BACKGROUND: A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but data on long-term immunity are limited. We assessed neutralizing antibody levels against measles and rubella among adults up to 11 years after receipt of a third MMR dose. METHODS: In this longitudinal study, healthy adults who received a third MMR dose as young adults (ages 18-28 years) were recalled around 5 years and 9-11 years after the third dose. Measles and rubella antibody levels were assessed by plaque-reduction and immunocolorimetric neutralization assays, respectively. Antibody concentrations <120 mIU/mL and <10 U/mL were considered potentially susceptible to measles and rubella, respectively. Geometric mean concentrations (GMCs) and 95% confidence intervals (CIs) over time were estimated from generalized estimating equation models. RESULTS: Approximately 5 and 9-11 years after receipt of the third dose, 405 and 304 adults were assessed, respectively. Measles GMC was 428 mIU/mL (95% CI, 392-468 mIU/mL) 5 years postvaccination, declining to 381 mIU/mL (95% CI, 339-428 mIU/mL) 11 years postvaccination. At the last follow-up visit (9-11 years postvaccination), 10% of participants were potentially susceptible to measles infection. Rubella GMCs were stable throughout the follow-up period (63 U/mL to 65 U/mL); none of the participants was susceptible to rubella at the last follow-up visit. CONCLUSIONS: Eleven years after receiving a third MMR dose, measles and rubella neutralizing antibody levels remained high in adults. However, on the basis of waning antibody levels, some adults may become susceptible to measles infection over time despite receipt of 3 vaccine doses.

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.

Enhanced replication of rubella virus (RuV) and replicons by de novo synthesized viral structural proteins has been previously described. Such enhancement can occur by viral capsid proteins (CP) alone in trans. It is not clear whether the CP in the virus particles, i.e., the exogenous CP, modulate viral genome replication. In this study, we found that exogenous RuV CP also enhanced viral genome replication, either when used to package replicons or when mixed with RNA during transfection. We demonstrated that CP does not affect the translation efficiency from genomic (gRNA) or subgenomic RNA (sgRNA), the intracellular distribution of the non-structural proteins (NSP), or sgRNA synthesis. Significantly active RNA replication was observed in transfections supplemented with recombinant CP (rCP), which was supported by accumulated genomic negative-strand RNA. rCP was found to restore replication of a few mutants in NSP but failed to fully restore replicons known to have defects in the positive-strand RNA synthesis. By monitoring the amount of RuV RNA following transfection, we found that all RuV replicon RNAs were well-retained in the presence of rCP within 24 h of post-transfection, compared to non-RuV RNA. These results suggest that the exogenous RuV CP increases efficiency of early viral genome replication by modulating the stage(s) prior to and/or at the initiation of negative-strand RNA synthesis, possibly through a general mechanism such as protecting viral RNA.

An examination of the nucleic acid sequence alignment of 48 full-length rubella virus genomes revealed that the 5' terminus of the genome is more conserved than the commonly used detection windows for rubella virus RNA located in the E1 protein coding region, suggesting that the 5' terminus could be a target for improving detection of all rubella virus genotypes. Two candidate primer sets were tested and the window between nucleotides (nts) 98 and 251 was found to have the greatest analytical sensitivity for detection of different genotypes. The new method had a limit of detection of four copies of rubella RNA per reaction with high specificity. The average coefficient variation of Ct was 2.2%. Concordance between the new method and currently used method, based on testing 251 clinical specimens collected from a rubella outbreak, was 99.4%. The assay was further improved upon by the incorporation of detection of both rubella virus RNA and mRNA from a cellular reference gene in a multiplex format. The multiplex format did not reduce the sensitivity or the reproducibility of rubella RNA detection and, of 60 specimens tested, the concordance between the single target and multiplex assays was 85.0%. To assess the utility of the multiplex assay for molecular surveillance, 62 rubella IgM positive serum samples from a rubella outbreak were tested, and eleven tested positive using the multiplex method while none were positive using the method targeting E1. These results show that the assay based on the new detection window near the 5' terminus of the genome can improve the detection of rubella virus for the purpose of molecular surveillance and case confirmation, with the added benefit of improved efficiency due to multiplexing.

On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,(†) with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.(§) On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).

IMPORTANCE: Vaccine-derived and wild-type rubella virus (RuV) has been identified within granulomas in patients with inborn errors of immunity, but has not been described in granulomas of healthy adults. OBJECTIVE: To determine the association between RuV and atypical granulomatous inflammation in immune-competent adults. DESIGN, SETTING, AND PARTICIPANTS: This case series, conducted in US academic dermatology clinics from January 2019 to January 2021, investigated the presence of RuV in skin specimens using RuV immunofluorescent staining of paraffin-embedded tissue sections, real-time reverse-transcription polymerase chain reaction, whole-genome sequencing with phylogenetic analyses, and cell culture by the US Centers for Disease Control and Prevention. Rubella immunoglobulin G, immunoglobulin M enzyme-linked immunoassay, and viral neutralization assays were performed for the sera of immunocompetent individuals with treatment refractory cutaneous granulomas and histopathology demonstrating atypical palisaded and necrotizing granulomas. Clinical immune evaluation was performed. MAIN OUTCOMES AND MEASURES: Identification, genotyping, and culture of vaccine-derived and wild-type RuV within granulomatous dermatitis of otherwise clinically immune competent adults. RESULTS: Of the 4 total immunocompetent participants, 3 (75%) were women, and the mean (range) age was 61.5 (49.0-73.0) years. The RuV capsid protein was detected by immunohistochemistry in cutaneous granulomas. The presence of RuV RNA was confirmed by real-time reverse-transcription polymerase chain reaction in fresh-frozen skin biopsies and whole-genome sequencing. Phylogenetic analysis of the RuV sequences showed vaccine-derived RuV in 3 cases and wild-type RuV in 1. Live RuV was recovered from the affected skin in 2 participants. Immunology workup results demonstrated no primary immune deficiencies. CONCLUSIONS AND RELEVANCE: The case series study results suggest that RuV (vaccine derived and wild type) can persist for years in cutaneous granulomas in clinically immunocompetent adults and is associated with atypical (palisaded and necrotizing type) chronic cutaneous granulomas. These findings represent a potential paradigm shift in the evaluation, workup, and management of atypical granulomatous dermatitis and raises questions regarding the potential transmissibility of persistent live RuV.

BACKGROUND: While administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults. METHODS: In this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot. RESULTS: Rubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women. CONCLUSIONS: Collectively, rubella-specific humoral immunity declines following vaccination, although subjects' antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.

Rubella infection in early pregnancy can lead to miscarriages, fetal death, or birth of an infant with congenital rubella syndrome (CRS). In Cameroon, like in many developing countries, rubella surveillance is not well-established. The aim of this study was to determine the prevalence of rubella virus specific antibodies among pregnant Cameroonians. We conducted a cross-sectional study for rubella infection among pregnant women attending antenatal clinics in the Center and South-West regions of Cameroon. Demographic data and blood were collected and tested for rubella specific antibodies (IgG and IgM), and for the IgM positive cases, IgG avidity and real time PCR was done. From December 2015 to July 2017, 522 serum samples were collected and tested from pregnant women. The seroprevalence of rubella specific IgG was 94.4%, presumably due to immunity induced by wild-type rubella virus. The seroprevalence of rubella specific IgM was 5.0%, possibly indicating rubella infection. However, IgG avidity testing of the IgM positive cases detected high avidity IgGs, ranging from 52.37% to 87.70%, indicating past rubella infection. 5.6% (29/522) of the participants had negative results for IgG to rubella virus, indicating susceptibility to rubella infection. None of the participants had received a rubella containing vaccine (RCV), but 51% (266/522) of the pregnant women lived in a house with a child with records of at least one dose of RCV. Rubella virus RNA was not detected in the urine of any IgM positive case. Findings from this study show that rubella infection is significant in Cameroon. Some pregnant women are still susceptible to rubella infection. For a better management of rubella infection in pregnancy in Cameroon, consideration should be taken to investigate for IgG-avidity test in cases with positive rubella IgM result to distinguish between recent from past rubella infection.

Rubella virus causes a mild disease; however, infection during the first trimester of pregnancy may lead to congenital rubella syndrome (CRS) in over 80% of affected pregnancies. Vaccination is recommended and has been shown to effectively reduce CRS incidence. Uganda plans to introduce routine rubella vaccination in 2019. The World Health Organization recommends assessing the disease burden and obtaining the baseline molecular virological data prior to vaccine introduction. Sera collected during case-based measles surveillance from January 2005 to July 2018 were tested for rubella IgM antibodies. Sera from confirmed rubella outbreaks from January 2012 to August 2017 were screened using real-time RT-PCR; for positive samples, a region within the E1 glycoprotein coding region was amplified and sequenced. Of the 23,196 suspected measles cases serologically tested in parallel for measles and rubella, 5,334 (23%) were rubella IgM positive of which 2,710 (50.8%) cases were females with 2,609 (96.3%) below 15 years of age. Rubella IgM positive cases were distributed throughout the country and the highest number detected in April, August and November. Eighteen (18%) of the 100 sera screened were real-time RT-PCR positive of which eight (44.4%) were successfully sequenced and genotypes 1G and 2B identified. This study reports on the seroprevalence and molecular epidemiology of rubella. Increased knowledge of former and current rubella viruses circulating in Uganda will enhance efforts to monitor the impact of vaccination as Uganda moves towards control and elimination of rubella and CRS. This article is protected by copyright. All rights reserved.

The measles, mumps and rubella (MMR) vaccine has an outstanding safety record and is highly efficacious. High coverage with MMR has led to the elimination of endemic measles, rubella, and congenital rubella syndrome in the US. The biggest challenges to global measles and rubella control and elimination are insufficient vaccination coverage globally and increasing hesitancy. Despite high two dose coverage rates, mumps has made a resurgence in the US and other countries. Mumps outbreaks have occurred primarily in close contact, high-density settings and most cases had received a second dose 10 or more years previously. Waning humoral immunity and antigenic variation of circulating wild-type mumps strains may play a role in the mumps resurgence.

The genetic characterization of measles viruses is an important tool for measles surveillance. Reverse cold chain requirements for the transportation of samples to reference laboratories are challenging in resource-limited settings. FTA(R) cards facilitate transport of virologic samples at ambient temperature as non-infectious material; however, the utility of FTA(R) cards for detection and genotyping of measles virus from clinical samples had not been evaluated. Throat swabs (TS) and oral fluid (OF) samples were collected from suspected measles cases in the Democratic Republic of the Congo. Virus detection (RT-qPCR) and genotyping (end-point RT-PCR) were compared for samples from 238 suspected cases; these samples were either transported using the reverse cold chain or at ambient temperature on FTA(R) cards. Virus detection showed excellent positive agreement for OF compared to TS (95.3%, CI [91.6, 97.4]), in contrast to 79.4% (CI 73.5, 84.3) for TS on FTA, and 85.5% (CI 80.2, 89.6) for OF on FTA compared to OF. Genotyping results obtained for a subset of samples indicated that 77.3% of all TS and 71.0% of OF would produce genotype information compared to 41.6% of TS and 41.3% of OF on FTA(R) cards. Similar results were found for 16 measles-negative samples that were confirmed as rubella cases. Measles genotype B3 and rubella genotype 2B were detected. FTA(R) cards have limited utility for virologic surveillance of sporadic cases of measles; however, they can be a useful tool for the expansion of virologic surveillance in countries where the reverse cold chain is not available.

BACKGROUND: Third doses of measles-mumps-rubella (MMR) vaccine have been administered during mumps outbreaks and in various non-outbreak settings. The immunogenicity of the rubella component has not been evaluated following receipt of a third dose of MMR vaccine. METHODS: Young adults aged 18-31years with documented two doses of MMR vaccine received a third dose of MMR vaccine between July 2009 and October 2010. Rubella neutralizing antibody titers were assessed before, 1month, and 1year after receipt of a third dose of MMR vaccine. RESULTS: Among 679 participants, 1.8% had rubella antibody titers less than 10 U/ml, immediately before vaccination, approximately 15years after receipt of a second dose of MMR vaccine. One month after receipt of a third dose of MMR vaccine, average titers were 4.5 times higher and >50% of participants had a 4-fold boost. Response was highest among those with titers less than 10 U/ml prior to vaccination (geometric mean titer ratio=18.8; 92% seroconversion) and decreased with increasing pre-vaccination titers. Average titers declined 1year postvaccination but remained significantly higher than pre-vaccination levels. The proportion classified as low-positive antibody levels increased from 3% 1month postvaccination to 24% 1year postvaccination. CONCLUSIONS: Vaccination with a third dose of MMR vaccine resulted in a robust boosting of rubella neutralizing antibody response that remained elevated 1year later. Young adults with low rubella titers are more likely to benefit from a third dose of MMR vaccine.

PURPOSE: Granulomas are a potentially severe condition that can last for several years in persons with primary immunodeficiency disorders (PIDD). We assessed the prevalence of granulomas in patients with PIDD. METHODS: We used the Truven Health MarketScan(R) 2005-2015 Commercial Claims and Encounters and 2006-2015 Medicaid databases and the US Immunodeficiency Network (USIDNET) PIDD registry (a program of the Immune Deficiency Foundation). Our study population consisted of persons age < 65 years with PIDD, defined as persons with >/= 2 claims with a diagnostic code for PIDD in MarketScan databases, or patients enrolled in USIDNET. Granulomas were identified using diagnostic codes in MarketScan or provider report in USIDNET. We calculated annual prevalence of PIDD and of granulomas among PIDD patients. RESULTS: We identified 247,474 and 40,395 persons with PIDD among commercially and Medicaid-insured persons, respectively. PIDD prevalence was 6.0/10,000 in 2005 and 11.7/10,000 in 2015 among commercially insured persons and 5.5/10,000 in 2006 and 9.6/10,000 in 2015 among Medicaid-insured persons. The prevalence of granulomas among PIDD patients was 1.2 and 1.5% among commercially and Medicaid-insured persons, respectively. In USIDNET, prevalence of granulomas was 4.4% (177/4021). The proportion with granulomas was similar across age groups in MarketScan, but varied from 2 to 9% in USIDNET. The reported prevalence of granulomas differed depending on PIDD condition: 1-2% in the MarketScan data and 0-13% in USIDNET. CONCLUSION: Granuloma prevalence in PIDD patients was 1-4%. Our study provides an estimate of the proportion of PIDD patients and suggests that granulomas are an uncommon occurrence among patients with PIDD.

The Second Year of Life project of the Global Health Security Agenda aims to improve immunization systems and strengthen measles and rubella surveillance, including building laboratory capacity. A new laboratory assessment tool was developed by the Centers for Disease Control and Prevention to assess the national laboratory in Ghana to improve molecular surveillance for measles and rubella. Results for the tool showed that the laboratory is well organized, has a good capacity for handling specimens, has a good biosafety system, and is proficient for diagnosis of measles and rubella by serologic analysis. However, there was little knowledge about molecular biology and virology activities (i.e., virus isolation on tissue culture was not available). Recommendations included training of technical personnel for molecular techniques and advocacy for funding for laboratory equipment, reagents, and supplies.

BACKGROUND: Antibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence. METHODS: Children vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4-6years of age were followed up to 12years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects. RESULTS: Most of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and <2-fold increase post-MMR2. Subjects with >/=2-fold experienced a slower decline (</=7.4%). GMT to rubella was 149 one month post-MMR2, declining 2.6% and 5.9% per year among those who received MMR1 at 12-15months and >15months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens. CONCLUSIONS: The rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations.

BACKGROUND: Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction. METHODS: A rubella antibody seroprevalence assessment was conducted using serum collected during 2008-2009 from 1605 pregnant women aged 15-46years attending 7 antenatal care sites in 3 of DRC's provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC. RESULTS: Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS. CONCLUSIONS: In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10-20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as vaccination of women of child bearing age through routine services.

In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP)* with the objective to eliminate measles and rubella in five World Health Organization (WHO) regions by 2020. In September 2013, countries in all six WHO regions had established measles elimination goals, and additional goals for elimination of rubella and congenital rubella syndrome were established in three regions (1). Capacity for surveillance, including laboratory confirmation, is fundamental to monitoring and verifying elimination. The 2012-2020 Global Measles and Rubella Strategic Plan of the Measles and Rubella Initiative(dagger) calls for effective case-based surveillance with laboratory testing for case confirmation (2). In 2000, the WHO Global Measles and Rubella Laboratory Network (GMRLN) was established to provide high quality laboratory support for surveillance (3). The GMRLN is the largest globally coordinated laboratory network, with 703 laboratories supporting surveillance in 191 countries. During 2010-2015, 742,187 serum specimens were tested, and 27,832 viral sequences were reported globally. Expansion of the capacity of the GMRLN will support measles and rubella elimination efforts as well as surveillance for other vaccine-preventable diseases (VPDs), including rotavirus, and for emerging pathogens of public health concern.

BACKGROUND: The burden of rotavirus morbidity and mortality is high in children under 5 years in developing countries and evaluations indicate waning protection from rotavirus immunization in the second year. An additional dose of rotavirus vaccine may enhance the immune response and lengthen the period of protection against disease, however co-administration should not interfere with immune responses to concurrently given vaccines. METHODS: Enrolling 480 9-month old participants from Matlab, Bangladesh, the primary objective was to establish non-inferiority of concomitant administration of measles-rubella (MR) vaccine and a 3rd dose of human monovalent rotavirus vaccine (HRV) [MR+HRV] compared to MR vaccine given alone [MR]. Secondary objectives included non-inferiority of rubella antibody seroconversion and evaluating rotavirus IgA/IgG seroresponses in MR+HRV participants. RESULTS: Two months post-vaccination, 75.3% and 74.3% of MR+HRV and MR group infants, respectively, had seroprotective levels of measles virus antibodies. 100.0% and 99.6%, respectively, showed anti-rubella IgG seroprotection. In the MR+HRV group, pre-vaccination anti-rotavirus IgA and IgG seropositivities (52.7% and 66.3%, respectively) increased to 69.6% and 88.3% post-vaccination. CONCLUSIONS: Vaccine-induced measles and rubella antibody responses are not negatively affected by concomitant administration of HRV. The HRV dose increases anti-rotavirus serum antibody titres and the proportion of infants with detectable anti-rotavirus antibody.

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs.

Rubella remains a social and economic burden due to the high incidence of congenital rubella syndrome (CRS) in some countries. For this reason, an accurate and efficient high-throughput measure of antibody response to vaccination is an important tool. In order to measure rubella-specific neutralizing antibodies in a large cohort of vaccinated individuals, a high-throughput immunocolorimetric system was developed. Statistical interpolation models were applied to the resulting titers to refine quantitative estimates of neutralizing antibody titers relative to the assayed neutralizing antibody dilutions. This assay, including the statistical methods developed, can be used to assess the neutralizing humoral immune response to rubella virus and may be adaptable for assessing the response to other viral vaccines and infectious agents.

We report a case of congenital rubella syndrome in a child born to a vaccinated New Jersey woman who had not traveled internationally. Although rubella and congenital rubella syndrome have been eliminated from the United States, clinicians should remain vigilant and immediately notify public health authorities when either is suspected.

IMPORTANCE: To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained. OBJECTIVE: To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING, AND PARTICIPANTS: Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES: Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels. RESULTS: Since 2001, US reported measles incidence has remained below 1 case per 1 000 000 population. Since 2004, rubella incidence has been below 1 case per 10 000 000 population, and CRS incidence has been below 1 case per 5 000 000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE: The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.

Information on the molecular epidemiology of rubella has been valuable in supporting efforts to control and eliminate rubella in several countries. The preferred samples for virus isolation or RNA detection, such as throat swabs, are often not available making it difficult to obtain a robust database of rubella virus sequences. A method for obtaining rubella virus genotypes from more commonly collected samples such as sera or dried blood spots using real-time RT-PCR to screen samples followed by nested set amplification is described. Rubella genotypes were obtained from dried blood spots and recent and archival sera collections. Eighteen percent of the RNAs extracted from the archival sera were real-time RT-PCR positive, and 44% of these RNAs were amplified successfully by nested RT-PCR and sequenced. Implementation of this technique could provide another tool to improve global rubella molecular surveillance.

The goal of eliminating rubella from the Americas by 2010 was established in 2003. Subsequently, a systematic nomenclature for wild-type rubella viruses (wtRVs) was established, wtRVs circulating in the region were catalogued, and importations of wtRVs into a number of countries were documented. The geographic distribution of wtRVs of various genotypes in the Americas, interpreted in the context of the global distribution of these viruses, contributed to the documentation of rubella elimination from some countries. Data from virologic surveillance also contributed to the conclusion that viruses of genotype 2B began circulating endemically in the Americas during 2006-2007. Viruses of one genotype (1C), which are restricted to the Americas, will likely disappear completely from the world as they are eliminated from the Americas. Efforts to expand virologic surveillance for wtRVs in the Americas will also provide additional data aiding the elimination of rubella from the region. For example, identification of vaccine virus in specimens from rash and fever cases found during elimination can identify such cases as vaccine associated.

On 29 October 2004, an expert panel was convened to review the status of elimination of rubella and congenital rubella syndrome (CRS) in the United States. Primarily based on 5 types of information presented-epidemiology of reported cases, molecular epidemiology, seroprevalence, vaccine coverage, and adequacy of surveillance-the panel unanimously agreed that rubella virus is no longer endemic in the United States. Since 2004, new data continue to support the conclusion that elimination has been achieved and maintained. In documenting elimination in the United States, each of the 5 types of data provided evidence for elimination and collectively provided much stronger evidence than any one type could individually. As countries document the elimination of rubella and CRS, many sources and types of data will likely be necessary. Rigorous data evaluation must be conducted to look for inconsistencies among the available data. To maintain elimination, countries should maintain high vaccine coverage, adequate surveillance, and rapid response to outbreaks.

The suspected measles case definition captures rubella cases. Therefore, measles surveillance will be improved in the course of the control and eventual elimination of rubella transmission. One aspect of rubella control, virologic surveillance, is reviewed here. A systematic nomenclature for rubella viruses (RVs) based on 13 genotypes has been established and is updated when warranted by increases in information about RVs. From 2005 through 2010, the genotypes of RVs most frequently reported were 1E, 1G, and 2B, and genotypes 1a, 1B, 1C, 1h, 1j, and 2C were less frequently reported. Virologic surveillance can support rubella control and elimination. Synopses of rubella virologic surveillance in various countries, regions, and globally are given, including characterization of viruses from imported cases in a country that has eliminated rubella and studies of endemic viruses circulating in countries without rubella control objectives. Current challenges are discussed.