ingest cdrApp 2017-07-06T13:05:39.027Z ccd64451-f0fc-4a42-94ad-226f4041fa4f modifyDatastreamByValue RELS-EXT cdrApp 2017-07-06T13:19:15.604Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-25T02:47:22.735Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-27T03:33:19.161Z modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-02-08T20:51:30.045Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-02-08T20:51:41.406Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-02-08T20:52:06.825Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-02-08T20:52:20.625Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-03-13T23:20:43.747Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-16T20:51:17.755Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-10T21:51:50.091Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-17T18:01:15.836Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-08T17:27:49.333Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-15T14:34:50.847Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T17:38:06.182Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-21T15:07:37.717Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-26T18:09:05.377Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-11T18:53:28.703Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-02-28T02:12:03.159Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-19T21:31:12.379Z Joann Gruber Author Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. Spring 2017 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. Spring 2017 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. Spring 2017 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017-05 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James C. Thomas Thesis advisor M. Alan Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation Epidemiology Michele Jonsson Funk Thesis advisor James C. Thomas Thesis advisor M. Alan Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children; gastroenteritis; low- and middle-income countries; rotavirus; vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James Thomas Thesis advisor M. Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children, gastroenteritis, low- and middle-income countries, rotavirus, vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James C. Thomas Thesis advisor M. Alan Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children; gastroenteritis; low- and middle-income countries; rotavirus; vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Epidemiology Michele Jonsson Funk Thesis advisor James C. Thomas Thesis advisor M. Alan Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Joann Gruber Creator Department of Epidemiology Gillings School of Global Public Health Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs. 2017 Epidemiology Public health children; gastroenteritis; low- and middle-income countries; rotavirus; vaccines eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Michele Jonsson Funk Thesis advisor James C. Thomas Thesis advisor M. Alan Brookhart Thesis advisor Michael Hudgens Thesis advisor Sylvia Becker-Dreps Thesis advisor text 2017-05 Gruber_unc_0153D_16889.pdf uuid:6b5fc93c-b98d-4c34-a225-b37c80e08b95 2017-04-17T19:06:30Z 2019-07-06T00:00:00 proquest yes application/pdf 2871242