The path to eradication of rubella.

Since 1969, rubella and its harmful effect on fetuses infected in utero can be prevented by rubella vaccine, usually given in combination with measles vaccine. The rubella vaccine is highly protective both in children and in adults including women intending to become pregnant. Owing to the use of combined measles and rubella vaccines, congenital rubella infection has been eliminated from the Western Hemisphere and nearly all of Europe. Such combined vaccination is now being applied throughout the world, posing the possibility of eventual rubella eradication. The existence of viruses of animals related to rubella does not appear to be a barrier to eradication of the human virus. However, persistent rubella virus in infants infected in utero and of immunosuppressed patients with granulomas may pose a problem for eradication. Nevertheless, this review posits that eradication of rubella is now feasible if routine vaccination of infants and surveillance for chronic infection are correctly applied.

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.

Teratology: from science to birth defects prevention.

One of the goals of birth defects research is to better understand risk or preventive factors for birth defects so that strategies for prevention can be developed. In this article, we have selected four areas of birth defects research that have led to the development of prevention strategies. These areas include rubella virus as a cause of congenital rubella syndrome, folic acid as a preventive factor for neural tube defects, cytomegalovirus infection as a cause of birth defects and developmental disabilities, and alcohol as a cause of fetal alcohol spectrum disorders. For each of these areas, we review key clinical and research findings that led to the identification of the risk or preventive factor, milestones in the development of prevention strategies, and the progress made thus far toward prevention.

Adequacy of surveillance to detect endemic rubella transmission in the United States.

BACKGROUND: Reported rubella cases in the United States are at the lowest numbers since the introduction of vaccine, suggesting that endemic transmission may have been interrupted. It is necessary to validate that the observed absence of rubella is due to the disappearance of disease rather than a failure of rubella surveillance. METHODS: Adequate rubella surveillance to detect ongoing transmission is characterized by evidence that rubella investigations are being conducted, detection of importations, and lack of spread from confirmed cases. We reviewed rubella surveillance data and activities from 5 sources: (1) data reported to the national surveillance system; (2) a survey of health departments and public health laboratories, including questions regarding any links between measles and rubella surveillance; (3) enhanced rubella surveillance activities in California and in New York City; (4) sentinel surveillance along the US-Mexico border; and (5) case detection in 8 large health maintenance organizations (HMOs). RESULTS: During 2002-2004, 35 cases of rubella were reported to the national system, including 12 (34%) imported cases. The 39 programs that responded to our survey reported conducting 1482 investigations for rubella; according to another national survey, 1921 investigations were conducted for measles. Forty-one laboratories responded to our survey and reported conducting 6428 tests for acute rubella. No previously undetected (or unreported) cases of rubella or congenital rubella syndrome were identified by our survey or reviews of surveillance in California, New York, and along the US-Mexico border, and no additional cases were detected in the HMO database. CONCLUSIONS: No previously unrecognized spread cases or outbreaks of rubella were detected. Surveillance in the United States is sufficiently sensitive to identify indigenous cases of rubella, if they were occurring, supporting the contention that rubella has been eliminated from the United States.

Efforts at rubella elimination in the United States: the impact of hemispheric rubella control.

We examined rubella vaccination trends, rubella surveillance, and disease patterns for the Americas, Mexico, and the United States, to evaluate the impact of hemispheric rubella control on rubella elimination in the United States during 1997-2004. In 1997, 130,375 rubella cases were reported in the Americas, with 38,042 reported in Mexico. Over the next 7 years, a rubella control initiative resulted in the administration of approximately 110 million rubella-containing vaccine doses in Latin America, with 77.7 million doses administered within Mexico. By 2004, the number of reported rubella cases had declined to 3103 in the Americas and 698 in Mexico. Concurrently, the number of rubella cases in the United States fell from 817 during 1997-1999 to <25 cases/year from 2001 onward, with loss of seasonality and geographic clustering, despite no change in vaccination rates. Implementation of rubella control strategies in the Americas, particularly in Mexico, appears to have facilitated rubella elimination in the United States.

The changing epidemiology of rubella in the 1990s: on the verge of elimination and new challenges for control and prevention.

CONTEXT: In 1989, the United States established a goal to eliminate indigenous rubella and congenital rubella syndrome (CRS) by 2000. Reported rubella cases are at record low levels; however, cases and outbreaks have occurred, primarily among unvaccinated foreign-born adults. OBJECTIVE: To evaluate the current epidemiology of rubella and CRS and assess progress toward elimination. DESIGN, SETTING, AND SUBJECTS: Analysis of rubella cases reported to the National Notifiable Diseases Surveillance System from 1990 through 1999 and CRS cases reported to the National Congenital Rubella Syndrome Registry from 1990 through 1999. Since 1996, US and international viral isolates have been sequenced. MAIN OUTCOME MEASURES: Incidence and characteristics of rubella and CRS cases; molecular typing of virus isolates. RESULTS: Annually from 1990 through 1999, the median number of reported rubella cases was 232 (range, 128-1412), and between 1992 and 1999, fewer than 300 rubella cases were reported annually, except in 1998. During the 1990s, the incidence of rubella in children younger than 15 years decreased (0.63 vs 0.06 per 100 000 in 1990 vs 1999), whereas the incidence in adults aged 15 to 44 years increased (0.13 vs 0.24 per 100 000). In 1992, incidence among Hispanics was 0.06 per 100 000 and increased to a high in 1998 of 0.97 per 100 000. From 1997 through 1999, 20 (83%) of 24 CRS infants were born to Hispanic mothers, and 21 (91%) of 23 CRS infants were born to foreign-born mothers. Molecular typing identified 3 statistically distinct genotypic groups. In group 1, the close relatedness of viruses suggests that a single imported source seeded an outbreak that did not spread beyond the Northeast. Similarly, within groups 2 and 3, relatedness of viruses obtained from clusters of cases suggests that single imported sources seeded each one. Diversity of viruses found in 1 state is consistent with the conclusion that several viruses were imported. Moreover, the similarity of viruses found across the country, combined with a lack of epidemiologic evidence of endemic transmission, support the conclusion that some viruses that are common abroad, particularly in Latin America and the Caribbean, were introduced into the United States on several separate occasions. CONCLUSIONS: The epidemiology of rubella and CRS has changed significantly in the last decade. These changes and molecular typing suggest that the United States is on the verge of elimination of the disease. To prevent future rubella outbreaks and CRS, current strategies must be enhanced and new strategies developed.