Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review.

BACKGROUND: The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries. METHODS: We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000-2010 for each country, region and globally. RESULTS: The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4-61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46-195) in the Western Pacific, excluding China, to 116 (95% CI: 56-235) and 121 (95% CI: 31-238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000-80,000) and SE Asia (49,000, 95% CI: 11,000-97,000). In 2010, 105,000 (95% CI: 54,000-158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000-169,000) in 1996. CONCLUSIONS: Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.

Systematic Review of the Manifestations of Congenital Rubella Syndrome in Infants and Characterization of Disability-Adjusted Life Years (DALYs).

Congenital rubella syndrome (CRS) continues to cause disability among unvaccinated populations in countries with no or insufficient rubella vaccine coverage to prevent transmission. We systematically reviewed the literature on birth outcomes associated with CRS to estimate the duration, severity, and frequency of combinations of morbidities. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English with primary data on the frequency of CRS manifestations for ≥20 cases and identified 65 studies representing 66 study populations that met our inclusion criteria. We abstracted available data on CRS cases with one or more hearing, heart, and/or eye defect following maternal rubella infection during the period of 0-20 weeks since the last menstrual period. We assessed the quality and weight of the available evidence using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Most of the evidence originates from studies in developed countries of cohorts of infants identified with CRS in the 1960s and 1970s, prior to the development of standardized definitions for CRS and widespread use of vaccine. We developed estimates of undiscounted disability-adjusted life years (DALYs) lost per CRS case for countries of different income levels. The estimates ranged from approximately 19 to 39 for high-income countries assuming optimal treatment and from approximately 29 to 39 DALYs lost per CRS case in low- and lower- middle-income countries assuming minimal treatment, with the lower bound based on 2010 general global burden of disease disability weights and the upper bound based on 1990 age-specific and treatment-specific global burden of disease disability weights. Policymakers and analysts should appreciate the significant burden of disability caused by CRS as they evaluate opportunities to manage rubella.

Assessment of the 2010 global measles mortality reduction goal: results from a model of surveillance data.

BACKGROUND: In 2008 all WHO member states endorsed a target of 90% reduction in measles mortality by 2010 over 2000 levels. We developed a model to estimate progress made towards this goal. METHODS: We constructed a state-space model with population and immunisation coverage estimates and reported surveillance data to estimate annual national measles cases, distributed across age classes. We estimated deaths by applying age-specific and country-specific case-fatality ratios to estimated cases in each age-country class. FINDINGS: Estimated global measles mortality decreased 74% from 535,300 deaths (95% CI 347,200-976,400) in 2000 to 139,300 (71,200-447,800) in 2010. Measles mortality was reduced by more than three-quarters in all WHO regions except the WHO southeast Asia region. India accounted for 47% of estimated measles mortality in 2010, and the WHO African region accounted for 36%. INTERPRETATION: Despite rapid progress in measles control from 2000 to 2007, delayed implementation of accelerated disease control in India and continued outbreaks in Africa stalled momentum towards the 2010 global measles mortality reduction goal. Intensified control measures and renewed political and financial commitment are needed to achieve mortality reduction targets and lay the foundation for future global eradication of measles. FUNDING: US Centers for Disease Control and Prevention (PMS 5U66/IP000161).

The cost-effectiveness of supplementary immunization activities for measles: a stochastic model for Uganda.

Supplemental Immunization Activities (SIAs) have become an important adjunct to measles control efforts in countries that endeavor to achieve higher levels of population immunity than can be achieved in a growing routine immunization system. Because SIAs are often supported with funds that have alternative uses, decision makers need to know how cost-effective they are compared with other options. This study integrated a dynamic stochastic model of measles transmission in Uganda (2010-2050) with a cost model to compare a strategy of maintaining Uganda's current (2008) levels of the first dose of routine measles-containing vaccine (MCV1) coverage at 68% with SIAs with a strategy using the same levels of MCV1 coverage without SIAs. The stochastic model was fitted with parameters drawn from district-level measles case reports from Uganda, and the cost model was fitted to administrative data from the Ugandan Expanded Program on Immunization and from the literature. A discount rate of 0.03, time horizon of 2010-2050, and a societal perspective on costs were assumed. Costs expressed in US dollars (2010) included vaccination costs, disease treatment costs including lost productivity of mothers, as well as costs of outbreaks and surveillance. The model estimated that adding on triennial SIAs that covered 95% of children aged 12-59 months to a system that achieved routine coverage rates of 68% would have an incremental cost-effectiveness ratio (ICER) of $1.50 ($US 2010) per disability-adjusted life year averted. The ICER was somewhat higher if the discount rate was set at either 0 or 0.06. The addition of SIAs was found to make outbreaks less frequent and lower in magnitude. The benefit was reduced if routine coverage rates were higher. This cost-effectiveness ratio compares favorably to that of other commonly accepted public health interventions in sub-Saharan Africa.

Assessing the cost-effectiveness of measles elimination in Uganda: local impact of a global eradication program.

BACKGROUND: Measles control has succeeded worldwide, and many countries have substantially reduced incidence and mortality. This has led to consideration of the feasibility of measles elimination in Uganda within the context of global eradication. Before an elimination program is initiated, it is important to consider its potential economic impact, including its cost-effectiveness. METHODS: Incremental cost-effectiveness ratios (ICERs) were estimated for measles mortality reduction and measles elimination in Uganda. A dynamic age-structured compartmental model of measles transmission was used to simulate scenarios and estimate health outcomes and costs. The main outcome measures were costs, measles cases, measles deaths, disability-adjusted life-years (DALYs), and ICERs measured as cost per DALY averted through either the year 2030 or 2050. RESULTS: Measles elimination by 2020 averted 130,232 measles cases, 3520 measles deaths, and 106,330 DALYs through the year 2030, compared with the next best scenario (95% mortality reduction by 2015), and it was the most cost-effective strategy, with ICERs of $556 per DALY averted (2030 time horizon) and $284 per DALY averted (2050 time horizon). CONCLUSIONS: Measles elimination in Uganda, as part of a global eradication program, is projected to be highly cost-effective and should be considered among the available policy options for dealing with the disease.

Strategic planning for measles control: using data to inform optimal vaccination strategies.

BACKGROUND: In response to repeated requests for assistance in evaluating the health benefit and cost implications of adjustments to national measles immunization strategies, the World Health Organization (WHO) has developed the Measles Strategic Planning (MSP) tool to harness routinely available data to estimate effectiveness and cost effectiveness of vaccination strategies. METHOD: The MSP tool estimates measles incidence and mortality through a country-specific cohort model, using a probability of infection dependent on population immunity levels. This method approximates measles transmission dynamics without requiring detailed data that would prohibit use in low- and middle-income countries. Coupled with cost data, the tool estimates incremental costs and cost effectiveness of user-defined vaccination strategies over 5-10 year planning periods. RESULTS: The MSP tool produces valid estimates of measles incidence in settings with low to moderate vaccination coverage. Early adopters report that the tool facilitates decision making by minimizing the amount of time required to assess the impact of vaccination strategies on population immunity. CONCLUSIONS: By clearly illustrating what vaccination strategies can effectively protect against measles at the least cost to immunization programs, the MSP tool supports evidence-based decision making for effective and comprehensive measles control.

Global eradication of measles: an epidemiologic and economic evaluation.

BACKGROUND: Measles remains an important cause of morbidity and mortality in children in developing countries. Due to the success of the measles mortality reduction and elimination efforts thus far, the WHO has raised the question of whether global eradication of measles is economically feasible. METHODS: The cost-effectiveness of various measles mortality reduction and eradication scenarios was evaluated vis-à-vis the current mortality reduction goal in six countries and globally. Data collection on costs of measles vaccination were conducted in six countries in four regions: Bangladesh, Brazil, Colombia, Ethiopia, Tajikistan, and Uganda. The number of measles cases and deaths were projected from 2010 to 2050 using a dynamic, age-structured compartmental model. The incremental cost-effectiveness ratios were then calculated for each scenario vis a vis the baseline. RESULTS: Measles eradication by 2020 was the found to be the most cost-effective scenario, both in the six countries and globally. Eradicating measles by 2020 is projected to cost an additional discounted $7.8 billion and avert a discounted 346 million DALYs between 2010 and 2050. CONCLUSIONS: In conclusion, the study found that, compared to the baseline, reaching measles eradication by 2020 would be the most cost-effective measles mortality reduction scenario, both for the six countries and on a global basis.