Carlos Castillo-Solórzano

Global Distribution of Measles Genotypes and Measles Molecular Epidemiology

A critical component of laboratory surveillance for measles is the genetic characterization of circulating wild-type viruses. The World Health Organization (WHO) Measles and Rubella Laboratory Network (LabNet), provides for standardized testing in 183 countries and supports genetic characterization of currently circulating strains of measles viruses. The goal of this report is to describe the lessons learned from nearly 20 years of virologic surveillance for measles, to describe the global databases for measles sequences, and to provide regional updates about measles genotypes detected by recent surveillance activities. Virologic surveillance for measles is now well established in all of the WHO regions, and most countries have conducted at least some baseline surveillance. The WHO Global Genotype Database contains >7000 genotype reports, and the Measles Nucleotide Surveillance (MeaNS) contains >4000 entries. This sequence information has proven to be extremely useful for tracking global transmission patterns and for documenting the interruption of transmission in some countries. The future challenges will be to develop quality control programs for molecular methods and to continue to expand virologic surveillance activities in all regions.

New Horizons in the Control of Rubella and Prevention of Congenital Rubella Syndrome in the Americas

Data from the regional measles surveillance system have documented widespread rubella virus circulation in many different countries in the Americas. In response to the ongoing endemic incidence of the disease and the potential for a major rubella epidemics in the region, the Pan American Health Organization Technical Advisory Group on Vaccine Preventable Diseases recommended the implementation of a regional initiative to strengthen rubella and congenital rubella syndrome (CRS) preventive efforts in 1997. This article summarizes and highlights the progress toward accelerated rubella control and CRS prevention in the English-speaking Caribbean and in Chile, Costa Rica, and Brazil. Useful knowledge is being generated for the adaptation of similar rubella strategies elsewhere. The findings also document the feasibility of implementing the recommended strategies and their rapid impact on disease burden.

Confirmation of Rubella within 4 Days of Rash Onset: Comparison of Rubella Virus RNA Detection in Oral Fluid with Immunoglobulin M Detection in Serum or Oral Fluid

ABSTRACT Rubella virus infection is typically diagnosed by the identification of rubella virus-specific immunoglobulin M (IgM) antibodies in serum, but approximately 50% of serum samples from rubella cases collected on the day of rash onset are negative for rubella virus-specific IgM. The ability to detect IgM in sera and oral fluids was compared with the ability to detect rubella virus RNA in oral fluids by reverse transcription-PCR (RT-PCR) by using paired samples taken within the first 4 days after rash onset from suspected rubella cases during an outbreak in Perú. Sera were tested for IgM by both indirect and capture enzyme immunoassays (EIAs), and oral fluids were tested for IgM by a capture EIA. Tests for IgM in serum were more sensitive for the confirmation of rubella than the test for IgM in oral fluid during the 4 days after rash onset. RT-PCR confirmed more suspected cases than serum IgM tests on days 1 and 2 after rash onset. The methods confirmed approximately the same number of cases on days 3 and 4 after rash onset. However, a few cases were detected by serum IgM tests but not by RT-PCR even on the day of rash onset. Nine RT-PCR-positive oral fluid specimens were shown to contain rubella virus sequences of genotype 1C. In summary, RT-PCR testing of oral fluid confirmed more rubella cases than IgM testing of either serum or oral fluid samples collected in the first 2 days after rash onset; the maximum number of confirmations of rubella cases was obtained by combining RT-PCR and serology testing.

Feasibility of global measles eradication after interruption of transmission in the Americas

Measles is one of the most infectious diseases. Before the introduction of the measles vaccine, nearly all children contracted measles. By the end of the 1980s, most countries of the world had incorporated the measles vaccine into their routine vaccination programs. Globally, some 345,000 deaths due to measles still occur every year. Eradication of measles would play an important role in improving child survival. The goal to eradicate measles from the Americas was set by the Pan-American Sanitary Conference in 1994. Progress to date has been remarkable. Measles is no longer an endemic disease in the Americas and interruption of transmission has been documented in most countries. As of December 2007, 5 years have elapsed since the detection of the last endemic case in Venezuela in November 2002. This experience demonstrates that interruption of measles transmission can be achieved and sustained over a long period of time. Global eradication should be feasible if the appropriate strategies are implemented. Even in a new paradigm in which eradication is not followed by the discontinuation of vaccination, eradication of measles should be a good investment to avoid expensive epidemics and save those children that would potentially die due to infection with the measles virus. It is not only a dream to think that we will see a world free of measles by the year 2015.

Fetal risk associated with rubella vaccination during pregnancy.

Background: Costa Rica implemented a nationwide measles-rubella vaccination campaign among men and women (15–39 years old) in May 2001. A protocol was developed to follow-up the vaccinated women who were unknowingly pregnant, to determine the risk of congenital rubella syndrome (CRS) or congenital rubella infection only associated with the administration of the rubella vaccine RA27/3 during pregnancy. Methods: To classify the prevaccination maternal immune status, a serum sample was taken at the initial evaluation to detect IgM and IgG rubella antibodies (enzyme-linked immunosorbent assay). All pregnancies were followed up and all newborns were evaluated. A cord serum sample of their children was taken at birth. We calculated odds ratio, OR (95% confidence interval, 95% CI) associated with miscarriage, stillbirth, prematurity, low birth weight, and the presence of defects compatible with CRS. Results: The prevaccination immune status was established in 797 women and 1191 mother and child pairs were analyzed. Adjusted OR for miscarriage (OR = 0.60, 95% CI = 0.26–1.39), stillbirth (OR = 1.32, 95% CI = 0.10–16.81), prematurity (OR = 0.25, 95% CI = 0.03–2.39), low birth weight (OR = 0.25, 95% CI = 0.03–2.23) and defects compatible with CRS (OR = 1.09, 95% CI = 0.34–3.54) showed no association between immune and susceptible maternal status. There were no cases of CRS and no children were IgM positive. Conclusions: No adverse pregnancy outcome such as miscarriages or CRS was documented in women who were vaccinated and unknowingly pregnant. These results support RA27/3 rubella vaccine safety.

Reducing the Global Burden of Congenital Rubella Syndrome: Report of the World Health Organization Steering Committee on Research Related to Measles and Rubella Vaccines and Vaccination, June 2004

Rubella and congenital rubella syndrome (CRS) continue to be important health problems in many countries. In June 2004, the World Health Organization Steering Committee on Research Related to Measles and Rubella Vaccines and Vaccination met to evaluate data from research and operational activities and to identify critical scientific issues and gaps in knowledge that need to be addressed to improve the global control of rubella and CRS. Information about surveillance for rubella, natural and vaccine-induced immunity to rubella, laboratory diagnosis, the molecular epidemiological profile of rubella virus, and mathematical modeling to assess the burden of CRS and the impact of rubella vaccination was reviewed. This report summarizes the presentations and recommendations for future research.

Strategies to eradicate rubella in the English-speaking Caribbean.

OBJECTIVE This report presents the strategies used to eradicate rubella in the Caribbean region and the challenges faced by that effort. METHODS Using the surveillance system for measles cases that was instituted in all countries in the Caribbean Community (CARICOM), 12 countries confirmed cases of rubella between 1992 and 1996. Rubella infections occurred in epidemic proportions in 6 countries during that period. RESULTS On the basis of the rubella prevalence data, rubella-congenital rubella syndrome (CRS) cost-benefit analysis, and cost-effectiveness of the mass campaign, the Council for Human and Social Development of CARICOM resolved, on April 21, 1998, that every effort would be made to eradicate rubella, as well as to prevent the occurrence of new cases of CRS by the end of 2000. Using the Pan American Health Organizations template for measles eradication, CARICOM proposed and implemented the main strategies for rubella and CRS eradication, and rubella mass campaigns were conducted in 18 countries. The target population, which included males and females (aged 20-40 years), was approximately 2.2 million. CONCLUSION The major challenges for rubella eradication are attaining high vaccine coverage in the adult population and maintaining an effective surveillance system able to detect rubella activity.

Elimination of Rubella and Congenital Rubella Syndrome in the Americas

In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling for rubella and congenital rubella syndrome (CRS) elimination in the Americas by the year 2010. To accomplish this goal, PAHO advanced a rubella and CRS elimination strategy including introduction of rubella-containing vaccines into routine vaccination programs accompanied by high immunization coverage, interruption of rubella transmission through mass vaccination of adolescents and adults, and strengthened surveillance for rubella and CRS. The rubella elimination strategies were aligned with the successful measles elimination strategies. By the end of 2009, all countries routinely vaccinated children against rubella, an estimated 450 million people had been vaccinated against measles and rubella in supplementary immunization activities, and rubella transmission had been interrupted. This article describes how the region eliminated rubella and CRS.

Rubella Elimination and Improving Health Care for Women

Health care for women can be improved by strengthening adult health services, improving health awareness and community participation, decentralizing decision-making, and using epidemiologic surveillance.

Accelerated rubella control and congenital rubella syndrome prevention strengthen measles eradication: The Costa Rican experience

In 2000, Costa Rica set a goal for accelerated rubella control and congenital rubella syndrome (CRS) prevention in conjunction with its established measles eradication goal. To achieve this goal, a National Plan of Action for the integration of a measles-rubella (MR) vaccination strategy was implemented. The components of the national plan included conducting a national vaccination campaign with a single dose of MR vaccine for men and women aged 15-39 years, establishing routine postpartum MR vaccination of all previously unvaccinated women, maintaining high coverage among children with two doses of measles-mumps-rubella vaccine, strengthening the integrated measles and rubella surveillance system, and developing a CRS surveillance system. This report summarizes the results of a successful adult campaign. Targeting MR vaccination appropriately and using the opportunity to strengthen surveillance for rash illness has benefits beyond accelerated rubella control and CRS prevention, including strengthening of the measles eradication program.