Susan E. Reef

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 Epidemiological Profile of Rubella and Congenital Rubella Syndrome in the United States, 1998–2004: The Evidence for Absence of Endemic Transmission

In 1969, the United States established its national rubella vaccination program. With the success of the program, 32 years later, reports of rubella reached record low numbers. To assess the achievement of elimination of rubella and congenital rubella syndrome (CRS) in the United States, 7 epidemiological criteria were used. Rubella cases reported to the National Notifiable Diseases Surveillance System from 1998 through 2004 and CRS cases reported to the National Congenital Rubella Syndrome Registry from 1998 through 2004 were analyzed. During 1998-2000, the median number of reported rubella cases was 272, whereas, during 2001-2004, the median number reported was 13. The incidence of rubella decreased significantly, from 0.1/100,000 population in 1998 to 0.005/100,000 population in 2004. Since 2001, 5 infants with CRS have been reported--3 were born in 2001, 1 was born in 2003, and 1 was born in 2004. The epidemiological evidence strongly supports the claim that rubella is no longer endemic in the United States. To prevent future rubella outbreaks and CRS cases, current strategies must be maintained.

Persistence of Rubella Antibodies after 2 Doses of Measles-Mumps-Rubella Vaccine

BACKGROUND Since 1990, most schoolchildren in the United States have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short- and long-term rubella immunogenicity of MMR2. METHODS At enrollment in 1994-1995, children (n = 307) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n = 306) was vaccinated at age 9-11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10). RESULTS Before administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns. CONCLUSIONS Rubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination.

Rubella Immunity Levels in the United States Population: Has the Threshold of Viral Elimination Been Reached?

After the 1989-1991 rubella resurgence, rubella vaccination efforts targeted children and women of childbearing age. Utilizing National Health and Nutrition Examination Survey data collected during 1988-1994 and 1999-2004, we assessed whether US levels of rubella seropositivity are consistent with rubella elimination and whether changes are consistent with immunization efforts. Serum samples with rubella antibody levels > or =10 IU tested by rubella immunoglobulin G enzyme immunoassay were considered to be positive. In 1999-2004, the overall age-adjusted rubella seropositivity level was 91.3% (95% confidence interval [CI], 90.5%-92.1%), a significant increase from 88.1% (95% CI, 86.9%-89.1%) in 1988-1994 (P<.001). Among children, seropositivity was highest in children 6-11 years of age (96.2%), followed by adolescents 12-19 years of age (93.7%). Both groups showed significant increases in immunity levels, in comparison with those in 1988-1994 (P<.001). Among adults, seropositivity among women increased (from 88.9% to 91.5%; P=.015), and there was no change among men (from 87.8% to 88.0%; P=.84). In 1999-2004, population rubella immunity levels were at or above the modeled threshold for elimination of rubella virus transmission. Increases in immunity levels are consistent with vaccination efforts.

Guidelines for the documentation and verification of measles, rubella, and congenital rubella syndrome elimination in the region of the Americas.

In the region of the Americas, goals for the elimination of endemic measles and rubella/congenital rubella syndrome (CRS) by the year 2000 and 2010, respectively were established. The successful implementation of measles elimination strategies in the region of the Americas resulted in the interruption of endemic measles transmission in 2002 and tremendous progress toward rubella and CRS elimination. In October 2007, the 27th Pan American Sanitary Conference adopted Resolution CSP27.R2 urging member states to begin documenting and verifying the interruption of endemic transmission of the measles and rubella viruses in the Americas. To ensure a standardized approach for the process of documentation and verification, the Pan American Health Organization/World Health Organization (PAHO/WHO) developed a regional plan of action to guide countries and their national commissions as they prepare and consolidate evidence of the interruption of endemic measles and rubella transmission. This article summarizes the plan of action including the essential criteria and components of the guidelines.

Rubella Vaccination of Unknowingly Pregnant Women During Mass Campaigns for Rubella and Congenital Rubella Syndrome Elimination, The Americas 2001–2008

BACKGROUND Due to the significant teratogenicity of rubella virus and the use of a live-attentuated vaccine, pregnancy is a contraindication of receipt of rubella vaccine (RCV). Data collected from several countries that have observed susceptible women who had received RCV during pregnancy documented that no infant with congenital rubella syndrome (CRS) has been born, so the risk is theoretical. As part of the regional initiative to eliminate rubella and CRS in the Americas, one of the key strategies was the vaccination of women of childbearing age. The implementation of mass vaccination campaigns targeting women of childbearing age in Argentina, Brazil, Costa Rica, Ecuador, El Salvador, and Paraguay provided an opportunity to further increase the body of knowledge on the safety of rubella vaccine if an unknowingly pregnant woman is vaccinated in early pregnancy. METHODS Using a standard protocol, women who were unknowingly pregnant or become pregnant ≤ 30 days after receiving RCV were evaluated to determine immunity status (eg, susceptible, immune, and unknown) at the time of vaccination. Susceptible pregnant women were observed to determine the outcome of the pregnancy. For pregnancies that resulted in live births, serum samples were obtained from the newborn for rubella immunoglobulin (Ig) M antibody testing. If the newborns serum sample was IgM positive, the infant was evaluated for manifestations of CRS. RESULTS During the period 2001-2008, 48748253 women of childbearing age were vaccinated in the region of the Americas, 39542253 (81%) of whom were vaccinated in the 6 selected countries. Of these women, 30139 (0.07%) were pregnant or became pregnant ≤1 month after receiving vaccine and were followed up. On the basis of serological evaluation, 2894 (10%) women were classified as susceptible at the time of vaccination; of their pregnancies, 1980 (90%) resulted in a live birth. Sera from 70 (3.5%) of these infants were rubella IgM antibody positive, but none of the infants had features of CRS as a result of rubella vaccination. The maximum theoretical risk for CRS following rubella vaccination of susceptible pregnant women was 0.2%. Conclusions. The results of these studies from 6 select countries provides additional evidence showing an absence of risk of CRS associated with administering rubella vaccine shortly before or during pregnancy.

Genetic Analysis of Rubella Viruses Found in the United States between 1966 and 2004: Evidence That Indigenous Rubella Viruses Have Been Eliminated

Wild-type rubella viruses are genetically classified into 2 clades and 10 intraclade genotypes, of which 3 are provisional. The genotypes of 118 viruses from the United States were determined by sequencing part of the E1 coding region of these viruses and comparing the resulting sequences with reference sequences for each genotype, using the Bayesian inference program MRBAYES. Three genotypes of rubella viruses were found in the United States too infrequently to be considered for indigenous transmission. A fourth genotype was found frequently until 1981, and a fifth genotype was found frequently until 1988, but neither was obtained from nonimported cases after 1988. A sixth genotype was found frequently during 1996-2000, likely because of multiple importations from neighboring countries. The results of the present genetic analysis of rubella viruses found in the United States are consistent with elimination of indigenous viruses by 2001, the year when rubella was considered to be eliminated on the basis of epidemiological evidence.

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

Efforts at Rubella Elimination in the United States: The Impact of Hemispheric Rubella Control

6300 (IQR,

Guidance for Isolation Precautions for Mumps in the United States: A Review of the Scientific Basis for Policy Change

3227-