Combining serological and contact data to derive target immunity levels for achieving and maintaining measles elimination.

BACKGROUND: Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90-95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns. METHODS: We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination. RESULTS: We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5-9-year-olds than established previously. CONCLUSIONS: The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5-9-year-olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.

Development of a District-Level Programmatic Assessment Tool for Risk of Measles Virus Transmission.

All six World Health Organization (WHO) regions have now set goals for measles elimination by or before 2020. To prioritize measles elimination efforts and use available resources efficiently, there is a need to identify at-risk areas that are offtrack from meeting performance targets and require strengthening of programmatic efforts. This article describes the development of a WHO measles programmatic risk assessment tool to be used for monitoring, guiding, and sustaining measles elimination efforts at the subnational level. We outline the tool development process; the tool specifications and requirements for data inputs; the framework of risk categories, indicators, and scoring; and the risk category assignment. Overall risk was assessed as a function of indicator scores that fall into four main categories: population immunity, surveillance quality, program performance, and threat assessment. On the basis of the overall score, the tool assigns each district a risk of either low, medium, high, or very high. The cut-off criteria for the risk assignment categories were based on the distribution of scores from all possible combinations of individual indicator cutoffs. The results may be used for advocacy to communicate risk to policymakers, mobilize resources for corrective actions, manage population immunity, and prioritize programmatic activities. Ongoing evaluation of indicators will be needed to evaluate programmatic performance and plan risk mitigation activities effectively. The availability of a comprehensive tool that can identify at-risk districts will enhance efforts to prioritize resources and implement strategies for achieving the Global Vaccine Action Plan goals for measles elimination.

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.

Measles - The epidemiology of elimination.

Tremendous progress has been made globally to reduce the contribution of measles to the burden of childhood deaths and measles cases have dramatically decreased with increased two dose measles-containing vaccine coverage. As a result the Global Vaccine Action Plan, endorsed by the World Health Assembly, has targeted measles elimination in at least five of the six World Health Organisation Regions by 2020. This is an ambitious goal, since measles control requires the highest immunisation coverage of any vaccine preventable disease, which means that the health system must be able to reach every community. Further, while measles remains endemic in any country, importations will result in local transmission and outbreaks in countries and Regions that have interrupted local endemic measles circulation. One of the lines of evidence that countries and Regions must address to confirm measles elimination is a detailed description of measles epidemiology over an extended period. This information is incredibly valuable as predictable epidemiological patterns emerge as measles elimination is approached and achieved. These critical features, including the source, size and duration of outbreaks, the seasonality and age-distribution of cases, genotyping pointers and effective reproduction rate estimates, are discussed with illustrative examples from the Region of the Americas, which eliminated measles in 2002, and the Western Pacific Region, which has established a Regional Verification Commission to review progress towards elimination in all member countries.

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.

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.

Comparing measles with previous eradication programs: enabling and constraining factors.

BACKGROUND: Five major disease eradication initiatives were initiated during the second half of the 20th century. The enabling and constraining factors-political, social, economic, and other-for these previous and current eradication programs can inform decision making regarding a proposed measles eradication initiative. METHODS: We reviewed the literature on the yaws, malaria, smallpox, guinea worm, and polio eradication programs and compared enabling and constraining factors for each of these programs with the same factors as they relate to a possible measles eradication initiative. RESULTS: A potential measles eradication program would enjoy distinct advantages in comparison with earlier eradication programs, including strong political and societal support, economic analyses demonstrating a high level of cost-effectiveness, and a rigorous upfront process, compared with previous eradication initiatives, that has validated the feasibility of achieving measles eradication. However, increasing population density, urbanization, and wars/civil conflicts will pose serious challenges. CONCLUSIONS: Measles eradication will be very challenging but probably not as difficult to achieve as polio eradication. Measles eradication should be undertaken only if the commitments and resources will be adequate to meet the political, social, economic, and technical challenges.

Has the 2005 measles mortality reduction goal been achieved? A natural history modelling study.

BACKGROUND: In 2002, the UN General Assembly Special Session on Children adopted a goal to reduce deaths owing to measles by half by the end of 2005, compared with 1999 estimates. We describe efforts and progress made towards this goal. METHODS: We assessed trends in immunisation against measles on the basis of national implementation of the WHO/UNICEF comprehensive strategy for measles mortality reduction, and the provision of a second opportunity for measles immunisation. We used a natural history model to evaluate trends in mortality due to measles. RESULTS: Between 1999 and 2005, according to our model mortality owing to measles was reduced by 60%, from an estimated 873,000 deaths (uncertainty bounds 634,000-1,140,000) in 1999 to 345,000 deaths (247,000-458,000) in 2005. The largest percentage reduction in estimated measles mortality during this period was in the western Pacific region (81%), followed by Africa (75%) and the eastern Mediterranean region (62%). Africa achieved the largest total reduction, contributing 72% of the global reduction in measles mortality. Nearly 7.5 million deaths from measles were prevented through immunisation between 1999 and 2005, with supplemental immunisation activities and improved routine immunisation accounting for 2.3 million of these prevented deaths. INTERPRETATION: The achievement of the 2005 global measles mortality reduction goal is evidence of what can be accomplished for child survival in countries with high childhood mortality when safe, cost-effective, and affordable interventions are backed by country-level political commitment and an effective international partnership.

Global measles elimination efforts: the significance of measles elimination in the United States.

Lessons learned from the successful end of endemic measles virus transmission (i.e., elimination) in the United States include the critical roles of strong political commitment, a regionwide initiative, adequate funding, and a broad coalition of partners. Implications of measles elimination in the United States for global measles control and regional elimination efforts include demonstration of the high vaccination coverage and, in turn, population immunity needed for elimination; the importance of accurate monitoring of vaccination coverage at local, state, and national levels; a vaccination strategy that includes at least 2 opportunities for measles immunization; and the essential role of integrated epidemiological and laboratory surveillance. The United States, with a population of 288 million, is, to our knowledge, the largest country to have ended endemic measles transmission. This experience provides evidence that sustained interruption of transmission can be achieved in large geographic areas, suggesting the feasibility of global eradication of measles.