Universal Rotavirus Vaccination Research Articles

Factors associated with antibiotic use in children hospitalized for acute viral gastroenteritis and the relation to rotavirus vaccination

ABSTRACT Evidence on unnecessary antibiotic use in children with acute viral gastroenteritis (AGE) is scarce. We characterized the extent and correlates of antibiotic use among children hospitalized with viral AGE. A single-center study enrolled children aged 0–59 months hospitalized for AGE between 2008 and 2015 in Israel. Information was collected on laboratory tests, diagnoses, antibiotic treatment, and rotavirus vaccination. Stool samples were tested for rotavirus antigen, GII-norovirus, and stool cultures were performed for bacterial enteropathogens. Data from 2240 children were analyzed. Rotavirus vaccine was given to 79% of eligible children. Rotavirus test was performed on 1419 (63.3%) children. Before the introduction of universal rotavirus vaccination (2008–2010), rotavirus positivity in stool samples was 37.0%, which declined to 17.3% during the universal vaccination years (2011–2015). Overall, 1395 participants had viral AGE. Of those, 253 (18.1% [95% CI 16.1–20.2]) had unnecessary antibiotic treatment, mostly penicillin 46.6%, ceftriaxone 34.0% and azithromycin 21.7%. A multivariable analysis showed an inverse association between rotavirus vaccination and unnecessary antibiotic treatment (odds ratio = 0.53 [95% CI 0.31–0.91]), while positive associations were found with performing chest-X-ray test (3.00 [1.73–5.23]), blood (3.29 [95% CI 1.85–5.86]) and urine cultures (7.12 [3.77–13.43]), levels of C-reactive protein (1.02 [1.01–1.02]) and leukocytes (1.05 [1.01–1.09]). The results were consistent in an analysis of children with laboratory-confirmed rotavirus or norovirus AGE, or after excluding children with CRP > 50 mg/L. In conclusion, antibiotic prescription was common among hospitalized children with viral AGE, which was inversely related to rotavirus vaccination, possibly due to less severe illness in the vaccinated children.

Projected Public Health Impact of a Universal Rotavirus Vaccination Program in France.

In June 2022, French health authorities issued a universal recommendation for routine administration and reimbursement of rotavirus vaccines in infants. Given this recent recommendation by French health authorities, we sought to understand the public health impact of a universal rotavirus vaccination strategy compared with no vaccination. A deterministic, age-structured, nonlinear dynamic transmission model, accounting for herd immunity, was developed. We considered 3 vaccination coverage scenarios: high (95%), medium (75%) and low (55%). Model parameter values were based on published modeling and epidemiological literature. Model outcomes included rotavirus gastroenteritis (RVGE) cases and healthcare resource utilization due to RVGE (hospitalizations, general practitioner or emergency department visits), as well as the number needed to vaccinate to prevent 1 RVGE case (mild or severe) and 1 RVGE-related hospitalization. Model calibration and analyses were conducted using Mathematica 11.3. Over 5 years following implementation, RVGE cases for children under 5 years are estimated to be reduced by 84% under a high vaccination coverage scenario, by 72% under a medium vaccination coverage scenario and by 47% under a low vaccination coverage scenario. Across all scenarios, the number needed to vaccinate to avert 1 RVGE case and hospitalization varied between 1.86-2.04 and 24.15-27.44, respectively. Rotavirus vaccination with high vaccination coverage in France is expected to substantially reduce the number of RVGE cases and associated healthcare resource utilization.

Prediction of effectiveness of universal rotavirus vaccination in Southwestern Vietnam based on a dynamic mathematical model

Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01–1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age.

The economic impact of the introduction of universal rotavirus vaccination on rotavirus gastroenteritis related hospitalisations in children in Ireland.

Rotavirus gastroenteritis (RVGE), a vaccine preventable disease, remains a common cause of severe gastroenteritis in children globally. Ireland introduced the universal rotavirus vaccination to the national immunisation programme in 2016. In this paper the economic impact on RVGE related hospitalisations amongst children under 5years is examined. Using national data from all Irish public hospitals, an Interrupted Times Series Analysis (ITSA) compares RVGE hospitalisations amongst children under 5years, pre- and post-vaccine introduction. Costs are estimated and ITSA results are compared to the counterfactual to estimate the economic impact of the vaccine. A probit model examines patient characteristics pre- and post-vaccine introduction. Vaccine introduction coincided with lowered RVGE related hospitalisations. While this effect was delayed (1year) there is evidence of a sustained impact. RVGE patients' post-vaccine introduction were likely to be over 2years (p=0.001) and length of stay was lower on average (p=0.095). The counterfactual analysis revealed 492 RVGE hospitalisations were avoided on average annually since the introduction of the vaccine. This has an estimated economic value of €0.92 million per annum. Following the introduction of the rotavirus vaccine in Ireland, hospitalisations for RVGE decreased significantly and those hospitalised were older and with a reduced length of stay on average. This has the potential for significant cost savings for the Irish healthcare system.

Economic assessment of childhood rotavirus vaccination in Bangladesh

Rotavirus is one of the most highly prevalent communicable diseases in Bangladesh. The objective of this study is to evaluate the benefit-cost ratio of childhood rotavirus vaccination program in Bangladesh. A spreadsheet-based model was used to estimate the benefit and cost of a nationwide universal rotavirus vaccination program against rotavirus infections among under-five children in Bangladesh. A benefit-cost analysis was performed to evaluate a universal vaccination program compared with a status quo. Data from various published vaccination-related studies and public reports were used. The introduction of a childhood rotavirus vaccination program in Bangladesh for 14.78 million under-five children is projected to prevent approximately 1.54 million rotavirus cases during the first 2 years including 0.7 million severe rotavirus infections. This study shows that among the WHO-prequalified rotavirus vaccines, the net societal benefit is the highest if the vaccination program adopts ROTAVAC® rather than Rotarix® or ROTASIIL®. For every dollar invested in the outreach-based ROTAVAC® vaccination program, society would gain $2.03 in return, while in a facility-based vaccination program, society would gain up to about $2.2. The findings of this study demonstrate that a universal childhood rotavirus vaccination program is a cost-beneficial investment of public money. Thus, the government should consider the introduction of rotavirus vaccination in their Expanded Program on Immunization since the rotavirus immunization policy in Bangladesh will be economically justifiable.

Explaining the formation of a plateau in rotavirus vaccine impact on rotavirus hospitalisations in Belgium

BackgroundObservational data on the reduction in hospitalisations after rotavirus vaccine introduction in Belgium suggest that vaccine impact plateaued at an unexpectedly high residual hospitalisation rate. The objective of this analysis was to identify factors that influence real-world vaccine impact. MethodsData were collected on hospitalisations in children aged ≤ 5 years with rotavirus disease from 11 hospitals since 2005 (the RotaBIS study). The universal rotavirus vaccination campaign started late in 2006. A mathematical model simulated rotavirus hospitalisations in different age groups using vaccine efficacy and herd effect, influenced by vaccine coverage, vaccine waning, and secondary infection sources. The model used optimisation analysis to fit the simulated curve to the observed data, applying Solver add-in software. It also simulated an ‘ideal’ vaccine introduction maximising hospitalisation reduction (maximum coverage, maximum herd effect, no waning), and compared this with the best-fit simulated curve. Modifying model input values identified factors with the largest impact on hospitalisations. ResultsCompared with the ‘ideal’ simulation, observed data showed a slower decline in hospitalisations and levelled off after three years at a higher residual hospitalisation rate. The slower initial decline was explained by the herd effect in unvaccinated children. The higher residual hospitalisation rate was explained by starting the vaccine programme in November, near the rotavirus seasonal peak. This resulted in low accumulated vaccine coverage during the first rotavirus disease peak season, with the consequential appearance of secondary infection sources. This in turn reduced the herd effect, resulting in a diminished net impact. ConclusionsOur results indicate that countries wishing to maximise the impact of rotavirus vaccination should start vaccinating well ahead of the rotavirus seasonal disease peak. This maximises herd effect during the first year leading to rapid and high reduction in hospitalisations. Secondary infection sources explain the observed data in Belgium better than vaccine waning.

Anti-rotavirus Properties and Mechanisms of Selected Gram-Positive and Gram-Negative Probiotics on Polarized Human Colonic (HT-29) Cells.

Probiotics have been investigated to improve the universal rotavirus (RV) vaccination as well as to ameliorate the RV infection. However, underlying mechanisms how probiotics mediate beneficial effects needs more investigation. Thus, in the present study, we used polarized HT-29 cells to assess the anti-RV properties of Gram-positive, (Lactobacillus acidophilus, Lacticaseibacillus rhamnosus GG, and Bifidobacterium subsp. Lactis Bb12) and Gram negative, (Escherichia coli Nissle 1917) probiotics and study their underlying mechanisms. Our results showed that pre-treatment of HT-29 cells for 4h with probiotics, significantly reduced (p < 0.05) human RV replication and this effect was most pronounced for E. coli Nissle followed by L. acidophilus and L. rhamnosus GG. Strikingly, only pre-treatment with live bacteria or their supernatants demonstrated anti-RV properties. Except Gram negative E. coli Nissle, the Gram-positive probiotics tested did not bind to RV. Ingenuity pathway analysis of tight junction (TJ)- and innate immune-associated genes indicated that E. coli Nissle or E. coli Nissle + RV treatments improved cell-cell adhesion and cell contact, while L. acidophilus or L. acidophilus + RV treatments also activated cell-cell contact but inhibited cell movement functions. RV alone inhibited migration of cells event. Additionally, E. coli Nissle activated pathways such as the innate immune and inflammatory responses via production of TNF, while RV infection activated NK cells and inflammatory responses. In conclusion, E. coli Nissle's ability to bind RV, modulate expression of TJ events, innate immune and inflammatory responses, via specific upstream regulators may explain superior anti-RV properties of E. coli Nissle. Therefore, prophylactic use of E. coli Nissle might help to reduce the RV disease burden in infants in endemic areas.

Enteropathogen Changes After Rotavirus Vaccine Scale-up.

To inform next steps in pediatric diarrhea burden reduction by understanding the shifting enteropathogen landscape after rotavirus vaccine implementation. We conducted a case-control study of 1788 medically attended children younger than 5 years, with and without gastroenteritis, after universal rotavirus vaccine implementation in Peru. We tested case and control stools for 5 viruses, 19 bacteria, and parasites; calculated coinfection-adjusted attributable fractions (AFs) to determine pathogen-specific burdens; and evaluated pathogen-specific gastroenteritis severity using Clark and Vesikari scales. Six pathogens were independently positively associated with gastroenteritis: norovirus genogroup II (GII) (AF 29.1, 95% confidence interval [CI]: 28.0-32.3), rotavirus (AF 8.9, 95% CI: 6.8-9.7), sapovirus (AF 6.3, 95% CI: 4.3-7.4), astrovirus (AF 2.8, 95% CI: 0.0-4.0); enterotoxigenic Escherichia coli heat stable and/or heat labile and heat stable (AF 2.4, 95% CI: 0.6-3.1), and Shigella spp. (AF 2.0, 95% CI: 0.4-2.2). Among typeable rotavirus cases, we most frequently identified partially heterotypic strain G12P[8] (54 of 81, 67%). Mean severity was significantly higher for norovirus GII-positive cases relative to norovirus GII-negative cases (Vesikari [12.7 vs 11.8; P < .001] and Clark [11.7 vs 11.4; P = .016]), and cases in the 6- to 12-month age range relative to cases in other age groups (Vesikari [12.7 vs 12.0; P = .0002] and Clark [12.0 vs 11.4; P = .0016]). Norovirus is well recognized as the leading cause of pediatric gastroenteritis in settings with universal rotavirus vaccination. However, sapovirus is often overlooked. Both norovirus and sapovirus contribute significantly to the severe pediatric disease burden in this setting. Decision-makers should consider multivalent vaccine acquisition strategies to target multiple caliciviruses in similar countries after successful rotavirus vaccine implementation.

Incidence and Mortality Trends of Acute Gastroenteritis and Pneumococcal Disease in Children Following Universal Rotavirus and Pneumococcal Conjugate Vaccination in Ecuador.

IntroductionEcuador introduced routine infant rotavirus (RV) vaccination in 2008 and pneumococcal conjugate vaccination (PCV) in 2011 to manage disease and mortality in children caused by gastroenteritis (GE) and by pneumonia (PNE) and invasive pneumococcal disease (IPD), respectively.MethodsThis retrospective ecological database study described vaccination coverage as well as the trends in incidence and mortality in the pre- versus post-vaccination periods and used time-trend analysis models to assess the impact of vaccination.ResultsRV vaccination coverage of the second dose was between 79–97% from 2008 to 2016. GE incidence and mortality showed a declining trend before vaccination which continued in the post-vaccination period. The model estimated a statistically significant decrease of 72.4% for GE mortality and 51.2% for GE incidence in the post-vaccination period. PCV vaccination coverage remained above 80% (second dose) and 40% (third dose) after 2011. PNE mortality showed a declining trend before vaccination and a continued decline after vaccination, while PNE incidence was more variable (sharp increase from 2005–2009 then decrease and eventual stabilisation). The model estimated a statistically significant decline of 41.1% for PNE mortality and a stable PNE incidence in the post- versus pre-vaccination period. IPD incidence and mortality yearly data showed large variability by year and low numbers, making it difficult to discern a trend. The model estimated a statistically significant reduction of 51.1% for IPD mortality and 31.5% for IPD incidence in the post- versus pre-vaccination period.ConclusionAfter the first 9 years of routine RV vaccination and 6 years of routine PCV vaccination in Ecuador, significant decreases in incidence and mortality in children < 5 years of age due to GE and pneumococcal disease have been observed.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00531-6.

Acute Gastroenteritis Morbidity and Mortality Trends Following Universal Rotavirus Vaccination in Children in Peru: Ecological Database Study with Time-Trend Analysis.

IntroductionRotavirus (RV) infection is the leading cause of severe diarrhea in children worldwide. It is responsible for around 25% of gastroenteritis (GE) cases, 33% of hospitalized GE cases, and an annual mortality rate of 113.4/100,000 in children < 5 years of age in Peru. RV infant vaccination is recommended by the World Health Organization and provides the best public health strategy to manage the disease. Universal RV vaccination was introduced in Peru in 2009.MethodsTrends in GE ambulatory visits, hospitalizations, and deaths in children < 5 years of age are described in the pre-vaccination (2004–2008) versus post-vaccination (2010–2018) periods. Time-trend analysis was performed (using generalized linear regression models) to assess the impact of vaccination nationwide and by region after adjusting for variables.ResultsBetween 2009 and 2011, vaccination coverage increased to over 80% in Peru. In infants < 1 year of age, GE ambulatory cases, hospitalizations, and deaths decreased in the post-vaccination period by 40.3%, 46.2%, and 55.5%, respectively (and in children < 5 years of age, by 34.4%, 41.9%, and 54.3%, respectively) compared with the pre-vaccination period. Results of the multivariate time-trend analysis also found significant decreases in the post-vaccination period of 10.7% (GE ambulatory cases), 17.2% (GE hospitalizations), and 37.3% (GE mortality) in children < 5 years of age. Data analyzed by region varied, with Costa and Sierra regions generally in line with the national findings; however, some findings were less robust for Selva due to fewer available data.ConclusionAfter 9 years of RV vaccination in Peru, there appears to be a statistically significant positive impact of vaccination, in terms of reducing GE-related mortality, hospitalizations, and ambulatory visits in infants and young children. For policymakers to understand regional differences and future vaccination needs, continued improvement in surveillance is needed.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00532-5.

Use of the Whole Country Insulin Consumption Data in Israel to Determine the Prevalence of Type 1 Diabetes in Children

Recent studies showed that rotavirus vaccination may affect the prevalence of type 1 diabetes (T1D). The aim of the study was to determine the prevalence of early childhood (<5 years) T1D before and during the introduction of rotavirus vaccination in Israel by syndromic surveillance. Data on insulin purchases reported by Israel's four Health Maintenance Organizations (HMOs) were retrieved from the National Program for Quality Indicators in Community Healthcare. During the prevaccination years (2002-2007), a steady increase in insulin purchases was reported in the young (<5 years). The period percent change (PC) of children <5 years old diagnosed with T1D inferred from purchased insulin prescriptions increased by 50.0%, and the annual percent change (APC) increased by 10.0% (p = 0.01). During the period of free, universal Rotavirus vaccination (2011-2018), the PC for T1D diagnoses among children <5 years of age decreased by 3.8% with an APC of -2.5% (p = 0.14). There was a significant difference (p = 0.002) between the increasing trend in insulin use before vaccination versus the decreasing trend after vaccination. Rotavirus vaccination correlated with attenuation of the increasing rate in the prevalence of T1D in <5-year-old children in Israel.

PIN30 Comparing Two Rotavirus Vaccines Strategies Versus NO Vaccine in China- a Cost-Effectiveness Analysis

Globally, rotaviruses are the most frequent causes of severe diarrhea in children under five years of age. China has experienced significant morbidity and mortality associated with rotavirus, creating a large economic burden. The domestic monovalent rotavirus vaccine and the universal pentavalent rotavirus vaccine are available in China. To determine the public health impact of a national rotavirus vaccination program, we performed a cost-effectiveness study from the perspective of the health care system.

PIN20 Cost-Effectiveness Analysis of Universal Vaccination with Pentavalent Vaccine in Russia

To assess the cost-effectiveness of universal pentavalent rotavirus vaccination compared to no vaccination from the societal perspective in Russia. We developed an age-structured deterministic dynamic transmission model and estimated the averted outcomes and cost-effectiveness of rotavirus vaccination over a time horizon of 50 years. Parameter values were obtained from the published modeling and epidemiologic literature for rotavirus transmission, registered vaccination prices (VAT: 2084.39/€27.40), Russian surveillance data, and consultation with local experts. Based on Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing data, we considered the under-reporting fraction to be 66.1%. (which means that the incidence data is constructed based on 33.9% confirmed data and 66.1% unconfirmed data). Over 50 years, rotavirus vaccination in Russia is expected to avert 16.29 million Rotavirus Gastroenteritis (RVGE) cases, resulting in a gain of 53,221 QALYs (or 1,064 QALYs annually) compared to no vaccination. From a societal perspective, without vaccination, the cost of care for RVGE cases was projected to be 346,752,521,944 (€4,558,346,702) over 50 years or 6,935,050,438 (€91,166,934) per year. Overall costs for the vaccination program and the breakthrough RVGE cases were estimated to be 235,387,111,815 (€3,094,356,917) or 4,707,742,236 (€61,887,138) per year. From a societal perspective, universal vaccination with pentavalent rotavirus vaccine is thus expected to be a cost-saving strategy compared to no vaccination in Russia, with societal savings of 2,227,308,202 (€29,279,796) annually. Universal rotavirus vaccination with a pentavalent vaccine in Russia assuming a coverage rate similar to other vaccines included in the national immunization program is projected to reduce the number of RVGE episodes in infants over a 50-year time horizon. In light of the averted health care resource utilization and productivity costs related to RVGE as projected in this study, vaccination with a pentavalent rotavirus vaccine is a cost-saving strategy from a societal perspective compared to no vaccination.

Identification of Acute Rotavirus Diarrhea and Analysis of its Risk Factors in Children Under-5 Years in Surabaya, Indonesia

Background: Diarrhea is the most common disease among children and still a major cause of morbidity and mortality. Among the various causes of acute diarrhea in children, rotavirus is the most frequent one, especially in developing countries where universal rotavirus vaccination has not been introduced, including Indonesia. Objectives: This study aimed to determine the percentage of acute rotavirus diarrhea in children and analyze its risk factors in Tanah Kali Kedinding Primary Health Care, Surabaya, Indonesia. Method: Stool specimens were collected from a total 116 children under-5 years visiting Tanah Kali Kedinding Primary Health Care in Surabaya, Indonesia due to acute diarrhea during September 2018 – January 2019. Rapid stool antigen immunochromatograhic test was used to identify group A rotavirus antigen. Some potential risk factors were analyzed. Results: Among 116 samples from children with acute diarrhea, 67 (57.8%) were identified group A rotavirus positive. Samples with rotavirus positive were obtained mostly form male (p=0.008). Malnutrition was associated with an increased risk of rotavirus infection (p=0.025). Male and malnutrition were about 3 times more likely to have rotavirus infection. Other risk factors including children’ age, history of exclusive breastfeeding, mothers’ education and the amount of income were not statistically associated with rotavirus diarrhea. Conclusion: The occurence of children with acute rotavirus diarrhea in this study was 57.8%. Some risk factors for rotavirus infection were gender and malnutrition. Control measures such as anticipating its risk factors need to be adapted, according to the further epidemiology investigation.

Pathogen-specific risk of seizure in children with moderate-to-severe diarrhoea: Case control study with follow-up.

To determine the pathogen-specific risk of seizure in under-five children hospitalised with moderate-to-severe diarrhoea (MSD) in rural settings. This was a prospective case-control study with follow-up, conducted in a sentinel facility of Global Enteric Multicenter Study in Mirzapur, a rural community of Bangladesh between 2007 and 2010. Children aged 0-59months who presented with MSD and seizure constituted the cases whereas those who did not have seizure comprised the controls. MSD was defined if the episodes were associated with dehydration or dysentery or required hospitalisation with diarrhoea or dysentery. All enrolled children were followed up at home within 50-90days of enrolment. A total of 64 cases and 128 randomly selected controls formed the analysable dataset. The result of logistic regression analysis after adjusting for potential confounders revealed that shigellosis (Shigella species, OR=5.34, 95% CI=2.37-12.04) particularly S. flexneri (OR=3.34, 95% CI=1.48-7.57), S. flexneri 6 (OR=23.24, 95% CI=2.79-193.85), S. sonnei (OR=6.90, 95% CI=2.34-19.85); norovirus (OR=6.77, 95% CI=1.69-27.11), fever (OR=16.75, 95% CI=1.81-154.70) and loss of consciousness (OR=35.25, 95% CI=1.71-726.20) were the independent risk factors for seizure in MSD children. At enrolment, cases had lower WHZ (P=0.006) compared to their peers, follow-up anthropometrics showed significant improvement in WHZ (P<0.001) and WAZ (P<0.05), whereas deterioration in HAZ (P<0.001) in both cases and controls. Childhood MSD episodes particularly due to Shigella and norovirus are often associated with seizure. Prompt identification and appropriate management of children with shigellosis may reduce occurrence and adverse consequences of seizure linked with MSD.

Association between rotavirus vaccination and intussusception in Australian children: A record linkage study.

Post-licensure surveillance studies have shown a small but increased risk of intussusception among infants in the days following rotavirus vaccination (RV). We assessed the temporal trends of intussusception-coded hospitalisations before and after the commencement of a universal rotavirus vaccination programme in Western Australia (WA) in 2007. We also assessed the perinatal factors and pathogens associated with these hospitalisations. Intussusception-coded hospitalisations occurring in a cohort of 367476 WA-born children (2000-2012) aged <5years were probabilistically linked to perinatal and pathology records. Age-specific incidence rates for overall and pathogen-specific intussusception-coded hospitalisations were calculated before (2000-2006) and after (2008-2012) RV introduction. Adjusted Cox proportional hazards models were used to assess perinatal risk factors for intussusception. The overall rate of intussusception-coded hospitalisation was 26.4 per 100000 child-years (95% confidence interval [CI] 24.0, 29.0) among children aged <5years, with rates being 70% higher (95% CI 39, 107) in the RV period than in the pre-RV period. Compared with the pre-RV period, rates were higher among those aged 12-23months (by 55%, 95% CI 5, 127) and 2-4years (by 84%, 95% CI 20, 182) in the RV period. However, the risk of intussusception-coded hospitalisations associated with intussusception management-related procedure code(s) was similar among all age groups in both birth periods. Among infants aged <12months, male sex, non-Aboriginal status, birth to multiparous mothers, and birth in RV era were independent risk factors associated with intussusception-coded hospitalisations. Adenovirus was strongly associated with intussusception (6.7 per 100000 child-years, 95% CI 5.3, 9.3). The risk of intussusception-coded hospitalisations was higher post-RV introduction, but not for intussusception-coded hospitalisations associated with procedure code(s). The increase was no higher in the vaccine-eligible age group than in older age groups, suggesting that the apparent increase is likely to be attributable to causes other than vaccination.

Effects of rotavirus vaccine on all-cause acute gastroenteritis and rotavirus hospitalizations in Israel: A nationwide analysis

BackgroundIn December 2010, the pentavalent rotavirus vaccine (RotaTeq) was added to the national immunization program in Israel. The study aim was to examine national reductions in all-cause acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children aged 0–59 months following the introduction of universal rotavirus immunization in Israel. MethodsWe extracted data from the Israel National Hospital Discharge Database. Hospitalization rates were calculated by dividing the annual number of all-cause AGE and RVGE hospitalizations by the number of children aged 0–59 months residing Israel. To assess rate reductions, we compared the mean hospitalization rate for the pre-vaccine years (2002–2008) with that for the universal vaccination years (2011–2017). Interrupted time-series analyses were undertaken. During 2008–2010 rotavirus vaccines were partially available. ResultsA total of 131,116 AGE hospitalizations were reported, of which 13,111 (10.0%) were coded as RVGE hospitalizations. The average annual all-cause AGE hospitalization rate during the pre-vaccine period was 147.9 (95% CI 146.7–149.0) per 10,000 children aged 0–59 months, and declined by 38.7–53.0% during the universal vaccination years. The average annual pre-vaccine RVGE hospitalization rate was 16.9 (95% CI 16.5–17.3) per 10,000 children, and declined by 89.1% during 2016–2017.Findings from interrupted time-series analyses showed significant impact of introducing universal rotavirus immunization on the declines of all-cause AGE and RVGE hospitalizations rates. A multivariable Autoregressive Integrated Moving Average model showed that the variable “immunization period” was a significant predictor of RVGE hospitalizations (t = 7.3, p < 0.001) for the universal vaccination years.The declines in hospitalizations rates of all-cause AGE were lower among Arab children compared to Jewish children, but the declines in RVGE rates were similar between the groups. ConclusionsNational hospitalization data demonstrated substantial and consistent reductions in all-cause AGE and RVGE hospitalizations following the implementation of universal rotavirus vaccination program.

Etiology and Prospectively-Evaluated Severity of Medically-Attended Pediatric Gastroenteritis Following Universal Rotavirus Vaccine Implementation, Peru

Etiology and Prospectively-Evaluated Severity of Medically-Attended Pediatric Gastroenteritis Following Universal Rotavirus Vaccine Implementation, Peru

Has Rotavirus Vaccination Decreased the Prevalence of Biliary Atresia?

Biliary atresia (BA) is a rare neonatal liver disease that causes cholestasis and is the leading indication for pediatric liver transplantation. Although the exact etiology of BA remains unknown, evidence from murine models supports the role of rotavirus infection in the development of BA. In 2006, universal rotavirus vaccination was implemented in the United States. The goal of this study was to determine if the prevalence of BA correlated with the number of annual rotavirus infections. We utilized data from the 1997 to 2012 Kids' Inpatient Database and the 1988 to 2015 Organ Procurement and Transplantation Network to determine the annual number of infant discharges with a primary diagnosis of BA and the number of infants with BA who received a liver transplant, respectively. We obtained the number of annual rotavirus infections from the National Respiratory and Enteric Virus Surveillance System and examined whether trends existed between the data from these 3 sources over time. From 1997 to 2006, the number of positive rotavirus antigen tests remained steady, however a rapid decrease was observed from 2006 to 2012 (8774 to 1277), coinciding with the uptake of rotavirus immunizations nationwide. The number of BA discharges doubled from 1997 to 2003 and again increased from 2006 to 2012 (67 to 137 and 117 to 156), while the number of liver transplants for BA changed very little from 1997 to 2012. The recent implementation of rotavirus vaccination has not had any substantial influence on the prevalence of BA in the United States.

PIN115 - BARRIERS TO ACCESS AND IMPLEMENTATION OF ROTAVIRUS VACCINATION IN EUROPE

Rotavirus (RV) is a major agent of gastroenteritis and an important cause of child death worldwide. Immunization has been available since 2006. (1) Twelve years after the authorization of two rotavirus vaccines of demonstrated efficacy and with a strongly positive benefit-risk profile, implementation in Europe remains low. The aim of this study is to review existing barriers to access and implementation of RV vaccination in Europe. A literature search using online electronic databases was conducted to collect information on national and local recommendations, costs and perception of barriers for implementation of RV vaccination in Europe. Relevant scientific articles published between 2010 and 2018 were included in the review. Some key factors have been identified as existing barriers to vaccine access and implementation. The direct and indirect costs for vaccination and the limited perception of RV severity by the families are two major barriers for large-scale implementation of RV vaccination programs in Europe. Insufficient information and lack of public awareness on the benefits of RV vaccination may lead to negative perceptions among the general public. However, some authorities may restrict access due to the wrong perception of disease burden. Among the other identified barriers are: economic assessment of universal RV vaccination, cost-effectiveness of RV vaccination, funding of RV vaccination, and safety issues. Decentralized systems are expected to see less access and implementation of RV vaccines. Negative public perceptions on the necessity of RV vaccines could be serious barriers to access and use of RV vaccines in the studied countries. The implementation of RV vaccines is still low. Barriers to implementation vary according to settings. Nevertheless, public health authorities should promote greater public engagement and education for health-care providers on vaccination benefits in order to implement RV vaccination.