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The recommended US infant immunization schedule includes doses of diphtheria, tetanus, acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) and hepatitis B virus (HepB) during the first 6 months of life. Little information is available about the timing of associated, complementary monovalent vaccine administration in infants receiving DTaP-based pentavalent combination vaccines.This was a retrospective cohort study of infants born between July 1, 2010, and June 30, 2018, in the US MarketScan commercial claims and encounters database. Descriptive statistics were used to assess vaccine administration patterns. Multivariate logistic regression was performed to explore factors associated with coadministration of DTaP-IPV/Hib and HepB.Among infants who received DTaP-HepB-IPV (n = 129,885), 93.7% had claims for at least 2 Hib doses; most (91.5%-98.3%) of these doses were administered on the same day as DTaP-HepB-IPV doses. Among infants who received DTaP-IPV/Hib (n=214,172), 95.3% had claims for ≥2 doses of HepB. Although coverage was high, 59.2% received the second HepB dose on the same day as the first DTaP-IPV/Hib dose, and 44.6% received the third dose of HepB on the same day as the third DTaP-IPV/Hib dose. Differences in coadministration of the second and third HepB doses with DTaP-IPV/Hib were associated with the region of residence, provider type, health plan type and coadministration of pneumococcal conjugate vaccine and rotavirus vaccine.Almost all infants received the appropriate, complementary monovalent vaccine series. However, this study found variability in the timing of HepB doses in relation to DTaP-IPV/Hib doses with many infants not completing the HepB series until 9 months of age.

Using National Immunization Survey Child and Teen (2008-2017), we associated state vaccination requirements with hepatitis A (Hep A) vaccination rates in children and adolescents. States with school entry or both childcare and school entry requirements were associated with 35%-40% higher Hep A vaccination rates, compared with states without such requirements.

Background Despite routine vaccination of children against hepatitis A (HepA), a large segment of the United States population remains unvaccinated, imposing a risk of hepatitis A virus (HAV) to adolescents and adults. In July of 2020, the Advisory Committee on Immunization Practices recommended that all children and adolescents aged 2–18 years who have not previously received a HepA vaccine be vaccinated. We evaluated the public health impact and cost-effectiveness of this HepA catch-up vaccination strategy. Methods We used a dynamic transmission model to compare adding a HepA catch-up vaccination of persons age 2–18 years to a routine vaccination of children 12–23 months of age with routine vaccination only in the United States. The model included various health compartments: maternal antibodies, susceptible, exposed, asymptomatic infectious, symptomatic infectious (outpatient, hospitalized, liver transplant, post- liver transplant, death), recovered, and vaccinated with and without immunity. Using a 3% annual discount rate, we estimated the incremental cost per quality-adjusted life year (QALY) gained from a societal perspective over a 100-year time horizon. All costs were converted into 2020 US dollars. Findings Compared with the routine vaccination policy at 12–23 months of age over 100 years, the catch-up program for unvaccinated children and adolescents aged 2–18 years, prevented 70,072 additional symptomatic infections, 51,391 outpatient visits, 16,575 hospitalizations, and 413 deaths. The catch-up vaccination strategy was cost-saving when compared with the routine vaccination strategy. In scenario analysis allowing administering a second dose to partially vaccinated children, the cost-effectiveness of was not favorable at a higher vaccination coverage ($196,701/QALY at 5% and $476,241/QALY at 50%). Interpretation HepA catch-up vaccination in the United States is expected to reduce HepA morbidity and mortality and save cost. The catch-up program would be optimized when focusing on unvaccinated children and adolescents and maximizing their first dose coverage.

In randomized active-comparator controlled studies, DTaP5-HB-IPV-Hib showed comparable immunogenicity and safety to other licensed vaccines. This study assessed persistence of anti-hepatitis B surface antigen (HBs) and anti-pertussis antibodies, when children were 4 to 5 years of age, 3 to 4 years after initial infant/toddler hexavalent vaccination. This was an extension of 2 European studies in which infants/toddlers received either DTaP5-HB-IPV-Hib or DTaP3-HB-IPV/Hib on a 2 + 1 or 3 + 1 schedule. Primary endpoints included percentages with anti-HBs ≥10 mIU/mL, and anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-pertactin (PRN), and anti-fimbriae types 2 & 3 (FIM) greater than or equal to the lower limit of quantitation (LLOQ). One month after 2 + 1 or 3 + 1 dosing, nearly all toddlers had anti-HBs ≥10 mIU/mL, and responded to the received pertussis antigens. Approximately 3 to 4 years later, 65.8%-70.2% in the DTaP5-HB-IPV-Hib and 82.0%-83.7% in the DTaP3-HB-IPV/Hib groups, respectively, had anti-HBs ≥10 mIU/mL. Percentages of children with pertussis antibodies above LLOQ after 2 + 1 dosing were 58.4% and 41.5% (anti-PT), 80.9% and 88.3% (anti-FHA), 66.1% and 72.6% (anti-PRN), and 94.4% and 3.3% (anti-FIM), in the DTaP5-HB-IPV-Hib and DTaP3-HB-IPV/Hib groups, respectively. This study demonstrated, as expected, waning of hepatitis B and pertussis antibodies during the 3 to 4 years after completion of a 3 + 1 or 2 + 1 hexavalent vaccination schedule. Nonetheless, anti-HBs levels ≥10 IU/mL and detectable antibodies against acellular pertussis antigens persisted in most study participants. The implications of these findings for the long-term prevention of hepatitis B and pertussis are further discussed.

Objectives: To assess the safety and reactogenicity of single oral dose of heat-stable rotavirus vaccine (HSRV) in healthy adults aged 18–45 years followed by assessment of safety, reactogenicity, and immunogenicity of three doses of HSRV in healthy infants aged 6–8 weeks at enrollment. Trial Design: Single-center randomized controlled, sequential, blinded (adults) and open-label (infants). Setting: Single site at International Center for Diarrheal Disease Research, Bangladesh (icddr,b). Participants: Fifty eligible adults randomized in 1:1 ratio (HSRV: Placebo) followed by 50 eligible infants randomized in 1:1 ratio (HSRV: Comparator (RotaTeq®, pentavalent human-bovine (WC3) reassortant live-attenuated, rotavirus vaccine)). Intervention: Adults received either a single dose of HSRV or placebo and followed for 14 days. Infants received three doses of either HSRV or comparator with a follow-up for 28 days after each dose. Main Outcome Measures: Solicited and unsolicited adverse events (AEs) along with any serious adverse events (SAEs) were part of the safety and reactogenicity assessment in adults and infants whereas serum anti-rotavirus IgA response rates were part of immunogenicity assessment in infants only. Post-vaccination fecal shedding of vaccine-virus rotavirus strains was also determined in adults and infants. Results: In this study, HSRV, when compared with placebo, did not result in increase in solicited adverse events (solicited AEs) in adults. In infants, HSRV had a safety profile similar to comparator vis-à-vis solicited AEs. In infants, fecal shedding of vaccine-virus strains was not detected in HSRV recipients but was observed in two comparator recipients. Percentage of infants exhibiting threefold rise in serum anti-rotavirus IgA titers from baseline to 1-month post-dose 3 in HSRV group was 88% (22/25) and 84% (21/25) in comparator group. Conclusion: HSRV was found to be generally well-tolerated in both adults and infants and immunogenic in infants.

Highlights • Vaccine preventable diseases continue to impact human health. • Web-based geographic temporal visualizations of large datasets were developed. • Data on rotavirus vaccination uptake and related medical visits was used as an example. • Visualizations show vaccine effectiveness by geographic levels and over time. • Project informs strategies to monitor the impact of new vaccines on SARS-CoV-2., Background Infectious diseases continue to cause significant impact on human health. Vaccines are instrumental in preventing infectious diseases and mitigating pandemics and epidemics. SARS-CoV-2 is the most recent example of an urgent pandemic that requires the development of vaccines. This study combined real-world data and geospatial visualization techniques to demonstrate methods to monitor and communicate the uptake and impact of existing and new vaccines. Methods Observational data of existing pediatric rotavirus vaccines were used as an example. A large US national insurance claims database was accessed to build an analytic dataset for a 20-year period (1996–2017). For each week and multiple geographic scales, animated spatial and non-spatial visualization techniques were applied to demonstrate changes in seasonal rotavirus epidemic curves and population-based disease rates before, during, and after vaccine introduction in 2006. The geographic scales included national, state, county and zip code tabulation areas. An online web-based digital atlas was built to display either continuous or snapshot visualizations of disease patterns, vaccine uptake, and improved health outcomes after vaccination (http://www.mapvaccines.com). Results Over 17 million zip code-weeks of data were available for analysis. The animations show geospatial patterns of rotavirus-related medical encounter rates peaking every year from November – February prior to vaccine availability in 2006. Visualizations showed increasing vaccination coverage rates at all geographic scales over time. Declines in medical encounter rates accelerated as vaccination coverage rapidly increased after 2010. The data maps also identified geographic hotspots with low vaccination rates and persistent disease rates. Conclusion This project developed novel web-based methods to communicate location and time-based vaccine uptake and the related reduction in medical visits due to viral infection. Future applications of the visualization could be used by health agencies to monitor known or novel disease patterns over time in conjunction with close assessment of current and future vaccine utilization.

VAQTA™ (Hepatitis A Vaccine, inactivated [HAVi]; Merck & Co., Inc., Kenilworth, NJ, USA) is currently licensed for prevention of disease caused by hepatitis A virus in persons ≥12 months of age. This report summarizes statistical models developed to evaluate the long-term persistence and duration of detectable hepatitis A antibody (total antibody levels with no distinction on class) after receipt of HAVi in healthy children and adolescents (V251-023 and V251-035) and in healthy adults (V251-034). The statistical models presented, conducted separately for each of the three studies, are based on models that have been used in the literature to estimate the duration of antibody to protect against human papillomavirus (HPV) disease. In the absence of observed study data on hepatitis A antibody persistence for vaccine recipients over several decades, an extrapolation from a kinetic model of antibody decay was used to estimate the duration of detectable antibody. Extrapolation of observed antibody titers from postvaccination, Year 2.5–3.5, Year 5–6, and Year 10 in 165 children and adolescents who received HAVi at Day 0 and Week 24 in V251-023 suggests that detectable levels of antibody may persist after the second dose for many years. This model suggests that 25 to 50 years Postdose 1 in a two-dose series of HAVi, 99.4% of the study population will have detectable levels of hepatitis A antibody.

To assess whether titers of anti-rotavirus immunoglobulin G persist during the post–rotavirus vaccine era, the Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) Cohort analyzed serum samples collected from Cincinnati-area mothers and young infants in 2017–2018. Rotavirus-specific antibodies continue to be transferred from US mothers to their offspring in the post–rotavirus vaccine era, despite dramatic decreases in childhood rotavirus gastroenteritis.

Background DTaP-IPV-Hib-HepB is a fully-liquid, hexavalent combination vaccine (Vaxelis™) approved for vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive disease due to Haemophilus influenzae type b (Hib). Hib capsular polysaccharide, polyribosylribitol phosphate (PRP), is conjugated to Neisseria meningitidis outer membrane protein complex (OMPC). Safety and immunogenicity of DTaP-IPV-Hib-HepB were evaluated in 6 Phase III clinical studies including > 5,200 children. Studies included vaccination schedules in the United States (2, 4, 6 months of age) and Europe (2, 3, 4, 12 months of age and 2,4,11–12 months of age). Methods Data pertaining to anti-PRP responses of DTaP-IPV-Hib-Hep B compared to control vaccines from 5 Phase III studies are summarized. Results Post-infant series, the percentage of participants that achieved protective antibody thresholds for PRP (anti-PRP titer ≥ 0.15 μg/mL and ≥ 1.0 μg/mL, respectively) were higher in DTaP-IPV-Hib-HepB recipients compared to recipients who received control vaccines. A high level of protective responses (96.6% at ≥ 0.15 μg/mL [95% CI:94.8, 97.9%]; 72.9% at ≥ 1.0 μg/mL [95% CI:69.2,76.4%]) were seen post-dose 2 of the 2 + 1 vaccination schedule and met superiority criteria over comparator, p-value In the same schedule, prior to administration of the toddler dose (in the second year of life), anti-PRP titers were higher in DTaP-IPV-Hib-HepB recipients (91.4% at ≥ 0.15 μg/mL; 46.8% at ≥ 1.0 μg/mL) as compared to recipients who received control vaccines (63.4% at ≥ 0.15 μg/mL; 17.1% at ≥ 1.0 μg/mL). One-month post-toddler dose, high levels of anti-PRP titers were achieved in both DTaP-IPV-Hib-HepB recipients (99.8% at ≥ 0.15 μg/mL; 96.6% at ≥ 1.0 μg/mL) and recipients who received control vaccines (99.5% at ≥ 0.15 μg/mL; 94.9% at ≥ 1.0 μg/mL). Conclusions These results support that DTaP-IPV-Hib-HepB induces a robust and sustained early Hib response. During the high-risk period for Hib disease after the infant vaccine and prior to the toddler dose; >90% of recipients maintained superior protective anti-PRP levels compared to control.

Background As the socioeconomic conditions in Jordan have improved over recent decades the disease and economic burden of Hepatitis A has increased. The purpose of this study is to assess the potential health and economic impact of a two-dose hepatitis A vaccine program covering one-year old children in Jordan. Methods We adapted an age-structured population model of hepatitis A transmission dynamics to project the epidemiologic and economic impact of vaccinating one-year old children for 50 years in Jordan. The epidemiologic model was calibrated using local data on hepatitis A in Jordan. These data included seroprevalence and incidence data from the Jordan Ministry of Health as well as hospitalization data from King Abdullah University Hospital in Irbid, Jordan. We assumed 90% of all children would be vaccinated with the two-dose regimen by two years of age. The economic evaluation adopted a societal perspective and measured benefits using the quality-adjusted life-year (QALY). Results The modeled vaccination program reduced the incidence of hepatitis A in Jordan by 99%, 50 years after its introduction. The model projected 4.26 million avoided hepatitis A infections, 1.42 million outpatient visits, 22,475 hospitalizations, 508 fulminant cases, 95 liver transplants, and 76 deaths over a 50 year time horizon. In addition, we found, over a 50 year time horizon, the vaccination program would gain 37,502 QALYs and save over $42.6 million in total costs. The vaccination program became cost-saving within 6 years of its introduction and was highly cost-effective during the first 5 years. Conclusion A vaccination program covering one-year old children is projected to be a cost-saving intervention that will significantly reduce the public health and economic burden of hepatitis A in Jordan. Electronic supplementary material The online version of this article (10.1186/s12879-018-3034-8) contains supplementary material, which is available to authorized users.

Although clinical trials of the pentavalent rotavirus vaccine (RotaTeq®, RV5) have demonstrated efficacy against RV gastroenteritis (RGE) in low and high-income settings, a clear correlate of protection or a measure of immune response that could predict efficacy has yet to be identified. This is the first time that immunogenicity data with both serum neutralized antibody (SNA) titers and anti-RV IgA titers from several clinical efficacy trials were pooled to provide a unique context for evaluating the correlation between immunogenicity and RGE risk or efficacy of RV5. The correlation between immunogenicity and RGE risk is evaluated with data at the individual subject level. The analyses show that higher Postdose 3 (PD3) G1 SNA titers are associated with lower odds of contracting any RGE. The correlation between immunogenicity and efficacy is assessed using aggregated population level data, which shows higher efficacy associated with higher PD3 G1 SNA geometric mean titer (GMT) ratio (between RV5 and placebo) and PD3 serum anti-RV IgA GMT ratio. Among high-income countries, efficacy plateaus over the range of PD3 G1 SNA GMT ratios and PD3 serum anti-RV IgA GMT ratios. From both individual- and population-level analyses, PD3 G1 SNA titers correlated most closely with the RGE risk or efficacy for RV5.

Background Combination vaccines reduce the number of injections and improve the timeliness of vaccination coverage. US Advisory Committee on Immunization Practices (ACIP) recommendations state that combination vaccines are generally preferred over equivalent individual component vaccines. Healthcare providers strongly influence parental decisions about vaccination. We sought a contemporary understanding of physician’s attitudes towards combination vaccine use in infants. Methods We conducted an online survey of US physicians (70 pediatricians and 30 family practitioners) who administer vaccines to infants aged 0-24 months and spend at least 2 days a week providing patient care. Information was collected on attitudes towards combination vaccines and factors that influence the choice of combination vaccine used in clinical practice. Descriptive analyses were performed. Results Physicians (mean age=50.2 years, range 30.0-70.0; 66% white; 37% women) reported a median of 4 injections (range 2-9) as the maximum that parents would accept at a single visit, and 71% routinely explained what combination vaccines are to parents. When deciding which pentavalent vaccine to use, physicians considered how the brand fits into the current vaccine schedule (71%); upfront purchase costs (64%); and availability as a prefilled syringe (61%). The main reasons for using combination vaccines were to reduce the number of injections (96%); ensure the infant is up-to-date with vaccinations (86%); and reduce the pain that the infant experiences with multiple injections (68%). More than half reported that their institution or practice has a program to incentivize infant vaccination according to schedule. If a hexavalent vaccine-based schedule was available, 76% of physicians said they would choose it over their current schedule comprising pentavalent or equivalent component vaccines. Conclusion Choice of pentavalent combination vaccine among pediatricians and family practitioners was largely dependent on convenience and cost-related factors. Over three-quarters would be inclined to use a hexavalent vaccine schedule if available. Disclosures Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Background The US vaccination schedule includes DTaP, IPV, Hib and HepB doses in the first 6 months of life. A previous analysis found variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. We explored factors associated with co-administration of DTaP-IPV/Hib and HepB on the same day. Methods This was a retrospective study using the MarketScan® commercial claims and encounters database. Infants born from 1 July 2010 - 30 June 2016, continuously enrolled in an insurance plan for ≥ 13 months and receiving ≥ 3 DTaP-IPV/Hib doses were included. Infants were assessed for HepB claims relative to the first and third DTaP-IPV/Hib doses. Because a HepB birth dose was assumed, the first HepB claim from 29 - 169 days following birth was counted as Dose 2, and the second claim from 170 days - 12 months as Dose 3. Associations between demographic, provider, and insurance characteristics, receipt of other pediatric vaccines, and co-administration of DTaP-IPV/Hib and HepB were analyzed using multivariate logistic regression. Results Among 165,553 infants who received a first DTaP-IPV/Hib dose, 60.7% received HepB Dose 2 on the same day. Among 162,217 infants who received a third DTaP-IPV/Hib dose, 45.1% received HepB Dose 3 on the same day. Infants in the Northeast were less likely (OR=0.38, 95%CI=0.36-0.39), while those in the West were more likely (OR=1.41, 95%CI=1.36-1.46) than infants in the South to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day. Infants vaccinated by pediatricians (OR=0.54, 95%CI=0.53-0.55) were less likely to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day compared to infants vaccinated by family physicians. Infants who received PCV on the same day as the first dose of DTaP-IPV/Hib were more likely to receive HepB Dose 2 (OR=6.96, 95%CI=6.30-7.70) that day. These factors were also associated with co-administration of the third dose of DTaP-IPV/Hib and HepB Dose 3. Conclusion Differences in co-administration of DTaP-IPV/Hib and HepB were associated with region of residence, provider type and co-administration of PCV. The reasons underlying these differences merit exploration. A hexavalent vaccine containing DTaP, IPV, Hib, and HepB could improve timeliness of HepB vaccination, while reducing the number of injections during infancy. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Background Widespread Hepatitis A (Hep A) outbreaks in the United States (US) have raised the importance of vaccination. Vaccination requirements for childcare and school entry could be an effective strategy to ensure compliance to recommended vaccination schedule. We assessed the association between state childcare and school entry requirements for Hep A vaccination and vaccine coverage rate among children and adolescents in the US. Methods We conducted a cross-sectional cohort study using National Immunization Survey-Child and Teen dataset between 2008 and 2017. We included children aged 19–35 months and adolescents aged 13–17 years residing in states with childcare entry requirement only (C); school entry requirement only (S); childcare AND school entry requirement (C+S); and neither of requirements in place in the survey year (Control). We developed a multivariate logistic regression model adjusting for demographics, survey year, state’s CDC vaccination recommendation status, stringency of requirement, and history of Hep A outbreak, accounting for the survey design. Results We included 150,653 children and 119,265 adolescents in the analysis. Vaccination initiation rate was 53.9% and 72.6% (C), 48.3% and 74.9% (S), 48.2% and 83.9% (C+S) in pre- and post-requirement periods, respectively. In multivariate analysis, all state requirements were associated with higher Hep A vaccination initiation compared to control states (C: odds ratio 1.51, 95% confidence interval 1.37–1.66; S: 1.82, 1.49–2.23; and C+S: 1.49, 1.38, 1.62). Predictors for high vaccination initiation included vaccine recommendation since 1999 vs 2006 (2.87, 2.63–3.13); exemption of enforcement (most restrictive vs lenient: 2.10, 1.68–2.63). In addition, non-White, Hispanic children aged between 19–35 months with insurance, >$75,000 family income household, mothers having college degree were more likely to initiate Hep A vaccination. The associations were similar for Hep A vaccination completion. Figure 1. Hep A vaccination initiation and completion rates between pre- and post-requirement periods (C=childcare entry requirement only; S=school entry requirement only; and C+S=childcare AND school entry requirement) Table 1. Multivariate association between state policy and vaccination initiation and completion rate Conclusion States with childcare and school entry requirements are more likely to initiate and complete Hep A vaccine compared to those without such policy. This interventional policy may help to control and prevent Hep A outbreaks in states where it is applied. Disclosures Yoonyoung Choi, PhD, MS, RPh, Merck (Employee) Alexandra Bhatti, JD, MPH, Merck (Employee) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) Jakub Simon, MD, MS, Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder)

Background Ten different vaccine series are recommended by the US Advisory Committee on Immunization Practices from birth to 18 months. Combination vaccines can reduce the number of injections and visits required to complete the schedule in a timely manner. There is limited current information on parents’ perception of the vaccine schedule and combination vaccines. Methods An online survey was completed by 100 parents who had at least one child under 2 years, were involved in vaccination decisions, and had accompanied their child to a vaccination appointment. Parents who reported not ever vaccinating their children were excluded. Parents’ perception of, and adherence to, the recommended schedule, communication with providers, and knowledge of combination vaccines were collected. Descriptive analyses were performed. Results Ninety-six percent of parents (mean age=30.7 years; range 19.0-50.0; 91% white) reported their provider as a source of vaccination information, followed by internet searches (63%), family and friends (45%). Most (84%) followed all their provider’s recommendations and trusted the information given to them (87%). State day care and pre-school requirements influenced vaccination decisions for nearly 80% of parents. Over 80% of parents thought it is important to protect against diseases covered by the vaccination schedule. One-third had at some time asked to delay or not administer vaccines; depending on the vaccine, up to 50% ultimately had their child vaccinated as recommended. Top reasons for delaying vaccination were to avoid crying and pain from multiple injections (82%), and the concern that too many vaccines would overwhelm the immune system (64%). Top reasons for refusal were religious views (57%) and the belief that the vaccine was not needed (52%). On average, parents would accept their child receiving 3 injections in one visit. Most parents were aware of combination vaccines (84%); however, one-third reported that their child had not received, or they were unaware of their child receiving, a combination vaccine. Conclusion Providers are in a strong position to influence vaccination decisions by parents. Whereas parents are motivated to avoid the pain of multiple injections, many are unaware that their children are receiving combination vaccines. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Safety and immunogenicity data from 5 clinical trials conducted in the US in children 12-to-23 months old where HAVi was administered alone or concomitantly with other pediatric vaccines (M-M-R®II, Varivax®, TRIPEDIA®, Prevnar®, ProQuad®, PedvaxHIB®, and INFANRIX®) were combined. Among 4,374 participants receiving ≥ 1 dose of HAVi, 4,222 (97%) had safety follow-up and the proportions reporting adverse events (AE) were comparable when administered alone (69.4%) or concomitantly with other pediatric vaccines (71.1%). The most common solicited injection-site AEs were pain/tenderness (Postdose 1: 25.8%; Postdose 2: 26.1%) and redness (Postdose 1: 13.6%; Postdose 2: 15.1%). The most common vaccine-related systemic AEs were fever (≥ 100.4ºF, 12.2%) and irritability (8.1%). Serious AEs (SAEs) were observed at a rate of 0.4%; 0.1% were considered vaccine-related. No deaths were reported within 14 days following a dose of HAVi. These integrated analyses also showed that protective antibody concentrations were elicited in 100% of toddlers after two doses and 92% after a single dose, regardless of whether HAVi was given concomitantly with other vaccines or alone. These results demonstrate that HAVi was well-tolerated whether given alone or concomitantly with other vaccines, with a low incidence of vaccine-related SAEs. HAVi was immunogenic in this age group regardless of whether administered with or without other pediatric vaccines and whether 1 or 2 doses were administered. HAVi did not impact the immune response to other vaccines. These data continue to support the routine use of HAVi with other pediatric vaccines in children ≥ 12 months of age.

Background The recommended US infant immunization schedule includes doses of DTaP, IPV, Hib and HepB during the first 6 months of life. The majority of infants receive DTaP as one of the two pentavalent combination vaccines (DTaP-IPV/Hib or DTaP-HepB-IPV); standalone HepB or Hib are used to complement these combinations in compliance with the recommendations. Little is known about the timing of standalone vaccine administration in relation to DTaP-based combination vaccines. Methods This was a retrospective observational cohort study using the US MarketScan commercial claims and encounters database. Infants included in the study were continuously enrolled in the same insurance plan for ≥13 months after birth, born from 1 July 2010 through 30 June 2016, and had received ≥3 doses of a pentavalent vaccine. Outcomes included the proportion of infants receiving concomitant pentavalent and standalone vaccines, and the deviation in days when these vaccines were not administered on the same date. Birth doses of HepB were not registered in the database but were presumed to have been received; therefore, the first registered HepB claim was considered to be HepB Dose-2, and the second claim was presumed to be HepB Dose-3. Results Among infants who received DTaP-IPV/Hib (n = 175,574), 94.8% had claims for ≥3 doses of HepB. Although coverage was high, only 60.7% received HepB Dose-2 on the same day as DTaP-IPV/Hib Dose-1 (around 2 months of age), and only 45.1% received HepB Dose-3 on the same day as DTaP-IPV/Hib Dose-3 (around 6 months of age) (Figure 1). Many infants (46.2%) received HepB Dose-3 after the third dose of DTaP-IPV/Hib. Among infants who received DTaP-HepB-IPV (n = 97,206), 89.9% had claims for the recommended number of Hib doses; most (91% to 98%) of these doses were administered on the same day as doses of DTaP-HepB-IPV (Figure 2). Conclusion There was variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. A newly licensed hexavalent vaccine, DTaP-IPV-Hib-HepB, could synchronize and simplify the HepB administration schedule ensuring that more infants have completed the series by 6 months of age. Disclosures All authors: No reported disclosures.

ObjectiveTo assess the population-level impact and cost-effectiveness of hepatitis A vaccination programs in the United States.MethodsWe developed an age-structured population model of hepatitis A transmission dynamics to evaluate two policies of administering a two-dose hepatitis A vaccine to children aged 12 to 18 months: 1) universal routine vaccination as recommended by the Advisory Committee on Immunization Practices in 2006 and 2) Advisory Committee on Immunization Practices’s previous regional policy of routine vaccination of children living in states with high hepatitis A incidence. Inputs were obtained from the published literature, public sources, and clinical trial data. The model was fitted to hepatitis A seroprevalence (National Health and Nutrition Examination Survey II and III) and reported incidence from the National Notifiable Diseases Surveillance System (1980–1995). We used a societal perspective and projected costs (in 2013 US $), quality-adjusted life-years, incremental cost-effectiveness ratio, and other outcomes over the period 2006 to 2106.ResultsOn average, universal routine hepatitis A vaccination prevented 259,776 additional infections, 167,094 outpatient visits, 4781 hospitalizations, and 228 deaths annually. Compared with the regional vaccination policy, universal routine hepatitis A vaccination was cost saving. In scenario analysis, universal vaccination prevented 94,957 infections, 46,179 outpatient visits, 1286 hospitalizations, and 15 deaths annually and had an incremental cost-effectiveness ratio of $21,223/quality-adjusted life-year when herd protection was ignored.ConclusionsOur model predicted that universal childhood hepatitis A vaccination led to significant reductions in hepatitis A mortality and morbidity. Consequently, universal vaccination was cost saving compared with a regional vaccination policy. Herd protection effects of hepatitis A vaccination programs had a significant impact on hepatitis A mortality, morbidity, and cost-effectiveness ratios.

During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase–polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains.

BACKGROUND This is a prospective, multicentered study conducted in 9 large urban areas in Russia, in order to determine the burden of rotavirus gastroenteritis in children

Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus vaccine efficacy is high in developed countries, efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus vaccine efficacy by infant characteristics in developing countries.An exploratory, post hoc analysis was conducted using randomized controlled trial data of the pentavalent rotavirus vaccine (RV5) conducted in Africa and Asia (NCT00362648). Infants received either 3 doses of vaccine/placebo and were followed for up to 2 years. Within subgroups, vaccine efficacies and 95% confidence intervals (CIs) against rotavirus gastroenteritis (RVGE) were estimated using Poisson regression. We assessed heterogeneity of efficacy by age at first dose, gender, breastfeeding status and nutrition status.African children receiving the first dose at8 weeks had lower efficacy (23.7%; 95% CI: -8.2%-46.3%) than those vaccinated at ≥8 weeks (59.1%; 95% CI: 34.0%-74.6%). Marginally statistically significant differences were observed by age at first dose, gender and underweight status in Ghana and gender in Asian countries.Heterogeneity of efficacy was observed for age at first dose in African countries. This was an exploratory analysis; additional studies are needed to validate these results.

Background Rotavirus is the leading cause of severe diarrhea in children worldwide. We systematically reviewed the burden of rotavirus gastroenteritis (RVGE) and distribution of rotavirus strains in Asia. Methods We searched MEDLINE, EMBASE and the World Health Organization (WHO) website for the term “rotavirus” and the name of each country. We included studies that were conducted in children between 2000 and 2011 and that examined the epidemiology, health and/or economic burden of RVGE, and G and P-type distribution in Eastern, South East, Southern and Central Asia. Random effects models were used to pool the proportions of RVGE. We also estimated child mortality due to RVGE using the updated WHO and United Nations Children's Fund's mortality estimates in 2008. Results The search identified 113 eligible articles. The incidence rates of rotavirus-related hospitalizations in children under 5 years of age ranged from 2.1 to 20.0 cases per 1000 children per year with the highest rates reported in Bangladesh, South Korea, Taiwan, Thailand, and Vietnam. Rotavirus accounted for 37.5% of year-round hospitalized gastroenteritis cases, with higher proportions reported in South East Asia. Rotavirus was associated with approximately 145,000 deaths every year in Asia, with the greatest numbers occurring in India, Pakistan, and Indonesia. The highest annual societal costs of treating RVGE were reported in China (US$365 million), followed by Japan (US$254 million) and India (US$41–72 million). A diversity of rotavirus G and P-types was observed across Asia and the distribution of strains differed by country and year. The most common strains were G1P[8] (23.6%), G2P[4] (11.8%), G3P[8] (18.9%), and G9P[8] (7.4%). Conclusions Rotavirus is associated with substantial hospitalizations and deaths among children and causes large healthcare expenditures throughout Asia. Safe and effective rotavirus vaccines could substantially reduce the burden of disease.

Rotavirus gastroenteritis (RVGE) is the leading cause of severe diarrhea in children worldwide. This paper provides an overview of the development, clinical evaluation, and postlicensure impact of RotaTeq™(Rotavirus Vaccine, Live, Oral, Pentavalent, Merck & Co., Inc.). RotaTeq, an oral vaccine, is uniquely designed to contain five human-bovine reassortant rotavirus strains expressing the human serotypes G1, G2, G3, G4, and P1A[8], which represent the most common human rotavirus serotypes responsible for ∼85% of RVGE worldwide. The development required novel solutions for manufacturing, testing, and formulation for each of the reassortants. In one of the largest vaccine clinical trials conducted, the vaccine was shown to be well tolerated and highly efficacious against severe RVGE. Efficacy has also been demonstrated in lower-income countries. In large U.S. postlicensure studies, there have been no safety signals identified, and RotaTeq has had a significant impact on reducing RVGE and its associated medical costs since licensure in 2006.

Phase III studies of an oral, live, pentavalent, human-bovine reassortant rotavirus vaccine (RotaTeq; Merck) in developed countries have demonstrated that it is well tolerated with regard to intussusception and other adverse events and is efficacious in preventing rotavirus gastroenteritis and associated healthcare encounters. However, it cannot be assumed that rotavirus vaccines will be equally efficacious in infants and young children in the developing world. Differences in host populations, associated health conditions, and the epidemiology of rotavirus disease could affect vaccine performance. Concern about the potential for differences in efficacy stems from studies of previous candidate rotavirus vaccines, including bovine and rhesus rotaviruses, which showed no or variable efficacy in developing regions. Given this history, the World Health Organization (WHO) recommended that the efficacy of "new" rotavirus vaccines should be demonstrated in diverse geo- graphic areas, including developing countries, before widespread implementation. Successful implementation of any rotavirus vaccine in the developing world requires additional clinical research and sharing of early introduction experiences. We discuss efforts to bring RotaTeq vaccine to the developing world. Critical steps to achieve this goal include the clinical evaluation of vaccine safety and efficacy in a multisite trial in Asia and Africa, evaluation of concomitant use with other pediatric vaccines routinely used, and vaccine assessment in special populations (premature, human immunodeficiency virus-infected, and malnourished infants). Com- pletion of WHO prequalification of RotaTeq and affordability are also key requirements to routine vaccine introduction. The RotaTeq Partnership with the Nicaraguan Ministry of Health provides an example of the successful introduction of this vaccine into a developing world country.

A pentavalent humanbovine reassortant oral rotavirus vaccine, RotaTeq®, was evaluated among nearly 70,000 infants in the Rotavirus Efficacy and Safety Trial (REST), of which 30,523 were from Europe. All infants were followed for serious adverse events as well as hospitalizations and emergency department (ED) visits. All adverse events, health care utilization, and RVGE regardless of severity were evaluated in the clinical efficacy cohort (N = 2686) in Finland. RotaTeq® was 98.3% (95% CI, 90.2100%) and 68.0% (95% CI 60.374.4%) efficacious against severe rotavirus gastroenteritis (RVGE) and all RVGE due to any serotype for two rotavirus seasons post-vaccination. The combined rate of hospitalizations and ED visits due to RVGE of any serotype was reduced by 94.5% (95% CI, 91.396.8%) for up to 2 years after vaccination. There were no statistically significant differences between RotaTeq® and placebo for any of the safety outcomes. In Europe, RotaTeq® was highly efficacious and well tolerated.

Summary Background Rotavirus gastroenteritis is a significant cause of morbidity and mortality. Objective To perform an integrated safety analysis of data from the Phase III studies of the pentavalent rotavirus vaccine (PRV). Methods Healthy 6- to 12-week-old infants received 3 doses of PRV or placebo at 4- to 10-week intervals in 3 Phase III, blinded, randomized, placebo-controlled trials. Active surveillance for serious adverse events (AE), including intussusception, was performed at 7, 14, and 42 days after each dose. Other AEs occurring within 42 days after each dose were documented on Vaccination Report Cards. Fecal shedding of vaccine-virus strains was evaluated by plaque assay and electropherotyping. Results Intussusception and other serious AEs were evaluated among 71 799 vaccinated sub- jects. Within 42 days after any dose, intussusception occurred among 6 PRV and 5 placebo recipients. All AEs were evaluated among 11 722 vaccinated subjects. Within the week following the first dose, the incidences of fever and irritability were similar among PRV and placebo recipients, although diarrhea and vomiting occurred more frequently among PRV recipients versus placebo recipients (10.4% vs. 9.1% and 6.7% vs. 5.4%, respectively). Fecal shedding of vaccine-virus strains occurred in 8.9% of 360 PRV recipients after the first dose. Conclusions Across the 3 Phase III clinical trials, PRV was well tolerated, with no increased clinical risk of intussusception. Fecal shedding of vaccine-virus strains occurred infrequently and in low amounts, suggesting the risk of transmission is unlikely.

Premature infants seem to be at greater risk of hospitalization from rotavirus gastroenteritis than term infants. Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine were assessed in premature infants enrolled in the large-scale, blinded, placebo-controlled rotavirus efficacy and safety trial (REST).Healthy infants 6-12 weeks of chronologic age at study entry were randomized to receive 3 oral doses of pentavalent rotavirus vaccine or placebo at 4- to 10-week intervals. Infants born ator =36 weeks of gestational age were eligible if thriving at the time of enrollment. Safety and efficacy were retrospectively assessed in these premature infants comparing vaccine with placebo recipients. Cases of rotavirus gastroenteritis were defined as forceful vomiting and/oror =3 watery or looser-than-normal stools within a 24-hour period, accompanied by detection of rotavirus antigen in the stool.A total of 2070 infants between 25 and 36 gestational weeks received at least 1 dose of vaccine or placebo; 1005 vaccine recipients and 1061 placebo recipients were evaluable for safety. Serious adverse events occurred in 55 vaccine recipients (5.5%) and 62 placebo recipients (5.8%). In a nested substudy of 308 premature infants evaluable for detailed safety (154 in each group), the frequencies of fever, diarrhea, vomiting, and irritability were comparable between vaccine and placebo recipients. Overall, 3 doses of the pentavalent vaccine reduced the rate of hospitalizations and emergency department visits in premature infants due to rotavirus gastroenteritis by 100% (95% CI: 82.2-100) compared with placebo. The vaccine also prevented 73.0% (95% CI: -2.2-95.2) of rotavirus gastroenteritis cases of any severity.In this post hoc analysis of healthy premature infants, the pentavalent rotavirus vaccine was generally well-tolerated and substantially reduced rotavirus-attributable hospitalizations and emergency department visits compared with placebo. Overall, vaccine safety and efficacy seemed to be generally comparable to the results in the REST study population as a whole. These results support vaccinating healthy premature infants on the same schedule as term infants.

A live pentavalent rotavirus vaccine (PRV) containing 5 human-bovine (WC3) reassortants expressing human serotypes G1, G2, G3, G4 and P1A[8] was evaluated in a blinded, placebo-controlled study. Possible interactions between PRV and concomitantly administered licensed pediatric vaccines were investigated in a United States-based nested substudy (Concomitant Use Study) of the Rotavirus Efficacy and Safety Trial.From 2002 to 2003, healthy infants approximately 6 to 12 weeks of age at entry were randomized to receive either 3 oral doses of PRV or placebo at 4- to 10-week intervals. Subjects were also to receive combined Haemophilus influenzae type b and hepatitis B vaccine (2 doses), diphtheria and tetanus toxoids and acellular pertussis vaccine (3 doses), inactivated poliovirus vaccine (2 doses) and pneumococcal conjugate vaccine (3 doses) on the same day; oral poliovirus vaccine was not administered. Immunogenicity was assessed by measuring antibody responses to PRV and antigens contained in the licensed vaccines. Cases of rotavirus gastroenteritis were defined by forceful vomiting and/or -3 watery or looser-than-normal stools within a 24-hour period, and detection of rotavirus antigen in the stool. Safety was assessed by reporting of adverse events using diary cards.The Concomitant Use Study enrolled 662 subjects in the PRV group and 696 subjects in the placebo group. For the 17 antigens in the concomitantly administered vaccines, antibody responses were similar in PRV and placebo recipients, except for moderately diminished antibody responses to the pertactin component of pertussis vaccine. Efficacy of PRV against rotavirus gastroenteritis of any severity was 89.5% (95% CI = 26.5-99.8%). PRV was generally well tolerated when given concomitantly with the prespecified vaccines.In this study, antibody responses to the concomitantly administered vaccines were generally similar in PRV and placebo recipients. PRV was efficacious and well tolerated when given concomitantly with pediatric vaccines licensed in the United States.

BACKGROUND. Rotavirus is the leading cause of dehydrating acute gastroenteritis in infants worldwide. Previous studies of a live pentavalent human-bovine reassortant rotavirus vaccine have shown it to be efficacious across a range of potencies. OBJECTIVE. Our goal was to evaluate the efficacy, immunogenicity, and safety of pentavalent rotavirus vaccine at the end of shelf life in healthy infants. PATIENTS AND METHODS. During 2002–2004, 1312 healthy infants ∼6 to 12 weeks old from the United States (47%) and Finland (53%) were randomly assigned to receive 3 oral doses of vaccine (vaccine at ∼1.1 × 107 infectious U per dose) or placebo ∼4 to 10 weeks apart. Infants were to be followed for acute gastroenteritis through 1 rotavirus season after vaccination and for adverse events postvaccination. RESULTS. Three doses of pentavalent rotavirus vaccine at the end of shelf life demonstrated efficacy against rotavirus gastroenteritis caused by human G-serotypes included in the vaccine (G1–G4). Efficacy against severe rotavirus gastroenteritis was 100%, and efficacy against any rotavirus gastroenteritis regardless of severity was 72.5%. A threefold rise in G1 serum neutralizing was observed in 57% and in anti-rotavirus immunoglobulin A in 96% of pentavalent rotavirus vaccine recipients. No statistically significant increase in vomiting, diarrhea, or irritability was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients within the 7-day period from each dose. A statistically significant increase in fevers (≥100.5°F, rectal equivalent) was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients after dose 1. CONCLUSIONS. This pentavalent human-bovine rotavirus vaccine was generally well tolerated, efficacious, and immunogenic at the end of shelf life.

We used a claims database to assess coverage for rotavirus (RV), diphtheria-tetanus-acellular pertussis, and pneumococcal conjugate vaccines among infants in the United States. Similar coverage was seen until 7 months of age, after which RV coverage lagged. Missed opportunities for vaccination at well-child visits were found to vary by age.

The objectives of this study were to determine the presenting symptoms, healthcare utilization, and lost time from work and day care associated with acute rotavirus gastroenteritis.During the winter to spring seasons of 2002-2003 or 2003-2004, children36 months of age presenting with acute gastroenteritis to urban and suburban pediatric outpatient practices affiliated with 5 academic centers across the United States were enrolled in similarly designed studies. The case definition requiredor=3 watery or looser-than-normal stools and/or forceful vomiting within a 24-hour period beginningor=72 hours before presentation. Stool samples were tested for rotavirus antigen by standard commercial assays. Symptom frequencies for laboratory-confirmed rotavirus and nonrotavirus gastroenteritis were compared by Fisher's exact test; the number of healthcare contacts and lost days from work or day care were compared with the median 2-sample test.Stool specimens were obtained from 284 of 303 (94%) participants; 115 (40%) of tested specimens were positive for rotavirus (range, 31-50% across the 5 centers). Compared with participants with nonrotavirus gastroenteritis, children with rotavirus gastroenteritis were more likely to have 1) vomiting (83% versus 66%; P = 0.003), 2) combined diarrhea and vomiting (75% versus 50%; P0.001), and 3) fever (60% versus 43%; P = 0.010). More time from work was lost by parents/guardians of children with rotavirus than nonrotavirus gastroenteritis (median 2 versus 0 day; P = 0.007). More day care was missed by children with rotavirus than nonrotavirus gastroenteritis (median 3 versus 1 day; P = 0.002).In this multicenter study, rotavirus consistently caused a sizable proportion of cases of acute gastroenteritis seen in pediatric outpatient practices in the United States during the winter and spring. Rotavirus gastroenteritis was more frequently associated with vomiting, combined diarrhea and vomiting, fever and lost time from work and day care than nonrotavirus gastroenteritis.

Background Rotavirus gastroenteritis, which causes substantial infant mortality and morbidity worldwide, is a vaccine-preventable disease. The purpose of this study was to evaluate different compositions and potencies (vaccine virus titers) of a live multivalent human-bovine (WC3) reassortant rotavirus vaccine in order to select the potency and composition of the vaccine for further development. Methods The efficacy, safety, and immunogenicity of a G1, G2, G3, G4, and P1A pentavalent composition at three different potencies, a G1, G2, G3, G4 quadrivalent composition, and a P1A monovalent composition of an oral human-bovine (WC3) reassortant rotavirus vaccine were compared in a blinded, placebo-controlled trial conducted between 1998 and 2001 enrolling 1,946 healthy Finnish infants 2-8 months of age. Results All potencies of the pentavalent and quadrivalent vaccines were efficacious (58-74%) against wild-type rotavirus gastroenteritis of any severity and 100% protective against severe rotavirus disease caused by vaccine G-serotypes through the first rotavirus season post-vaccination. The monovalent P1A vaccine was 53% efficacious against moderate-and-severe rotavirus gastroenteritis. Protection against rotavirus gastroenteritis of any severity was demonstrated through two and three rotavirus seasons for all vaccine compositions. After the third dose, the percentage of infants with >or=3-fold rise in baseline serum neutralizing antibody titers against G1 ranged from 62% to 86% for recipients of the pentavalent vaccine, depending on the potency. The incidence of fever, irritability, vomiting, and diarrhea did not significantly differ between vaccine and placebo groups. A 7-month-old male developed intussusception 9 days after the first dose of the low-potency pentavalent vaccine. Conclusions Based on the results of this trial, a pentavalent composition (G1, G2, G3, G4, and P1A) of human-bovine (WC3) reassortant rotavirus vaccine with a potency similar to that of the middle-potency pentavalent vaccine ( approximately 8 x 10(6) plaque-forming units/dose) was selected for further development.

The strategy of decreasing the morbidity and mortality associated with rotavirus gastroenteritis through vaccination is supported by studies demonstrating that wild-type rotavirus infection protects against subsequent rotavirus disease. Primary infection with wild-type rotavirus typically induces homotypic immunity. Vaccination of infants with a multivalent vaccine directed against prevalent rotavirus serotypes is the strategy most likely to provide the broadest degree of protection against rotavirus gastroenteritis. The pentavalent human-bovine reassortant rotavirus vaccine (HBRV) is directed against each of the most prevalent rotavirus serotypes, including G1, G2, G3, G4, and P1. The safety, immunogenicity, and efficacy of different reassortant compositions and formulations of the HBRV have been evaluated in clinical trials. An HBRV dose of > or =8 x 10(6) plaque-forming units has demonstrated 68.8%-76.6% efficacy against any rotavirus gastroenteritis, regardless of severity, and approximatel 100% efficacy against severe rotavirus gastroenteritis for the first rotavirus infection season after vaccination. The HBRV has been generally well tolerated, with no increase in the incidence of fever, vomiting, diarrhea, or behavioral changes among vaccine recipients, compared with placebo recipients, during the 14- and 42-day periods after administration of any dose. Shedding of vaccine strains in feces is uncommon. A large-scale trial is under way to evaluate the efficacy and safety of the manufacturing-scale formulation of pentavalent HBRV.

Asthma prevalence is increasing. Child care centers can play an important role in controlling asthma morbidity in young children. Therefore, we assessed asthma-related environmental practices in licensed centers and asthma awareness among child care staff. Two cross-sectional surveys were mailed to 1,250 randomly selected California licensed facility child care centers in 2002. Site directors were asked about the presence of items that can trigger asthma and asthma experience in their centers and were requested to distribute surveys to three child care staff members. Staff surveys assessed asthma knowledge, attitudes, and beliefs using previously validated questions. Univariate and multivariate analyses examined frequencies and relations between responses and asthma-related factors. A total of 284 (24%) site directors and 666 (18%) staff members completed surveys. The median number of children enrolled at the centers was 48 (range, 1–1,356), with a median of 2 children with asthma (range, 0–55). During th...

The pentavalent human-bovine reassortant rotavirus vaccine is indicated as a 3-dose series with first dose administered orally at 6 to 12 weeks with subsequent doses at 4 to 10 week intervals. In pre-licensure phase III trials, the majority followed this schedule, but there were 2956 instances where infants received a dose of pentavalent human-bovine reassortant rotavirus vaccine/placebo >10 weeks after the previous dose. Among this subset, the efficacy against any severity of disease, the reduction in utilization of healthcare resources and the safety profile after vaccination were comparable with overall results.

The efficacy of a live, oral, pentavalent rotavirus vaccine against G1-4 rotavirus gastroenteritis (RVGE) was retrospectively assessed based on breastfeeding frequency among 5098 infants in a placebo-controlled trial. The efficacy against any RVGE severity for infants never breastfed, sometimes breastfed, or exclusively breastfed was 68.3%, 82.2%, and 68.0%, respectively. The efficacy against severe RVGE was 100%, 95.4%, and 100%, respectively. Breastfeeding did not seem to adversely impact the efficacy of pentavalent rotavirus vaccine.

Background In randomized clinical studies, over 11,800 children, 12 months to 6 years of age, were administered ProQuad ® , a combination measles, mumps, rubella, and varicella vaccine (MMRV). This paper describes the safety following a 2-dose regimen of MMRV administered to children in the second year of life. Methods Safety data from five clinical studies were combined for all children who were scheduled to receive two doses of MMRV ∼3–6 months apart. All vaccinated children were followed for safety following each dose of MMRV. Results Of 3112 children who received a first dose of MMRV, 2780 (89.3%) received a second dose of MMRV. Overall, 70.5% and 57.7% of children reported ≥1 adverse experiences following first and second doses of MMRV, respectively. Injection-site redness was statistically significantly higher postdose 2 than postdose 1, while injection-site pain/tenderness was statistically significantly higher postdose 1 compared to postdose 2. Rashes were statistically significantly lower postdose 2 compared to postdose 1. Ten febrile seizures (8 postdose 1, 2 postdose 2) were reported following MMRV vaccination. The incidence of febrile seizures postdose 1 of MMRV was 0.26% (8/3019) compared to 0.07% (2/2695) postdose 2 of MMRV. Conclusions Administration of two doses of MMRV has an acceptable safety profile in children 12 to 23 months of age. There is a small increase in the risk of febrile seizures following the first dose of MMRV as compared to the component vaccines, but the risk for any individual child is relatively low.

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (REST) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the subsequent dose (Analysis B) were analyzed. In Analysis A, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype between doses 1 and 2 by 100% (95% confidence interval [CI]: 72-100%) or 82% (95% CI: 39-97%), respectively, and between doses 2 and 3, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype by 91% (95% CI: 63-99%) or 84% (95% CI: 54-96%), respectively. Similar rate reductions were observed in Analysis B. These data suggest that RV5 provides a high level of protection between doses against hospitalizations and ED visits for RVGE starting as early as 14 days after the first dose.

RotaTeq is an oral pentavalent rotavirus vaccine (RV5) that has shown high and consistent efficacy in preventing rotavirus gastroenteritis (RGE) in randomized clinical trials conducted mostly in industrialized countries. We projected the effectiveness of RV5 against RGE-related hospitalizations and deaths in six Asian countries by using a simple mathematical model. Model inputs included rotavirus surveillance data collected during 2006–2007 in China, 2001–2002 in Hong Kong, 2005–2007 in India, 2005–2007 in South Korea, 2005–2007 in Taiwan and 2001–2003 in Thailand; the numbers of rotavirus-related deaths in each country; and published rotavirus serotype-specific efficacy of RV5. The model projected an overall effectiveness in the region of 82% to 89% against RGE-related hospitalizations and a substantial reduction in RGE-related deaths, suggesting that RV5 could substantially reduce the burden of rotavirus disease in Asia.