The impact of rotavirus vaccination in the prevalence of gastroenteritis and comorbidities among children after suboptimal rotavirus vaccines implementation in Taiwan: A population-based study.

ABSTRACT: In Taiwan, rotavirus vaccination was implemented in 2006 in the private sector. The population-based impact of rotavirus vaccination on gastroenteritis and comorbidities of children remains under-investigated.We analyzed the annual prevalence of rotavirus-related disease, including gastroenteritis, convulsions, epilepsy, type I diabetes mellitus, intussusception, and biliary atresia among children under 5 years of age. Data were collected from Taiwan's National Health Insurance Research Database, a nationwide population-based database. A 16-year retrospective cohort study was conducted between 2000 and 2015.Among children <5 years of age, the prevalence of gastroenteritis decreased after 2012 (44,259.69 per 100 thousands) and remained lower through 2015 (39,931.11per 100 thousands, P < .001). The prevalence of convulsions rose steadily and significantly from 2007 (775.90 per 100 thousands) to 2015 (962.17 per 100 thousands, P < .001). The prevalence of epilepsy decreased significantly until reaching a nadir in 2013 (from 501.56 to 293.53 per 100 thousands, P < .001). The prevalence of biliary atresia tended upward, and surged suddenly in 2007 with a peak in 2013 (18.74 per 100 thousands). Among infants (<1 year of age) from 2000 to 2015, the prevalence of gastroenteritis declined steadily, and more rapidly after 2007 (22,513 to 17,285 per 100 thousands).In Taiwan, after introducing rotavirus vaccination, gastroenteritis in young children decreased, especially in infancy. However, gastroenteritis is still common in children, given other emerging pathogens. Our results highlight the impact of rotavirus vaccines on children's health in Taiwan and provide indications for future preventive medicine and healthcare strategies in children.

Determinants of self-paid rotavirus vaccination status in Kanazawa, Japan, including socioeconomic factors, parents' perception, and children's characteristics.

BACKGROUND: Japan's National Immunization Program does not cover rotavirus vaccine and no government subsidies are available. This study aimed to measure the uptake of and determinants that influenced self-paid rotavirus vaccination, including socioeconomic status and relative poverty. METHODS: We conducted a cross-sectional study at health check-ups for all children aged 18 months in Kanazawa, Japan, between December 2017 and July 2018. Community nurses collected information on self-paid vaccination history, parents' perceptions of and recommendations for rotavirus vaccine, and socioeconomic status in interviews using a unified questionnaire. We used multivariable logistic regression to assess vaccine uptake and possible determinants. RESULTS: In total, 1282 participants were enrolled. The estimated rotavirus vaccine coverage was 72.9%. Perceptions that rotavirus gastroenteritis was serious and that the rotavirus vaccine was effective, pediatricians' recommendations, information from the city office, magazine and Internet articles, and higher parental education level were associated with higher rotavirus vaccine uptake. Lower household income was associated with decreased rotavirus vaccine uptake. Vaccine expense, fear of adverse reactions to the vaccine, number of household members and siblings, and children's characteristics were not correlated with rotavirus vaccination. Poverty was associated with decreased rotavirus vaccine uptake, even after adjustment for other determinants (adjusted odds ratio 0.49, 95% confidence interval: 0.26-0.90). CONCLUSION: Parents' perceptions, socioeconomic status, relative poverty, and pediatricians' recommendations are determinants of vaccination. This study suggests that appropriate information about rotavirus vaccine, subsidies for those of lower socioeconomic status, and national recommendations are necessary to achieve higher coverage.

Introduction of rotavirus vaccination in Palestine: An evaluation of the costs, impact, and cost-effectiveness of ROTARIX and ROTAVAC.

INTRODUCTION: The Palestinian Ministry of Health (MOH) started a routine rotavirus immunization program with ROTARIX in May 2016, with support for vaccine procurement and introduction provided through a global development organization. In 2018, financial responsibility for rotavirus vaccine procurement was transferred to the Palestinian government, which elected to shift to ROTAVAC vaccine because of its lower price per dose. This study aims to assess the cost, impact, and cost-effectiveness of rotavirus vaccination, specifically evaluating the economic implications of the change in vaccine product, accounting for the different characteristics of each rotavirus vaccine used. METHODS: We conducted primary and secondary data collection to assess the introduction, procurement, supply chain, and service delivery costs related to each vaccine. We used the UNIVAC model to project costs and benefits of rotavirus vaccination over a 10-year period comparing the use of ROTARIX versus no vaccination; ROTAVAC versus no vaccination; and ROTAVAC versus ROTARIX. We undertook scenario and probabilistic analyses to capture uncertainty in some of the study parameters. We used a 3% discount rate, and all costs are in 2018 US$. RESULTS: The cost to deliver one dose was lower for ROTAVAC than ROTARIX (US$2.36 versus $2.70), but the total cost per course, excluding vaccine cost, favored ROTARIX ($7.09 versus $5.39). Both vaccines had high probability of being cost-effective interventions in Palestine compared to no vaccine. Because of lower vaccination program costs for ROTAVAC, however, switching from ROTARIX to ROTAVAC was cost-saving. CONCLUSION: National decision-makers should consider systematically assessing multiple criteria beyond vaccine price when comparing the health and economic value of several products in order to fully account for all characteristics including product presentation, number of doses per course, cold chain volume, cost of delivery, and wastage.

Cross-sectional study on rotavirus A (RVA) infection and assessment of risk factors in pre- and post-weaning piglets in India.

Rotavirus A (RVA) infections are known to retard the piglets' growth and minimize the profit to the pig farming community. Between August 2014 and July 2017, in a cross-sectional study, we surveyed 13 organized pig farms located in the eight states of India representing northern, north-eastern and southern regions, to identify the risk factors associated with RVA infection in pre- and post-weaning piglets. Faecal samples (n = 411) comprising of non-diarrhoeic (n = 320) and diarrhoeic (n = 91) were collected and screened for RVA infection using VP6 gene-based RT-PCR. RVA positivity of 52.5% (168/320) in non-diarrhoeic and 59.3% (54/91) in diarrhoeic piglets was noticed. Further, 53.3% (120/225) and 54.8% (102/186) of the samples from pre- and post-weaned samples were positive for RVA, respectively. To note, no statistically significant association was noticed between RVA infection, health and weaning status. Additionally, a questionnaire-based survey was conducted to identify the risk factors for RVA infections in piglets. The analysis revealed that good ventilation (OR 0.2, 95% CI 0.15-0.39), use of deep well water (OR 0.2, 95% CI 0.13-0.43) and feeding of commercial feed (OR 0.3, 95% CI 0.18-0.41) were associated with reduced risk of RVA infection compared with poor ventilation, use of shallow well water and feeding of own milled feed, respectively. Contrarily, mixed farms (OR 2.1, 95% CI 1.26-3.37), use of heater or cooler (OR 5.9, 95% CI 3.74-9.30), sheds in different elevation (OR 2.5, 95% CI 1.20-5.01) and weekly and occasional use of disinfectant for surface cleaning (OR 1.8, 95% CI 1.12-2.96) were associated with higher RVA infection. Mitigating the risk factors might help in better health management of piglets and increase the economic return to pig farming community in the country.

Detection, Quantification, and Microbial Risk Assessment of Group A Rotavirus in Rivers from Uruguay.

The aim of this study was to detect, quantify, and assess the risk of infection and illness for Group A Rotavirus (RVA) in the watersheds of the Santa Lucia and Uruguay rivers in Uruguay. Monthly sampling was carried out for one year in six sites in the watershed of the Santa Lucía River and four in the Uruguay River. All the collection sites are used for recreational activities. Viral concentration was performed with the adsorption-elution method, and detection and quantification of RVA was carried out by TaqMan quantitative PCR (qPCR). Quantitative microbial risk assessment was applied to estimate the daily and annual risk of RVA infection, as well as the daily risk of illness considering direct exposure through recreational activity. RVA was detected in 42% (20/48) of the analyzed samples in the Uruguay River and 40% (29/72) in the Santa Lucía River. The virus was present in all the analyzed points in both watersheds. A pattern of seasonality, characterized by a higher detection frequency of the virus during coldest month of the year, was observed in both basins. The mean concentration for RVA was 1.3 × 105 genomic copies/L. The microbiological risk assessment shows that Santa Lucía watershed presented the highest daily risk of infection (6.41E-01) and illness (3.20E-01) estimated for the point downstream of Florida City; meanwhile for Uruguay River, the highest probabilities of infection (6.82E-01) and illness (3.41E-01) were estimated for the collection site for drinking water intake in Salto city. These results suggest that RVA contamination of these important rivers negatively impact on their microbiological quality since they are used for recreation and drinking water intake, demonstrating that the disposal of waste from cities located in their riverside confers a constant threat of infection for the general population, especially for children.

Burden of rotavirus infection in hospitalized elderly individuals prior to the introduction of rotavirus vaccination in Sweden.

BACKGROUND: Rotavirus gastroenteritis (GE) in the elderly has been much less studied than in children. OBJECTIVES: The aim of this study was to determine the morbidity and mortality for elderly hospitalized patients with rotavirus GE prior to the introduction of rotavirus vaccination in Sweden, and to investigate the epidemiology of rotavirus genotypes in these patients. STUDY DESIGN: All patients 60 years or older who were hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, and were rotavirus positive in a clinical diagnostic test from 2009 to 2016, were included. Medical records were reviewed and rotavirus genotyping real-time PCR was performed. RESULTS: One hundred and fifty-nine patients were included, corresponding to an annual incidence of hospitalization due to rotavirus GE of 16/100 000 inhabitants aged 60 years or older. G2P[4] was the most common genotype, followed by G1P[8] and G4P[8]. The majority of patients had community-onset of symptoms and no or few pre-existing health disorders. Four patients (2.5%) died within 30 days of sampling. Patients with hospital-onset rotavirus GE had a longer median length of stay following diagnosis compared with patients with community-onset of symptoms (19 vs. 5 days, p = 0.001) and higher 30-day mortality (8.6% (3/35) vs. < 1% (1/124), p = 0.03). CONCLUSIONS: Hospitalization due to rotavirus GE among the elderly seems to mainly affect otherwise healthy individuals and is associated with low 30-day mortality.

Variation in rotavirus vaccination coding in state US Medicaid data.

Differences in state Medicaid policies and practices may result in variation in the recording of individual-level vaccination claims, which may present challenges for vaccination research using state Medicaid data. We describe differences in procedure coding for rotavirus vaccination in four states' Medicaid programs by identifying rotavirus vaccine-specific codes and oral vaccine administration codes. The proportion of vaccinated children with vaccine-specific and oral vaccine administration codes differed substantially across states: two states used vaccine-specific codes almost exclusively (95.9% and 99.0%); one had exclusively oral vaccine administration codes (>99.9%); another had a mixture (32.1% vaccine-specific codes, 40.0% oral vaccine administration codes, and 27.9% both). Depending on the research question, studies using Medicaid data in states without (or with incomplete) vaccine-specific coding may be infeasible. Prior to initiating research, investigators should carefully evaluate state Medicaid policies and patterns of vaccination uptake, as vaccine reimbursement policies and availability of vaccine claims may vary.

Impact on affected families and society of severe rotavirus infections in Swedish children assessed in a prospective cohort study.

BACKGROUND: Few prospective cohort studies have estimated the overall impact of severe rotavirus gastroenteritis (RVGE) leading to hospitalization on families and society. We assessed human and economic resources needed to care for an affected average child aged <5 years in Sweden. METHODS: The study was conducted in Astrid Lindgren Children's Hospital which serves approximately 14% of all Swedish children <5 years of age. All children admitted with acute gastroenteritis in the study period were tested for rotavirus. Health care consumption was collected prospectively and publically available unit costs used to calculate direct costs. Non-medical and indirect costs were collected in interviews with families using a standardized questionnaire during the hospital stay and approximately 14 days post-discharge. RESULTS: 144/206 children (70%) with laboratory-confirmed RVGE were included. The median age was 14 months. The average total cost per hospitalized child was €3894, of which €2169 (56%) was due to direct healthcare-related costs (including Emergency Department visits and in-patient care), €104 (2%) to non-medical direct costs and €1621 (42%) to indirect costs due to productivity loss. Carers of children with severe RVGE were absent from work on average five days per study child: four days during hospitalization of affected child and one day due to gastroenteritis in the carer. CONCLUSIONS: Costs for RVGE are dominated by direct costs which are similar to some other countries in Europe, but indirect costs due to productivity loss are also important, and should be considered in decisions to introduce rotavirus vaccines into national vaccination programmes.

Costos de hospitalización por diarrea en niños durante el período de circulación de rotavirus en el Noroeste Argentino / Hospitalization costs associated with diarrhea among children during the period of rotavirus circulation in the Northwest region of Argentina

Objetivo. Evaluar los costos médicos directos, gastos de bolsillo y costos indirectos en casos de diarrea aguda hospitalizada en <5 años, en el Hospital de Niños Héctor Quintana de la provincia de Jujuy, durante el período de circulación de rotavirus en la región Noroeste de Argentina. Métodos. Estudio de corte trasversal de costos de enfermedad. Fueron incluidos todos los niños hospitalizados <5 años con diagnóstico de diarrea aguda y deshidratación durante el período de circulación de rotavirus, entre el 1/5/2013 y el 31/10/2013. La evaluación de costos médicos directos se realizó mediante la revisión de historias clínicas, y los gastos de bolsillo y costos indirectos, mediante una encuesta. Para el intervalo de confianza del 95% del costo promedio por paciente, se realizó un análisis probabilístico de 10 000 simulaciones por remuestreo (boostraping). Resultados. Fueron enrolados 105 casos. La edad promedio fue de 18 meses (desvío estándar 12); 62 (59%) fueron varones. El costo médico directo, gasto de bolsillo y pérdida de dinero por lucro cesante promedio por caso fue de AR$ 3413, 6 (2856, 35-3970, 93) (USD 577, 59), AR$ 134, 92 (85, 95-213, 57) (USD 22, 82) y de AR$ 301 (223, 28380, 02) (USD 50, 93), respectivamente. El total del costo por evento hospitalizado fue de AR$ 3849, 52 (3298-4402, 25) (USD 651, 35). Conclusiones. El valor de costo total por evento hospitalizado se encuentra dentro de lo esperado para Latinoamérica. La distribución de costos presenta una proporción importante de costos médicos directos en relación con los gastos de bolsillo (3, 5%) y costos indirectos (7, 8%).

Objective. To assess direct medical costs, out-of-pocket expenses, and indirect costs in cases of hospitalizations for acute diarrhea among children <5 years of age at Hospital de Niños "Héctor Quintana" in the province of Jujuy during the period of rotavirus circulation in the Northwest region of Argentina. Methods. Cross-sectional study on disease-related costs. All children <5 years of age, hospitalized with the diagnosis of acute diarrhea and dehydration during the period of rotavirus circulation between May 1st and October 31st of 2013, were included. The assessment of direct medical costs was done by reviewing medical records whereas out-of-pocket expenses and indirect costs were determined using a survey. For the 95% confidence interval of the average cost per patient, a probabilistic bootstrapping analysis of 10 000 simulations by resampling was done. Results. One hundred and five patients were enrolled. Their average age was 18 months (standard deviation: 12); 62 (59%) were boys. The average direct medical cost, out-of-pocket expense, and lost income per case was ARS 3413.6 (2856.35-3970.93) (USD 577.59), ARS 134.92 (85.95-213.57) (USD 22.82), and ARS 301 (223.28380.02) (USD 50.93), respectively. The total cost per hospitalization event was ARS 3849.52 (32984402.25) (USD 651.35). Conclusions. The total cost per hospitalization event was within what is expected for Latin America. Costs are broken down into direct medical costs (significant share), compared to out-of-pocket expenses (3.5%) and indirect costs (7.8%).

Hospitalization costs associated with diarrhea among children during the period of rotavirus circulation in the Northwest region of Argentina. / Costos de hospitalización por diarrea en niños durante el período de circulación de rotavirus en el Noroeste Argentino.

OBJETIVE: To assess direct medical costs, outof-pocket expenses, and indirect costs in cases of hospitalizations for acute diarrhea among children <5 years of age at Hospital de Niños "Héctor Quintana" in the province of Jujuy during the period of rotavirus circulation in the Northwest region of Argentina. METHODS: Cross-sectional study on diseaserelated costs. All children <5 years of age, hospitalized with the diagnosis of acute diarrhea and dehydration during the period of rotavirus circulation between May 1st and October 31st of 2013, were included. The assessment of direct medical costs was done by reviewing medical records whereas out-of-pocket expenses and indirect costs were determined using a survey. For the 95% confidence interval of the average cost per patient, a probabilistic bootstrapping analysis of 10 000 simulations by resampling was done. RESULTS: One hundred and five patients were enrolled. Their average age was 18 months (standard deviation: 12); 62 (59%) were boys. The average direct medical cost, out-of-pocket expense, and lost income per case was ARS 3413.6 (2856.35-3970.93) (USD 577.59), ARS 134.92 (85.95-213.57) (USD 22.82), and ARS 301 (223.28-380.02) (USD 50.93), respectively. The total cost per hospitalization event was ARS 3849.52 (3298-4402.25) (USD 651.35). CONCLUSIONS: The total cost per hospitalization event was within what is expected for Latin America. Costs are broken down into direct medical costs (significant share), compared to out-of-pocket expenses (3.5%) and indirect costs (7.8%).

OBJETIVO: Evaluar los costos médicos directos, gastos de bolsillo y costos indirectos en casos de diarrea aguda hospitalizada en <5 años, en el Hospital de Niños Héctor Quintana de la provincia de Jujuy, durante el período de circulación de rotavirus en la región Noroeste de Argentina. MÉTODOS: Estudio de corte trasversal de costos de enfermedad. Fueron incluidos todos los niños hospitalizados <5 años con diagnóstico de diarrea aguda y deshidratación durante el período de circulación de rotavirus, entre el 1/5/2013 y el 31/10/2013. La evaluación de costos médicos directos se realizó mediante la revisión de historias clínicas, y los gastos de bolsillo y costos indirectos, mediante una encuesta. Para el intervalo de confianza del 95% del costo promedio por paciente, se realizó un análisis probabilístico de 10 000 simulaciones por remuestreo (boostraping). RESULTADOS: Fueron enrolados 105 casos. La edad promedio fue de 18 meses (desvío estándar 12); 62 (59%) fueron varones. El costo médico directo, gasto de bolsillo y pérdida de dinero por lucro cesante promedio por caso fue de AR$ 3413,6 (2856,35-3970,93) (USD 577,59), AR$ 134,92 (85,95-213,57) (USD 22,82) y de AR$ 301 (223,28-380,02) (USD 50,93), respectivamente. El total del costo por evento hospitalizado fue de AR$ 3849,52 (3298-4402,25) (USD 651,35). CONCLUSIONES: El valor de costo total por evento hospitalizado se encuentra dentro de lo esperado para Latinoamérica. La distribución de costos presenta una proporción importante de costos médicos directos en relación con los gastos de bolsillo (3,5%) y costos indirectos (7,8%).

Impact of self-financed rotavirus vaccines on hospital stays and costs in Spain after a 3-year introductory period.

Vaccination has reduced rotavirus hospitalizations by 25% in European regions with low-moderate vaccine availability. We aimed to quantify the reduction in hospital costs after the longest period in which Rotarix® and Rotateq® were simultaneously commercially available in Spain. Cases, length of stay (LOS), and diagnosis-related groups (DRGs) were retrieved from the Minimum Basic Data Set. Healthcare expenditure was estimated through the cost accounting system Gescot®. DRGs were clustered: I, non-bacterial gastroenteritis with complications; II, without complications; III, requiring surgical/other procedures or neonatal cases (highest DRG weights). Comparisons between pre (2003-2005)- and post-vaccine (2007-2009) hospital stays and costs by DRG group were made. Rotaviruses were the most common agents of specific-coded gastroenteritis (N = 1657/5012). LOS and extended LOS of rotaviruses fell significantly in 2007-2009 (ß-coefficient = -0·43, 95% confidence intervals (95% CI) -0·68 to -0·17; and odds ratio 0·62, 95% CI 0·50-0·76, respectively). Overall, costs attributable to rotavirus hospitalizations fell approximately €244 per patient (95% CI -365 to -123); the decrease in DRG group III was €2269 per patient (95% CI -4098 to -380). We concluded modest savings in hospital costs, largely attributable to cases with higher DRG weights, and a faster recovery. A universal rotavirus vaccination program deserves being re-evaluated, regarding its potential high impact on both at-risk children and societal costs.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

BACKGROUND: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. METHODS: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. RESULTS: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). CONCLUSIONS: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.

Burden of Childhood Rotavirus Disease in the Outpatient Setting of the Russian Federation.

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 <5 years of age and the genotypes circulating during 1 rotavirus season. METHODS: From November 2012 to May 2013, surveillance was conducted in Moscow, Saint-Petersburg, Vologda, Krasnodar, Krasnoyarsk, Novosibirsk, Yaroslavl, Khanty-Mansiysk and Vladivostok. Children <5 years of age presenting at outpatient clinics with acute gastroenteritis (AGE) of less than 72 hours duration were enrolled in the study. Stool samples were tested for rotavirus and positive samples were P- and G-typed. Clinical symptoms were captured by physicians and parents on Day 1. Symptom severity was analyzed by Vesikari scoring system. The direct expenses of parents caused by AGE were obtained from questionnaires provided to parents by phone. RESULTS: A total of 501 were children enrolled. Stool samples were analyzed for 487 (97%) children, and 151 (31%) of those were rotavirus positive. Rotavirus gastroenteritis was associated with more severe clinical course (Vesikari score 11.4 ± 2.2) versus non-rotavirus gastroenteritis (Vesikari score 9 ± 3). The identified serotypes were G4P[8] 38.9%, G1P[8] 34.2%, G3P[8] 6%, G9P[8] 6%, G2P[4] 2% and G4P[4] 0.7%. The mean overall expenses of parents caused by rotavirus and non-rotavirus gastroenteritis were 143.7 USD and 128.8 USD, respectively. CONCLUSIONS: Rotavirus accounted for 31% of all AGE-related outpatient visits. The major rotavirus genotypes were G1P[8] and G4P[8]. Rotavirus gastroenteritis was associated with significantly more severe clinical symptoms than non-rotavirus gastroenteritis. The average costs of rotavirus cases for parents of children were elevated against the same indications for non-rotavirus. These findings underscore the need for a safe and effective rotavirus vaccine in Russia.

Burden of Rotavirus Diarrhea in Under five Indian Children.

NEED AND PURPOSE: Rotavirus is the most common cause of severe diarrhea in infants and young children worldwide. The burden of rotavirus diarrhea in Indian children is not well established. The present study reviewed the epidemiology of rotavirus diarrhea in hospitalized children and in the community, molecular serotyping and under-five mortality caused by rotavirus diarrhea. METHODS: Publications, reporting rotavirus diarrhea in Indian children, were retrieved through a systematic search of databases including Medline, PubMed, IndMed, websites of WHO, UNICEF, National Family Health Survey, Ministry of Health and Family Welfare, and Government of India. Human studies in English language were included. Age group selected was 0 month to 5 years. No restrictions were applied in terms of study design and time frame. CONCLUSIONS: Stool sample positivity varied from 4.6% in Kolkata to 89.8% in Manipur, among hospitalized children, and from 4% in Delhi to 33.7% in Manipur in community. Most cases of rotavirus diarrhea in India are caused by G1, G2, and G untypeable strains with distinct regional variations. Rotavirus was identified as an etiological agent in 5.2 to 80.5% cases of nosocomial diarrhea. Data are lacking for rotavirus mortality.

Cost of rotavirus diarrhea for programmatic evaluation of vaccination in Vietnam.

BACKGROUND: Rotavirus is the most common etiology of diarrhea-associated hospitalizations and clinic visits in Vietnamese children < 5 years old. To estimate the economic burden of rotavirus-associated formal healthcare encounters, an economic study was conducted. METHODS: A cost-of-illness study was performed from a societal perspective. Data were collected from children below the age of five years who presented to a clinic or hospital with symptoms of acute gastroenteritis (AGE). Patient-specific information on resource use and cost was obtained through caregiver interviews and medical chart review. Costs are presented in 2014 US dollar ($). RESULTS: A total of 557 children with symptoms of AGE were enrolled from March through June 2009, with mean age of 16.5 months. Of the 340 outpatients and 217 admitted patients enrolled, 41 % tested rotavirus positive. It was found that, from a societal perspective, the mean total cost of AGE was $175. Costs of patients with and without rotavirus were $217 and $158, respectively. From multiple regression analysis, it was found that rotavirus infection, patient age and receiving oral rehydration solution before visiting health facility had significant effect on the costs. CONCLUSIONS: This study clearly demonstrated substantial economic burden of AGE including rotavirus disease. They were significantly greater than the previously reported cost estimates in Vietnam. These updated costs of illness result in more favorable vaccine cost-effectiveness than in previous economic evaluations.

Population-Level Impact of Ontario's Infant Rotavirus Immunization Program: Evidence of Direct and Indirect Effects.

OBJECTIVE: To evaluate the direct and indirect population impact of rotavirus (RV) immunization on hospitalizations and emergency department (ED) visits for acute gastroenteritis (AGE) in Ontario before and after the publicly-funded RV immunization program. METHODS: Administrative data was used to identify ED visits and hospitalizations for all Ontarians using ICD-10 codes. We used two outcome definitions: RV-specific AGE (RV-AGE) and codes representing RV-, other viral and cause unspecified AGE ("overall AGE"). The pre-program and public program periods were August 1, 2005 to July 31, 2011; and August 1, 2011 to March 31, 2013, respectively. A negative binominal regression model that included the effect of time was used to calculate rates and rate ratios (RRs) and 95% confidence intervals (CIs) for RV-AGE and overall AGE between periods, after adjusting for age, seasonality and secular trends. Analyses were conducted for all ages combined and age stratified. RESULTS: Relative to the pre-program period, the adjusted RRs for RV-AGE and overall AGE hospitalizations in the public program period were 0.29 (95%CI: 0.22-0.39) and 0.68 (95%CI: 0.62-0.75), respectively. Significant reductions in RV-AGE hospitalizations were noted overall and for the following age bands: < 12 months, 12-23 months, 24-35 months, 3-4 years, and 5-19 years. Significant declines in overall AGE hospitalizations were observed across all age bands, including older adults > = 65 years (RR 0.80, 95%CI: 0.72-0.90). The program was associated with adjusted RRs of 0.32 (95% CI: 0.20-0.52) for RV-AGE ED visits and 0.90 (95% CI: 0.85-0.96) for overall AGE ED visits. CONCLUSIONS: This large, population-based study provides evidence of the impact of RV vaccine in preventing hospitalizations and ED visits for RV-AGE and overall AGE, including herd effects.

Use of Patients With Diarrhea Who Test Negative for Rotavirus as Controls to Estimate Rotavirus Vaccine Effectiveness Through Case-Control Studies.

BACKGROUND: Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls). METHODS: We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups. RESULTS: Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used. CONCLUSIONS: The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies.

A Preliminary Assessment of Rotavirus Vaccine Effectiveness in Zambia.

BACKGROUND: Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province. METHODS: Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100. RESULTS: A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%). CONCLUSIONS: We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease.

Impact of Rotavirus Vaccination on Diarrheal Hospitalizations in Children Aged <5 Years in Lusaka, Zambia.

BACKGROUND: Monovalent rotavirus vaccine was introduced in the routine public health immunization program in Lusaka, Zambia, in January 2012 and was rolled out countrywide in November 2013. We examined the effect of rotavirus vaccination on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE at a large referral hospital in Lusaka. METHODS: Data were derived from ongoing hospital-based AGE surveillance from January 2009 to December 2014. Pre-rotavirus vaccine introduction (2009-2011) and post-rotavirus vaccine introduction (2013-2014) periods were compared for annual changes in hospitalizations for AGE and rotavirus; 2012 was excluded as a transition year. Hospital administrative discharge data were used to compare trends in all-cause diarrhea discharges and in-hospital diarrhea deaths captured by HIMS pre- and post-rotavirus vaccine introduction. RESULTS: Between January 2009 and December 2014, 5937 children <5 years of age presenting with AGE had their stools collected and tested for rotavirus by enzyme immunoassay. The rotavirus positivity rate declined from 40.1% (449/1121) in prevaccine years to 30.2% (250/828;P< .001) in 2013 and 24.7% (157/635;P< .001) in 2014. The greatest reduction was noted in infants, with the rotavirus positivity rate in this age group declining from 40.9% in prevaccine years to 34.0% (P= .009) in 2013 and 26.2% (P< .001) in 2014. Following rotavirus vaccine introduction, seasonal peaks of rotavirus and all-cause AGE were dwarfed. From HIMS data, compared to the prevaccine era, reductions of 18%-29% in all-cause diarrhea hospitalizations and 27%-33% in-hospital diarrhea deaths among children <1 year of age were observed in 2013 and 2014. CONCLUSIONS: We observed a significant reduction in AGE-associated in-hospital morbidity and mortality following rotavirus vaccine introduction. The greatest reduction was seen in infants <1 year who accounted for 84.4% of rotavirus hospitalizations prior to vaccine introduction.

Health Impact of Rotavirus Vaccination in Developing Countries: Progress and Way Forward.

Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105, these vaccines have been implemented in the national immunization programs of 79 countries, including 36 low-income countries that are eligible for support for vaccine purchase from Gavi, the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions, and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries, vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis.