Impact of rotavirus vaccine on acute gastroenteritis emergency department visits and hospitalizations in a highly-vaccinated urban cohort

doi:10.4236/ojped.2011.14012

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Open Journal of Pediatrics, 2011, 1, 41-44

doi:10.4236/ojped.2011.14012 Published Online December 2011 (http://www.SciRP.org/journal/ojped/ OJPed

)

Published Online December 2011 in SciRes. http://www.scirp.org/journal/OJPed

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.

Email: [email protected]

Received 7 October 2011; revised 14 November 2011; accepted 22 November 2011.

ABSTRACT

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

1. INTRODUCTION

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. MATERIALS AND METHODS

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

EHR.

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

administration).

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. RESULTS

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 <

0.0001).

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.

4. DISCUSSION

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% -

S. M. Nolan et al. / Open Journal of Pediatrics 1 (2011) 41-44

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%)

AGE ED Visit IRR

(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.

5. ACKNOWLEDGEMENTS

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.

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AGE as an outcome, we cannot truly assess the reduc-

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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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