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

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

Developing a manufacturing process to deliver a cost effective and stable liquid human rotavirus vaccine

Despite solid evidence of the success of rotavirus vaccines in saving children from fatal gastroenteritis, more than 82 million infants worldwide still lack access to a rotavirus vaccine. The main barriers to global rotavirus vaccine coverage include cost, manufacturing capacity and suboptimal efficacy in low- and lower-middle income countries. One vaccine candidate with the potential to address the latter is based on the novel, naturally attenuated RV3 strain of rotavirus, RV3-BB vaccine administered in a birth dose strategy had a vaccine efficacy against severe rotavirus gastroenteritis of 94% at 12 months of age in infants in Indonesia. To further develop this vaccine candidate, a well-documented and low-cost manufacturing process is required. A target fully loaded cost of goods (COGs) of ≤$3.50 per course of three doses was set based on predicted market requirements. COGs modelling was leveraged to develop a process using Vero cells in cell factories reaching high titers, reducing or replacing expensive reagents and shortening process time to maximise output. Stable candidate liquid formulations were developed allowing two-year storage at 2–8 °C. In addition, the formulation potentially renders needless the pretreatment of vaccinees with antacid to ensure adequate gastric acid neutralization for routine oral vaccination. As a result, the formulation allows small volume dosing and reduction of supply chain costs. A dose ranging study is currently underway in Malawi that will inform the final clinical dose required. At a clinical dose of ≤6.3 log₁₀ FFU, the COGs target of ≤$3.50 per three dose course was met. At a clinical dose of 6.5 log₁₀ FFU, the final manufacturing process resulted in a COGs that is substantially lower than the current average market price, 2.44 USD per dose. The manufacturing and formulation processes were transferred to BioFarma in Indonesia to enable future RV3-BB vaccine production.     

Targeted hepatitis E vaccination for women of childbearing age is cost-effective in China

BackgroundHepatitis E virus (HEV) infection is hyper-endemic in China, it is characterized with a high morbidity of fulminant hepatitis and mortality in pregnant women. The first hepatitis E vaccine, HEV 239, was licensed in China in 2011 which provides an effective preventive measure.ObjectiveTo evaluate the cost-effectiveness of vaccination with HEV 239 in women of childbearing age in China and whether HEV antibody screening should be considered before vaccination.MethodsA decision tree-Markov model was constructed to simulate HEV infection in a closed female cohort with an average first-marriage age of 25 years and evaluate health and economic outcomes of two potential vaccination strategies, direct vaccination and combined screening and vaccination, from a societal perspective. An incremental cost-effectiveness ratio (ICER, additional costs per disability-adjusted life-year (DALY) averted) was calculated for each vaccination strategy versus no vaccination and between two vaccination strategies. Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of the model findings.ResultsICERs of direct vaccination and combined screening and vaccination versus no vaccination were $4040 and $3114 per DALY averted, respectively, much lower than 1-time Chinese per-capita GDP ($8127). Direct vaccination would need additional $45,455 for each DALY averted compared with combined screening and vaccination, far more than the 3-time per-capita GDP. Probabilistic sensitivity analyses confirmed our findings that two vaccination strategies would be cost-effective if the willingness-to-pay reached the 1-time per-capita GDP, and that combined screening and vaccination would be more cost-effective than direct vaccination strategy.ConclusionVaccinating women of childbearing age with HEV 239 would cost less than the 1-time per-capita GDP for each DALY averted in China, and the vaccination with a prior screening would be the optimal option.     

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children

BackgroundTwo rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries.MethodsFrom February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8–59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 − odds ratio of vaccination) × 100%.ResultsTotally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls.ConclusionsBoth vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.     

Cost effectiveness of trivalent and quadrivalent influenza vaccines in 50- to 64-year-old adults in Korea

BackgroundInfluenza causes severe complications in at-risk populations, resulting in significant morbidity and mortality. Vaccination is the most effective measure to prevent infection and complications caused by seasonal influenza. However, no study has analyzed the cost-effectiveness of influenza vaccines in 50- to 64-year-olds in South Korea.ObjectiveWe examined the application of the National Immunization Program (NIP) in 50- to 64-year-olds and compared the cost-effectiveness of quadrivalent influenza vaccine (QIV) with that of trivalent influenza vaccine (TIV) in South Korea.MethodsOne-year static model was assumed by constructing separate decision trees for age subgroups: 50–54, 55–59, and 60–64. Each subgroup was divided into at-risk and not-at-risk groups. Using circulation data from previous studies and Korea Centers for Disease Control and Prevention, we estimated the probabilities of influenza infection, outpatient treatment, hospitalization, and deaths. Medical cost was estimated from 2015 to 2017 National Health Insurance Sharing Service claim data, while productivity losses from work absenteeism or death were estimated from labor and economic surveys of Korean government. Disutility was estimated based on previous studies.ResultsCompared with non-vaccination, incremental cost-effectiveness ratios (ICERs) for the 50–54, 55–59, and 60–64 age groups for TIV were US$2010.90, US$2004.58, and US$1865.55, respectively, while for QIV were US$2187.17, US$2190.89, and US$2074.52, respectively. Compared with TIV, ICERs for QIV were US$4445.66, US$4578.06, and US$4751.93, respectively. All the aforementioned ICER values were lower than the 2017 Korean GDP per capita of US$29,742.839.ConclusionImplementing the NIP in the 50- to 64-year-old age group was found to be cost effective. Since both TIV and QIV were cost effective, we recommend QIV as the preferred option, based on its greater protection against Influenza B.     

Economic evaluation of the introduction of rotavirus vaccine in Hong Kong

BackgroundRotavirus is a common cause of severe gastroenteritis in young children in Hong Kong (HK) with a high economic burden. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into the HK Government’s Childhood Immunisation Programme (CIP) and to include the potential protective effect of the vaccine against seizures.MethodsA decision-support model was customised to estimate the potential impact, cost-effectiveness and benefit-risk of rotavirus vaccination in children below 5 years over the period 2020–2029 in HK. Two doses of Rotarix® and three doses of RotaTeq® were each compared to no vaccination. Rotavirus treatment costs were calculated from a governmental health sector perspective (i.e., costs of public sector treatment) and an overall health sector perspective (both governmental and patient, i.e., costs of public sector treatment, private sector treatment, transport and diapers). We ran probabilistic and deterministic uncertainty analyses.ResultsIntroduction of rotavirus vaccination in HK could prevent 49,000 (95% uncertainty interval: ~44,000–54,000) hospitalisations of rotavirus gastroenteritis and seizures and result in ~50 (95% uncertainty interval: ~25–85) intussusception hospitalisations, over the period 2020–2029 (a benefit-risk ratio of ~1000:1), compared to a scenario with no public or private sector vaccine use. The discounted vaccination cost would be US$51–57 million over the period 2020–2029 based on per-course prices of US$72 (Rotarix®) or US$78 (RotaTeq®), but this would be offset by discounted treatment cost savings of US$70 million (government) and US$127 million (governmental and patient health sector). There was a greater than 94% probability that the vaccine could be cost-saving irrespective of the vaccine product or perspective considered. All deterministic ‘what-if’ scenarios were cost-saving from an overall health sector perspective (governmental and patient).ConclusionsRotavirus vaccination is likely to be cost-saving and have a favourable benefit-risk profile in HK. Based on the assumptions made, our analysis supports its introduction into CIP.     

Impact of rotavirus vaccine on paediatric rotavirus hospitalisation and intussusception in New Zealand: A retrospective cohort study

BackgroundRotavirus results in a significant burden of hospitalisations and deaths globally. Rotavirus vaccine has been used in New Zealand since July 2014. The aim of this study was to assess the safety and effectiveness of RotaTeq® vaccine in New Zealand between 2006 and 2016.MethodsA national cohort study of 723,695 children aged less than 6 years was carried out using linked administrative datasets. Study outcomes were hospitalisation for intussusception, rotavirus, and all-cause gastroenteritis. Intussusception hospitalisation rates were calculated from 2006 to 2016, and rotavirus and all-cause gastroenteritis hospitalisation rates from 2011 to 2016. We examined the effect of RotaTeq® vaccination on rotavirus and all-cause gastroenteritis hospitalisation rates using Poisson regression. Adjusted incidence rate ratios controlled for sex, year of birth, ethnicity, socioeconomic deprivation, and district health board area.ResultsSignificant reductions in the incidence of rotavirus hospitalisation were seen in all age groups, ethnicities, and deprivation following the introduction of RotaTeq®. There was a 92.6% reduction in hospitalisation incidence in the vaccinated cohort (p < 0.0001). There was also a 48% reduction in all-cause gastroenteritis hospitalisation incidence in the vaccinated cohort (p < 0.0001). The average annual intussusception rate in children aged less than 3 years was 26.2 per 100,000, with no significant change over time (p = 0.847).ConclusionsIn New Zealand the introduction of RotaTeq® resulted in a significant reduction in rotavirus hospitalisation, and a halving in all-cause gastroenteritis hospitalisation. There has been no change in the overall incidence of intussusception or clear change in patterns of cases, although intussusception cases did occur within risk period immediately post vaccine.     

Dynamics of G2P[4] strain evolution and rotavirus vaccination: A review of evidence for Rotarix

Rotavirus (RV) gastroenteritis is a vaccine-preventable disease that creates high medical and economic burden in both developed and developing countries. Worldwide, more than 100 countries have introduced RV vaccines in their national immunization programs, and the remarkable impact of reducing the burden of severe childhood gastroenteritis has been unequivocally demonstrated. Currently, 2 oral vaccines (Rotarix, GSK and RotaTeq, Merck) are widely utilized. Recent temporary increases in the relative prevalence of G2P[4] RV strains have been observed in countries implementing RV vaccination. This comprehensive literature review aims to provide an insight on RV genotype evolution in the context of mass vaccination with Rotarix, particularly in the case of G2P[4]. In the post-vaccine era, strain surveillance data indicated temporal and spatial changes in countries both with and without RV vaccination programs. Annual fluctuations in G2P[4] prevalence seem to occur naturally, with no substantial differences between countries using Rotarix, RotaTeq or mixed vaccination programs. Moreover, Rotarix has been shown to be efficacious and effective against gastroenteritis caused by non-vaccine strains, including G2P[4]. These data indicate that shifts in RV genotype distribution are likely to constitute an inherent process of virus evolution to infect the human gut. Following RV vaccine introduction, incidences of RV gastroenteritis declined dramatically and mass vaccination will likely maintain this status, despite possible fluctuations in the relative distribution of genotypes. There is no conclusive evidence of unusual burst of new or vaccine-escape strains since global RV vaccines use. The emergence of strains with a potential to increase the current burden of RV disease should be continuously monitored and can only be established by exhaustive characterization of strains, including whole genomic sequencing. Given the natural fluctuations in RV strains over time, caution is advised when interpreting temporal changes in RV strain dynamics, as they could mistakenly be attributed to vaccination.     

Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis

BackgroundRotavirus caused an estimated 151,714 deaths from diarrhea among children under 5 in 2019. To reduce mortality, countries are considering adding rotavirus vaccination to their routine immunization program. Cost-effectiveness analyses (CEAs) to inform these decisions are not available in every setting, and where they are, results are sensitive to modeling assumptions, especially about vaccine efficacy. We used advances in meta-regression methods and estimates of vaccine efficacy by location to estimate incremental cost-effectiveness ratios (ICERs) for rotavirus vaccination in 195 countries.MethodsBeginning with Tufts University CEA and Global Health CEA registries we used 515 ICERs from 68 articles published through 2017, extracted 938 additional one-way sensitivity analyses, and excluded 33 ICERs for a sample of 1,418. We used a five-stage, mixed-effects, Bayesian metaregression framework to predict ICERs, and logistic regression model to predict the probability that the vaccine was cost-saving. For both models, covariates were vaccine characteristics including efficacy, study methods, and country-specific rotavirus disability-adjusted life-years (DALYs) and gross domestic product (GDP) per capita. All results are reported in 2017 United States dollars.ResultsVaccine efficacy, vaccine cost, GDP per capita and rotavirus DALYs were important drivers of variability in ICERs. Globally, the median ICER was $2,289 (95% uncertainty interval (UI): $147–$38,993) and ranged from $85 per DALY averted (95% UI: $13–$302) in Central African Republic to $70,599 per DALY averted (95% UI: $11,030–$263,858) in the United States. Among countries eligible for support from Gavi, The Vaccine Alliance, the mean ICER was $255 per DALY averted (95% UI: $39–$918), and among countries eligible for the PAHO revolving fund, the mean ICER was $2,464 per DALY averted (95% UI: $382–$3,118).ConclusionOur findings incorporate recent evidence that vaccine efficacy differs across locations, and support expansion of rotavirus vaccination programs, particularly in countries eligible for support from Gavi, The Vaccine Alliance.     

Validation of parental reports of rotavirus vaccination of their children compared to the national immunization registry

BackgroundThe introduction of rotavirus vaccines into national immunization programs necessitates vaccine effectiveness evaluations. Parental report of vaccination status is a simple and accessible source of information; however, its validity is unclear.AimsTo validate parental reports of rotavirus immunization compared to documentation of vaccination in national immunization registry, and to assess vaccine effectiveness by each method.MethodsParents of 1272 children aged 2–59 months from northern Israel hospitalized for gastroenteritis in 2011–2015 were interviewed on the sociodemographics and rotavirus vaccination status of their child. Rotavirus immunization status based on parental report was compared to that documented in the national immunization registry, which was considered the gold standard. Stool samples collected from patients were tested for rotavirus antigen by immunochromotgraphy. In a rotavirus test-negative case-control study, vaccination history was compared between children found positive for rotavirus and those who tested negative. Vaccine effectiveness for ≥ 1 dose vs. zero doses was calculated as: (1-adjusted odds ratio) * 100.ResultsThe sensitivity and specificity of parental report of their child's immunization with a rotavirus vaccine were 97% (95% CI 96–98), and 75% (95% CI 65–82), respectively. Kappa coefficient was 0.69 (p < 0.001) for the agreement between the two methods. Rotavirus vaccine effectiveness was 72% (95% CI 54–84) when using parental report of rotavirus immunization and 79% (95% CI 62–88) when using the registry.ConclusionParental report of their child's immunization with a rotavirus vaccine demonstrated high sensitivity, although the specificity was relatively low. Vaccine effectiveness was similar regardless of method used to determine rotavirus immunization status. Parental report of vaccination status can be useful in vaccine effectiveness assessment.     

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

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

Timeliness and factors associated with rotavirus vaccine uptake among Australian Aboriginal and non-Aboriginal children: A record linkage cohort study

ObjectivesRotavirus vaccines (RV), included in Australia’s National Immunisation Program from mid-July 2007, are unique in strict time limits for administration. Here, we report on timeliness of RV uptake, compare cumulative RV coverage to age 12 months with DTPa, and assess factors associated with receipt of RV among Aboriginal and non-Aboriginal children.MethodsBirth records for 681,456 children born in two Australian states in 2007–2012 were probabilistically linked to national immunisation records. We assessed on-time coverage (defined as receipt of vaccine dose between 4 days prior to scheduled date and the recommended upper limit) for RV and compared this to diphtheria-tetanus-pertussis (DTPa) vaccine. Logistic regression modelling was used to assess independent determinants of receipt of RV.ResultsCompared to non-Aboriginal infants, on-time RV coverage was lower for all doses among Aboriginal infants. Post the upper age limit of RV dose2, DTPa dose2 coverage increased by 9–16% to ≥90%, whereas RV coverage remained around 77% (Aboriginal) and 85% (non-Aboriginal). Compared to first-born children, the adjusted odds of receiving ≥1 RV dose if born to a mother with ≥3 previous births was 0.30 (95%CI: 0.27–0.34) among Aboriginal, and 0.53 (95%CI: 0.51–0.55) among non-Aboriginal children. Prematurity (<33 weeks), low birthweight (<1500 g), maternal age <20 years, maternal smoking during pregnancy and living in a disadvantaged area were independently associated with decreased vaccine uptake.ConclusionsAboriginal children are at greater risk of rotavirus disease than non-Aboriginal children and delayed vaccine receipt is substantially higher. Although specific programs targeting groups at risk of delayed vaccination might improve RV coverage, relaxation of upper age restrictions is most readily implementable, and its overall risk-benefit should be evaluated.     

Cost-effectiveness of quadrivalent versus trivalent influenza vaccine for elderly population in China

BackgroundInfluenza-associated excess death occurred most in the elderly. We aimed to assess the cost-effectiveness of quadrivalent influenza vaccine (QIV) versus trivalent influenza vaccine (TIV) for prevention of influenza infection among elderly population in China.MethodsA decision-analytic model was developed to compare 1-year clinical and economic outcomes of three influenza vaccination options (no vaccination, TIV, and QIV) in a hypothetical cohort of Chinese elderly aged 69 years. Outcome measures included cost, influenza infection rate, influenza-related mortality rate, quality-adjusted life-years (QALY) loss, and incremental cost-effectiveness ratio (ICER) from societal perspective. Sensitivity analyses were performed to examine the uncertainty of model inputs.ResultsBase-case results showed no vaccination was dominated (more costly at higher QALY loss) by TIV and QIV. QIV was more costly (USD56.29 versus USD54.28) with lower influenza infection rate (0.608 versus 0.623), mortality rate (0.00199 versus 0.00204), and QALY loss (0.01213 versus 0.01243) than TIV. QIV was cost-effective compared to TIV with ICER of 6,700 USD/QALY below the willingness-to-pay threshold (29,580 USD/QALY). One-way sensitivity analysis found the cost-effectiveness of QIV was subject to the relative risk of vaccine effectiveness of QIV versus TIV, and TIV would be cost-effective if the relative risk was below 1.05. In 10,000 Monte Carlo simulations, the probabilities of QIV, TIV, and no vaccination to be cost-effective were 86.3%, 13.7%, and 0%, respectively.ConclusionQIV appears to be a cost-effective option compared to TIV and no influenza vaccination for elderly population in China.     

A case-control study of risk factors for intussusception among infants in eastern France after the introduction of the rotavirus vaccine

ObjectiveThe objective of the present study was to investigate the risk factors for intussusception (IS) among infants, including vaccination against rotavirus.MethodsCase-control study with systematic inclusion of all infants aged <1 year with suspected IS admitted to emergency departments in the eastern region of France between 1 April 2008 and 31 March 2012. All cases classed level 1 according to the Brighton classification were matched to 4 hospital controls. Two exposure windows were examined; exposure to the first dose of rotavirus vaccine in the 7 and in the 14 days prior to the occurrence of IS.ResultsA total of 115 cases were matched with 457 controls. The average vaccination coverage rate over the 4 years of study was 8.6%. Rotavirus vaccine was not found to be significantly associated with the occurrence of IS in the 7 days (odds ratio (OR) not calculated; p = 0.99) and in the 14 days after administration of one dose vaccine (OR 1.33, 95% confidence interval (CI) 0.14–12.82). Infant formula alone or combined with breastfeeding was associated with an excess risk of IS (OR 2.74, 95% CI 1.10–6.79). A history of gastroenteritis within 2 weeks prior to hospitalisation was also associated with an increased risk (OR 2.24, 95% CI 1.07–4.67).ConclusionOur study indicates that infant formula alone or combined with breastfeeding is a risk factor for IS. A small, non-significant increase in the risk of IS was observed after rotavirus vaccination, although the low vaccine coverage rate likely precluded detection of a significant increase in risk.     

Cost-benefit analysis of a national influenza vaccination program in preventing hospitalisation costs in Australian adults aged 50–64 years old

IntroductionInfluenza causes a significant burden among Australian adults aged 50–64, however, vaccine coverage rates remain suboptimal. The National Immunisation Program (NIP) currently funds influenza vaccinations in this age group only for those at high risk of influenza complications.AimsThe main aim of this study was to determine whether a strategy of expanding the government-funded vaccination program to all adults 50–64 in preventing influenza-related hospitalisations will be cost beneficial to the government.MethodsA cost-benefit analysis from a governmental perspective was performed using parameters informed by publicly available databases and published literature. Costs included cost of vaccinations and general practitioner consultation while benefits included the savings from averted respiratory and acute myocardial infarction (AMI) hospitalisations.ResultsIn the base-case scenario, the proposed policy would prevent 314 influenza/pneumonia, 388 other respiratory and 1482 AMI hospitalisations in a year. The government would save $8.03 million with an incremental benefit-cost ratio of 1.40. Most savings were due to averted AMI hospitalisations. In alternative scenarios cost savings ranged from saving of $31.4 million to additional cost to the government of $15.4 million, with sensitive variation in vaccine administration practices (through general practitioner or pharmacists) and vaccine effectiveness estimates.DiscussionExtension of the NIP to include adults 50–64 years of age is likely to be cost beneficial to the government, although this finding is sensitive to vaccine administration cost, which varies if provided through general practitioners or pharmacists; and to variation in vaccine effectiveness. An increased role of pharmacists in immunisation programs would likely result in cost savings in an expanded adult immunisation program.     

Cost-effectiveness of human papillomavirus vaccination in girls living in Latin American countries: A systematic review and meta-analysis

BackgroundCervical cancer is a major public health problem in Latin America. Cost-effectiveness studies help stakeholders with decisions regarding human papillomavirus (HPV) vaccination programs, one of the main prevention measures. Our objective was to synthesize the results of cost-effectiveness studies of HPV vaccination in girls, to understand factors influencing cost-effectiveness in the region.MethodsWe systematically searched databases as well as repositories from conferences, Ministries of Health and Health Technology Assessment offices. Incremental cost-effectiveness ratios (ICERs) were extracted, with data converted to international dollars (I$) and inflated to 2019 values. We used the gross domestic product per capita as threshold for judging the cost-effectiveness of vaccination. We calculated the geometric mean ICER by type of vaccine, whether screening (cytology or HPV test) was used as comparator, effectiveness measure, perspective, source of funding, year of cost, and country.ResultsWe found 24 studies. Despite the methodological differences, most studies concluded that HPV vaccination of girls in Latin American countries was either cost-saving or cost-effective. The mean ICER was I$ 3,804 for the bivalent vaccine, I$ 640 for the quadrivalent and I$ 358 for a generic HPV-16/18 vaccine. The mean ICER was lower in the studies that used HPV DNA test instead of cytology (I$ 122 vs I$ 1,841) as comparator; used the societal perspective (I$ 235 vs. I$ 1,986); were funded by non-profit sources instead of by pharmaceutical industry (I$ 421 vs. I$ 2,676); and used costs obtained prior to 2008 (I$ 365 vs I$ 1,415). We observed great variation in the mean ICERs by effectiveness measure (I$ 402 for per disability adjusted life years, I$ 461 for life year saved, and I$ 1,795 for quality adjusted life years).ConclusionsMost studies concluded that HPV vaccination of girls in Latin America countries was cost-saving or cost-effective, despite heterogeneity between models.     

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.     

Evaluation of non-specific effects of human rotavirus vaccination in medical risk infants

BackgroundThe WHO recommends research into non-specific effects of vaccination. For rotavirus vaccines, these have not yet been well established. We studied non-specific effects up to 18 months of age using data from a quasi-experimental before-after study comparing cohorts of rotavirus vaccinated and unvaccinated infants with medical risk conditions.MethodsInfants were enrolled at six weeks of age before and after a stepped-wedge implementation of a hospital-based risk-group rotavirus vaccination program. Other infant vaccinations were administered according to the Dutch National Immunization Program and similar in both cohorts. Non-specific effect outcomes were prospectively collected using monthly questionnaires and included acute hospitalization (excluding for acute gastroenteritis), monthly incidence of acute respiratory illness and eczema. We used time-to-event analysis and negative binomial regression to assess the effect of at least one dose of rotavirus vaccination for each of these outcomes.FindingsThe analysis included 496 rotavirus unvaccinated and 719 vaccinated medical risk infants. In total, 1067 (88%) were premature, 373 (31%) small for gestational age and 201 (17%) had a congenital pathology. The adjusted hazard ratio for first acute hospitalization was 0·91 (95 %CI 0·76;1·16) for rotavirus vaccinated versus unvaccinated infants. Adjusted incidence rate ratio for acute respiratory illness was 1·05 (95 %CI 0·96;1·15) and for eczema 0·89 (95 %CI 0·69;1·15).ConclusionThe results suggest no, or minimal non-specific effects from rotavirus vaccination on acute hospitalization, acute respiratory illness or eczema in medical risk infants.Trial registration: as NTR5361 in the Dutch trial registry, www.trialregister.nl.     

Modelling the relative cost-effectiveness of the RTS,S/AS01 malaria vaccine compared to investment in vector control or chemoprophylaxis

BackgroundThe World Health Organization has recommended a 4-dose schedule of the RTS,S/AS01 (RTS,S) vaccine for children in regions of moderate to high P. falciparum transmission. Faced with limited supply and finite resources, global funders and domestic malaria control programs will need to examine the relative cost-effectiveness of RTS,S and identify target areas for vaccine implementation relative to scale-up of existing interventions.MethodsUsing an individual-based mathematical model of P. falciparum, we modelled the cost-effectiveness of RTS,S across a range of settings in sub-Saharan Africa, incorporating various rainfall patterns, insecticide-treated net (ITN) use, treatment coverage, and parasite prevalence bands. We compare age-based and seasonal RTS,S administration to increasing ITN usage, switching to next generation ITNs in settings experiencing insecticide-resistance, and introduction of seasonal malaria chemoprevention (SMC) in areas of seasonal transmission.ResultsFor RTS,S to be the most cost-effective intervention option considered, the maximum cost per dose was less than $9.30 USD in 90.9% of scenarios. Nearly all (89.8%) values at or above $9.30 USD per dose were in settings with 60% established bed net use and / or with established SMC, and 76.3% were in the highest PfPR_2-10 band modelled (40%). Addition of RTS,S to strategies involving 60% ITN use, increased ITN usage or a switch to PBO nets, and SMC, if eligible, still led to significant marginal case reductions, with a median of 2,653 (IQR: 1,741 to 3,966) cases averted per 100,000 people annually, and 82,270 (IQR: 54,034 to 123,105) cases averted per 100,000 fully vaccinated children (receiving at least three doses).ConclusionsUse of RTS,S results in reductions in malaria cases and deaths even when layered upon existing interventions. When comparing relative cost-effectiveness, scale up of ITNs, introduction of SMC, and switching to new technology nets should be prioritized in eligible settings.     

Risk of intussusception after monovalent rotavirus vaccine (Rotavac) in Indian infants: A self-controlled case series analysis

BackgroundAn association between rotavirus vaccination and intussusception has been documented in post-licensure studies in some countries. We evaluated the risk of intussusception associated with monovalent rotavirus vaccine (Rotavac) administered at 6, 10 and 14 weeks of age in India.MethodsActive prospective surveillance for intussusception was conducted at 22 hospitals across 16 states from April 2016 through September 2017. Data on demography, clinical features and vaccination were documented. Age-adjusted relative incidence for 1–7, 8–21, and 1–21 days after rotavirus vaccination in children aged 28–364 days at intussusception onset was estimated using the self-controlled case-series (SCCS) method. Only Brighton Collaboration level 1 cases were included.ResultsOut of 670 children aged 2–23 months with intussusception, 311 (46.4%) children were aged 28–364 days with confirmed vaccination status. Out of these, 52 intussusception cases with confirmed receipt of RVV were included in the SCCS analysis. No intussusception case was observed within 21 days of dose 1. Only one case occurred during 8–21 days after the dose 2. Post-dose 3, two cases in 1–7 days and 7 cases during 8–21 days period were observed. There was no increased risk of intussusception during 1–7 days after the doses 1 and 2 (zero cases observed) or dose 3 (relative incidence [RI], 1.71 [95% confidence interval {CI} 0.0–5.11]). Similarly, no increased risk during 8–21 days after the dose 1 (zero cases observed), dose 2 (RI, 0.71 [95% CI, 0.0–3.28]) or dose 3 (RI, 2.52 [95% CI, 0.78–5.61]). The results were similar for 1–21 day periods after the doses separately or pooled.ConclusionsThe risk of intussusception during the first 21 days after any dose of rotavirus vaccine (Rotavac) was not higher among the Indian infants than the background risk, based on limited SCCS analysis of 52 children.