The Costs and Valuation of Health Impacts of Measles and Rubella Risk Management Policies.

National and global health policymakers require good information about the costs and benefits of their investments in measles and rubella immunization programs. Building on our review of the existing measles and rubella health economics literature, we develop inputs for use in regional and global models of the expected future benefits and costs of vaccination, treatment, surveillance, and other global coordination activities. Given diversity in the world and limited data, we characterize the costs for countries according to the 2013 World Bank income levels using 2013 U.S. dollars (2013$US). We estimate that routine immunization and supplemental immunization activities will cost governments and donors over 2013$US 2.3 billion per year for the foreseeable future, with high-income countries accounting for 55% of the costs, to vaccinate global birth cohorts of approximately 134 million surviving infants and to protect the global population of over 7 billion people. We find significantly higher costs and health consequences of measles or rubella disease than with vaccine use, with the expected disability-adjusted life year (DALY) loss for case of disease generally at least 100 times the loss per vaccine dose. To support estimates of the economic benefits of investments in measles and/or rubella elimination or control, we characterize the probabilities of various sequelae of measles and rubella infections and vaccine adverse events, the DALY inputs for health outcomes, and the associated treatment costs. Managing measles and rubella to achieve the existing and future regional measles and rubella goals and the objectives of the Global Vaccine Action Plan will require an ongoing commitment of financial resources that will prevent adverse health outcomes and save the associated treatment costs.

Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies.

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

Health economics of rubella: a systematic review to assess the value of rubella vaccination.

BACKGROUND: Most cases of rubella and congenital rubella syndrome (CRS) occur in low- and middle-income countries. The World Health Organization (WHO) has recently recommended that countries accelerate the uptake of rubella vaccination and the GAVI Alliance is now supporting large scale measles-rubella vaccination campaigns. We performed a review of health economic evaluations of rubella and CRS to identify gaps in the evidence base and suggest possible areas of future research to support the planned global expansion of rubella vaccination and efforts towards potential rubella elimination and eradication. METHODS: We performed a systematic search of on-line databases and identified articles published between 1970 and 2012 on costs of rubella and CRS treatment and the costs, cost-effectiveness or cost-benefit of rubella vaccination. We reviewed the studies and categorized them by the income level of the countries in which they were performed, study design, and research question answered. We analyzed their methodology, data sources, and other details. We used these data to identify gaps in the evidence and to suggest possible future areas of scientific study. RESULTS: We identified 27 studies: 11 cost analyses, 11 cost-benefit analyses, 4 cost-effectiveness analyses, and 1 cost-utility analysis. Of these, 20 studies were conducted in high-income countries, 5 in upper-middle income countries and two in lower-middle income countries. We did not find any studies conducted in low-income countries. CRS was estimated to cost (in 2012 US$) between $4,200 and $57,000 per case annually in middle-income countries and up to $140,000 over a lifetime in high-income countries. Rubella vaccination programs, including the vaccination of health workers, children, and women had favorable cost-effectiveness, cost-utility, or cost-benefit ratios in high- and middle-income countries. CONCLUSIONS: Treatment of CRS is costly and rubella vaccination programs are highly cost-effective. However, in order for research to support the global expansion of rubella vaccination and the drive towards rubella elimination and eradication, additional studies are required in low-income countries, to tackle methodological limitations, and to determine the most cost-effective programmatic strategies for increased rubella vaccine coverage.

[Effectiveness, population-level effects, and heath economics of measles and rubella vaccination]. / Effektivität, Populationseffekte und Gesundheitsökonomie der Impfungen gegen Masern und Röteln.

Vaccination against measles and rubella has been included in national immunization programs worldwide for several decades. In this article, we present the evidence related to the effectiveness of measles and rubella vaccination based on published systematic reviews, and we describe the epidemiological and health economic effects of vaccination at a population level. Several observational studies demonstrate the high effectiveness (> 90 %) of both measles and rubella vaccination. The global measles mortality reduction and the dramatic decrease in rubella and measles incidences after introduction of routine immunization contribute to the very high quality of evidence. The countries of the Americas have proved that it is feasible to eliminate measles and rubella by strengthening infant immunization through routine vaccination services and by conducting supplemental immunization activities in other childhood age groups so as to close immunity gaps. An economic evaluation of measles and rubella vaccination specifically for the healthcare system in Germany does not exist. However, we conducted a systematic review and identified 11 health-economic studies from other industrialized countries and one for a hypothetical industrialized country. Results indicate that vaccination against measles and rubella had either a cost-effective or even a cost-saving potential, which could be assumed with some limitations also for the German setting. In conclusion, there is compelling evidence that the available vaccines are very effective and that measles and rubella elimination is feasible if adequate vaccination strategies are implemented. In Germany, catch-up vaccination programs are urgently needed for children, adolescents, and young adults specifically in the western federal states.

Advocacy and resource mobilization for rubella elimination in Guatemala.

This review describes the advocacy efforts to mobilize resources for the campaign to vaccinate men and women aged 9-39 years, with a goal of eliminating rubella and congenital rubella syndrome in Guatemala. The country's investment in health has been historically low (0.9% of gross domestic product), and there has been a wide gap between the availability of economic resources and the need for economic resources for the immunization campaign. The review contains a summary of the investment made, the results of advocacy and resource mobilization, the vaccination coverage attained, and the campaign's impact on the disease.

How much does it cost to measure immunity? A costing analysis of a measles and rubella serosurvey in southern Zambia.

BACKGROUND: Serosurveys are a valuable surveillance tool because they provide a more direct measure of population immunity to infectious diseases, such as measles and rubella, than vaccination coverage estimates. However, there is concern that serological surveys are costly. We adapted a framework to capture the costs associated with conducting a serosurvey in Zambia. METHODS: We costed a nested serosurvey in Southern Province, Zambia that collected dried blood spots from household residents in a post-campaign vaccine coverage survey. The financial costs were estimated using an ingredients-based costing approach. Inputs included personnel, transportation, field consumable items, social mobilization, laboratory supplies, and capital items, and were classified by serosurvey function (survey preparation, data collection, biospecimen collection, laboratory testing, and coordination). Inputs were stratified by whether they were applicable to surveys in general or attributable specifically to serosurveys. Finally, we calculated the average cost per cluster and participant. RESULTS: We estimated the total nested serosurvey cost was US $68,558 to collect dried blood spots from 658 participants in one province in Zambia. A breakdown of the cost by serosurvey phase showed data collection accounted for almost one third of the total serosurvey cost (32%), followed by survey preparation (25%) and biospecimen collection (20%). Analysis by input categories indicated personnel costs were the largest contributing input to overall serosurvey costs (51%), transportation was second (23%), and field consumables were third (9%). By combining the serosurvey with a vaccination coverage survey, there was a savings of $43,957. We estimated it cost $4,285 per average cluster and $104 per average participant sampled. CONCLUSIONS: Adding serological specimen collection to a planned vaccination coverage survey provided a more direct measurement of population immunity among a wide age group but increased the cost by approximately one-third. Future serosurveys could consider ways to leverage existing surveys conducted for other purposes to minimize costs.

Assessing the Effectiveness and Cost-Benefit of Test-and-Vaccinate Policy for Supplementary Vaccination against Rubella with Limited Doses.

Elevating herd immunity level against rubella is essential to prevent congenital rubella syndrome (CRS). Insufficient vaccination coverage left susceptible pockets among adults in Japan, and the outbreak of rubella from 2012 to 2013 resulted in 45 observed CRS cases. Given a limited stock of rubella-containing vaccine (RCV) available, the Japanese government recommended healthcare providers to prioritize vaccination to those confirmed with low level of immunity, or to those likely to transmit to pregnant women. Although a test-and-vaccinate policy could potentially help reduce the use of the limited stockpile of vaccines, by selectively elevating herd immunity, the cost of serological testing is generally high and comparable to the vaccine itself. Here, we aimed to examine whether random vaccination would be more cost-beneficial than the test-and-vaccinate strategy. A mathematical model was employed to evaluate the vaccination policy implemented in 2012-2013, quantifying the benefit-to-cost ratio to achieve herd immunity. The modelling exercise demonstrated that, while the test-and-vaccinate strategy can efficiently achieve herd immunity when stockpiles of RCV are limited, random vaccination would be a more cost-beneficial strategy. As long as the herd immunity acts as the goal of vaccination, our findings apply to future supplementary immunization strategy.

Sociodemographic and economic characteristics of susceptibility to rubella among women preparing for pregnancy in rural China.

OBJECTIVES: Infection with rubella virus during pregnancy can result in congenital defects and adverse pregnancy outcomes. The risk of rubella infection is greatly determined by the level of rubella antibodies in the serum. A survey of rubella antibody seronegativity rates was conducted in 780 000 women in rural China who were planning a pregnancy, in order to evaluate the herd susceptibility in different age groups and by high, middle, and low GDP per capita regions. METHODS: In order to evaluate the herd susceptibility to rubella, a nationwide population-based study of rural Chinese women who were planning to have a baby and who were aged 21-49 years was instigated. As a part of the National Free Pre-conception Health Examination Project covering 29 provinces in 2012, a physical check-up program was provided to women who planned to become pregnant within the next 6 months. All medical data were from serological samples tested by ELISA, and the participants' immunity status was categorized based on levels of rubella antibodies. Economic data were also collected to explore the association between herd susceptibility and socioeconomic characteristics in the women of childbearing age. RESULTS: A total 264 306 of 782 293 recruited women preparing for pregnancy tested susceptible to rubella (33.79%). The seronegativity rate in women with a history of vaccination was significantly lower than that in women who had not received the vaccination or did not know their vaccination history (23.76%, 33.70%, and 35.68%, respectively). The seronegativity rates were 26.89%, 37.86%, and 32.61% in high, middle, and low GDP per capita areas, respectively. After stratified analysis and adjusting for other factors by multiple logistic regression, the lower seronegativity rates in women in high GDP per capita regions compared to women in middle and low GDP per capita regions remained in the different age groups and subgroups of immunization history. CONCLUSIONS: There is a clear difference in rubella-specific susceptibility among rural women preparing for pregnancy of different sociodemographic and economic backgrounds. The number of rubella-susceptible rural women preparing for pregnancy, especially in relatively low GDP per capita regions in China, was high. Offering rubella vaccination to women who are rubella-susceptible and who plan to become pregnant should become one of the priorities in the field of public health work in China.

Impact of State Public Health Spending on Disease Incidence in the United States from 1980 to 2009.

OBJECTIVE: To understand the relationship between state-level spending by public health departments and the incidence of three vaccine preventable diseases (VPDs): mumps, pertussis, and rubella in the United States from 1980 to 2009. DATA SOURCES: This study uses state-level public health spending data from The Census Bureau and annual mumps, pertussis, and rubella incidence counts from the University of Pittsburgh's project Tycho. STUDY DESIGN: Ordinary least squares (OLS), fixed effects, and random effects regression models were tested, with results indicating that a fixed effects model would be most appropriate model for this analysis. PRINCIPAL FINDINGS: Model output suggests a statistically significant, negative relationship between public health spending and mumps and rubella incidence. Lagging outcome variables indicate that public health spending actually has the greatest impact on VPD incidence in subsequent years, rather than the year in which the spending occurred. Results were robust to models with lagged spending variables, national time trends, and state time trends, as well as models with and without Medicaid and hospital spending. CONCLUSION: Our analysis indicates that there is evidence of a significant, negative relationship between a state's public health spending and the incidence of two VPDs, mumps and rubella, in the United States.

[Economic evaluation on different two-dose-vaccination-strategies related to Measles, Mumps and Rubella Combined Attenuated Live Vaccine].

OBJECTIVE: To evaluate the economic effect of Measles, Mumps and Rubella Combined Attenuated Live Vaccine (MMR) under different two-dose vaccination programs. METHODS: A hypothetical birth cohort of 750 000 infants over their lifetime, was followed up from birth through death in Zhejiang province. The current MMR vaccination strategie would include three different ones: 1) Childlern were vaccinated with Measles-Rubella Combined Attenuated Live Vaccine and MMR, respectively at the age of 8 months and 18 months. 2) Children receive MMR at 8 months and 18 months, 3) Strategy 1 plus an additional vaccination of MMR at 4 years of age. Incremental cost-effectiveness ratio (ICER), incremental cost-benefit ratio (ICBR) and incremental net benefit (INB) were applied to calculate the health economic difference for Strategy 2 and Strategy 3 as compared to Strategy 1. Univariate sensitivity analysis was used to assess the robustness of results with main parameters, including the rate of immunization coverage, effectiveness of the vaccines, incidence and burdens of the related diseases, cost of vaccines and the vaccination program itself. RESULTS: ICER, ICBR and INB for Strategy 2 and Strategy 3 appeared as 2 012.51∶1 RMB Yuan per case and 4 238.72∶1 RMB Yuan per case, 1∶3.14 and 1∶1.58, 21 277 800 RMB Yuan and 9 276 500 RMB Yuan, respectively. Only slight changes (<20%) were found under the univariate sensitivity analysis, with varied values on main parameters. CONCLUSION: Based on the current national immunization program, infants vaccinated with MMR at 8 months of age, generated more health economic effects than the Strategy 3.

Rubella in Panama: still a problem.

In 1986 there were 3795 cases of acquired rubella reported in the Republic of Panama (177/100,000 population) of which 1550 were from the Metropolitan Region (261/100,000 population). Fifty-four neonates (218/100,000 of those born alive), born predominantly in two medical centers within the capital, were identified with compatible or confirmed congenital rubella manifesting as cardiopathies and neurologic defects in 68.5%; low birth weight in 61%; ocular defects in 48%; muscular tone alterations and psychomotor retardation in 35 and 33%, respectively; and hearing loss and purpura in 29.6%. It is estimated that the annual direct cost of care for these 54 patients would be close to $123,730, and this confirms the high cost of continuing care compared with the use of a safe, economical and efficient vaccine.

[Comparison of cost and benefits of each model for rubella immunization in Japan].

MMR (measles-mumps-rubella) immunization in Japan was suspended in 1993 due to the high incidence of mumps meningitis as a complication. As a result, immunization coverage for rubella still remains at the 50-60% level in Japan. One way to increase the coverage rate is to increase the frequency of immunization. We calculated the predicted positivity rate of the antibody and cost and the benefits is three models of double vaccination, i.e., vaccination twice. The first model consists of simply two identical vaccinations. The second model consists of two vaccinations with mass vaccination at school for the second immunization. The third model consists of two vaccinations with screening of the urinary antibody for rubella in the second immunization. To calculate the predicted values we used coefficients from Ibara City. The predicted positivity rates and cost increases ranged from 60% to 90% and from 7.3 billion to 12.8 billion yen from the first to third models, respectively. Screening for the urinary antibody should be much cheaper than the presumed price because more than a million subjects will be screened. Since it would cost less than half the price, the third model should be best for the positivity rate of the antibody and cost and benefits. Therefore, we think that third model is the best correction until MMR immunization can be reintroduced.

[Health and economic benefits of mandatory regular vaccination in Slovakia. IV. Measles, rubella and mumps]. / Zdravotná a ekonomická návratnost' povinného pravidelného ockovania v Slovenskej republike. IV. Morbilli, rubeola a parotitis.

The epidemiological situation as regards measles, rubella and mumps in Slovakia before vaccination and after its introduction in 1996, is analysed. On the basis of model costs of treatment of these diseases before vaccination and costs of treatment in 1996 including costs of vaccination, the authors calculated the total saved costs (549.7 mil. Sk), cost-effectiveness (10,680 Sk), as well as the cost-benefit.

Enabling implementation of the Global Vaccine Action Plan: developing investment cases to achieve targets for measles and rubella prevention.

Global prevention and control of infectious diseases requires significant investment of financial and human resources and well-functioning leadership and management structures. The reality of competing demands for limited resources leads to trade-offs and questions about the relative value of specific investments. Developing investment cases can help to provide stakeholders with information about the benefits, costs, and risks associated with available options, including examination of social, political, governance, and ethical issues. We describe the process of developing investment cases for globally coordinated management of action plans for measles and rubella as tools for enabling the implementation of the Global Vaccine Action Plan (GVAP). We focus on considerations related to the timing of efforts to achieve measles and rubella goals independently and within the context of ongoing polio eradication efforts, other immunization priorities, and other efforts to control communicable diseases or child survival initiatives. Our analysis suggests that the interactions between the availability and sustainability of financial support, sufficient supplies of vaccines, capacity of vaccine delivery systems, and commitments at all levels will impact the feasibility and timing of achieving national, regional, and global goals. The timing of investments and achievements will determine the net financial and health benefits obtained. The methodology, framing, and assumptions used to characterize net benefits and uncertainties in the investment cases will impact estimates and perceptions about the value of prevention achieved overall by the GVAP. We suggest that appropriately valuing the benefits of investments of measles and rubella prevention will require the use of integrated dynamic disease, economic, risk, and decision analytic models in combination with consideration of qualitative factors, and that synthesizing information in the form of investment cases may help stakeholders manage expectations as they chart the course ahead and navigate the decade of vaccines.

Economic analysis of measles elimination program in the Republic of Korea, 2001: a cost benefit analysis study.

BACKGROUND: In this study, we modeled the cost benefit analysis for three different measles vaccination strategies based upon three different measles-containing vaccines in Korea, 2001. We employed an economic analysis model using vaccination coverage data and population-based measles surveillance data, along with available estimates of the costs for the different strategies. In addition, we have included analysis on benefit of reduction of complication by mumps and rubella. METHODS: We evaluated four different strategies: strategy 1, keep-up program with a second dose measles-mumps-rubella (MMR) vaccine at 4-6 years without catch-up campaign; strategy 2, additional catch-up campaign with measles (M) vaccine; strategy 3, catch-up campaign with measles-rubella (MR) vaccine; and strategy 4, catch-up campaign with MMR vaccine. The cost of vaccination included cost for vaccines, vaccination practices and other administrative expenses. The direct benefit of estimated using data from National Health Insurance Company, a government-operated system that reimburses all medical costs spent on designated illness in Korea. RESULTS: With the routine one-dose MMR vaccination program, we estimated a baseline of 178,560 measles cases over the 20 years; when the catch-up campaign with M, MR or MMR vaccines was conducted, we estimated the measles cases would decrease to 5936 cases. Among all strategies, the two-dose MMR keep-up program with MR catch-up campaign showed the highest benefit-cost ratio of 1.27 with a net benefit of 51.6 billion KRW. CONCLUSION: Across different vaccination strategies, our finding suggest that MR catch-up campaign in conjunction with two-dose MMR keep-up program was the most appropriate option in terms of economic costs and public health effects associated with measles elimination strategy in Korea.

Research priorities for global measles and rubella control and eradication.

In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibility of measles eradication concluded that (1) measles can and should be eradicated, (2) eradication by 2020 is feasible if measurable progress is made toward existing 2015 measles mortality reduction targets, (3) measles eradication activities should occur in the context of strengthening routine immunization services, and (4) measles eradication activities should be used to accelerate control and elimination of rubella and congenital rubella syndrome (CRS). The expert advisory panel also emphasized the critical role of research and innovation in any disease control or eradication program. In May 2011, a meeting was held to identify and prioritize research priorities to support measles and rubella/CRS control and potential eradication activities. This summary presents the questions identified by the meeting participants and their relative priority within the following categories: (1) measles epidemiology, (2) vaccine development and alternative vaccine delivery, (3) surveillance and laboratory methods, (4) immunization strategies, (5) mathematical modeling and economic analyses, and (6) rubella/CRS control and elimination.

[Epidemiology of hospitalizations caused by rubella in the general population in Spain (1997-2006)]. / Epidemiología de las hospitalizaciones causadas por rubéola en la población general en España (1997-2006).

BACKGROUND: Rubella is benign in children, but in pregnant women it can produce Congenital Rubella Syndrome (CRS) with severe consequences for the foetus. In spite of vaccination coverage in Spain being above 95%, isolated cases and outbreaks continue to occur. The aim of this study is to estimate the incidence of hospitalisations due to rubella in Spain (1997-2006). METHODS: Utilising the basic minimum dataset (National System of Epidemiological Surveillance) we calculated: rate of hospitalisation, average stay and cost. RESULTS: There were 267 hospitalisations, amongst them 144 due to rubella during pregnancy, 1 due to CRS and 8 due to encephalomyelitis. The overall rate of hospitalisation was 0.065 per 105 inhabitants (IC95%=0.0649-0.0654). The average stay was 3 days. The average cost of a hospitalisation was 2,082 euros, and if complicated by encephalomyelitis it rose to 8.191 euros. CONCLUSION: There continue to be hospitalisations due to rubella, basically due to problems in gestation and to complications in the existing susceptible population group.

Avaliação econômica da rubéola e de estratégia de controle em situação de surto em Fortaleza (Ceará), Brasil / Economic evaluation of rubella and control strategies during an outbreak in Fortaleza (Ceará), Brazil

Em 2007, o país vivenciou uma epidemia de rubéola, com 8.683 casos confirmados. Realizou-se uma avaliação econômica da rubéola e de uma estratégia de controle em surto ocorrido em Fortaleza em 2007. Dois estudos de avaliação econômica foram conduzidos. O primeiro foi uma análise de custo-enfermidade dos casos confirmados, e o segundo, uma análise de custo-efetividade entre duas estratégias de intervenção relacionadas à rubéola. Comparou-se o custo-efetividade da vacinação emergencial (i.e., operação limpeza) com o prestar assistência de saúde aos casos confirmados de rubéola. O estudo considerou as perspectivas econômicas do governo brasileiro por intermédio do Ministério da Saúde e também da sociedade, em que custos diretos e indiretos da prevenção e do tratamento da rubéola foram incluídos nas análises. O custo-enfermidade total dos 21 casos de rubéola foi de R$ 2.008,54 (médio R$ 95,65) e R$ 14.009,20 (médio R$ 667,10), desde as perspectivas do governo e sociedade, respectivamente. Os valores estimados para o custo-enfermidade total no país foram de aproximadamente R$ 831 mil para o governo e R$ 5.8 milhões para a sociedade. A análise de custo-efetividade incremental mostrou que a operação limpeza foi considerada dominante sobre a assistência aos casos de rubéola, produzindo maiores benefícios (i.e., redução dos casos de rubéola) a um menor custo. Esses resultados mostraram-se robustos em uma série de análises de sensibilidade. A análise de custo-efetividade nos mostrou que a alternativa de vacinação emergencial apresentou uma melhor relação de custo-efetividade e resultou em uma economia de recursos em ambas as perspectivas adotadas.