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      Public Health Impact of Complete and Incomplete Rotavirus Vaccination among Commercially and Medicaid Insured Children in the United States

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          Abstract

          Background

          This study ( NCT01682005) aims to assess clinical and cost impacts of complete and incomplete rotavirus (RV) vaccination.

          Methods

          Beneficiaries who continuously received medical and pharmacy benefits since birth were identified separately in Truven Commercial Claims and Encounters (2000–2011) and Truven Medicaid Claims (2002–2010) and observed until the first of end of insurance eligibility or five years. Infants with ≥1 RV vaccine within the vaccination window (6 weeks-8 months) were divided into completely and incompletely vaccinated cohorts. Historically unvaccinated (before 2007) and contemporarily unvaccinated (2007 and after) cohorts included children without RV vaccine. Claims with International Classification of Disease 9 th edition (ICD-9) codes for diarrhea and RV were identified. First RV episode incidence, RV-related and diarrhea-related healthcare resource utilization after 8 months old were calculated and compared across groups. Poisson regressions were used to generate incidence rates with 95% confidence intervals (CIs). Mean total, inpatient, outpatient and emergency room costs for first RV and diarrhea episodes were calculated; bootstrapping was used to construct 95% CIs to evaluate cost differences.

          Results

          1,069,485 Commercial and 515,557 Medicaid patients met inclusion criteria. Among commercially insured, RV incidence per 10,000 person-years was 3.3 (95% CI 2.8–3.9) for completely, 4.0 (95% CI 3.3–5.0) for incompletely vaccinated, and 20.9 (95% CI 19.5–22.4) for contemporarily and 40.3 (95% CI 38.6–42.1) for historically unvaccinated. Rates in Medicaid were 7.5 (95% CI 4.8–11.8) for completely, 9.0 (95% CI 6.5–12.3) for incompletely vaccinated, and 14.6 (95% CI 12.8–16.7) for contemporarily and 52.0 (95% CI 50.2–53.8) for historically unvaccinated. Mean cost for first RV episode per cohort member was $15.33 (95% CI $12.99-$18.03) and $4.26 ($95% CI $2.34-$6.35) lower for completely vaccinated versus contemporarily unvaccinated in Commercial and Medicaid, respectively.

          Conclusions

          RV vaccination results in significant reduction in RV infection. There is evidence of indirect benefit to unvaccinated individuals.

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          Most cited references17

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          Effect of human rotavirus vaccine on severe diarrhea in African infants.

          Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.) 2010 Massachusetts Medical Society
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            Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP).

            Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. Before initiation of the rotavirus vaccination program in the United States in 2006, approximately 80% of U.S. children had rotavirus gastroenteritis by age 5 years. Each year during the 1990s and early 2000s, rotavirus resulted in approximately 410,000 physician visits, 205,000272,000 emergency department visits, and 55,00070,000 hospitalizations among U.S. infants and children, with total annual direct and indirect costs of approximately $1 billion. In February 2006, a live, oral, human-bovine reassortant rotavirus vaccine (RotaTeq(R) [RV5]) was licensed as a 3-dose series for use among U.S. infants for the prevention of rotavirus gastroenteritis, and the Advisory Committee on Immunization Practices (ACIP) recommended routine use of RV5 among U.S. infants (CDC. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55[No. RR-12]). In April 2008, a live, oral, human attenuated rotavirus vaccine (Rotarix(R) [RV1]) was licensed as a 2-dose series for use among U.S. infants, and in June 2008, ACIP updated its rotavirus vaccine recommendations to include use of RV1. This report updates and replaces the 2006 ACIP statement for prevention of rotavirus gastroenteritis. ACIP recommends routine vaccination of U.S. infants with rotavirus vaccine. RV5 and RV1 differ in composition and schedule of administration. RV5 is to be administered orally in a 3-dose series, with doses administered at ages 2, 4, and 6 months. RV1 is to be administered orally in a 2-dose series, with doses administered at ages 2 and 4 months. ACIP does not express a preference for either RV5 or RV1. The recommendations in this report also address the maximum ages for doses, contraindications, precautions, and special situations for the administration of rotavirus vaccine.
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              Understanding Reduced Rotavirus Vaccine Efficacy in Low Socio-Economic Settings

              Introduction Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance. Methods We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy. Results Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES. Discussion The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 January 2016
                2016
                : 11
                : 1
                : e0145977
                Affiliations
                [1 ]GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania, United States of America
                [2 ]Analysis Group, Inc., Boston, Massachusetts, United States of America
                [3 ]Rutgers University, School of Public Health, Piscataway, New Jersey, United States of America
                [4 ]Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
                Groningen Research Institute of Pharmacy, NETHERLANDS
                Author notes

                Competing Interests: GlaxoSmithKline Biologicals SA funded this study/research and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also took in charge all costs associated with the development and publication of this manuscript. Girishanthy Krishnarajah is an employee of and has restricted shares in the GlaxoSmithKline group of companies. Mei Sheng Duh and Caroline Korves are employees of Analysis Group which received funding from GSK to conduct this research and receives funding to conduct other drug safety and health outcomes research from multiple pharmaceutical companies. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: GK MSD CK KD. Analyzed the data: GK MSD CK KD. Wrote the paper: GK MSD CK KD.

                Article
                PONE-D-14-16758
                10.1371/journal.pone.0145977
                4709043
                26751375
                ed6ee392-ed10-4987-be66-c072bd517b3e
                © 2016 Krishnarajah et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 May 2014
                : 14 November 2015
                Page count
                Figures: 0, Tables: 6, Pages: 18
                Funding
                GlaxoSmithKline Biologicals SA funded this study/research and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also took in charge all costs associated with the development and publication of this manuscript.
                Categories
                Research Article
                Custom metadata
                The authors obtained data from a third party, Truven Health Analytics, Inc. The legal contract with Truven Health Analytics, Inc. precludes the authors from making the data available to others. If readers are interested in obtaining the data for this study, they could purchase these data from Truven Health Analytics, Inc.; Patricia Harris ( patricia.harris@ 123456truvenhealth.com ) is the point of contact.

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