% of
RVV-immunized children were up-to-date with recom-
mended preventative care visits, whereas 39% and 6% of
non-immunized children were up-to-date (p values <
3.2. AGE ED Visits and Hospitalizations
For both cohorts, there was a trend toward protection for
RVV-immunized children against AGE ED visits and
hospitalizations. However, the only statistically signifi-
cant protective effect was seen for the 2007 cohort in the
2008 season against hospitalizations (IRR 0.33, 95% CI
(0.11, 0.96)) with a VE of 67% (Table 1).
Sub-analyses demonstrated that the 3-dose regimen
was most protective against AGE hospitalizations in the
youngest age group (those 6 weeks of age at entry into the
first RV season) for the 2007 cohort in season 2008 (IRR
= 0.21, 95% CI (0 .06, 0.82), VE 79%) compared with 1
(IRR = 0.48, 95% CI (0.05, 4.29)) or 2 doses (IRR = 0 .42,
95% CI (0.09 , 1.95)). There was no signifi c ant p r ot ect i ve
vaccination effect in the older age groups regardless of
RVV dose number for either outcome.
In this cohort study of an urban pediatric healthcare
network with high rates of vaccination, we found a sig-
nificant reduction in AGE hospitalizations among RVV-
immunized children in the 2008 season. We demon-
strated by age and dose-stratified analysis that the 3-dose
RVV regimen was most effective in preventing AGE
hospitalizations among the you ngest ch ildren in the 2007
cohort during the second RV season.
For AGE hospitalizations, RVV-immunized children
from the 2007 cohort were protected in the 2008 season
with VE of 67%. This finding is similar to other cohort
studies which demonstrated VE ranging from 59% -
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Table 1. IRR for AGE-related ED visits and hospitalizations.
2007 Cohort 2008 Cohort
2007 Season 2008 Season 2008 Season
RVV Immunized
N = 2031 RVV Non-Immunized
N = 1247 RVV Immunized
N = 2031 RVV Non-Immunized
N = 1247 RVV Immunized
N = 2395 RVV Non-Immunized
N = 310
AGE ED Visitsa 88 (4.3%) 71 (5.7%) 151 (7.4%) 65 (5.2%) 184 (7.7%) 22 (7.1%)
(95% CI)b 0.69
(0.27, 1.76) 0.67
(0.41, 1.11) 0.70
(0.25, 1.99)
AGE Hospitalizations a 32 (1.6%) 19 (1.5%) 18 (0.9%) 8 (0.6%) 48 (2%) 8 (2.6%)
AGE Hospitalization IRR
(95% CI)b 0.41
(0.15, 1.11) 0.33*
(0.11, 0.96) 0.46
(0.10, 2.13)
aPercentag e fo llo wing numb er is the p ercent of AGE ED vis it s or hospit ali zati ons for total N of each co lu mn; bIRR’s adjust ed fo r ag e at star t o f 1st s easo n, race,
presence of a chronic condition, preventative visits up-to-date at 14months, non-rota immunizations up-to-date by 7 months, total sick visits, time in cohort, and
include a term for interaction between RV immunization and age; *Value statistically significant.
66% [8,9]. The reason for greater VE among younger
infants in the 2007 cohort in the 2008 season is unclear
and has not been previously described. Those infants
received their RVV doses more recently so may have
had higher titers of anti-RV antibodies and, therefore,
increased protection during the 2008 season as compared
with older children from the 2007 cohort. The smaller
number of unvaccinated patients in the 2008 cohort may
have affected our ability to detect a statistical difference
between RVV-immunized and non-immunized patients
in that cohort. In the context of findings by Clark et al.,
which describe a 77% reduction in hospitalizations for
community-acquired RV disease at CHOP for the 2008
season compared with the mean from 13 prior seasons
[10], we believe indirect protection by herd immunity is
a likely possibility for our inability to detect a significant
vaccine effect in this highly vaccinated population.
We thank the network of primary care physicians, their patients and
families for their contribution to clinical research through the Pediatric
Research Consortium (PeRC) at CHOP. And we thank Jonathan Cros-
sette and Svetlana Ostapenko from the CHOP Center for Biomedical
Informatics for their assistance with data abstraction for this study.
The project described was supported by Award Number F32HD062184
from the Eunice Kennedy Shriver National Institute Of Child Health &
Human Development and by a research grant from the Merck Investi-
gator-Initiated Studies Program of Merck Sharp & Dohme Corp. The
content is solely the responsibility of the authors and does not neces-
sarily represent the official views of the Eunice Kennedy Shriver Na-
tional Institute Of Child Health & Human Development or the National
Institutes of Health or those of Merck Sharp & Dohme Corp.
There were several limitations for this study. By using
AGE as an outcome, we cannot truly assess the reduc-
tion in RV disease due to RVV. However, viral stool
pathogen testing was not uniformly conducted so we
could not capture RV-specific disease as a retrospective
outcome. Despite previous validation, identifying AGE
outcomes using ICD-9-CM codes, may introduce bias
due to error in both physician diagnosis and the re-
cording of codes. Also, we used retrospective data and
only captured ED visits and hospitalizations at CHOP’s
main hospital. If parents sought care for their children
elsewhere, our data capture may be incomplete.
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