Impact of high coverage of monovalent human rotavirus vaccine on Emergency Department presentations for rotavirus gastroenteritis

IntroductionAustralia was one of the first countries to introduce nationally funded rotavirus vaccination. The program has had a substantial impact on both rotavirus and all-cause acute gastroenteritis (AGE) hospitalisations and rotavirus laboratory tests. Evidence for an impact on Emergency Department (ED) presentations is limited. This study assessed changes in ED presentations for rotavirus in children aged <5 years in New South Wales, Australia, following introduction of monovalent human rotavirus vaccine (RV1, Rotarix^®, GlaxoSmithKline Australia Pty Ltd., Victoria, Australia).MethodA time series analysis to examine trends in total non-admitted ED presentations for all-cause AGE and in the rotavirus-attributable fraction using data on rotavirus positive laboratory tests.ResultsA decline in the rate of non-admitted ED presentations for all-cause AGE was observed for all ages, being most notable in 1 year old children. Compared with the pre-vaccination period, we estimated the average weekly rate was lower across the first 4.5 years of the program for both all-cause AGE (18.3%; 70.5 versus 57.5 per 100,000 population) and rotavirus attributable (55.4%; 17.3 versus 7.7 per 100,000 population) presentations. In the fourth year of the program, estimated annual rotavirus attributable presentations were 77% lower than the pre-vaccination annual mean (996 versus 4300 per year).ConclusionThe program was associated with a substantial decline in rotavirus attributable non-admitted AGE presentations to ED among children aged <5 years.     

An economic analysis of rotavirus vaccination in Italy

We have evaluated health and economic benefits of a universal infant vaccination with two rotavirus vaccines registered in Italy, on the bases of the burden of rotavirus gastroenteritis (RVGE) in a birth cohort of 520,000 Italian infants followed until 5 years of age. Estimates from published and unpublished sources of disease burden, costs, vaccine coverage, efficacy trials of both vaccines, and price were used to estimate cost-effectiveness from the perspectives of the Italian National Health Service (NHS) and society. According to our estimates, a universal rotavirus vaccination program would avoid 10,679 hospitalizations, 39,202 emergency visits, and 44,223 at home visits. At €65.6 per vaccination courses, the program would cost €30,700,800 and realize a net loss of €9,057,928 from the Italian NHS perspective. On the contrary, the program would provide a net savings of €24,324,198 from the societal perspective. From the Italian NHS perspective, the break-even price per vaccination course should be reduced at least to €46.25 to achieve a zero cost-effectiveness ratio.     

Impact of rotavirus vaccination on intussusception hospital admissions in England

BackgroundAn increased risk of intussusception has been reported following rotavirus vaccination. We sought to determine whether introduction of rotavirus vaccination in England in July 2013 was associated with a change in the burden of total and age group-specific childhood hospital admissions for intussusception.MethodsWe identified all children aged 0–36 months admitted to hospitals in England with intussusception using the Hospital Episode Statistics dataset. We performed a retrospective ecological analysis comparing hospital admission rates for intussusception during the periods before (2008/2009–2012/2013) and after (2014/2015–2017/2018) introduction of rotavirus vaccination using modified Poisson regression and interrupted time series analysis. Length of hospital stay and clinical outcomes were also examined.ResultsThe mean annual admission rate for intussusception in infants over the ten-year study period was 31.5 per 100,000 person-years. An increase in the admission rate in the 8–16 weeks age group (RR 1.46, 95% CI 1.12–1.91), those receiving vaccination, was compensated for by decreases in the 17–24 weeks (RR 0.77, 0.63–0.94), 25–32 weeks (RR 0.71, 0.59–0.86) and 41–52 weeks (RR 0.80, 0.66–0.98) age groups. Using interrupted time series analysis, we observed a significant decrease in incidence in the 0–12 months age group (RR 0.80, 0.67–0.96), but not in the overall 0–36 months age group (RR 1.09, 0.98–1.20). There was no significant change in the proportion of children requiring surgical intervention or with major complications of intussusception. Length of hospital stay decreased among infants receiving surgery for intussusception.ConclusionsOur results suggest that introduction of rotavirus vaccination in England has resulted in a downward shift in the age at which intussusception occurs in infants, with no overall increase in hospital admission rate or disease severity. These findings support the view that the benefits of rotavirus vaccination outweigh the small increased risk of intussusception in the early post-vaccination period.     

Impact of transmission dynamics on the cost-effectiveness of rotavirus vaccination

The objective of this study is to estimate the cost-effectiveness of mass vaccination of US infants with the recently available rotavirus vaccine, RotaTeq. We developed a dynamic transmission model of rotavirus to incorporate herd immunity into cost-effectiveness analysis. Our study indicates that a rotavirus vaccination program would prevent about 90% of rotavirus incidence, mortality, hospitalization and emergency department visits annually. We conclude that a universal rotavirus vaccine program in the US would cost $77.30 per case averted from the health care and give a net saving of $80.75 per case averted from the societal perspectives, respectively. The cost per QALY gained was found to be $104,610 when we considered child with one caregiver, making the rotavirus vaccination program a cost-effective intervention.     

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

BackgroundRotavirus 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 5 years is examined.MethodsUsing national data from all Irish public hospitals, an Interrupted Times Series Analysis (ITSA) compares RVGE hospitalisations amongst children under 5 years, 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.ResultsVaccine introduction coincided with lowered RVGE related hospitalisations. While this effect was delayed (1 year) there is evidence of a sustained impact. RVGE patients' post-vaccine introduction were likely to be over 2 years (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.ConclusionsFollowing 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.     

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe

BackgroundUniversal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands.MethodsFor this observational retrospective cohort study, time series data (2001–2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics.ResultsThe population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4–7 weeks.ConclusionsThe introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.     

Impact of rotavirus vaccination on rotavirus and all-cause gastroenteritis in peri-urban Kenyan children

A monovalent rotavirus vaccine (RV1) was introduced into the National Immunization Program in Kenya in July 2014. We examined the impact of the vaccine on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE and strain distribution at a large referral hospital which serves a predominantly peri-urban population in Central Kenya. Data on rotavirus AGE and strain distribution were derived from ongoing hospital-based AGE surveillance. Hospital administrative data were used to compare trends in all-cause AGE. Pre-vaccine (July 2009–June 2014) and post-vaccine (July 2014–June 2016) periods were compared for changes in hospitalization for all-cause AGE and rotavirus AGE and strain distribution. Following the vaccine introduction, the proportion of children aged <5 years hospitalized for rotavirus declined by 30% (95% CI: 19–45%) in the first year and 64% (95% CI: 49–77%) in the second year. Reductions in rotavirus positivity were most pronounced among the vaccine-eligible group (<12 months) in the first year post-vaccination at 42% (95% CI: 28–56%). Greater reductions of 67% (95% CI: 51–79%) were seen in the second year in the 12–23 months age group. Similarly, hospitalizations for all-cause AGE among children <5 years of age decreased by 31% (95% CI: 24–40%) in the first year and 58% (95% CI: 49–67%) in the second year of vaccine introduction. Seasonal peaks of rotavirus and all-cause AGE were reduced substantially. There was an increased detection of G2P[4], G3P[6] and G3P[8], which coincided temporally with the timing of the vaccine introduction. Thus, introducing the rotavirus vaccine into the routine immunization program in Kenya has resulted in a notable decline in rotavirus and all-cause AGE hospitalizations in Central Kenya. This provides early evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunizations.     

Cost-effectiveness of rotavirus vaccination programs in Taiwan

Background

In Taiwan, two rotavirus vaccines are available on the private market, but are not included in the National Immunization Program (NIP). To help assess whether to include rotavirus vaccines in the NIP, we examined the potential impact and cost-effectiveness of vaccination, from the health care system perspective alone.

Methods

We used a Microsoft Excel-based model to assess rotavirus vaccination impact on rotavirus disease burden and the cost-effectiveness of 2-dose and 3-dose vaccination programs among a birth cohort of Taiwanese children followed for 5 years. Principal model inputs included data on rotavirus disease burden and related healthcare costs, vaccination cost and coverage rates, and vaccine efficacy. Principal model outputs included the number of health-related events and costs averted and incremental cost per disability-adjusted life year averted.

Results

A national rotavirus vaccination program, regardless of number of doses per course, would prevent 4 deaths, >10,500 hospitalizations, and >64,000 outpatient visits due to rotavirus infection among children <5 years annually, resulting in ∼80%, 90%, and 70% declines in these outcomes, respectively, and a ∼$7 million decline in annual medical costs. A national 2- or 3-dose vaccination program would be cost-saving up to $13.30/dose ($26.60/course) or $7.98/dose ($23.94/course), respectively; very cost-effective up to $24.08 per dose ($48.16/course) or $15.18/dose ($45.54/course), respectively; and cost-effective up to $45.65/dose ($91.30/course) or $29.59/dose ($88.77/course), respectively.

Conclusions

A national rotavirus vaccination program could substantially reduce rotavirus disease burden among Taiwanese children and be potentially cost-effective, depending on the vaccine price.     

Impact of the national rotavirus vaccination programme on acute gastroenteritis in England and associated costs averted

BackgroundIntroduction of infant oral rotavirus vaccination in the UK in July 2013 has resulted in decreased hospitalisations and Emergency Department (ED) visits for acute gastroenteritis (AGE), for both adults and children. We investigated reductions in AGE incidence seen in primary care in the two years after vaccine introduction, and estimated the healthcare costs averted across healthcare settings in the first year of the vaccination programme.MethodsWe used primary care data from the Clinical Practice Research Datalink and age-stratified time-series analyses to derive adjusted incidence rate ratios (IRR_a) for AGE in the first two years of the post-vaccination era (July 2013-April 2015) compared to the pre-vaccination era (July 2008-June 2013). We estimated cases averted among children aged <5 years in the first year of the vaccination programme by comparing observed numbers of AGE cases in 2013–2014 to numbers predicted from the time-series models. We then estimated the healthcare costs averted for general practice consultations, ED visits and hospitalisations.ResultsIn general practice, AGE rates in infants (the target group for vaccination) decreased by 15% overall after vaccine introduction (IRR_a = 0.85; 95%CI = 0.76–0.95), and by 41% in the months of historically high rotavirus circulation (IRR_a = 0.59; 95%CI = 0.53–0.66). Rates also decreased in other young children and to a lesser degree in older individuals, indicating herd immunity. Across all three settings (general practice, EDs, and hospitalisations) an estimated 87,376 (95% prediction interval: 62,588–113,561) AGE visits by children aged <5 years were averted in 2013–14, associated with an estimated £12.5 million (9,209–16,198) reduction in healthcare costs.ConclusionsThe marked decreases in the general practice AGE burden after rotavirus vaccine introduction mirror decreases seen in other UK healthcare settings. Overall, these decreases are associated with substantial averted healthcare costs.     

Effectiveness of monovalent rotavirus vaccine in a high-income,predominant-use setting

Background and objectivesWe assessed monovalent rotavirus (RV1) vaccine effectiveness (VE) in a high-income setting with RV1 predominant use, and examined the burden of pediatric rotavirus gastroenteritis following the implementation of an RV1-only vaccination program.MethodsWe conducted active rotavirus gastroenteritis surveillance among children 8 weeks to <3 years of age at three hospitals. Participant information and vaccination histories were collected via parent/guardian interview and medical records. Stool specimens were tested for rotavirus; positive specimens were genotyped. The effect of increasing RV1 coverage on rotavirus prevalence was examined as a weekly time series via binomial regression with a log link function, using either categorical season or mean 2-dose rotavirus seasonal vaccine coverage as the exposure variable. As compared with RV1 vaccine formulation, rotavirus genotypes were classified as homotypic, partly-heterotypic, or heterotypic; prevalence of each was compared by season. A test-negative case-control design was used to examine RV1 VE against hospitalization or emergency visits.ResultsWe enrolled 866 participants in active surveillance; of these, 384 (44.3%) were eligible for VE analyses. After adjustment for season, we detected a 70.1% (95% CI: 21.9%, 88.6%) relative decrease in rotavirus prevalence in the 2013–14 season compared with 2012–13 season. On average, a 1% increase in ≥2-dose rotavirus coverage among children 1 year of age was associated with a 3.8% (95% CI: 1.8%, 5.8%) relative decrease in rotavirus prevalence. Rotavirus homotypic strain prevalence decreased, with 77% (95% CI: 68%, 89%) versus 8% (95% CI: 0%, 36%) prevalence during the 2011–12 and 2013–14 seasons, respectively. Adjusted 2-dose RV1 VE was 91.2% (95% CI: 61.6%, 98.0%).ConclusionsRV1 vaccine was highly effective to prevent rotavirus hospitalizations and emergency visits among children <3 years of age in a high-income setting with its predominant use. Our estimates were similar to high-income settings with concurrent RV1 and pentavalent vaccine use.     

Impact and cost-effectiveness of rotavirus vaccination in Bangladesh

IntroductionDiarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners.MethodsThis analysis used Pan American Health Organization’s TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates.ResultsOver ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to $142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from $615/DALY to $1514/DALY averted.ConclusionThe discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh.     

Cost effectiveness evaluation of a rotavirus vaccination program in Argentina

BackgroundRotavirus diarrhea is one of the most important vaccine-preventable causes of severe diarrhea in children worldwide. There are two live-attenuated virus vaccines licensed, Rotarix® (RV1) a monovalent vaccine by GlaxoSmithKline and a pentavalent vaccine, RotaTeq® (RV5), by Merck & Co., with similar results. This study aim was to evaluate the cost-effectiveness of the utilization of RV1 compared with RV5 in Argentina.MethodsA deterministic Markov model based on the lifetime follow up of a static cohort was used. Quality Adjusted Life Years (QALYs) as a measure of results, the perspective of the health care system and a 5% discount rate for health benefits and costs has been used. A review of the literature to obtain epidemiologic and resources utilization of rotavirus diarrhea was performed. The sources used to estimate epidemiologic parameters were the National Health Surveillance System, the national mortality statistics and national database of hospital discharges records. Costs were obtained from different health subsectors and are expressed in local currency.ResultsBoth vaccination alternatives were less costly and more effective than the strategy without vaccination (total costs $ 69,700,645 and 2575 total QALYs lost). When comparing RV1 vs. RV5, RV1 was less expensive ($ 60,174,508 vs. $ 67,545,991 total costs) and more effective (1105 vs. 1213 total QALYs lost) than RV5, RV1 being therefore a dominating strategy. Probabilistic sensitivity analysis showed results to be robust with a 100% probability of being cost-effective at a WTP threshold of 1 GDP per capita when comparing the RV1 vs. no vaccination.ConclusionBoth RV1 and RV5 schedules dominate the no vaccination strategy and RV5 was dominated by RV1. This information is a valuable input regarding the incorporation of this kind of vaccines into the national vaccination programs.     

Cost-effectiveness of universal rotavirus vaccination in reducing rotavirus gastroenteritis in Ireland

We evaluated the cost-effectiveness of universal infant rotavirus (RV) vaccination compared to current standard of care of “no vaccination”. Two RV vaccines are currently licensed in Ireland: Rotarix™ and RotaTeq™.A cohort model used in several European countries was adapted using Irish epidemiological, resource utilisation and cost data. The base case model considers the impact of Rotarix vaccination on health-related quality of life of children under five years old from a healthcare payer perspective. Other scenarios explored the use of RotaTeq, impact on one caregiver, on societal costs and on cases that do not seek medical attention. Cost was varied between the vaccine list price (€100/course) in the base case and an assumed tender price (€70/course). One-way and probabilistic sensitivity analyses were conducted.Implementing universal RV vaccination may prevent around 1970 GP visits, 3280 A&E attendances and 2490 hospitalisations. A vaccination programme was estimated to cost approximately €6.54 million per year but €4.65 million of this would be offset by reducing healthcare resource use. The baseline ICER was €112,048/QALY and €72,736/QALY from the healthcare payer and societal perspective, respectively, falling to €68,896 and €43,916/QALY, respectively, if the impact on one caregiver was considered. If the price fell to €70 per course, universal RV vaccination would be cost saving under all scenarios. Results were sensitive to vaccination costs, incidence of RV infection and direct medical costs.Universal RV vaccination would not be cost-effective under base case assumptions. However, it could be cost-effective at a lower vaccine price or from a wider societal perspective.     

Burden of rotavirus disease in young children in Iceland – Time to vaccinate?

BackgroundAcute gastroenteritis poses a significant burden on young children, families, health care facilities and societies. Rotavirus is the most common pathogen, but rotavirus infections are vaccine preventable. Information on the epidemiology of gastroenteritis in Icelandic children has until now not been available and rotavirus vaccination is currently not offered to Icelandic infants. The objective of this study was to assess the burden of rotavirus acute gastroenteritis in young children in Iceland and determine the potential benefit of adding rotavirus vaccine to the Icelandic childhood immunization schedule.MethodsFor a two-year period, children < 6 years old attending a children’s emergency department for acute gastroenteritis were recruited at the Children’s Hospital in Reykjavík, Iceland. Demographic information and Vesikari scores were registered. Stool samples were analyzed for pathogens. Duration of symptoms, treatment given, and secondary household infections were among the collected information. Annual cost of the infections in young children was estimated based on health care expenditures and lost days of parental work.Results325 children were included in the study, 75% of which were ≤ 24 months old. A pathogen was identified in 80% of cases, of which rotavirus was identified in 54%. Rotavirus caused a more severe disease than other pathogens, more often leading to fluid treatment in the emergency department and admissions. Median duration of rotavirus-illness was six days and caused a median of four days lost from work by parents. The estimated annual cost of rotavirus acute gastroenteritis was €2.9 million.ConclusionsRotavirus causes significant disease burden in young children. Although rarely life-threatening in high income countries, the costs for society are substantial. The inclusion of rotavirus vaccine in the national immunization schedule will reduce the disease burden and would be cost-saving in Iceland.     

Cost-effectiveness of rotavirus vaccination in Bolivia from the state perspective

Background

In Bolivia, in 2008, the under-five mortality rate is 54 per 1000 live births. Diarrhea causes 15% of these deaths, and 40% of pediatric diarrhea-related hospitalizations are caused by rotavirus illness (RI). Rotavirus vaccination (RV), subsidized by international donors, is expected to reduce morbidity, mortality, and economic burden to the Bolivian state. Estimates of illness and economic burden of RI and their reduction by RV are essential to the Bolivian state's policies on RV program financing. The goal of this report is to estimate the economic burden of RI and the cost-effectiveness of the RV program.

Methods

To assess treatment costs incurred by the healthcare system, we abstracted medical records from 287 inpatients and 6751 outpatients with acute diarrhea between 2005 and 2006 at 5 sentinel hospitals in 4 geographic regions. RI prevalence rates were estimated from 4 years of national hospital surveillance. We used a decision-analytic model to assess the potential cost-effectiveness of universal RV in Bolivia.

Results

Our model estimates that, in a 5-year birth cohort, Bolivia will incur over US$3 million in direct medical costs due to RI. RV reduces, by at least 60%, outpatient visits, hospitalizations, deaths, and total direct medical costs associated with rotavirus diarrhea. Further, RV was cost-savings below a price of US$3.81 per dose and cost-effective below a price of US$194.10 per dose. Diarrheal mortality and hospitalization inputs were the most important drivers of rotavirus vaccine cost-effectiveness.

Discussion

Our data will guide Bolivia's funding allocation for RV as international subsidies change.     

Impact of non-routine rotavirus vaccination on hospitalizations for diarrhoea and rotavirus infections in Spain

This study shows hospital discharges related to all-cause diarrhoea and rotavirus infection in children up to five years of age from 2005 to 2009 in Spain. Rotavirus vaccines have been available in Spain since late 2006 and early 2007. They are neither funded nor reimbursed by the National Health Care System. However, they are recommended by the Spanish Association of Pediatricians and prescribed by paediatricians. The vaccination coverage was 17% in 2007, 35% in 2008 and 38% in 2009. Among a total of 111,738 hospitalizations recorded, 24% (N = 26,500) were coded as rotavirus and 14% (N = 16,217) as diarrhoea of undetermined aetiology. The overall annual incidence of hospitalization was 991,235 and 144 per 100,000 children up to five years of age for all-causes diarrhoea, rotavirus infection and diarrhoea of undetermined aetiology respectively. The annual rate significantly decreased during the study period.     

Economic evaluation of a publicly funded hepatitis A travel vaccination program in Ontario,Canada

Background

Hepatitis A virus (HAV) causes acute liver infection and is spread through the fecal-oral route. Travel to countries in HAV-endemic regions (e.g., Asia and Latin America) is a well-described risk factor for infection. Currently, Ontario publicly funds hepatitis A vaccination for some populations at high risk of HAV infection but not for all travellers to endemic countries. The objective of this study was to determine the cost-effectiveness of expanding publicly funded HAV vaccination to people planning travel to HAV-endemic regions, from the Ontario healthcare payer perspective.

Changing molecular epidemiology of rotavirus infection after introduction of monovalent rotavirus vaccination in Scotland

BackgroundRotaviruses (RV) are the leading cause of gastroenteritis in children less than five years of age worldwide. Rotarix®, a live attenuated monovalent vaccine containing a RV strain of G1P[8] specificity has been included in the childhood immunisation schedule from June 2013 in Scotland. This study aimed to characterise the prevalent RV strains in Scotland before and after the introduction of the RV vaccine.MethodsRV positive faecal samples from Scottish virology laboratories covering the years 2012–2015 were genotyped. Viral RNA was extracted from faecal suspensions. VP7 and VP4 gene specific primers were used for multiplex hemi-nested PCRs and sequencing. Mann-Whitney U test and Chi-square test were used for statistical comparison.ResultsThere was a decrease in RV positive samples from the Scottish virology laboratories from 7409 samples in the pre-vaccination years (2009–2013) to 760 in 2014–2015, with an annual reduction of RV infections by 74.4% (RR-3.95; 95%-CI, 3.53–4.42, p < 0.001). 362 samples from the pre-vaccination period and 278 samples from the post-vaccination were genotyped. There was a drop in prevalence of G1P[8] strains (72.1%, 95%-CI, 67.42–76.33 to 15%, 95%-CI, 11.38–19.79) after introduction of the vaccine. In the post-vaccination period G2P[4] was the dominant strain in Scotland (21.9%, 95%-CI, 17.48–27.17) with increase in G9P[8] (12.9%, 95%-CI, 9.50–7.41), G12P[8] (12.2%, 95%-CI, 8.89–16.60) and G3P[8] (11.9%, 95%-CI, 8.58–16.20) infections. Phylogenetic analysis of the VP7 and VP4 genes showed no major differences between the pre and post-vaccination G1P[8] strains.ConclusionThis laboratory based surveillance study shows significant reduction in reported RV cases and a shift in proportion from G1P[8] to G2P[4] strains after introduction of RV vaccination in Scotland. The genotyping data from a subset of the total reported RV cases will be used to ascertain cross protection against strains and identify vaccine induced RV strain shifts in the years to come.     

Impact and effectiveness of monovalent rotavirus vaccine in Tajik children

BackgroundIn 2015, Tajikistan became the second country in Central Asia to introduce rotavirus vaccine into its national immunization program. Before vaccine introduction, rotavirus was estimated to cause > 40% of pediatric diarrhea hospitalizations in Tajikistan. We aimed to assess the impact of rotavirus vaccine introduction on rotavirus disease burden and estimate rotavirus vaccine effectiveness (VE).MethodsUsing surveillance data from 2013 through 2019, we examined trends in monthly hospital admissions among children < 5 years old, before and after rotavirus vaccine introduction. Poisson regression was used to quantify decreases. VE was estimated using a test-negative case control design, with data from admissions during 2017 – 2019. Immunization records were obtained from clinics.ResultsAmong enrolled children, rotavirus positivity declined from 42% to 25% in the post-vaccine introduction period, a decrease of 41% (95% Confidence Interval [CI]: 36 – 45%). Declines were greatest in children < 12 months of age. Estimated VE of a complete course of rotavirus vaccine was 55% (95% CI: 21 – 73%) among children 5 – 59 months of age and 64% (95% CI: 36 – 80%) among children 5 – 23 months of age. VE point estimates were higher among children receiving both doses of rotavirus vaccine non-concurrently with OPV and among children receiving their first dose of rotavirus vaccine at 4 – 11 months of age, but CIs were wide and overlapping.ConclusionsOur data demonstrate that rotavirus vaccine introduction was associated with a substantial reduction in pediatric rotavirus hospitalization burden in Tajikistan, and that rotavirus vaccination is effective in Tajik children.     

Cost-effectiveness of rotavirus vaccination in the Philippines: A modeling study

IntroductionRotavirus gastroenteritis (RVGE) remains a leading cause of hospitalization and death in children under five years of age in the Philippines. Rotavirus (RV) vaccination was introduced into the national immunization program (NIP) in 2012 but has since been limited to one region due to cost considerations and conflicting local cost-effectiveness estimates. Updated estimates of the cost-effectiveness of RV vaccination are required to inform prioritization of national immunization activities.MethodsWe calculated the potential costs and benefits of rotavirus vaccination over a 10-year-period (2021–2031) from a government and societal perspective, comparing four alternative rotavirus vaccines: Rotavac, Rotasiil, Rotarix and Rotateq. For each vaccine, a proportionate outcomes model was used to calculate the expected number of disease events, DALYs, vaccination program costs, and healthcare costs, with and without vaccination. The primary outcome measure was the cost per DALY averted. Assuming each product would generate similar benefits, the dominant (lowest cost) product was identified. We then calculated the cost-effectiveness (US$ per Disability Adjusted Life Year [DALY] averted) of the least costly product and compared it to willingness-to-pay thresholds of 0.5 and 1 times the national GDP per capita ($3,485), and ran deterministic and probabilistic sensitivity analyses.ResultsIntroducing any of the four rotavirus vaccines would avert around 40% of RVGE visits, hospitalizations, and deaths over the period 2021–2031. Over the same ten-year period, the incremental cost of vaccination from a government perspective was estimated to be around $104, $105, $220, and $277 million for Rotavac, Rotasiil, Rotarix and Rotateq, respectively. The equivalent cost from a societal perspective was $58, $60, $178 and $231 million. The cost-effectiveness of the least costly product (Rotavac) was $1,148 ($830–$1682) from a government perspective and $646 ($233–1277) from a societal perspective. All other products offered similar benefits but at a higher cost. There is a >99% probability that Rotavac would be cost-effective at a willingness-to-pay threshold set at 0.5 times the national GDP per capita.ConclusionBoth Rotavac and Rotasiil are likely to be cost-effective options in the Philippines, but it is not possible to say definitively which product should be preferred. Rotarix and Rotateq are expected to offer similar benefits at more cost, so would need to be priced far more competitively to be considered for introduction.