Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States
Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States
Minesh P. Shah 0 1
Rebecca M. Dahl 1
Umesh D. Parashar 1
Benjamin A. Lopman 1
0 Epidemic Intelligence Service, Office of Public Health Scientific Services, Centers for Disease Control & Prevention, Atlanta, Georgia, United States of America, 2 Division of Viral Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control & Prevention, Atlanta, Georgia, United States of America, 3 Maximus Federal, Atlanta, Georgia, United States of America, 4 Department of Epidemiology, Rollins School of Public Health, Emory University , Atlanta, Georgia , United States of America
1 Editor: Miren Iturriza-GoÂmara, University of Liverpool , UNITED KINGDOM
Hospitalizations for rotavirus and acute gastroenteritis (AGE) have declined in the US with rotavirus vaccination, though biennial peaks in incidence in children aged less than 5 years occur. This pattern may be explained by lower rotavirus vaccination coverage in US children (59% to 73% from 2010±2015), resulting in accumulation of susceptible children over two successive birth cohorts.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.
Retrospective cohort analysis of claims data of commercially insured US children aged <5
years. Age-stratified hospitalization rates for rotavirus and for AGE from the 2002±2015
rotavirus seasons were examined. Median age and rotavirus vaccination coverage for
biennial rotavirus seasons during pre-vaccine (2002±2005), early post-vaccine (2008±2011)
and late post-vaccine (2012±2015) years.
Age-stratified hospitalization rates decreased from pre-vaccine to early post-vaccine and
then to late post-vaccine years. The clearest biennial pattern in hospitalization rates is the
early post-vaccine period, with higher rates in 2009 and 2011 than in 2008 and 2010. The
pattern diminishes in the late post-vaccine period. For rotavirus hospitalizations, the median
age and the difference in age between biennial seasons was highest during the early
postvaccine period; these differences were not observed for AGE hospitalizations. There was
no significant difference in vaccination coverage between biennial seasons.
These observations provide conflicting evidence that incomplete vaccine coverage drove
the biennial pattern in rotavirus hospitalizations that has emerged with rotavirus vaccination
in the US. As this pattern is diminishing with higher vaccine coverage in recent years, further
increases in vaccine coverage may reach a threshold that eliminates peak seasons in
Prior to the 2006 recommendation of rotavirus vaccination in the United States (U.S.),
rotavirus was the leading cause of severe acute gastroenteritis (AGE) in children, with characteristic
annual peaks in incidence during winter-spring months [
]. The burden of rotavirus has
dramatically declined with vaccination, evidenced by decreased episodes of illness,
hospitalizations and emergency room visits for AGE [2±5]. Along with this decline, the epidemiology of
rotavirus has also changed to exhibit a biennial pattern, evidenced by higher rotavirus
incidence during rotavirus seasons (January-June) during odd years compared to lower incidence
in even years [
This biennial pattern of rotavirus incidence peaks is unique to the U.S. among high-income
countries that introduced national rotavirus vaccination programs around the same time;
rotavirus incidence has fallen and remained flat in Austria, Australia, Belgium and Finland [6±9].
Vaccine effectiveness [
] and circulating strain distribution [
] are similar in the U.S.
and these other countries, suggesting that these factors are unlikely to explain the unique
postrotavirus vaccine epidemiology in the U.S. Compared to the other high-income countries
that achieved high (84±93%) rotavirus vaccine coverage soon after introduction , vaccine
uptake grew slowly in the U.S., with less than 70% coverage prior to 2013, when coverage
reached 72.6%, and has since plateaued at 71.7% in 2014 and 73.2% in 2015 .
We hypothesize that the biennial pattern that emerged in the U.S., but absent in similar
epidemiological settings, might be due to lower vaccine coverage. A sufficient number of
susceptible children are required to sustain efficient transmission and a large seasonal epidemic. Prior
to rotavirus vaccination programs, this threshold was achieved every year with each birth
cohort made up of entirely susceptible children. Vaccination has reduced the annual number
of susceptible children [
]. Our hypothesis is that the observed biennial peaks in rotavirus
activity in the immediate years following vaccine introduction were driven by the requirement
of two successive birth cohorts to accumulate a sufficiently large pool of susceptible children to
drive efficient rotavirus transmission. As vaccine coverage increased in more recent years, the
number of susceptible children continues to decrease each year, leading to peaks of lower
Historical precedent for this phenomenon has been observed with measles virus in England
]. Prior to measles vaccination, seasonal peaks in measles hospitalizations were observed
every 2 years. After vaccine introduction, lower and less frequent peaks were observed until
vaccine coverage reached 90% in school-aged children, at which point the peaks disappeared
This hypothesis has yet to be empirically supported for rotavirus, and we would expect
certain patterns to be consistent with this explanation. First, we would expect an older age
distribution in the peak rotavirus seasons (odd calendar years), as the additional cases in those years
would occur in those susceptible children who avoided exposure in their first year of life (a low
transmission year), and became ill only when exposed in their second year of life (a high
transmission year). Second, we would expect that a larger proportion of the children who became ill
with rotavirus were unvaccinated in the peak rotavirus seasons than the low rotavirus seasons,
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evidence of the necessity of a threshold of susceptible (unvaccinated) patients to drive high
transmission. Further, we would not expect to see the annual variation in hospitalizations or
age prior to rotavirus vaccine introduction, and for these patterns to diminish as vaccine
coverage increases in the most recent years. Using an insurance claims database, we analyzed the
age distribution and vaccine coverage among children hospitalized with rotavirus and AGE
during rotavirus seasons from 2002±2005 (pre-vaccine), 2008±2011 (early post-vaccine), and
2012±2015 (late post-vaccine) years. 2006±2007 were excluded as transitional years.
Data from the 1997±2015 Truven Health Marketscan1 Commercial Claims and Encounters
Database were analyzed [
]. The commercial database collects data from large employers,
health plans and captures de-identified patient-level data from inpatient, outpatient and
prescription drug administrative claims for >230 million individuals ages 0 to 64 represented
from all 50 states. Medicaid recipients are not included. In 2015, 145 employers and 15 health
plans contributed to Marketscan databases. As 2002 was the first year that all age groups under
60 months were represented in Marketscan, we restricted our analysis to claims filed from
January 1, 2002 ±June 30, 2015. Infants residing in states with universal vaccine programs could
have received rotavirus vaccination without a corresponding claim, and thus were excluded
from this analysis [
]. Once a state was excluded it remained excluded even if the status of the
vaccine program changed. From 2007±2012, 13 states were excluded (Alaska, Idaho, Maine,
Massachusetts, New Hampshire, New Mexico, North Dakota, Oregon, Rhode Island,
Vermont, Washington, Wisconsin, Wyoming). After 2013, we also added states Connecticut and
South Dakota to the exclusion list.
Children under the age of 60 months with a hospitalization from January-June specifically for
rotavirus or any AGE were eligible for inclusion in the analysis. Hospitalizations were
classified by the presence of a relevant code for primary discharge diagnosis or 1 of 15 other possible
discharge diagnoses in the inpatient-admissions table, similar to previous analyses of similar
administrative datasets [
As hospital coding for rotavirus is specific but may lack sensitivity [
], we included
International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes
for both rotavirus (008.61) and AGE: viral enteritis, 008.6±008.8 (including rotavirus, 008.61);
bacterial enteritis, 001.0±005.9 (excluding 003.2) and 008.0±008.5; parasitic intestinal disease,
006.0±007.9 (excluding 006.3±006.6); presumed infectious diarrhea, 009.0±009.3; presumed
noninfectious diarrhea, 558.9; and diarrhea not otherwise specified, 787.91.
As birth dates are not reported in the database, the earliest claim date with the ICD-9-CM
codes for live born infants, V30-V39, was used to define the enrollee's date of birth. Age at
time of hospitalization was calculated as the difference in months from the date of birth to the
date of hospitalization. Age was grouped into 0±1, 2±3, 4±5, 6±11, 12±17, 18±23, 24±35, 36±47,
and 48±59 months. Rotavirus seasons were defined as January-June months of each year, with
even rotavirus seasons referring to 2002, 2004, 2006, 2008, 2010, 2012, and 2014 and odd
rotavirus seasons referring to 2003, 2005, 2007, 2009, 2011, 2013 and 2015. Using enrollment data,
we calculated person-years from the date of the birth claim until the first AGE inpatient claim
or until loss of insurance enrollment or end of study period (June 30, 2015). To account for the
impact of age at risk, we used the Lexis expansion to stratify each infant's contributing
personyears by age groups and follow-up period (San Hong) [
]. Seasonal rates for rotavirus and
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AGE admission were calculated for each age group by dividing the number of admissions by
the number of person-years for all enrollees in each age group. If the hospitalization event
occurred after the child was censored or lost to follow-up, then the hospitalization was
excluded. Poisson regression models were used to estimate rotavirus and AGE hospitalization
rates and 95% confidence intervals. Rates were calculated in SAS 9.4 (SAS Institute, Cary, NC).
Age at hospitalization
For enrollees who were hospitalized for rotavirus or any AGE, the median and interquartile
age in months at the time of hospitalization were compared during pre-vaccine, early vaccine,
and post-vaccine biennial rotavirus seasons using Wilcoxon two-sample tests. To visualize the
temporal course of age-stratified hospitalization rates, heatmaps were created using the matrix
package in R (R Foundation for Statistical Computing, Vienna, Austria).
Rotavirus vaccination coverage
Evidence for receipt of rotavirus vaccination was determined by using the Current Procedural
Terminology codes 90680 and 90681 for the two rotavirus vaccines licensed in the U.S.,
Rotateq1 (RV5, Merck and Co, Whitehouse Station, NJ) and Rotarix1 (RV1, GSK Biologicals,
Rixensart, Belgium), respectively. Vaccination coverage was calculated using a numerator of the
number of enrollees with one or more claims for rotavirus vaccination prior to hospitalization
and a denominator of the number of children who were age-eligible for rotavirus vaccine at
the time of hospitalization for rotavirus or AGE. To be age-eligible, children were required to
be at least 2 months old at the time of hospitalization and to be born after June 2006. We
calculated the mean and 95% CI for vaccination coverage for all children under 60 months and
stratified by age group. Vaccination coverage was compared during pre-vaccine, early vaccine,
and post-vaccine biennial rotavirus seasons with Mantel-Haenszel chi-square or Fisher's exact
tests, using SAS.
In a total of 2,735,860 children < 60 months of age, there were 3,172 hospitalizations coded for
rotavirus and 22,712 hospitalizations coded for AGE from 2002±2015. Of all hospitalizations,
2,872 (91%) rotavirus and 13,739 (60%) AGE hospitalizations occurred during rotavirus
seasons (January to June). Age-stratified hospitalization rates for rotavirus decreased from
prevaccine to early vaccine years and further decreased during post-vaccine years (Fig 1A). In
pre-vaccine years, hospitalization rates were highest in 6±23 month olds, with evidence of
yearly variation but without consistent pattern. In early post-vaccine years, hospitalization
rates are higher in 2009 and 2011 compared with 2008 and 2010, and especially in children
>12 months old. In late post-vaccine years, the biennial pattern is not as strong;
hospitalization rates are higher for older children in 2013 and 2015 compared with 2012 and 2014, but
the annual variation is far more modest than in early vaccine years.
Similar to rotavirus, hospitalization rates for AGE also declined from pre-vaccine to early
post-vaccine and late post-vaccine years (Fig 1B). AGE hospitalization rates during
pre-vaccine years were highest in 6±35 month olds, with no consistent pattern in annual variation. In
early post-vaccine years, AGE hospitalization rates were again higher in 2009 and 2011
compared to the preceding years, with higher rates particularly noticed in 2009 for 18±47 month
old children. In late post-vaccine years, the biennial pattern again becomes weaker.
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Fig 1. Hospitalization rates stratified by age among children <60 months. (A) Rotavirus- and (B) acute
gastroenteritis- coded hospitalizations during rotavirus seasons (Jan-Jun), 2002±2015.
Age at hospitalization
The median age at hospitalization for rotavirus hospitalizations was higher during odd seasons
compared to even seasons for all three time periods evaluated (Table 1). The median age, and
the absolute difference in median age in biennial seasons, was higher in early post-vaccine
years (18 months in odd seasons, 14 months in even seasons) compared to pre-vaccine years
(14 months in odd seasons, 12 months in even seasons). In late post-vaccine years, the
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difference in median age decreased to match the pre-vaccine year difference (17.5 months in
odd seasons, 15 months in even seasons).
For AGE hospitalizations, the median age was also higher in odd seasons compared to even
seasons, although there was no discernible difference in this relationship during pre-vaccine,
early post-vaccine, and late post-vaccine years (Table 2).
The annual variation in age at hospitalization for rotavirus (Fig 2A) and gastroenteritis (Fig
2B) did not have a consistent pattern. Age generally increased following rotavirus vaccine
introduction, but was not consistently higher in odd years compared with even years.
Rotavirus vaccination coverage
Vaccination coverage, defined as the receipt of at least 1 rotavirus vaccination prior to
hospitalization, increased in late post-vaccine years compared to early post-vaccine years, but was
not different in biennial seasons for both rotavirus and gastroenteritis hospitalizations (Tables
1 and 2). Vaccination coverage generally increased over time, though there were some notable
Hospitalization rate2 (per 10,000 p-y)
Median age (mo)
Rotavirus vaccine-eligible hospitalizations,
1. 2006±2007 excluded as transition years
2. Hospitalization rate for children 0±59 months
Abbreviation: P-y = person-years
Pre-Vaccine (2002±2005) Early Post-Vaccine (2008±2011) Late Post-Vaccine (2012±2015)
Odd Seasons Even Seasons p-value Odd Seasons Even Seasons p-value Odd Seasons Even Seasons p-value
1,823 1,271 2,424 1,786 1,547 1,620
131.2 124.0 60.7 54.4 38.0 34.8
125.3±137.3 117.4±131.0 58.4±63.2 51.9±57.0 36.1±39.9 33.1±36.5
13 11 <.0001 11 10 <.0001 12 10 <.0001
7±20 6±17 4±22 3±17 5±23 3±20
N/A 2,187 1,474 1,515 1,524
Fig 2. Age distribution for hospitalized children. Mean (◆), median (-), and inter-quartile range (box) of age of
children <60 months hospitalized for (A) rotavirus and (B) acute gastroenteritis during rotavirus seasons (Jan-Jun),
findings in the annual change in coverage. For rotavirus hospitalizations, vaccination coverage
was higher in 2012 than in 2013, and in 2014 than in 2015 (Fig 3A). For gastroenteritis
hospitalizations, vaccination coverage was higher in 2010 than in 2011, and 2012 than in 2013, but
did not decrease in 2015 compared with 2014 (Fig 3B).
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Fig 3. Vaccination coverage for hospitalized children. Percentage of age-eligible children < 60 months receiving at
least one rotavirus vaccine dose prior to hospitalization for (A) rotavirus and (B) acute gastroenteritis during rotavirus
seasons (Jan-Jun), 2008±2015.
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Age-stratified vaccination coverage yielded conflicting results. For rotavirus
hospitalizations, vaccination coverage was not different in biennial years during both early and late
postvaccine years, with the exception of higher vaccine coverage in odd seasons for 18±23 month
olds during early post-vaccine years (Table 3). For gastroenteritis admissions in early
post-vaccine years, vaccination coverage was higher in even seasons for 24±35 month olds, but higher
in odd seasons for 6±11 month old children (Table 4). During the late post-vaccine years,
vaccination coverage was higher in even seasons for children 12±17 months and 24±47
months, but was higher in odd seasons for 2±3 month olds.
Our analyses of a robust dataset of childhood hospitalizations for rotavirus and AGE provide
conflicting results in evaluating the hypothesis of incomplete vaccination coverage driving the
observed odd calendar year biennial peaks in rotavirus incidence in the United States since
rotavirus vaccine introduction in 2006. Rotavirus and AGE hospitalization rates have
decreased steadily decreased following rotavirus vaccine introduction. In early post-vaccine
years (2008±2011), during which vaccine coverage slowly increased and never reached >70%,
hospitalization rates were higher for older children during odd seasons. In more recent (late
post-vaccine) years, annual and age-group changes in hospitalization rates are less
pronounced, resulting in lower magnitude of peak seasons, and coinciding with years of higher
vaccination coverage. These changes in hospitalization rates are consistent with the hypothesis
of vaccine coverage driving changes in timing and size of peak rotavirus seasons.
However, annual changes in the age and vaccination coverage in children hospitalized for
rotavirus and AGE are less convincing, and at times inconsistent with the changes in
hospitalization rates. The age at hospitalization was higher in odd seasons compared with even seasons,
even in pre-vaccine years. For rotavirus codes, the difference in age during odd seasons
increased to 4 months in early post-vaccine years before returning to 2 months in late
postvaccine years, and age was higher following vaccine introduction, providing some support to
the concept that peak seasons are driven by infections in older children. However, these
differences were not seen in AGE hospitalizations.
Furthermore, overall vaccine coverage in hospitalized children was not higher in even
seasons compared to odd seasons. Lower vaccine coverage in older (>12 month old) children
during odd seasons was expected, especially in the early post-vaccine years. However, there
were no differences in the vaccine coverage for any age group in any time period for rotavirus
hospitalizations. For AGE hospitalizations, the late post-vaccine years had more consistent
lower vaccination coverage in odd seasons than early post-vaccine years. This is an unexpected
finding as the difference in hospitalization rates during biennial seasons is less pronounced in
late post-vaccine years than in early post-vaccine years.
Taken together, these results provide mixed and conflicting evidence that higher
hospitalization rates seen in odd years is driven by rotavirus infections in older, unvaccinated children
who are being exposed to rotavirus at an older age than they would have been prior to vaccine
introduction. While vaccination coverage has a role in the changing pattern of rotavirus
hospitalizations, other factors, such as differential susceptibility of older children to the dominant
circulating rotavirus genotypes since vaccine introduction [
], should be considered,
although the genotype distribution has not followed a similar biennial pattern.
Our study has some limitations. First, uninsured and Medicaid populations are not
represented in MarketScan data, which may affect generalizability of our findings. Medicaid
recipients may have lower childhood vaccination coverage than commercial insurance [
thus could have stronger biennial patterns than observed in this analysis. However, this being
a time series analysis, we are most concerned with time varying biases. Second, changes in
hospitalization rates could be driven by changes in admitting patterns or insurance coding rather
than true illness. It is reassuring that we found a similar biennial pattern for hospitalization
rates, age at hospitalization and vaccination coverage as has been seen for laboratory rotavirus
detection and hospitalizations in other studies using different data sources [2±4]. Third, herd
immunity and indirect protection of unvaccinated children complicate proving direct causal
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association between vaccination coverage and disease patterns [
]. Fourth, the large declines
in rotavirus and gastroenteritis hospitalizations following vaccine introductions have led to a
small number of observations when stratified by age and year. Thus, vaccination coverage
estimates in Tables 3 and 4 have large confidence intervals, especially in recent years. The low
number of observations further precludes disaggregation by state or region, vaccine type, or
incomplete vaccination series.
In conclusion, these results show that the biennial peak in U.S. rotavirus and AGE
hospitalizations since vaccine introduction could be driven in part by incomplete vaccination, and
therefore the build-up of susceptible children, in consecutive birth cohorts. However,
incomplete vaccination is not a sufficient and complete explanation, and other factors should be
investigated. The biennial pattern that emerged in the U.S. following vaccine introduction
may be beginning to diminish in magnitude during peak seasons. It is possible that this pattern
will continue to change with increased rotavirus vaccination coverage, and perhaps reach a
threshold that prevents peaks altogether.
S1 Table. Data file. Data file for Marketscan rotavirus and acute gastroenteritis hospitalization
Disclaimer: The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the Centers for Disease Control and Prevention.
Conceptualization: Minesh P. Shah, Umesh D. Parashar, Benjamin A. Lopman.
Data curation: Rebecca M. Dahl.
Formal analysis: Minesh P. Shah, Rebecca M. Dahl.
Investigation: Minesh P. Shah, Umesh D. Parashar, Benjamin A. Lopman.
Methodology: Minesh P. Shah, Rebecca M. Dahl, Benjamin A. Lopman.
Software: Rebecca M. Dahl.
Supervision: Umesh D. Parashar, Benjamin A. Lopman.
Visualization: Benjamin A. Lopman.
Writing ± original draft: Minesh P. Shah.
Writing ± review & editing: Minesh P. Shah, Rebecca M. Dahl, Umesh D. Parashar, Benjamin
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1. Parashar UD , Alexander JP , Glass RI . Prevention of rotavirus gastroenteritis among infants and children. Recommendations of the Advisory Committee on Immunization Practices (ACIP) . MMWR Recommendations and reports: Morbidity and mortality weekly report Recommendations and reports / Centers for Disease Control . 2006 ; 55 (Rr-12): 1 ± 13 . Epub 2006/08/12. PMID: 16902398 .
2. Rha B , Tate JE , Payne DC , Cortese MM , Lopman BA , Curns AT , et al. Effectiveness and impact of rotavirus vaccines in the United StatesÐ2006±2012 . Expert review of vaccines . 2014 ; 13 ( 3 ): 365 ± 76 . Epub 2014/01/08. https://doi.org/10.1586/14760584. 2014 .877846 PMID: 24392657 .
3. Leshem E , Moritz RE , Curns AT , Zhou F , Tate JE , Lopman BA , et al. Rotavirus vaccines and health care utilization for diarrhea in the United States ( 2007 ± 2011 ). Pediatrics. 2014 ; 134 ( 1 ): 15 ± 23 . Epub 2014/06/11. https://doi.org/10.1542/peds.2013-3849 PMID: 24913793 .
4. Leshem E , Tate JE , Steiner CA , Curns AT , Lopman BA , Parashar UD . Acute gastroenteritis hospitalizations among US children following implementation of the rotavirus vaccine . Jama . 2015 ; 313 ( 22 ): 2282 ± 4 . Epub 2015/06/10. https://doi.org/10.1001/jama. 2015 .5571 PMID: 26057291 .
5. Shah MP , Tate JE , Steiner CA , Parashar UD . Decline in Emergency Department Visits for Acute Gastroenteritis Among Children in 10 US States After Implementation of Rotavirus Vaccination, 2003 to 2013 . The Pediatric infectious disease journal . 2016 ; 35 ( 7 ): 782 ± 6 . Epub 2016/04/19. https://doi.org/10. 1097/INF.0000000000001175 PMID: 27088585 .
6. Zlamy M , Kofler S , Orth D , Wurzner R , Heinz-Erian P , Streng A , et al. The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections . BMC Infect Dis . 2013 ; 13 : 112 . Epub 2013/03/05. https://doi.org/10.1186/ 1471 -2334-13-112 PMID: 23452879 .
7. Jayasinghe S , Macartney K. Estimating rotavirus gastroenteritis hospitalisations by using hospital episode statistics before and after the introduction of rotavirus vaccine in Australia . Vaccine. 2013 ; 31 ( 6 ): 967 ± 72 . Epub 2012/12/19. https://doi.org/10.1016/j.vaccine. 2012 . 11 .099 PMID: 23246261 .
8. Sabbe M , Berger N , Blommaert A , Ogunjimi B , Grammens T , Callens M , et al. Sustained low rotavirus activity and hospitalisation rates in the post-vaccination era in Belgium, 2007 to 2014 . Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin . 2016 ; 21 ( 27 ). Epub 2016 /07/16. https://doi.org/10.2807/ 1560 - 7917 .es. 2016 . 21 .27.30273 PMID: 27418466 .
9. Hemming-Harlo M , Markkula J , Huhti L , Salminen M , Vesikari T. Decrease of Rotavirus Gastroenteritis to a Low Level Without Resurgence for 5 Years After Universal RotaTeq(R) Vaccination in Finland . The Pediatric infectious disease journal. 2016. Epub 2016 /07/28. https://doi.org/10.1097/inf. 0000000000001305 PMID: 27455440 .
10. Tate JE , Parashar UD . Rotavirus vaccines in routine use. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America . 2014 ; 59 ( 9 ): 1291 ± 301 . Epub 2014/07/23. https:// doi.org/10.1093/cid/ciu564 PMID: 25048849 .
11. BaÂnyai K , LaÂszloÂ B , Duque J , Steele AD , Nelson EAS , Gentsch JR , et al. Systematic review of regional and temporal trends in global rotavirus strain diversity in the pre rotavirus vaccine era: Insights for understanding the impact of rotavirus vaccination programs . Vaccine . 2012 ; 30 , Supplement 1:A122± A30 . http://dx.doi.org/10.1016/j.vaccine. 2011 . 09 .111.
12. Leshem E , Lopman B , Glass R , Gentsch J , BaÂnyai K , Parashar U , et al. Distribution of rotavirus strains and strain-specific effectiveness of the rotavirus vaccine after its introduction: a systematic review and meta-analysis . The Lancet Infectious Diseases . 2014 ; 14 ( 9 ): 847 ± 56 . http://dx.doi.org/10.1016/S1473- 3099 ( 14 ) 70832 - 1 . PMID: 25082561 13 .
World Health Organization (WHO). WHO vaccine-preventable diseases: monitoring system Geneva, Switzerland , updated August 8 , 2016 . Accessed September 13 , 2016 ]. http://www.who.int/ immunization/monitoring_surveillance/data/en/.
14. Hill HA , Elam-Evans LD , Yankey D , Singleton JA , Dietz V . Vaccination Coverage Among Children Aged 19 ±35 MonthsÐUnited States , 2015 . MMWR Morbidity and mortality weekly report . 2016 ; 65 ( 39 ): 1065 ± 71 . Epub 2016/10/07. https://doi.org/10.15585/mmwr.mm6539a4 PMID: 27711036 .
15. Aliabadi N , Tate JE , Haynes AK , Parashar UD . Sustained decrease in laboratory detection of rotavirus after implementation of routine vaccination- United States , 2000 ± 2014 . MMWR Morbidity and mortality weekly report . 2015 ; 64 ( 13 ): 337 ± 42 . Epub 2015/04/10. PMID: 25856253 .
16. Fine PEM , Clarkson JA . Measles in England and WalesÐI: An Analysis of Factors Underlying Seasonal Patterns . International Journal of Epidemiology . 1982 ; 11 ( 1 ):5± 14 . https://doi.org/10.1093/ije/11.1.5 PMID: 7085179
17. Goldacre MJ , Maisonneuve JJ . Hospital admission rates for measles and mumps in England: historical perspective . The Lancet . 382 ( 9889 ): 308 ±9. http://dx.doi.org/10.1016/S0140- 6736 ( 13 ) 61635 - 9 .
18. Truven Health, editor. MarketScan Commercial Claims and Encounters Database . Ann Arbor, MI.
19. Cortes JE , Curns AT , Tate JE , Cortese MM , Patel MM , Zhou F , et al. Rotavirus vaccine and health care utilization for diarrhea in U.S. children . The New England journal of medicine . 2011 ; 365 ( 12 ): 1108 ± 17 . Epub 2011/10/14. https://doi.org/10.1056/NEJMoa1000446 PMID: 21992123 .
20. Hsu VP , Staat MA , Roberts N , Thieman C , Bernstein DI , Bresee J , et al. Use of active surveillance to validate international classification of diseases code estimates of rotavirus hospitalizations in children . Pediatrics . 2005 ; 115 ( 1 ): 78 ± 82 . Epub 2005/01/05. https://doi.org/10.1542/peds.2004-0860 PMID: 15629984 .
21. Matson DO , Staat MA , Azimi P , Itzler R , Bernstein DI , Ward RL , et al. Burden of rotavirus hospitalisations in young children in three paediatric hospitals in the United States determined by active
22. San Hong LL, Sarah. Lexis ExpansionÐAge-at-Risk Adjustment for Survival Analysis . Lex Jansen; 2013 .
23. Bowen MD , Mijatovic-Rustempasic S , Esona MD , Teel EN , Gautam R , Sturgeon M , et al. Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States , 2008 ± 2013 . Journal of Infectious Diseases . 2016 ; 214 ( 5 ): 732 ±8. https://doi.org/10.1093/infdis/jiw233 PMID: 27302190
24. Payne DC , Staat MA , Edwards KM , Szilagyi PG , Weinberg GA , Hall CB , et al. Direct and indirect effects of rotavirus vaccination upon childhood hospitalizations in 3 US Counties , 2006 ± 2009 . Clinical infectious diseases: an official publication of the Infectious Diseases Society of America . 2011 ; 53 ( 3 ): 245 ± 53 . Epub 2011/06/28. https://doi.org/10.1093/cid/cir307 PMID: 21705316 .