Rotavirus-associated Hospitalizations Research Articles

Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease

Rotavirus infection is a common cause of gastroenteritis in children that can trigger autoimmune processes, but the nature of this interaction remains poorly understood. To estimate the association of rotavirus infection with the risk of subsequent autoimmune disease. This population-matched cohort study used data from children and adolescents (aged younger than 18 years) in South Korea (national registers from January 1, 2002, to December 31, 2017). The cohort consisted of 86 157 patients in the exposure group who had experienced rotavirus-associated hospitalization and the same number of matched patients in the unexposed group. Data analyses were from May 1, 2020, through October 20, 2022. Hospitalization for rotavirus infection. The main outcome was childhood autoimmune diseases during the study defined by diagnoses according to the National Health Insurance Database. Hazard ratios (HRs) with 95% CIs for autoimmune diseases were estimated using a Cox model, with multiple confounding factors controlled. This cohort study consisted of 1 914 461 individuals born in South Korea from 2002 to 2005 who were potentially eligible. After exclusions, there were 86 517 individuals in the exposed group and 86 517 in the unexposed group after 1:1 incidence density sampling. The study included 49 072 (57.0%) male patients. The median (IQR) age at diagnosis of rotavirus-associated hospitalization was 1.5 (0.9-2.7) years, and the HR for autoimmune disease in the exposed group was 1.24 (95% CI, 1.19-1.28) for a mean (SD) follow-up time of 12.1 (3.2) years. The use of more stringent definitions for exposure and outcomes in a multivariable stratified analysis also indicated that rotavirus-associated hospitalization was associated with an increased risk of subsequent autoimmune disease (HR, 1.22 [95% CI, 1.16-1.28]). Sensitivity analysis showed that individuals with rotavirus-associated hospitalization was related to multiple autoimmune syndromes (2 or more: HR, 1. 51 [95% CI, 1. 31-1. 73]; 3 or more: HR, 1. 79 [95% CI, 1.18-2.72]) and that the number of rotavirus-associated hospitalization were associated with higher risks for autoimmune disease in a dose-dependent manner (single hospitalization event: HR, 1.20 [95% CI, 1.16-1.24]; multiple events HR, 1.60 [95% CI, 1.49-1.72]). Our results indicate that rotavirus-associated hospitalization is significantly associated with subsequent autoimmune disease during childhood. Clinicians should be aware of the heightened susceptibility to autoimmune disease in individuals with prior rotavirus-associated hospitalization.

Current Update on Rotavirus in-Silico Multiepitope Vaccine Design.

Rotavirus gastroenteritis is one of the leading causes of pediatric morbidity and mortality worldwide in infants and under-five populations. The World Health Organization (WHO) recommended global incorporation of the rotavirus vaccine in national immunization programs to alleviate the burden of the disease. Implementation of the rotavirus vaccination in certain regions of the world brought about a significant and consistent reduction of rotavirus-associated hospitalizations. However, the efficacy of licensed vaccines remains suboptimal in low-income countries where the incidences of rotavirus gastroenteritis continue to happen unabated. The problem of low efficacy of currently licensed oral rotavirus vaccines in low-income countries necessitates continuous exploration, design, and development of new rotavirus vaccines. Traditional vaccine development is a complex, expensive, labor-intensive, and time-consuming process. Reverse vaccinology essentially utilizes the genome and proteome information on pathogens and has opened new avenues for in-silico multiepitope vaccine design for a plethora of pathogens, promising time reduction in the complete vaccine development pipeline by complementing the traditional vaccinology approach. A substantial number of reviews on licensed rotavirus vaccines and those under evaluation are already available in the literature. However, a collective account of rotavirus in-silico vaccines is lacking in the literature, and such an account may further fuel the interest of researchers to use reverse vaccinology to expedite the vaccine development process. Therefore, the main focus of this review is to summarize the research endeavors undertaken for the design and development of rotavirus vaccines by the reverse vaccinology approach utilizing the tools of immunoinformatics.

Impact of rotavirus vaccination on rotavirus hospitalizations in Taiwanese children

In 2006, two rotavirus vaccines were licensed in Taiwan but were not added to the national immunization schedule. National Health Insurance data from 2003 through 2017 were used to compare rotavirus-associated pediatric hospitalizations before and after vaccine introduction. Rotavirus hospitalization rates among children < 5 years of age significantly declined by 24% (95% confidence interval [CI] 23 – 25%) in post-vaccine compared to pre-vaccine rotavirus seasons. Rotavirus hospitalization rates declined by 42% (95% CI 39 – 44%) among infants < 12 months of age, and by 38% (95% CI 36 – 40%) among children 12 – 23 months of age. These findings suggest that, despite not being included in the national immunization schedule, rotavirus vaccines had a measurable impact on reducing rotavirus hospitalization burden among Taiwanese children.

Continued Evidence of the Impact of Rotavirus Vaccine in Children Less Than 3 Years of Age From the United States New Vaccine Surveillance Network: A Multisite Active Surveillance Program, 2006-2016.

Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in 3 United States counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006 to 2016. Children < 3 years of age hospitalized or visiting the ED with AGE were enrolled from January 2006 through June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006-2007 defined as the prevaccine period and 2008-2016 as the postvaccine period. Rotavirus genotype trends were compared over time. Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the postvaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the prevaccine period with a significantly lower proportion (7%) in the postvaccine period (P < .001). G2P[4] remained stable (8% to 14%) in both periods, whereas G3P[8] and G12P[8] increased in proportion from pre- to postvaccine periods (1% to 25% and 17% to 40%), respectively. The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children < 3 years of age, and a shift in the residual genotypes from G1P[8] to other genotypes.

Identifying signatures of the impact of rotavirus vaccines on hospitalizations using sentinel surveillance data from Latin American countries

BackgroundPassive surveillance data are often the only available source of data that can be used to evaluate the population-level impact of vaccination, but such data often suffer from important limitations such as changes in surveillance efforts. This study provides an example of how to identify important signatures of rotavirus vaccine impact, including evaluating the overall effectiveness and changes in rotavirus seasonal dynamics. MethodsWe used data from a standardized sentinel rotavirus surveillance network in six Latin American countries (Bolivia, El Salvador, Guatemala, Honduras, Paraguay, and Venezuela) from 2004 to 2017. A random-effects model was used to evaluate changes in the proportion of rotavirus-associated hospitalizations following vaccine introduction. Harmonic regression models were used to estimate vaccine impact on the number of rotavirus hospitalizations, controlling for trends in rotavirus-negative cases. Changes to rotavirus seasonality were evaluated using center of gravity analysis, wavelet analysis, and harmonic regression. ResultsAll countries observed declines in the proportion of rotavirus-positive acute diarrhea samples with a mean reduction of 16% (95% confidence interval: 10–22%). We estimate that each 10% increase in vaccine coverage was associated with declines in the number of rotavirus-positive cases, ranging from 4.3% (1.3–7.2%) in Honduras to 21.4% (16.8–25.9%) in Venezuela. The strength of the seasonal peak in rotavirus incidence became smaller after vaccine introduction in Guatemala, Honduras, and Venezuela. Seasonal peaks also shifted later in the surveillance year, especially in higher-mortality countries. ConclusionsThe combination of methods we applied have different strengths that allow us to identify common signatures of rotavirus vaccine impact.

Impact of the Introduction of Rotavirus Vaccine on Hospital Admissions for Diarrhea Among Children in Kenya: A Controlled Interrupted Time-Series Analysis.

BackgroundMonovalent rotavirus vaccine, Rotarix (GlaxoSmithKline), was introduced in Kenya in July 2014 and is recommended to infants as oral doses at ages 6 and 10 weeks. A multisite study was established in 2 population-based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalizations (RVHs).MethodsHospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhea hospitalizations among children aged <5 years in 2 health facilities in Kenya. A controlled interrupted time-series analysis was undertaken to compare RVH pre– and post–vaccine introduction using rotavirus-negative cases as a control series. The change in incidence post–vaccine introduction was estimated from a negative binomial model that adjusted for secular trend, seasonality, and multiple health worker industrial actions (strikes).ResultsBetween January 2010 and June 2017 there were 1513 and 1652 diarrhea hospitalizations in Kilifi and Siaya; among those tested for rotavirus, 28% (315/1142) and 23% (197/877) were positive, respectively. There was a 57% (95% confidence interval [CI], 8–80%) reduction in RVHs observed in the first year post–vaccine introduction in Kilifi and a 59% (95% CI, 20–79%) reduction in Siaya. In the second year, RVHs decreased further at both sites, 80% (95% CI, 46–93%) reduction in Kilifi and 82% reduction in Siaya (95% CI. 61–92%); this reduction was sustained at both sites into the third year.ConclusionsA substantial reduction in RVHs and all-cause diarrhea was observed in 2 demographic surveillance sites in Kenya within 3 years of vaccine introduction.

Effectiveness of Monovalent Rotavirus Vaccine Against Hospitalization With Acute Rotavirus Gastroenteritis in Kenyan Children.

BackgroundRotavirus remains a leading cause of pediatric diarrheal illness and death worldwide. Data on rotavirus vaccine effectiveness in sub-Saharan Africa are limited. Kenya introduced monovalent rotavirus vaccine (RV1) in July 2014. We assessed RV1 effectiveness against rotavirus-associated hospitalization in Kenyan children.MethodsBetween July 2014 and December 2017, we conducted surveillance for acute gastroenteritis (AGE) in 3 Kenyan hospitals. From children age-eligible for ≥1 RV1 dose, with stool tested for rotavirus and confirmed vaccination history we compared RV1 coverage among rotavirus positive (cases) vs rotavirus negative (controls) using multivariable logistic regression and calculated effectiveness based on adjusted odds ratio.ResultsAmong 677 eligible children, 110 (16%) were rotavirus positive. Vaccination data were available for 91 (83%) cases; 51 (56%) had 2 RV1 doses and 33 (36%) 0 doses. Among 567 controls, 418 (74%) had vaccination data; 308 (74%) had 2 doses and 69 (16%) 0 doses. Overall 2-dose effectiveness was 64% (95% confidence interval [CI], 35%–80%); effectiveness was 67% (95% CI, 30%–84%) for children aged <12 months and 72% (95% CI, 10%–91%) for children aged ≥12 months. Significant effectiveness was seen in children with normal weight for age, length/height for age and weight for length/height; however, no protection was found among underweight, stunted, or wasted children.ConclusionsRV1 in the Kenyan immunization program provides significant protection against rotavirus-associated hospitalization which persisted beyond infancy. Malnutrition appears to diminish vaccine effectiveness. Efforts to improve rotavirus uptake and nutritional status are important to maximize vaccine benefit.

Hospital based surveillance and molecular characterization of rotavirus in children less than 5 years of age with acute gastroenteritis in Nepal

BackgroundRotavirus remains a significant causative agent of childhood acute gastroenteritis, particularly among children less than 5 years of age. Although precise data on childhood mortality associated with diarrheal disease in Nepal is not available, it is estimated that22% of all rotavirus deaths globally occurs in neighboring country of India. In spite of the substantial burden of rotavirus gastroenteritis in the Indian subcontinent, rotavirus vaccine has not been introduced in Nepal. Continuous surveillance for monitoring rotavirus disease burden and molecular characterization is needed prior to rotavirus vaccine introduction in Nepal. MethodsA total of 3310 stool samples (2849 hospitalized cases and 461 non-hospitalized cases), were collected from patients <5 years of age from January 2013 to December 2016 and tested for rotavirus antigen by ELISA (ProSpecT, USA). A subset of ELISA positive stool samples was genotyped. Demographic data were collected. ResultsDuring the four-year surveillance period, the overall burden of rotavirus infection was 24% among hospitalized children which was much higher than among non-hospitalized children (12%). The majority of children hospitalized with rotavirus gastroenteritis were less than 2 years of age (86%). Rotavirus-associated gastroenteritis hospitalizations occur year-round in Nepal, but a distinct peak in winter (up to 40% among hospitalized) was observed. Of 735 ELISA positive samples, 492 were genotyped by RT-PCR. The most prevalent genotype was G12P[6] (45.3%), followed byG2P[4](12.2%), G1P[8] (9.6%), G9P[4](7.3%), and G9P[8](4.5%). Mixed infection accounted for 4.4% of cases, 6.2% were partially typed and 10.5% of the samples were G and P untypable. ConclusionsA high burden of rotavirus gastroenteritis and a diversity of circulating rotavirus strains in Nepal were observed. Recommendation to introduce a rotavirus vaccine with known vaccine effectiveness would help in reducing the severity of Rotavirus diarrheal disease in children less than 5 years of age.

An update from hospital-based surveillance for rotavirus gastroenteritis among young children in Bangladesh, July 2012 to June 2017

IntroductionIn preparation for the introduction of a rotavirus vaccine into the routine immunization program of Bangladesh in 2018, we report data and highlight evolving genotypes from five years of active hospital-based rotavirus surveillance which began in July 2012. MethodsWe enrolled and collected fresh stool from every fourth child < 5 years admitted with acute gastroenteritis (AGE) at 8 participating surveillance hospitals. Rotavirus infections were detected by enzyme immune assay. Twenty-five percent of rotavirus isolates were genotyped using reverse transcription polymerase chain reaction. ResultsWe found that 64% (4832/7562) of children < 5 years of age admitted with AGE had evidence of rotavirus infection. The majority (57%) of patients with rotavirus infection were <12 months of age. The most common strains were G1P[8] (43%), G12P[8] (15%) and G9P[8] (9%); 11% of children had mixed infection.G3P[8], which has not been reported in Bangladesh since 2001, was documented for the first time in our surveillance system. ConclusionsThe high burden of rotavirus-associated hospitalizations highlights the potential value of rotavirus vaccination in Bangladesh. Continued surveillance is important for monitoring the impact of vaccination as well as monitoring evolving genotypes.

Evidence of the impact of monovalent rotavirus vaccine on childhood acute gastroenteritis hospitalization in Togo

BackgroundMonovalent rotavirus vaccine (RV1) was introduced in the immunization schedule of Togo in June 2014. We evaluated the impact of rotavirus vaccines on acute gastroenteritis (AGE) and rotavirus-associated hospitalizations in Togolese children. MethodsSentinel surveillance for AGE (defined as ≥3 liquid or semi-liquid stools/24 h lasting <7 days) hospitalizations among children <5 years of age was conducted in two sites in the capital city, Lome. ELISA was used for diagnosis of rotavirus infection in children with AGE. Additionally, review of hospitalization registers was performed at five hospitals to assess trends in AGE hospitalizations among children aged <5 years. For the vaccine impact assessment, pre-rotavirus vaccine introduction (July 2010-June 2014) and post-rotavirus vaccine introduction (July 2014-June 2016) periods were compared for annual changes in proportions of hospitalizations associated with AGE and rotavirus. ResultsDuring the pre-vaccine period, sentinel surveillance showed that 1017 patients were enrolled and 57% (range, 53–62%) tested positive for rotavirus, declining to 42% (23% reduction) in the first post-vaccine year and to 26% (53% reduction) in the second post-vaccine year; declines were most marked among infants. The patient register review showed that, compared with pre-vaccine rotavirus seasons, declines in hospitalizations due to all-cause AGE during post-vaccine rotavirus seasons were 48% among <1 year age-group in both first and second years following vaccine introduction. Among 1–4 year olds no reduction was noted in the first year and a 19% decline occurred in the second year. ConclusionsWe report rapid and marked reduction in the number of AGE hospitalizations and the proportion of AGE hospitalizations attributable to rotavirus in the first two years post- RV1 implementation in Togo. It is necessary to monitor long-term vaccine impact on rotavirus disease burden through continued surveillance.

Rotavirus hospitalizations among children

BackgroundIn January 2015, Tajikistan introduced the monovalent rotavirus vaccine into the national immunization program. Our objective was to estimate pre-vaccine burden of rotavirus-associated hospitalizations in children <5 years of age in Tajikistan. MethodsDuring January 2013–December 2014, active surveillance for acute gastroenteritis (AGE)-associated hospitalizations in children <5 years of age was conducted by sentinel surveillance site staff. Patients’ demographic and clinical data were summarized and a stool sample was collected. An Enzyme Linked Immunosorbent Assay was used for diagnosis of rotavirus infection and subset of the specimens was sent for polymerase chain reaction (PCR) genotyping. ResultsOf 2860 eligible children enrolled and tested, 1207 (42%) were positive for rotavirus. An increase in the number and proportion of rotavirus cases attributed to rotavirus season, with positivity rates >40%, was annually observed during June–September.The median age of rotavirus patients was 9 months and 939/1207 (78%) rotavirus patients were aged 6–23 months. Most (1097/1203; 91%) rotavirus patients were treated with intravenous fluids. G1P[8] was the predominant genotype during both years of surveillance, accounting for 133/222 (60%) of genotyped cases. ConclusionRotavirus is a major cause of hospitalization due to severe AGE in children <5 years of age in Tajikistan, accounting for >40% of cases. Continued, enhanced rotavirus surveillance may allow documentation of changes in rotavirus disease burden following vaccine introduction and assessment of vaccine effectiveness.

Impact of rotavirus vaccine on acute gastroenteritis in children under 5 years in Senegal: Experience of sentinel site of the Albert Royer Children's Hospital in Dakar

BackgroundAcute gastroenteritis (AGE) is a leading cause of morbidity and mortality among children <5 years of age in developing countries, with rotavirus being the most common infectious etiology. In November 2014, monovalent rotavirus vaccine was introduced in Senegal. We determined the impact of rotavirus vaccine on hospitalizations for all-cause and rotavirus related AGE in children <60 months of age. MethodsWe examined two data sources from the national referral hospital. Using sentinel surveillance data from March 2011 to February 2017, we examined the proportion of AGE hospitalizations among children <60 months of age attributable to rotavirus, stratified by age groups (0–11, 12–23 and 24–59 months). Using pediatric logbook data from March 2010 to February 2017, we examined the proportion of all childhood hospitalizations attributable to AGE, among the same age groups. ResultsIn sentinel surveillance, 673 patients <60 months were hospitalized for AGE, with 30% (203/673) due to rotavirus. In pre-vaccine years, the median proportion of rotavirus-positive hospitalizations was 42%; this proportion declined by 76% to 10% rotavirus positive in 2015–2016 (p < .001) and by 59% to 17% in 2016–2017 (p < .001). From the logbook data, among all children <60 months, a median of 11% of all hospitalizations in the pre-vaccine period were due to AGE, with 2015–2016 seeing a 16% decline (p < .001), to 9% of all hospitalizations, and 2016–2017 seeing a 39% decline (p < .001), to 7% of all hospitalizations. Declines in both rotavirus-associated and all-cause AGE hospitalizations were most marked among infants, with a suggestion of herd effect among older children seen in the surveillance data. ConclusionRotavirus vaccine demonstrated a significant impact on rotavirus-associated hospitalizations and all-cause AGE hospitalizations in the first two seasons after vaccine introduction in Senegal. Our data support the continued use of this vaccine in national immunization program.

Long-term impact of self-financed rotavirus vaccines on rotavirus-associated hospitalizations and costs in the Valencia Region, Spain

BackgroundRotavirus vaccines are available in Spain from 2007. They are recommended by the Spanish Pediatric Association, but not funded by the National Health System (NHS) and its coverage rate reached 40-50%. The hospitalization rate reduction of rotavirus caused gastroenteritis (RVAGE) directly attributable to vaccination remains unclear due to the large differences described in published studies, ranging from 14 to 44.5% in children <5 years of age, even with similar vaccination coverage. These results could be partly explained by variability in hospitalization policies, different study designs and the timeframe of observation. In addition, the direct economic impact of the reduction of hospitalizations has never been estimated. Therefore, there is a need to analyze the long-term impact of rotavirus vaccines on RVAGE and all cause gastroenteritis (AGE) hospitalizations and the national health system associated costs, minimizing potential confounders or biases.MethodsA population-based, ecological study using the hospital discharge registry’s Minimum Basic Data Set (MBDS) and the vaccine register (SIV) was performed, among Valencia Region’s children <5 years old, during 2002 - 2015. RVAGE and AGE hospitalization risk was analyzed by vaccine coverage and adjusted by the total hospitalization rate for all causes to avoid external biases. The impact of AGE-associated health care utilization in prevaccine (2003–2006) versus postvaccine (2008–2014) years was also assessed.ResultsAfter vaccines licensure, the incidence of RVAGE-associated hospitalizations decreased markedly. A general vaccine coverage-related reduction in RVAGE or AGE-hospitalizations risk was observed in all age groups. Compared with unvaccinated children, RVAGE hospitalization risk decreased by 67% (95% CI: 55-67), 71% (95% CI: 58-81) and 68% (95% CI: 18-92) in children 0, 1 and 4 years of age, respectively, with a vaccination coverage between 40 and 42%. Overall, the hospital related costs were reduced around EUR 6 Mill per 105 children in 7 years.ConclusionsDespite the low-medium vaccine coverage, the introduction of rotavirus vaccines had a specific coverage-related response impact in the hospitalizations for RVAGE and AGE in children <5 years and their use substantially reduced hospital related costs. The model used reassures that the estimated impact is due to the vaccination and not to other external factors.

The rotavirus vaccine development pipeline

Rotavirus disease is a leading global cause of mortality and morbidity in children under 5years of age. The effectiveness of the two globally used oral rotavirus vaccines quickly became apparent when introduced into both developed and developing countries, with significant reductions in rotavirus-associated mortality and hospitalizations. However, the effectiveness and impact of the vaccines is reduced in developing country settings, where the burden and mortality is highest.New rotavirus vaccines, including live oral rotavirus candidates and non-replicating approaches continue to be developed, with the major aim to improve the global supply of rotavirus vaccines and for local implementation, and to improve vaccine effectiveness in developing settings. This review provides an overview of the new rotavirus vaccines in development by developing country manufacturers and provides a rationale why newer candidates continue to be explored. It describes the new live oral rotavirus vaccine candidates as well as the non-replicating rotavirus vaccines that are furthest along in development.

Sustained High Effectiveness of RotaTeq on Hospitalizations Attributable to Rotavirus-Associated Gastroenteritis During 4 Years in Finland.

Key pointsThe effectiveness of pentavalent rotavirus vaccine against rotavirus-associated hospitalization was more than 90% 4 years after introduction into the national immunization program in Finland. A major impact on hospitalization for all-cause gastroenteritis was observed also.BackgroundRotavirus vaccination with exclusive use of RotaTeq was added to the National Immunization Programme (NIP) of Finland in September 2009. The objective of our study was to estimate the effectiveness and impact of RotaTeq after 4 years of follow-up.MethodsBetween 2009 and 2013, we conducted a prospective surveillance study of children aged <16 years with acute gastroenteritis (AGE) and admitted in 2 hospitals in Finland. Rotavirus and other gastroenteritis viruses were detected in stool samples by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays. The effectiveness of RotaTeq was investigated by using a case-control design; wild-type rotavirus-positive children were classified as “cases” and rotavirus-negative children as “controls.” Hospital discharge records were used to estimate the impact of RotaTeq on rotavirus-associated AGE (RV-AGE) and all-cause AGE (AC-AGE) hospitalizations of age-eligible children in the NIP by comparing the prevaccination (2001–2006) and post-NIP seasons (2009–2013).ResultsThe crude estimate of the effectiveness of RotaTeq to prevent RV-AGE hospitalization in NIP age-eligible children was 94.4% (95% confidence interval, 79.8%–98.4%). No change in prevalent wild-type rotavirus genotypes was observed. Vaccine-derived rotaviruses were detected in 8% of the children with RV-AGE, with a probable causal association in 2 children. Hospital discharge records revealed that RV-AGE and AC-AGE hospitalizations in children aged <16 years decreased in the two post-NIP seasons by 79% and 58%, respectively, compared to those in the prevaccination seasons.ConclusionsOver 4 years of follow-up, high rotavirus vaccine coverage in the NIP (>95%) has led to a major reduction in RV-AGE and AC-AGE hospitalizations without a resurgence of rotavirus activity. However, rotavirus continues to circulate in older unvaccinated children.

Early Evidence of Impact of Monovalent Rotavirus Vaccine in Togo.

Togo introduced monovalent rotavirus vaccine starting 19 June 2014. We compared all-cause acute gastroenteritis (AGE) hospitalizations and rotavirus-associated hospitalizations during the prevaccine period (July 2008-June 2014) to 1 year after vaccine introduction (July 2014-June 2015). The proportion of children with AGE who tested positive for rotavirus declined from 53% (645/1223) in prevaccine years to 36% (68/187) in the postvaccine year (P< .01). The decline only occurred in children <1 year of age who were eligible for vaccination and was greatest during the rotavirus season months, supporting that it was associated with vaccine implementation.

Real-World Effectiveness of Pentavalent Rotavirus Vaccine Among Bedouin and Jewish Children in Southern Israel.

Pentavalent rotavirus vaccine (RV5) was introduced into the Israeli National Immunization Program in January 2011. We determined RV5 vaccine effectiveness (VE) in southern Israel, a region characterized by 2 distinct populations: Bedouins living in a low- to middle-income, semirural setting, and Jews living in a high-income, urban setting. We enrolled vaccine-eligible children who visited the emergency department (ED) or were hospitalized due to acute gastroenteritis (AGE) during the first 3 rotavirus seasons after RV5 vaccine introduction (2011-2013). Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models were used to calculate VE estimates by age, clinical setting, and ethnicity. Of 515 enrolled patients, 359 (70%) were Bedouin. Overall, 185 (36%) patients were rotavirus positive; 79 of 119 (66%) were G1P[8] genotype. The adjusted VE for a full 3-dose course of RV5 against ED visit or hospitalization was 63% (95% confidence interval [CI], 38%-78%). RV5 provided G1P[8] genotype-specific effectiveness of 78% (95% CI, 58%-88%). By age, RV5 VE was 64% (95% CI, 21%-84%) and 71% (95% CI, 39%-86%) among children aged 6-11 months and 12-23 months, respectively. By clinical setting, RV5 VE was 59% (95% CI, 23%-78%) against hospitalization, and 67% (95% CI, 11%-88%) against ED visit. The adjusted VE of a full RV5 course among Bedouin children was 62% (95% CI, 29%-79%). RV5 significantly protected against rotavirus-associated ED visits and hospitalizations in a diverse population of vaccine-eligible children living in southern Israel.

Healthcare Costs of Rotavirus and Other Types of Gastroenteritis in Children in Norway.

Norway has initiated a publicly funded rotavirus immunization program for all age-eligible children in 2014. We aimed to estimate the healthcare costs of rotavirus gastroenteritis in children younger than 5 years old. We identified all gastroenteritis cases in children younger than 5 years old treated during 2009-2013 through the national claims database for primary care and the national hospital registry. We estimated direct medical costs of rotavirus-associated primary care consultations and hospital encounters (inpatient admission, outpatient visit and ambulatory care). We performed a range of one-way sensitivity analyses to explore uncertainty in the cost estimates. Before vaccine introduction, the mean healthcare cost of rotavirus gastroenteritis in children younger than 5 years old was €4,440,337 per year. Among rotavirus-associated costs, 92% were hospital costs and the remaining 8% were primary care costs. The mean annual cost of rotavirus-associated hospital encounters was €4,083,691, of which 95% were costs of inpatient hospital admissions. The average healthcare cost of medically attended gastroenteritis in children younger than 5 years old was approximately €8 million per year, of which rotavirus-related costs represented 56%. Healthcare costs of rotavirus gastroenteritis in Norway are substantial. The cost-effectiveness of ongoing rotavirus immunization program should be reassessed.

A universal infant rotavirus vaccine program in two delivery models: Effectiveness and adverse events following immunization

Rotavirus is the most common cause of diarrhea leading to hospitalization in young children. Rotavirus vaccines are available in Canada but have not been introduced in all provinces. In a controlled trial, 2 study sites (Prince Edward Island and the Capital District Health Authority (District 9, Nova Scotia) introduced universal rotavirus vaccine programs for infants at 2 and 4 months of age beginning 1 December 2010, using public health nurse or general practitioner-delivery models, respectively. A third site (Saint John, NB) served as the non-intervention control setting. Vaccine coverage, rotavirus hospitalizations, intussusception and all-cause diarrhea were monitored. A universal rotavirus vaccine program with >90% coverage was associated with reductions in rotavirus-associated hospitalizations (from a peak of 52.8 hospitalizations/100,000 population to 0 hospitalizations) in infants < 12 months and 1 to < 2 y of age 12 months after program implementation. No apparent reduction occurred in the site with vaccine coverage of < 40%, or in the non-intervention control site. No cases of intussusception were associated with vaccine receipt, and no increase in all-cause diarrhea was observed. A universal infant rotavirus vaccine program with high coverage was associated with reductions in rotavirus and no safety signals; no reduction was observed in settings with low vaccine coverage.

High Burden of Rotavirus Gastroenteritis in Young Children in Rural Western Kenya, 2010–2011

Diarrhea is a leading cause of hospitalization and death in children <5 years of age. To facilitate evaluation of the impact of rotavirus vaccine introduction in western Kenya, we estimated baseline rates of rotavirus-associated hospitalization and mortality among children <5 years of age. From January 2010 to December 2011, we collected demographic, clinical and laboratory data for children <5 years of age seeking care at the district hospital and 2 outpatient facilities within a Health and Demographic Surveillance System (HDSS). Children with acute gastroenteritis (AGE), defined as ≥3 loose stools and/or ≥1 episode of unexplained vomiting followed by loose stool within a 24-hour period, were asked to provide a stool sample for rotavirus ELISA testing. Rates of rotavirus-associated hospitalization and mortality were estimated using time of residence in the HDSS to calculate person-years of observation. To estimate the rotavirus-associated mortality rate, we applied the percentage positive for rotavirus among AGE hospitalizations to verbal autopsy estimates of diarrhea deaths in the HDSS. There were 4991 hospitalizations of children <5 years of age; 1134 (23%) were for AGE and stool specimens were obtained from 790 (70%). Rotavirus was detected in 211 (27%) specimens. Among 4951 <5 outpatient sick visits, 608 (12%) were for AGE; 320 (51%) provided specimens and 62 (20%) were positive for rotavirus. Rotavirus AGE accounted for 501 <5 hospitalizations per 100,000 person-years of observation. Rotavirus-associated <5 mortality was 136 deaths per 100,000 person-years of observation. Continued surveillance of rotavirus AGE will provide timely data on the population-level impact of rotavirus vaccine following its likely introduction in 2014.