Peter M. Strebel

Estimates of measles case fatality ratios: a comprehensive review of community-based studies.

BACKGROUND Global deaths from measles have decreased notably in past decades, due to both increases in immunization rates and decreases in measles case fatality ratios (CFRs). While some aspects of the reduction in measles mortality can be monitored through increases in immunization coverage, estimating the level of measles deaths (in absolute terms) is problematic, particularly since incidence-based methods of estimation rely on accurate measures of measles CFRs. These ratios vary widely by geographic and epidemiologic context and even within the same community from year-to-year. METHODS To understand better the variations in CFRs, we reviewed community-based studies published between 1980 and 2008 reporting age-specific measles CFRs. RESULTS The results of the search consistently document that measles CFRs are highest in unvaccinated children under age 5 years; in outbreaks; the lowest CFRs occur in vaccinated children regardless of setting. The broad range of case and death definitions, study populations and geography highlight the complexities in extrapolating results for global public health planning. CONCLUSIONS Values for measles CFRs remain imprecise, resulting in continued uncertainty about the actual toll measles exacts.

Progress Toward Control of Rubella and Prevention of Congenital Rubella Syndrome—Worldwide, 2009

Rubella, usually a mild rash illness in children and adults, can cause serious consequences when a pregnant woman is infected, particularly in early pregnancy. These serious consequences include miscarriage, fetal death or an infant born with birth defects (i.e., congenital rubella syndrome (CRS)). The primary purpose for rubella vaccination is the prevention of congenital rubella infection including CRS. Since 1969, several rubella virus vaccines have been licensed for use; however, until the 1990s, use of rubella-containing vaccine (RCV) was limited primarily to developed countries. In 1996, it was estimated that 110,000 infants with CRS were born annually in developing countries. In 2000, the first World Health Organization rubella vaccine position paper was published to guide introduction of RCV in national childhood immunization schedules. From 1996 to 2009, the number of countries that introduced RCV into their national routine childhood immunization programs increased by 57% from 83 countries in 1996 to 130 countries in 2009. In addition, three of the six WHO regions established rubella control and CRS prevention goals: Region of the Americas and Europe rubella elimination by 2010 and 2015, respectively, and Western Pacific Region-accelerated rubella control and CRS prevention by 2015. Also, during this time period, the number of rubella cases reported decreased from 670,894 in 2000 to 121,344 in 2009. Rubella control and prevention of CRS can be accelerated by integrating with current global measles mortality reduction and regional elimination activities.

The estimated mortality impact of vaccinations forecast to be administered during 2011-2020 in 73 countries supported by the GAVI Alliance

INTRODUCTION From August to December 2011, a multidisciplinary group with expertise in mathematical modeling was constituted by the GAVI Alliance and the Bill & Melinda Gates Foundation to estimate the impact of vaccination in 73 countries supported by the GAVI Alliance. METHODS The number of deaths averted in persons projected to be vaccinated during 2011-2020 was estimated for ten antigens: hepatitis B, yellow fever, Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, rotavirus, Neisseria meningitidis serogroup A, Japanese encephalitis, human papillomavirus, measles, and rubella. Impact was calculated as the difference in the number of deaths expected over the lifetime of vaccinated cohorts compared to the number of deaths expected in those cohorts with no vaccination. Numbers of persons vaccinated were based on 2011 GAVI Strategic Demand Forecasts with projected dates of vaccine introductions, vaccination coverage, and target population size in each country. RESULTS By 2020, nearly all GAVI-supported countries with endemic disease are projected to have introduced hepatitis B, Hib, pneumococcal, rotavirus, rubella, yellow fever, N. meningitidis serogroup A, and Japanese encephalitis-containing vaccines; 55 (75 percent) countries are projected to have introduced human papillomavirus vaccine. Projected use of these vaccines during 2011-2020 is expected to avert an estimated 9.9 million deaths. Routine and supplementary immunization activities with measles vaccine are expected to avert an additional 13.4 million deaths. Estimated numbers of deaths averted per 1000 persons vaccinated were highest for first-dose measles (16.5), human papillomavirus (15.1), and hepatitis B (8.3) vaccination. Approximately 52 percent of the expected deaths averted will be in Africa, 27 percent in Southeast Asia, and 13 percent in the Eastern Mediterranean. CONCLUSION Vaccination of persons during 2011-2020 in 73 GAVI-eligible countries is expected to have substantial public health impact, particularly in Africa and Southeast Asia, two regions with high mortality. The actual impact of vaccination in these countries may be higher than our estimates because several widely used antigens were not included in the analysis. The quality of our estimates is limited by lack of data on underlying disease burden and vaccine effectiveness against fatal disease outcomes in developing countries. We plan to update the estimates annually to reflect updated demand forecasts, to refine model assumptions based on results of new information, and to extend the analysis to include morbidity and economic benefits.

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.

A new global framework for immunization monitoring and surveillance

Each year despite the availability of low-cost interventions such as vaccines that could prevent millions of deaths nearly 11 million children worldwide die before the age of five. Failure to reach the Millennium Development Goal 4 (MDG 4) for child survival will result in an estimated 40 million childrens lives lost by 2015. As nearly a quarter of global under-five mortality is attributable to vaccine-preventable diseases (VPD) vaccination can contribute significantly to attaining the MDG 4. An unprecedented array of life-saving vaccines is now available or in late stages of development. However the decision to invest in vaccine introduction must be evidence-based and requires reliable data. Vaccine-preventable disease surveillance and programme monitoring provide the scientific and factual database essential for informed decision-making and appropriate public health action. In 2005 WHO and UNICEF published the Global Immunization Vision and Strategy 2006-2015 (GIVS) which defines the strategies and goals that will maximize the impact of immunization. One of the key components of achieving the GIVS goals is the need for strong systems for disease surveillance and programme monitoring. Recent developments such as the availability and accessibility of new vaccines for the worlds poorest countries the need to achieve and sustain the global polio eradication goal the new goal of reducing measles mortality by 90% by 2010 the new International Health Regulations and the threat of emerging or pandemic diseases make a renewed and more comprehensive approach to surveillance and programme monitoring a necessity. To address this need WHO together with its global immunization partners developed a Global Framework for Immunization Monitoring and Surveillance (GFIMS). (excerpt)

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.

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.

Global use of rubella vaccines, 1980-2009.

In most developing countries, rubella vaccine has not been included in the Expanded Programme on Immunization because of lack of information on the burden of disease caused by rubella virus, increased cost associated with adding rubella vaccine, and the concern that if high vaccine coverage cannot be achieved and maintained, the risk of congenital rubella syndrome (CRS) may increase. Data for 2009 reported by countries to the World Health Organization (WHO) and United Nations Childrens Fund through the annual Joint Reporting Form were used to indicate patterns in the worldwide use of rubella vaccines, describe the number of reported rubella and CRS cases by WHO Region, and explore factors associated with decisions by countries to introduce rubella vaccine in their national childhood immunization programs. The number of WHO Member States using rubella-containing vaccine (RCV) in their national childhood immunization schedule increased from 83 (43%) in 1996 to 130 (67%) in 2009. Although scheduled ages for rubella vaccination vary across countries and regions, most countries have a 2-dose schedule using a combined measles-mumps-rubella vaccine. Among 130 countries using RCV in 2009, median coverage with the first dose of measles-containing vaccine (MCV1) was 95% (interquartile range [IQR], 90%-98%), compared with a median MCV1 coverage of 76% (IQR, 64%-88%) in countries not using RCV. The median per capita gross national income among 130 countries using RCV was US

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

6300 (IQR,

A World Without Measles

3227-