The n e w e ng l a n d j o u r na l of
original article
From the Epidemic Intelligence Service,
Office of Workforce and Career Develop-
ment (J.E.C.), Division of Viral Diseases
(J.E.C., A.T.C., J.E.T., M.M.C., M.M.P.,
U.D.P.), and Immunization Services Divi-
sion (F.Z.), Centers for Disease Control
and Prevention, Atlanta. Address reprint
requests to Dr. Parashar at the Centers
for Disease Control and Prevention, 1600
Clifton Rd., MS A-47, Atlanta, GA 30333,
or at uparashar@cdc.gov.
N Engl J Med 2011;365:1108-17.
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1108
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m e dic i n e
Rotavirus Vaccine and Health Care
Utilization for Diarrhea in U.S. Children
Jennifer E. Cortes, M.D., Aaron T. Curns, M.P.H., Jacqueline E. Tate, Ph.D.,
Margaret M. Cortese, M.D., Manish M. Patel, M.D., Fangjun Zhou, Ph.D.,
and Umesh D. Parashar, M.B., B.S., M.P.H.
A bs t r ac t
Background
Routine vaccination of U.S. infants with pentavalent rotavirus vaccine (RV5) began
in 2006.
Methods
Using MarketScan databases, we assessed RV5 coverage and diarrhea-associated health
care use from July 2007 through June 2009 versus July 2001 through June 2006 in
children under 5 years of age. We compared the rates of diarrhea-associated health
care use in unvaccinated children in the period from January through June (when
rotavirus is most prevalent) in 2008 and 2009 with the prevaccine rates to estimate
indirect benefits. We estimated national reductions in the number of hospitaliza-
tions for diarrhea, and associated costs, by extrapolation.
Results
By December 31, 2008, at least one dose of RV5 had been administered in 73% of
children under 1 year of age, 64% of children 1 year of age, and 8% of children 2 to
4 years of age. Among children under 5 years of age, rates of hospitalization for
diarrhea in 20012006, 20072008, and 20082009 were 52, 35, and 39 cases per
10,000 person-years, respectively, for relative reductions from 20012006 by 33%
(95% confidence interval [CI], 31 to 35) in 20072008 and by 25% (95% CI, 23 to 27)
in 20082009; rates of hospitalization specifically coded for rotavirus infection
were 14, 4, and 6 cases per 10,000 person-years, respectively, for relative reductions
in the rate from 20012006 by 75% (95% CI, 72 to 77) in 20072008 and by 60%
(95% CI, 58 to 63) in 20082009. In the JanuaryJune periods of 2008 and 2009, the
respective relative rate reductions among vaccinated children as compared with
unvaccinated children were as follows: hospitalization for diarrhea, 44% (95% CI,
33 to 53) and 58% (95% CI, 52 to 64); rotavirus-coded hospitalization, 89% (95% CI,
79 to 94) and 89% (95% CI, 84 to 93); emergency department visits for diarrhea,
37% (95% CI, 31 to 43) and 48% (95% CI, 44 to 51); and outpatient visits for diar-
rhea, 9% (95% CI, 6 to 11) and 12% (95% CI, 10 to 15). Indirect benefits (in unvac-
cinated children) were seen in 20072008 but not in 20082009. Nationally, for the
20072009 period, there was an estimated reduction of 64,855 hospitalizations,
saving approximately $278 million in treatment costs.
Conclusions
Since the introduction of rotavirus vaccine, diarrhea-associated health care utiliza-
tion and medical expenditures for U.S. children have decreased substantially.
n engl j med 365;12 nejm.org september 22, 2011
The New England Journal of Medicine
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 Rotavirus Vaccine and Health Care for Diarrhea
B
efore February 2006, when routine
vaccination of infants in the United States
with pentavalent rotavirus vaccine (RV5)
was recommended, rotavirus diarrhea caused an
estimated 400,000 visits to physicians offices,
200,000 emergency department visits, 55,000 hos-
pitalizations, and 20 to 60 deaths annually among
children under 5 years of age in the United States,
for an annual total medical cost of approximately
$300 million.1,2 RV5 is administered orally in chil-
dren in three doses, one each given at 2, 4, and
6 months of age.3,4 In trials, use of RV5 reduced
the incidence of rotavirus-related hospitalizations
or emergency department visits by more than 90%
and outpatient visits by 84%.5,6
Severe rotavirus disease has declined substan-
tially since the introduction of RV5.7-11 Few reports
have correlated declines in disease with popula-
tion vaccine coverage. Also, most reports have
documented declines in hospitalizations only. Data
regarding the effect of RV5 on diarrhea treated in
ambulatory settings are limited.
We used MarketScan databases to correlate RV5
coverage with changes in the rates of diarrhea-
associated hospitalizations, emergency department
and outpatient visits, and treatment costs after
RV5 introduction. We examined both direct and
indirect vaccine benefits and estimated the na-
tional reduction in hospitalizations for diarrhea
and associated costs after the start of RV5 admin-
istration.
Me thods
Data Source
Data from the 20012009 MarketScan Commer-
cial Claims and Encounters database were ana-
lyzed.12 MarketScan data are derived from insur-
ance claims and contain de-identified information
from various public and private health plans, in-
cluding health maintenance organizations, fully or
partially capitated health plans, preferred-provider
organizations, point-of-service plans, indemni-
ty plans, and consumer-directed health plans.
Medicaid recipients are not included. In 2007,
MarketScan databases contained nearly 30 mil-
lion enrollees from all 50 U.S. states. Data from
approximately 2 million children under 5 years
of age were captured during the study period.
Diarrhea-associated health care events were
identified with the use of the following Interna-
tional Classification of Diseases, 9th Revision, Clinical
n engl j med 365;12 nejm.org september 22, 2011
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Modification (ICD-9-CM) codes: viral enteritis,
008.6008.8 (including rotavirus, 008.61); bac-
terial enteritis, 001.0005.9 (excluding 003.2) and
008.0008.5; parasitic intestinal disease, 006.0
007.9 (excluding 006.3006.6); presumed infec-
tious diarrhea, 009.0009.3; presumed noninfec-
tious diarrhea, 558.9; and diarrhea not otherwise
specified, 787.91. An event identified as the pri-
mary discharge diagnosis or 1 of 15 other possible
discharge diagnoses for the inpatient-admissions
table was classified as a hospitalization. An event
identified in 1 of the 2 diagnosis fields in the
outpatient-services table was classified as an out-
patient visit. Events were classified as emergency
department visits (not hospitalizations or outpa-
tient visits) if urgent care facility or emergency
room was specified in either the inpatient-servic-
es table or the outpatient-services table. Patients
evaluated in more than one setting for the same
diarrhea episode may have had multiple encoun-
ters recorded in the database for the one episode.
RV5 Coverage
Using data from the January 2006June 2009 pe-
riod, we assessed RV5 coverage (defined as admin-
istration of at least one dose of RV5) in a subgroup
of children with continuous enrollment in one in-
surance plan from birth through at least 3 months
of age. The criterion of continuous enrollment en-
sured that nearly all vaccinations billed for were
captured. Children from 13 states with universal
vaccination programs that include RV5 or where
RV5 inclusion could not be ascertained (Alaska,
Idaho, Massachusetts, Maine, North Dakota, New
Hampshire, New Mexico, Oregon, Rhode Island,
Vermont, Washington, Wisconsin, and Wyoming)
were excluded from the coverage assessment. Vac-
cinations in these states were not likely to have
been billed to third-party payers and thus would
probably not be recorded in this database.
Within the coverage cohort, we identified en-
rollees who received RV5 by using the Current
Procedural Terminology (CPT) code 90680 and
identified those who received the monovalent ro-
tavirus vaccine (RV1), recommended in June 2008,
by using the CPT code 90681. Coverage on Decem-
ber 31, 2007, and on December 31, 2008, was as-
sessed on the basis of age group and region. To
validate results, we compared coverage with at
least one dose of diphtheriatetanusacellular per-
tussis vaccine (DTaP) by 3 months of age in the
MarketScan database with coverage reported by
1109
 The n e w e ng l a n d j o u r na l of m e dic i n e

the National Immunization Survey, considered the 1 year of age had received at least one RV1 dose as
U.S. standard for vaccine coverage.13 of December 31, 2008).

Trends in Diarrhea-Associated Direct Benefits

health care Utilization
We examined diarrhea-associated health care utili-
zation rates for enrollees under 5 years of age who
were seen in inpatient, emergency department,
and outpatient settings. We also assessed rates of
rotavirus-coded hospitalization (i.e., hospitaliza-
tion for diarrhea with the ICD-9-CM code for rota-
virus, 008.61); the numbers of emergency depart-
ment or outpatient visits for diarrhea that had the
rotavirus-specific code were too small to analyze.
Data from all states, including those with univer-
sal vaccination programs, were included in the
analysis of trends. Because the information in the
database was restricted to children who were en-
rolled in an insurance plan, we used the number of
days each child was enrolled per calendar month
and year of the study as the follow-up time in cal-
culating utilization rates per 10,000 person-years
of follow-up.
To compare diarrhea-associated health care uti
lization rates before and after the introduction of
RV5, we evaluated rates over each of two 1-year post
vaccine periods (July 2007June 2008 and July 2008
June 2009) and compared them with the annual
mean rates during the 5-year prevaccine baseline
period (July 2001June 2006), according to age
group (<1 year, 1 year, and 2 to 4 years) and cen-
sus region (Northeast, Midwest, South, and West).
Because rotavirus is most prevalent from January
through June, we also restricted analyses to this
6-month period, for improved specificity. The
period from July 2006 through June 2007 was
considered a transition year and was excluded
from analyses, since recommendations for RV5
use were not published until August 2006.4
Vaccine Benefits
We restricted analyses of direct and indirect vaccine
benefits to children who were age-eligible to re-
ceive at least one RV5 dose before the 2008 rotavi-
rus season (i.e., who were 3 through 23 months of
age by January 2008) and who were continuously
enrolled in the same insurance plan from birth
through June 2008. We used the same approach for
the 2009 rotavirus season. Children from states
with universal vaccination programs were exclud-
ed. In addition, children who received RV1 were
excluded (only approximately 1% of children under
To examine direct vaccine benefits, we compared
rates of rotavirus-coded hospitalization and di-
arrhea-associated health care utilization rates in
the JanuaryJune 2008 and 2009 periods among
vaccinated versus age-eligible, unvaccinated chil-
dren. Since RV5 was recently introduced, vaccine
coverage by month of birth was not uniform be-
fore the study period. Therefore, risk ratios and
95% confidence intervals were adjusted for month
of birth by means of Poisson regression for hospi-
talizations and binomial regression for emergency
department and outpatient visits. The adjusted es-
timates were subtracted from 1 to obtain adjusted
rate reductions.
Indirect Benefits
To examine indirect benefits of the vaccine (i.e.,
indirect protection of unvaccinated persons be-
cause vaccinated persons did not contract and
transmit disease), we compared rates of rotavirus-
coded hospitalization and diarrhea-associated
health care utilization rates among age-eligible,
unvaccinated children from January through June
in 2008 and in 2009 with prevaccine rates for
children under 2 years of age. The relative rate re-
ductions and 95% confidence intervals were cal-
culated with the use of standardized morbidity
ratios, with prevaccine rates as the baseline data.14
Estimation of National Reductions
in Hospitalization Rates and Costs
By extrapolating observed diarrhea-associated hos-
pitalization rates from July 2007 through June
2009 to the 2009 U.S. population under 5 years of
age, we estimated the national burden of diarrhea-
associated hospitalizations after the introduction
of RV5. We then determined the median total pay-
ments for diarrhea-associated hospitalizations and
converted them to 2009 constant dollars on the
basis of the Bureau of Labor Statistics Consumer
Price Index for medical care.15 Median payments
were multiplied by the number of diarrhea-asso-
ciated hospitalizations to estimate national pay-
ments. Baseline payments were derived according
to prevaccine rates. The estimated reduction in hos-
pitalization costs was calculated as the difference
between national payments before and after the
introduction of RV5.

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 Rotavirus Vaccine and Health Care for Diarrhea

Table 1. Mean Annual Rates of Hospitalization for Rotavirus-Coded Diarrhea among Children under 5 Years of Age before and after Rotavirus-
Vaccine Introduction in 2006 and Vaccine Coverage in December 2007 and 2008, According to Age Group and Region.

Variable 20012006* 20072008 20082009

Rate Coverage on Coverage on
Hospitalization Hospitalization Reduction December 31, Hospitalization Rate Reduction December 31,
Rate Rate (95% CI) 2007 Rate (95% CI) 2008
no./10,000 person-yr percent no/10,000 person-yr percent
Age group
<5 yr 14 4 75 (7277) 17 6 60 (5863) 32
<1 yr 16 3 81 (7784) 64 4 78 (7481) 73
1 yr 33 9 72 (6976) 23 9 74 (7177) 64
24 yr 8 2 72 (6776) 0 6 26 (1932) 8
Region
Northeast 10 2 82 (7488) 16 4 63 (5371) 30
Midwest 15 4 75 (7178) 17 7 50 (4456) 31
South 19 4 80 (7882) 19 6 66 (6369) 34
West 8 4 45 (3354) 15 2 71 (6477) 29

* For 20012006, the mean of the annual rates is shown.

Coverage was defined as receipt of at least 1 dose of RV5 by December 31, 2007, or December 31, 2008, in children who had been in the data-
base since birth and for at least 3 months continuously. Coverage for children under 1 year of age was restricted to those who were eligible
for vaccination (i.e., those 3 through 11 months of age).
Regional estimates are for children under 5 years of age.

R e sult s pattern of rotavirus-coded hospitalizations (Fig. 1).

Rotavirus-Vaccine Coverage
In a cohort of nearly 300,000 children under 5 years
of age from 37 states, 32% had received at least
one dose of RV5 by December 31, 2008, with the
percentage increasing steadily since vaccine licen-
sure. At the same time point, coverage was 73%
among children under 1 year of age, 64% among
1-year-olds, and 8% among 2-to-4-year-olds; rates
were similar across regions (Table 1). In the same
cohort, the proportion of children who had re-
ceived at least one DTaP dose by 3 months of age
was 88%, as compared with 89% according to the
National Immunization Survey.13
Trends in Diarrhea-Associated Health Care
Utilization
During the 20012009 period, a total of 40,574
hospitalizations, 170,082 emergency department
visits, and 1,254,613 outpatient visits that were
associated with diarrhea were recorded among
children under 5 years of age. Baseline monthly
diarrhea-associated health care utilization rates
peaked in the FebruaryMarch period of each year
in all settings, which is similar to the seasonal
In 20072008, this winterspring peak had a de-
layed onset and was blunted, as compared with
the peak in prevaccine years, in all settings. In
20082009, the winterspring peak was present
but was smaller in magnitude than the peak in
prevaccine years.
In 20072008, annual rates of hospitalization
for rotavirus-coded diarrhea among children under
5 years of age declined by 75% (calculated accord-
ing to numbers before rounding), from a baseline
of 14 hospitalizations per 10,000 person-years to
4 per 10,000 person-years (Table 1). Declines were
similar across age groups despite variations in vac-
cine coverage, including negligible coverage among
2-to-4-year-olds. In 20082009, annual rates of
hospitalization for rotavirus-coded diarrhea de-
clined by 60% from baseline rates, and the de-
clines by age group were proportional to vaccine
coverage; rates declined by 26% among children
2 to 4 years of age (with 8% coverage [defined as
administration of at least one dose of RV5] in this
age group), whereas the rate declined by 76%
among children 1 year of age or younger (approxi-
mately 68% coverage). The Northeast, Midwest,
and South had rates that decreased by 75% or

n engl j med 365;12 nejm.org september 22, 2011 1111

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Figure 1. Diarrhea-Associated Health Care Utilization

A Hospitalizations among Children under 5 Years of Age According to
200 Diarrhea Month and Setting, January 2001June 2009.
Rotavirus-coded Rates per 10,000 person-years are shown for hospitaliza-
diarrhea tions (Panel A), emergency department visits (Panel B),
Hospitalizations per 10,000 Person-Yr

160 and outpatient visits (Panel C).

more in 20072008 and by 50% or more in 2008

120
2009. In contrast, the West had a 45% decrease in
20072008 but a 71% decrease in 20082009.
80 After RV5 was introduced, annual rates of di-
arrhea-associated hospitalization among all chil-
dren under 5 years of age were 33% and 25% lower
40 in 20072008 and 20082009, respectively, than in
20012006 (Table 2). Annual rates of emergency
department and outpatient visits declined by 9%
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 and 3%, respectively, in 20072008. The annual
rates in 20082009 in both settings were similar
B Emergency Department Visits to the prevaccine rates. In both periods, 1-year-old
500
children had the largest decreases in rates of diar-
rhea-associated hospitalization. Although the hos-
400
pitalization rate in 20072008 was reduced by 34%
among children 2 to 4 years of age, the reduction
Visits per 10,000 Person-Yr

in 20082009 was a modest 9%. Rates of emer-

300 gency department and outpatient visits were re-
duced among children under 1 year of age and
among 1-year-old children in each postvaccine year.
200
Children 2 to 4 years of age had higher rates of
emergency department and outpatient visits in
100
20082009 than in the prevaccine years.
Overall, for children under 5 years of age, all
regions had significant reductions in the rates of
0 hospitalization for diarrhea, with the South hav-
2001 2002 2003 2004 2005 2006 2007 2008 2009
ing the largest decreases over the 2-year period
C Outpatient Visits after vaccine introduction (Table 1 in the Supple-
3000 mentary Appendix, available with the full text of
this article at NEJM.org). The Northeast and Mid-
west rates decreased from 34% each in 20072008
2500
to 13% and 20%, respectively, in 20082009. In
Visits per 10,000 Person-Yr

contrast, reductions in the West increased from

2000
17% in 20072008 to 30% in 20082009. In
20072008, emergency department and outpatient
1500 visits declined in all regions except the West, but
to a lesser extent than hospitalizations. Although
1000 declines were not maintained in 20082009 in
the other regions, emergency department and out-
500
patient visits for diarrhea did decline in the West.
When analyses were restricted to the rotavirus
season, January through June, in both 2008 and
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2009, declines in rates of diarrhea-associated hos-
pitalizations among children under 1 year of age

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 Table 2. Mean Annual Rates of Diarrhea-Associated Health Care Utilization among Children under 5 Years of Age before and after Rotavirus-Vaccine Introduction, According to Age
Group and Health Care Setting.*

Age Group JulyJune JanuaryJune

Health Care Utilization Rate Rate Reduction (95% CI) Health Care Utilization Rate Rate Reduction (95% CI)
20012006 20072008 20082009 20072008 20082009 20022006 2008 2009 2008 2009
no./10,000 person-yr percent no./10,000 person-yr percent
Hospitalizations
<5 yr 52 35 39 33 (31 to 35) 25 (23 to 27) 78 41 51 47 (45 to 49) 34 (32 to 36)
<1 yr 65 50 45 24 (20 to 27) 30 (27 to 34) 103 61 60 41 (37 to 45) 41 (37 to 45)
1 yr 96 56 60 41 (38 to 44) 38 (35 to 41) 150 70 76 53 (50 to 56) 49 (46 to 52)
24 yr 32 21 29 34 (31 to 37) 9 (5 to 13) 46 25 40 46 (42 to 49) 12 (8 to 16)
Emergency department
visits
<5 yr 185 169 188 9 (7 to 10) 2 (3 to 0) 254 195 240 23 (22 to 25) 6 (4 to 7)
<1 yr 212 204 185 4 (1 to 6) 13 (11 to 15) 320 244 243 24 (21 to 26) 24 (22 to 26)
1 yr 324 282 298 13 (11 to 15) 8 (6 to 10) 462 332 369 28 (26 to 30) 20 (18 to 22)
24 yr 130 119 155 9 (7 to 11) 19 (21 to 17) 166 134 198 19 (16 to 21) 20 (22 to 17)

The New England Journal of Medicine

n engl j med 365;12 nejm.org september 22, 2011
Outpatient visits
<5 yr 1348 1303 1360 3 (3 to 4) 1 (1 to 0) 1659 1404 1530 15 (15 to 16) 8 (7 to 8)
<1 yr 1713 1608 1499 6 (5 to 7) 13 (12 to 13) 2377 1870 1816 21 (20 to 22) 24 (23 to 24)
Rotavirus Vaccine and Health Care for Diarrhea

1 yr 2376 2264 2355 5 (4 to 5) 1 (0 to 2) 2926 2393 2547 18 (17 to 19) 13 (12 to 14)

Copyright 2011 Massachusetts Medical Society. All rights reserved.

24 yr 871 871 984 0 (1 to 1) 13 (14 to 12) 1002 922 1104 8 (7 to 9) 10 (11 to 9)

* Regional data are provided in Table 1 in the Supplementary Appendix.

For 20012006 and 20022006, the mean of the annual rates is shown.

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1113
 The n e w e ng l a n d j o u r na l
and those 1 year old were greater than but similar
in pattern to those observed annually (Table 2, and
Table 1 in the Supplementary Appendix). Rates of
hospitalization for diarrhea among 2-to-4-year-
olds were reduced in both years, although to a
lesser extent in 2009. The rates of emergency de-
partment and outpatient visits for diarrhea were
reduced in 20072008, but they were increased in
20082009. According to region, rates of diarrhea-
associated hospitalization in 20072008 decreased
by approximately 50% each in the Northeast, Mid-
west, and South and by 25% in the West. In 2008
2009, the rate reductions were approximately 25%
in the Northeast and Midwest, 43% in the South,
and 31% in the West.
Direct Benefits of Vaccine
Vaccinated children had 89% fewer rotavirus-coded
hospitalizations than unvaccinated children in
each of the two postvaccine rotavirus seasons (Ta-
ble 3, and Table 2 in the Supplementary Appendix).
The magnitude of direct vaccine benefits was sim-
ilar across regions, but because of the small num-
ber of rotavirus-coded hospitalizations in the
Northeast in 2008 and in the West in 2009, esti-
mates were unreliable. Rates were also significant-
ly reduced among vaccinated children as compared
with unvaccinated children for both 20072008
and 20082009 for hospitalization for diarrhea
of any cause (44% and 58%, respectively), emer-
gency department visits (37% and 48%), and out-
patient visits (9% and 12%).
Indirect Benefits of Vaccine
Substantial reductions occurred in rates of health
care utilization for diarrhea of any cause and for
rotavirus-coded diarrhea among age-eligible, un-
vaccinated children in all settings during the Janu-
aryJune period of 2008, as compared with pre-
vaccine rates, with the exception of rates in the
West (Table 4, and Table 3 in the Supplementary
Appendix). Such reductions did not occur during
the JanuaryJune period of 2009 in most regions
in the inpatient and emergency department set-
tings, but substantial reductions did occur in the
outpatient setting.
Estimated National Reduction
in Hospitalizations and Associated Costs
We estimated that, nationally, 64,855 hospitaliza-
tions for diarrhea were averted among children un-
der 5 years of age during the 2 postvaccine years
studied. By applying this reduction to the median
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of m e dic i n e
payment for a diarrhea-associated hospitaliza-
tion in the MarketScan database in 20082009, we
estimated that hospitalization costs were reduced
by $278 million for the 2-year period (Table 5).
Discussion
Rates of diarrhea-associated hospitalizations and
ambulatory visits among U.S. children under
5 years of age declined during both rotavirus sea-
sons (in 20072008 and 20082009) after the intro-
duction of RV5. The findings that reductions were
greater during the months when rotavirus was
prevalent and that rates of rotavirus-coded hospi-
talization declined by 60% to 75% support the
suggestion that the observed changes were largely
attributable to declines in the rate of rotavirus dis-
ease. Nationally, we estimated that approximately
65,000 diarrhea-associated hospitalizations were
prevented during the 20072009 period, resulting
in a reduction of $278 million in treatment costs.
Our findings confirm other reports of a decline
in rotavirus activity in the United States after the
introduction of rotavirus vaccine.7-11,16,17 They also
show the effect of the vaccine on emergency de-
partment and outpatient visits for diarrhea. The
observed 89% reduction in the most specific
outcome, rotavirus-coded hospitalizations, in vac-
cinated children as compared with unvaccinated
children is consistent with the efficacy of the vac-
cine in prelicensure trials.5 Although the reduc-
tion in hospitalizations for diarrhea from any
cause (by 44%) in vaccinated versus unvaccinated
children in 20072008 was somewhat lower than
the 59% reduction seen in prelicensure trials,5 the
reduction in 20082009 (by 59%) was virtually
identical.18 The smaller reduction in 20072008
may be attributable, in part, to the marked de-
cline in rotavirus activity in that season, which
probably diminished the proportion of hospital-
izations for diarrhea from any cause that were
attributable to rotavirus.
Although the direct benefits of vaccination were
similar in 20072008 and 20082009, the indirect
benefits differed. In 20072008, indirect benefits
were evidenced by declines in rotavirus disease that
greatly exceeded expected declines, given the level
of RV5 coverage, and that were also substantial
among unvaccinated 2-to-4-year-olds. In addition,
in all regions except the West, diarrhea-associated
rates of health care utilization among age-eligible,
unvaccinated children during the 20072008 pe-
riod were lower than baseline prevaccine rates, a
 Rotavirus Vaccine and Health Care for Diarrhea

Table 3. Reduction in Rates of Diarrhea-Associated Hospitalization among Children Who Received at Least One Dose
of RV5 versus Unvaccinated Children Who Were Age-Eligible for RV5, According to Study Period and Region.*

Region JanuaryJune 2008 JanuaryJune 2009

Hospitalization Rate Reduction Hospitalization Rate Reduction
Rate (95% CI) Rate (95% CI)
Vaccinated Unvaccinated Vaccinated Unvaccinated
no./10,000 person-yr percent no./10,000 person-yr percent
Rotavirus-coded diarrhea
All 3 24 89 (79 to 94) 5 42 89 (84 to 93)
Northeast 0 5 5 17 75 (35 to 96)
Midwest 1 25 90 (68 to 97) 4 51 92 (83 to 96)
South 5 24 88 (73 to 94) 6 46 88 (80 to 93)
West 1 35 94 (39 to 99) 0 16
Any diarrhea
All 57 91 44 (33 to 53) 53 131 58 (52 to 64)
Northeast 51 65 50 124 57 (25 to 76)
Midwest 30 82 52 (33 to 66) 46 131 64 (53 to 73)
South 71 96 43 (28 to 55) 59 137 56 (46 to 63)
West 64 113 51 (19 to 71) 43 106 61 (38 to 76)

* Children who were age-eligible for vaccine were 3 through 23 months old at the start of each study period (January 1, 2008,
and January 1, 2009) and were continuously enrolled in their insurance plan from birth through the end of each study
period (June 30, 2008, and June 30, 2009). Vaccination status was determined by the presence or absence of a current
procedural terminology code for receipt of at least one dose of RV5. Children who had received one or more doses of
RV1 (<1% of age-eligible children) were excluded. Rates were adjusted for month of birth. For rates of health care utili-
zation in emergency department and outpatient settings, see Table 2 in the Supplementary Appendix.
Rate reductions for rotavirus-coded diarrhea and any diarrhea events in the Northeast and rotavirus-coded diarrhea in
the West became unreliable owing to small numbers of events.

finding that supports indirect benefits. In 2008
2009, however, the indirect benefits were smaller
and were inconsistent across settings.
Regional variation in the effect of vaccination
was also observed. In 20072008, the West had a
smaller decline in the rate of diarrhea-associated
hospitalizations than other regions, and the rate of
emergency department visits for diarrhea increased
as compared with prevaccine rates. Furthermore,
in the JanuaryJune period in 2008, among age-
eligible, unvaccinated children under 2 years of
age, rates of hospitalization for rotavirus-coded
diarrhea, as well as rates of health care utilization
for any diarrhea, exceeded prevaccine rates in the
West but declined in all other regions. RV5 cov-
erage and direct vaccine benefits were similar in
the West and in other regions, suggesting that
the discrepant data cannot be attributed to these
factors. A recent mathematical-modeling study
revealed a correlation between the traditional ear-
lier onset of rotavirus activity in the West, as com-
pared with other U.S. regions, and the birth rate
in Western states, which is approximately 10%
higher than in other regions19,20; this relationship
may be the result of faster growth of the popula-
tion of susceptible infants through new births.
Similarly, greater vaccine coverage may be needed
in the West to reduce rotavirus transmission to
the same extent as that seen in other regions with
lower coverage. The finding that in 20082009 re-
ductions in the West were more marked than in
other regions supports this hypothesis.
Some limitations of our study should be con-
sidered. First, we lacked data on uninsured and
Medicaid populations, as well as information on
race or ethnic group and on socioeconomic status,
all of which affect extrapolation to the general
U.S. population.
Second, no reliable, timely data on RV5 cover-
age were available to validate our estimates; how-
ever, concordance between our DTaP coverage data
and the National Immunization Survey data are
reassuring.
Third, states with universal vaccination pro-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 4. Rates and Rate Reductions for Diarrhea-Associated Hospitalization among Unvaccinated Children after RV5
Introduction, According to Study Period and Region.*

Region Hospitalization Rate Rate Reduction (95% CI)

20022006 2008 2009 2008 2009
number/10,000 person-yr percent
Rotavirus-coded diarrhea
All 45 24 42 46 (37 to 54) 6 (6 to 17)
Northeast 31 5 17 83 (48 to 94) 45 (10 to 73)
Midwest 49 25 51 50 (35 to 61) 4 (26 to 14)
South 60 25 46 60 (49 to 68) 24 (9 to 36)
West 21 35 16 65 (134 to 17) 21 (38 to 55)
Any diarrhea
All 125 91 131 27 (21 to 32) 5 (12 to 2)
Northeast 109 65 124 40 (18 to 56) 14 (48 to 12)
Midwest 122 82 131 33 (23 to 42) 7 (21 to 5)
South 155 96 137 38 (31 to 45) 12 (3 to 20)
West 81 113 106 39 (69 to 15) 30 (63 to 4)

* Data for 20022006 were averaged among children under 2 years of age during the JanuaryJune period of each year.
Data for 2008 and 2009 were averaged among unvaccinated children who were age-eligible for the vaccine: those 3 through
23 months of age by January 1, 2008, and January 1, 2009. Rate reductions for diarrhea-associated emergency department
and outpatient visits are provided in Table 3 in the Supplementary Appendix.

grams were excluded from analyses of vaccine
coverage and direct and indirect benefits. As a con
sequence, for the Northeast, where 5 of the 13 ex
cluded states are located, we were unable to gener-
ate reliable estimates for direct vaccine benefits in
inpatient settings.
Fourth, although we adjusted for age-related
variation in the risk of rotavirus disease and chang-
es in vaccine coverage over time by controlling for
month of birth, we may not have accounted for all
confounders.
Fifth, we examined data from only two post-
vaccine rotavirus seasons and cannot be certain
that observed changes were due solely to RV5 use.
Secular trends in the incidence of rotavirus and
other diarrheal pathogens could affect our find-
ings,9 particularly for emergency department and
outpatient settings, where rotavirus accounts for
a smaller proportion of all diarrhea events than
it does in hospitals.
Sixth, rotavirus testing and coding are not con-
sistently performed in health care settings and
could be influenced by knowledge of the childs
vaccination status. Thus, the effect of RV5 admin-
istration cannot be measured by means of data-
base evaluations alone, and other study designs,
which include laboratory testing for rotavirus in
patients with diarrhea, should be considered.
Seventh, although we estimated the postvac-
cination reduction in the costs of hospitalization
for diarrhea nationally, a formal costbenefit analy
sis that includes other key factors (e.g., the cost of
the vaccine program) is required to fully assess
the economic effect of vaccination.
Finally, we did not include information reflect-
ing either the health or economic effects of ad-
verse events related to rotavirus vaccination in our
analysis. A small increase in the risk of intussus-
ception (by 1 to 2 cases per 100,000 vaccinated
infants) has recently been reported in association
with rotavirus vaccination in Latin America and
Australia.21,22 Although this risk has not been
documented in the United States, if it is present,
it would translate into an excess of approximately
50 intussusceptions in a fully vaccinated national
birth cohort.23 Multiplying this number by the
median payment for visits in the MarketScan data-
base with an ICD-9-CM code for intussusception
(560.0) in inpatient, emergency department, and
outpatient settings results in an estimated total
health care cost of approximately $532,000. Thus,
this level of risk and its economic impact would
be far outweighed by the health and economic
benefits of vaccination reported in this study.
In conclusion, since the implementation of rou-
tine rotavirus vaccination of infants in the United

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 Rotavirus Vaccine and Health Care for Diarrhea

Table 5. Estimated Reductions in the Number and Cost of Diarrhea-Associated Hospitalizations among Children
under 5 Years of Age, after the Introduction of Rotavirus Vaccine.

Variable* Number and Cost Reduction

20012006 20072008 20082009 20072008 20082009 20072009
No. of hospitalizations 110,688 73,778 82,703 36,890 27,965 64,855
Cost of hospitalizations ($) 473,770,195 315,842,541 354,051,300 157,927,653 119,718,894 277,646,547

* Numbers of hospitalizations were derived by applying average rates of hospitalization for July 2001June 2006, July
2007June 2008, and July 2008June 2009 to the 2009 U.S. Census population estimate for children under 5 years of
age. Treatment costs were calculated by multiplying the number of hospitalizations by the inflation-adjusted median
payment per hospitalization during the July 2008June 2009 period ($4,281).

States, diarrhea-associated health care utilization
and medical expenditures have declined. Direct
vaccine benefits were consistent across the two
postvaccine seasons studied and were similar to
the benefits in prelicensure trials. Although in-
direct benefits were seen in 20072008, they were
smaller in 20082009. Continued surveillance is
needed to further characterize direct and indi-
rect vaccine effects, including those of the re-
cently approved rotavirus vaccine RV1, on diar-
rhea-associated health care utilization among U.S.
children.
The findings and conclusions of this report are those of the
authors and do not necessarily represent the views of the Cen-
ters for Disease Control and Prevention.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.

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