Cost and health impact analysis of herpes zoster vaccination in Norway.

BACKGROUND: A decision analytic model was developed to estimate the cost-effectiveness of a national vaccination program against herpes zoster in Norway. METHODS: The model analyzed six vaccination scenarios that included the live-attenuated zoster vaccine under different target ages of vaccination (60, 65, and 70 years) compared with no vaccination. A catch-up program implemented in the first year of the vaccination was included in three of the scenarios. The model followed the population of Norway over a 40-year time horizon to estimate costs and outcomes associated with vaccination. Immunization costs, costs related to herpes zoster (both healthcare sector and non-healthcasre sector), the quality of life gains due to avoided cases of herpes zoster, and quality-of-life losses due to vaccine-related adverse events were estimated. RESULTS AND CONCLUSIONS: A national vaccination program would result in reduction of the number of herpes zoster cases and decreased burden of illness. Vaccinating adults at 65 years of age with catch-up up to 70 years in the first year of the program was the most cost-effective strategy with the incremental cost per quality-adjusted life-year gained at NOK (Norwegian Krone) 245,459 from the societal perspective and NOK 248,637 from the health care system perspective.

Economic burden of varicella in Europe in the absence of universal varicella vaccination.

BACKGROUND: Though the disease burden of varicella in Europe has been reported previously, the economic burden is still unknown. This study estimated the economic burden of varicella in Europe in the absence of Universal Varicella Vaccination (UVV) in 2018 Euros from both payer (direct costs) and societal (direct and indirect costs) perspectives. METHODS: We estimated the country specific and overall annual costs of varicella in absence of UVV in 31 European countries (27 EU countries, plus Iceland, Norway, Switzerland and the United Kingdom). To obtain country specific unit costs and associated healthcare utilization, we conducted a systematic literature review, searching in PubMed, EMBASE, NEED, DARE, REPEC, Open Grey, and public heath websites (1/1/1999-10/15/2019). The number of annual varicella cases, deaths, outpatient visits and hospitalizations were calculated (without UVV) based on age-specific incidence rates (Riera-Montes et al. 2017) and 2018 population data by country. Unit cost per varicella case and disease burden data were combined using stochastic modeling to estimate 2018 costs stratified by country, age and healthcare resource. RESULTS: Overall annual total costs associated with varicella were estimated to be €662,592,061 (Range: €309,552,363 to €1,015,631,760) in Europe in absence of UVV. Direct and indirect costs were estimated at €229,076,206 (Range €144,809,557 to €313,342,856) and €433,515,855 (Range €164,742,806 to €702,288,904), respectively. Total cost per case was €121.45 (direct: €41.99; indirect: €79.46). Almost half of the costs were attributed to cases in children under 5 years, owing mainly to caregiver work loss. The distribution of costs by healthcare resource was similar across countries. France and Germany accounted for 49.28% of total annual costs, most likely due to a combination of high numbers of cases and unit costs in these countries. CONCLUSIONS: The economic burden of varicella across Europe in the absence of UVV is substantial (over 600 M€), primarily driven by caregiver burden including work productivity losses.

Clinical and economic impact of universal varicella vaccination in Norway: A modeling study.

BACKGROUND: Norway has not implemented universal varicella vaccination, despite the considerable clinical and economic burden of varicella disease. METHODS: An existing dynamic transmission model of varicella infection was calibrated to age-specific seroprevalence rates in Norway. Six two-dose vaccination strategies were considered, consisting of combinations of two formulations each of a monovalent varicella vaccine (Varivax® or Varilrix®) and a quadrivalent vaccine against measles-mumps-rubella-varicella (ProQuad® or PriorixTetra®), with the first dose given with a monovalent vaccine at age 15 months, and the second dose with either a monovalent or quadrivalent vaccine at either 18 months, 7 or 11 years. Costs were considered from the perspectives of both the health care system and society. Quality-adjusted life-years saved and incremental cost-effectiveness ratios relative to no vaccination were calculated. A one-way sensitivity analysis was conducted to assess the impact of vaccine efficacy, price, the costs of a lost workday and of inpatient and outpatient care, vaccination coverage, and discount rate. RESULTS: In the absence of varicella vaccination, the annual incidence of natural varicella is estimated to be 1,359 per 100,000 population, and the cumulative numbers of varicella outpatient cases, hospitalizations, and deaths over 50 years are projected to be 1.81 million, 10,161, and 61, respectively. Universal varicella vaccination is projected to reduce the natural varicella incidence rate to 48-59 per 100,000 population, depending on the vaccination strategy, and to reduce varicella outpatient cases, hospitalizations, and deaths by 75-85%, 67-79%, and 75-79%, respectively. All strategies were cost-saving, with the most cost-saving as two doses of Varivax® at 15 months and 7 years (payer perspective) and two doses of Varivax® at 15 months and 18 months (societal perspective). CONCLUSIONS: All modeled two-dose varicella vaccination strategies are projected to lead to substantial reductions in varicella disease and to be cost saving compared to no vaccination in Norway.

Healthcare costs associated with varicella and herpes zoster in Norway.

BACKGROUND: Norway does not implement routine vaccination against varicella or herpes zoster. Despite substantial health burden associated with both diseases, their economic impact is not well described. The aim of the present study was to document the healthcare costs associated with both conditions in a Norwegian setting. METHODS: We used registry data about patients' contacts with primary and specialized healthcare services from 2008 to 2014 to estimate the costs associated with varicella and herpes zoster in the primary and hospital care sector. We calculated the individual costs by treatment facility (general practitioner and emergency primary care clinic) in primary care and by treatment level (inpatient, outpatient or ambulatory treatment) at hospitals. RESULTS: We estimate that the annual healthcare cost of patients with varicella and herpes zoster are NOK 85 million (approximately € 9 million). Of the annual costs, 73% are associated with herpes zoster and 27% are due to varicella. The majority (54%) of the total annual cost is represented by patients with herpes zoster treated in hospital. CONCLUSION: Varicella and herpes zoster impose a substantial financial burden on the national healthcare services in Norway. Most of the costs are incurred by herpes zoster, which could be prevented by vaccination.

Re-evaluation of the cost-effectiveness and effects of childhood rotavirus vaccination in Norway.

BACKGROUND: Rotavirus vaccination was included into the Norwegian childhood immunisation programme in 2014. Before implementation, rotavirus vaccination was found to be cost-effective from a societal perspective, but not from a healthcare perspective. Since introduction, new data on the incidence and economic effects of rotavirus disease have become available. We assessed early epidemiological effects of the rotavirus vaccination programme and re-evaluated its cost-effectiveness in Norway for the years 2015-2019. METHODS: Using a dynamic transmission model, we compared the epidemiological effects of the ongoing two-dose vaccination programme with Rotarix®, and a hypothetical 3-dose programme with RotaTeq® with no vaccination. A baseline cost of € 54 per fully vaccinated child was used. Cost-effectiveness was computed from a healthcare and societal perspective, using a decision analytical model. Data on healthcare use and costs, productivity losses and health utilities were based on published and own estimates. Uncertainty was accounted for in one-way, multi-way, and probabilistic sensitivity analyses. RESULTS: During 2015-2019, 114,658 home care cases, 34,571 primary care cases, 7,381 severe cases, and 2 deaths associated with rotavirus disease were avoided due to vaccination. Under baseline assumptions vaccination was cost-effective from a healthcare perspective with a cost per QALY of € 47,447 for Rotarix® and € 52,709 for RotaTeq®. The break-even price was € 70 for Rotarix® and € 67 for RotaTeq®. Vaccination was cost-saving from the societal perspective, and also from a healthcare perspective for vaccine prices below € 25 and € 22 per vaccinated child for Rotarix® and RotaTeq®, respectively. CONCLUSION: Ongoing childhood rotavirus vaccination in Norway has reduced the rotavirus disease burden substantially, and is cost-effective compared with no vaccination.

Lost workdays and healthcare use before and after hospital visits due to rotavirus and other gastroenteritis among young children in Norway.

BACKGROUND: Cost-effectiveness of rotavirus vaccination is affected by assumptions used in health economic evaluations. To inform such evaluations, we assessed healthcare use before and after hospitalisations due to rotavirus and other acute gastroenteritis (AGE) among children <5years of age in Norway and estimated daycare and work absenteeism. METHODS: We conducted post-discharge interviews with caregivers of 282 children hospitalised with AGE at two hospitals in Norway during April 2014-February 2017. We collected data on healthcare use and absenteeism from daycare and work. We examined healthcare seeking and absenteeism patterns for RV-specific and other gastroenteritis. RESULTS: Caregivers of 485 (37%) of 1 298 hospitalised children were invited to participate, and 282 (58%) completed the questionnaire. Among these, 106 (38%) were rotavirus-positive, 119 (42%) were rotavirus-negative, and for 57 (20%) children no rotavirus testing was performed. Overall, 97% of children had been in contact with a healthcare provider before hospital admission and 28% had contacted a healthcare provider after discharge. Children that attended daycare were absent from daycare for a mean of 6.3days (median 5days). Caregivers of these children reported work absenteeism in 74% of cases. The mean duration of work absenteeism among caregivers was 5.9days (median 5days) both for RV-positive and RV-negative cases. CONCLUSION: In Norway, work absenteeism and healthcare use before and after hospitalisation due to rotavirus and non-rotavirus gastroenteritis are considerable and impose an economic burden on the healthcare system and society.

Varicella-zoster virus susceptibility and primary healthcare consultations in Norway.

BACKGROUND: Currently Norway does not recommend universal varicella vaccination for healthy children. This study assessed susceptibility to varicella-zoster virus (VZV) in the Norwegian population for the first time. METHODS: A national convenience sample of residual sera was tested for anti-VZV IgG by ELISA. We estimated age-specific seropositivity to VZV, controlling for sex and geographical distribution. We assessed differences between the proportions using the chi-square test and multivariable logistic regression. Seroprevalence data were compared to the varicella and herpes zoster-associated consultation rates in patients attending primary healthcare. RESULTS: Although 73.2 % (n = 1,540) of all samples were positive for VZV, only 11.2 % of samples collected from 1-year-olds were seropositive. There was a sharp increase in the proportion of seropositive in 3- and 5-year-olds (40.2 % and 65.4 %, respectively). By the school entry age of 6 years, 69.8 % of children were seropositive. The age-specific annual consultation rate for varicella in primary healthcare peaked in 1-year-olds, with 2,627 cases per 100,000 population. The profile of varicella-related consultations in primary healthcare mirrored the VZV seropositivity profile. The herpes zoster-related consultations in primary healthcare peaked in people over 70 years of age (702 cases per 100,000 population). CONCLUSIONS: VZV seroprevalence in Norway was somewhat lower than in some other European countries. The age-specific varicella-related consultation rates in primary healthcare mirrored the age profile of VZV seroprevalence.

Burden of Rotavirus Disease in Norway: Using National Registries for Public Health Research.

BACKGROUND: Norway introduced routine rotavirus immunization for all children born on or after September 1, 2014. We estimated the healthcare burden of all-cause gastroenteritis and rotavirus disease in children <5 years old to establish the prevaccine baseline and support the ongoing immunization program. METHODS: We examined national registry data on gastroenteritis-associated primary care consultations and hospitalizations for 2009-2013 and data on all deaths in children <5 years old reported during 2000-2013. We also established rotavirus hospital surveillance from February 2014 through January 2015. RESULTS: Before vaccine introduction, 114.5 cases per 1000 children <5 years old were treated in primary care and 11.8 children per 1000 were hospitalized with gastroenteritis annually. During hospital surveillance, rotavirus was detected in 65% (95% confidence interval: 60-70) of inpatient gastroenteritis cases. We estimated that 4.0 inpatient and 2.3 outpatient cases per 1000 children were seen in hospital with rotavirus disease annually, suggesting that 1 in 32 children was hospitalized by age 5. Additional 30.6 rotavirus cases per 1000 children consulted primary care annually or 1 in every 7 children by the age of 5 years. Rotavirus-associated mortality was estimated at 0.17 deaths per 100,000 children <5 years old, corresponding to 1 death every second year. CONCLUSIONS: Rotavirus remains the primary cause of severe gastroenteritis in children in Norway. The unique population-based registers, in combination with an established rotavirus surveillance platform, provide a well-suited setting to evaluate the impact of rotavirus vaccination.

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

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

Dynamic modeling of cost-effectiveness of rotavirus vaccination, Kazakhstan.

The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at

Economic burden of rotavirus disease in children under 5 years in Kazakhstan.

BACKGROUND: We aimed to estimate the societal costs of rotavirus cases among children less than 5 years in Kazakhstan, an upper-middle income country in Central Asia. METHODS: Data on medical, non-medical and indirect costs were collected for 190 patients less than 5 years, hospitalized with severe diarrhea in 2009 in two pediatric hospitals. Data on resource use for moderate and mild diarrhea cases were obtained from published sources. A probabilistic sensitivity analysis was performed to explore uncertainty in cost estimates. RESULTS: Approximately 4,000 severe, 30,700 moderate, and 122,900 mild rotavirus cases were estimated annually in children <5 years old. The mean societal cost of a severe, moderate and mild rotavirus case was estimated at US$ 454, 82, and 21, respectively. The total annual cost of rotavirus disease was $37.53 million or on average $107.36 for a child under 5 years old in Kazakhstan. Ninety-four percent of total costs (35.13 million) are indirect costs (productivity losses) from fatal cases and parents' job absenteeism, while direct medical costs account for 2.04 million (5.4%), and direct non-medical for 0.46 million (1.2%). CONCLUSIONS: Rotavirus-associated diarrhea represents a significant economic burden in Kazakhstan, largely due to indirect costs. The costs of rotavirus infections should be considered when planning further preventive actions, including the introduction of rotavirus vaccination.

Rotavirus infection in hospitalized children and estimates of disease burden in Kyrgyzstan, 2005-2007.

To estimate the rotavirus-associated burden in Kyrgyzstan, we conducted hospital surveillance among children <5 years old with diarrhoea during 2005-2007. Of 3756 children hospitalized with diarrhoea, 26% had rotavirus detected in stool samples by an enzyme immunoassay. The virus genotype G1P[8] was identified in 60% of 190 characterized samples from 2005 to 2006. The estimated risk for rotavirus hospitalization by age 5 years was 1 in 28 children. One quarter of all gastroenteritis hospitalizations in children <5 years old in Kyrgyzstan may be attributable to rotavirus. Rotavirus vaccination could be an important health intervention to reduce the burden of rotavirus gastroenteritis.

Rotavirus gastroenteritis in uzbekistan: implications for vaccine policy in central Asia.

BACKGROUND: To determine the value of rotavirus vaccines in Central Asia, we conducted surveillance of rotavirus in Uzbekistan, the country with the largest birth cohort in the region. Uzbekistan is eligible for international funds to introduce new vaccines. METHODS: We screened stool samples for rotavirus that were collected from children aged <5 years with gastroenteritis in 2 hospitals during 2005-2006. Using surveillance information and other data, we estimated national numbers of rotavirus-associated events per year. RESULTS: Of 3537 enrolled children, 1046 (30%) had rotavirus detected in stool specimens. Children aged <2 years accounted for 841 (80%) of all rotavirus infections. The G1P[8] genotype was identified in 27 (52%) of 52 typed samples collected in 2005. Rotavirus is estimated to cause 1174-1857 deaths and 6394-6558 hospitalizations among children aged <5 years annually. The cumulative risk of hospitalization for rotavirus by age 5 years is 1 in 94-96 children, and the risk of rotavirus-related death is 1 in 330-524 children. CONCLUSIONS: One-third of all hospitalizations for gastroenteritis and almost 5% of all deaths among children aged <5 years in Uzbekistan may be attributable to rotavirus. Introduction of rotavirus vaccines into the national immunization program at the current subsidized prices could be cost-effective.

Costs of diarrheal disease and the cost-effectiveness of a rotavirus vaccination program in kyrgyzstan.

INTRODUCTION: We examined the cost-effectiveness of a rotavirus immunization program in Kyrgyzstan, a country eligible for vaccine funding from the GAVI Alliance. METHODS: We estimated the burden of rotavirus disease and its economic consequences by using national and international data. A cost-effectiveness analysis was conducted from government and societal perspectives, along with a range of 1-way sensitivity analyses. RESULTS: Rotavirus-related hospitalizations and outpatient visits cost US$580,864 annually, of which $421,658 (73%) is direct medical costs and $159,206 (27%) is nonmedical and indirect costs. With 95% coverage, vaccination could prevent 75% of rotavirus-related hospitalizations and deaths and 56% of outpatient visits and could avert $386,193 (66%) in total costs annually. The medical break-even price at which averted direct medical costs equal vaccination costs is $0.65/dose; the societal break-even price is $1.14/dose for a 2-dose regimen. At the current GAVI Alliance-subsidized vaccine price of $0.60/course, rotavirus vaccination is cost-saving for the government. Vaccination is cost-effective at a vaccine price $9.41/dose, according to the cost-effectiveness standard set by the 2002 World Health Report. CONCLUSIONS: Addition of rotavirus vaccines to childhood immunization in Kyrgyzstan could substantially reduce disease burden and associated costs. Vaccination would be cost-effective from the national perspective at a vaccine price $9.41 per dose.