Measles and rubella elimination in the WHO Region for Europe: progress and challenges.

Globally measles remains one of the leading causes of death among young children even though a safe and cost-effective vaccine is available. The World Health Organization (WHO) European Region has seen a decline in measles and rubella cases in recent years. The recent outbreaks have primarily affected adolescents and young adults with no vaccination or an incomplete vaccination history. Eliminating measles and rubella is one of the top immunization priorities of the European Region as outlined in the European Vaccine Action Plan 2015-2020. Following the 2010 decision by the Member States in the Region to initiate the process of verifying elimination, the European Regional Verification Commission for Measles and Rubella Elimination (RVC) was established in 2011. The RVC meets every year to evaluate the status of measles and rubella elimination in the Region based on documentation submitted by each country's National Verification Committees. The verification process was however modified in late 2014 to assess the elimination status at the individual country level instead of at regional level. The WHO European Region has made substantial progress towards measles and rubella elimination over the past 5 years. The RVC's conclusion in 2016 that 70% and 66% of the 53 Member States in the Region had interrupted the endemic transmission of measles and rubella, respectively, by 2015 is a testament to this progress. Nevertheless, where measles and rubella remain endemic, challenges in vaccination service delivery and disease surveillance will need to be addressed through focused technical assistance from WHO and development partners.

Immunity to polio, measles and rubella in women of child-bearing age and estimated congenital rubella syndrome incidence, Cambodia, 2012.

Significant gaps in immunity to polio, measles, and rubella may exist in adults in Cambodia and threaten vaccine-preventable disease (VPD) elimination and control goals, despite high childhood vaccination coverage. We conducted a nationwide serological survey during November-December 2012 of 2154 women aged 15-39 years to assess immunity to polio, measles, and rubella and to estimate congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were detected by IgG ELISA and polio antibodies by microneutralization testing. Age-structured catalytic models were fitted to rubella serological data to predict CRS cases. Overall, 29.8% of women lacked immunity to at least one poliovirus (PV); seroprevalence to PV1, PV2 and PV3 was 85.9%, 93.4% and 83.3%, respectively. Rubella and measles antibody seroprevalence was 73.3% and 95.9%, respectively. In the 15-19 years age group, 48.2% [95% confidence interval (CI) 42.4-54.1] were susceptible to either PV1 or PV3, and 40.3% (95% CI 33.0-47.5) to rubella virus. Based on rubella antibody seroprevalence, we estimate that >600 infants are born with CRS in Cambodia annually. Significant numbers of Cambodian women are still susceptible to polio and rubella, especially those aged 15-19 years, emphasizing the need to include adults in VPD surveillance and a potential role for vaccination strategies targeted at adults.

Identification of serologic markers for school-aged children with congenital rubella syndrone

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. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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.

Progress toward measles and rubella elimination in Egypt.

Measles and rubella were common infectious diseases in Egypt during the prevaccine era. Monovalent measles vaccine was introduced in 1977, and measles vaccination coverage increased from <50% to >90% from 1980 to 1999; however, measles outbreaks continued to occur at 2- to 4-year intervals during this period. After the introduction of a second routine dose of measles vaccine as a combined measles-mumps-rubella (MMR) vaccine in 1999 and the implementation of measles immunization campaigns targeting 6- to 16-year-old children during 2000-2003, reported measles cases dramatically decreased by 2003. In 2002, Egypt established a goal to eliminate measles and rubella and to prevent congenital rubella syndrome (CRS) by 2010. Large-scale rubella and measles outbreaks in 2005-2007, however, led to a revision of the plan of action to achieve the 2010 goals. A nation-wide measles-rubella immunization campaign, targeting children, adolescents, and young adults 2-20 years old, was conducted in 2 phases during 2008-2009 and achieved coverage >95%. With the decrease to record low levels of cases of measles and rubella in 2009 and 2010, Egypt should achieve measles and rubella elimination in the near future, but high coverage(>95%) with 2 doses of measles-rubella vaccine needs to be maintained, measles-rubella surveillance strengthened, and CRS surveillance developed.

A systems level strategy for analyzing the cell death network: implication in exploring the apoptosis/autophagy connection.

The mammalian cell death network comprises three distinct functional modules: apoptosis, autophagy and programmed necrosis. Currently, the field lacks systems level approaches to assess the extent to which the intermodular connectivity affects cell death performance. Here, we developed a platform that is based on single and double sets of RNAi-mediated perturbations targeting combinations of apoptotic and autophagic genes. The outcome of perturbations is measured both at the level of the overall cell death responses, using an unbiased quantitative reporter, and by assessing the molecular responses within the different functional modules. Epistatic analyses determine whether seemingly unrelated pairs of proteins are genetically linked. The initial running of this platform in etoposide-treated cells, using a few single and double perturbations, identified several levels of connectivity between apoptosis and autophagy. The knock down of caspase3 turned on a switch toward autophagic cell death, which requires Atg5 or Beclin-1. In addition, a reciprocal connection between these two autophagic genes and apoptosis was identified. By applying computational tools that are based on mining the protein-protein interaction database, a novel biochemical pathway connecting between Atg5 and caspase3 is suggested. Scaling up this platform into hundreds of perturbations potentially has a wide, general scope of applicability, and will provide the basis for future modeling of the cell death network.

Rubella seroprevalence among women aged 15-39 years in Morocco.

This study was designed to determine the age-specific rubella seroprevalence in women of childbearing age in Morocco and to contribute to the development of a rubella vaccination strategy in the country. Of 967 women aged 15-39 years tested in 2000, 161 (16.6%) were susceptible to rubella based on absence of IgG antibodies. A significantly higher rate of susceptibility among women aged 15-19 years was observed (29.3%) compared with age 35-39 years (8.3%). An estimated 77,562 live births occur annually to rubella-susceptible women. No statistical difference in seroprevalence was seen between women in rural and urban areas (81.5% and 85.0% respectively). A substantial risk of rubella infection exists for Moroccan women of childbearing age.

Rubella seroprevalence among women aged 15-39 years in Morocco

This study was designed to determine the age-specific rubella seroprevalence in women of childbearing age in Morocco and to contribute to the development of a rubella vaccination strategy in the country. Of 967 women aged 15-39 years tested in 2000, 161 [16.6%] were susceptible to rubella based on absence of IgG antibodies. A significantly higher rate of susceptibility among women aged 15-19 years was observed [29.3%] compared with age 35-39 years [8.3%]. An estimated 77 562 live births occur annually to rubella-susceptible women. No statistical difference in seroprevalence was seen between women in rural and urban areas [81.5% and 85.0% respectively]. A substantial risk of rubella infection exists for Moroccan women of childbearing age

The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein.

The alternative reading frame (ARF) mRNA encodes two pro-death proteins, the nucleolar p19ARF and a shorter mitochondrial isoform, named smARF (hsmARF in human). While p19ARF can inhibit cell growth by causing cell cycle arrest or type I apoptotic cell death, smARF is able to induce type II autophagic cell death. Inappropriate proliferative signals generated by proto-oncogenes, such as c-Myc and E2F1, can elevate both p19ARF and smARF proteins. Here, we reveal a novel means of regulation of smARF protein steady state levels through its interactions with the mitochondrial p32. The p32 protein physically interacts with both human and murine smARF, and colocalizes with these short isoforms to the mitochondria. Remarkably, knocking down p32 protein levels significantly reduced the steady state levels of smARF by increasing its turn over. As a consequence, the ability of ectopically expressed smARF to induce autophagy and to cause mitochondrial membrane dissipation was significantly reduced. In contrast, the protein levels of full-length p19ARF, which mainly resides in the nucleolus, were not influenced by p32 depletion, suggesting that p32 exclusively stabilizes the mitochondrial smARF protein. Thus the interaction with p32 provides a means of specifically regulating the expression of the recently identified autophagic inducer, smARF, and adds yet another layer of complexity to the multifaceted regulation of the ARF gene.

Rubella mass campaigns.

The availability of vaccines that contain both measles and rubella components allows for the elimination of both diseases. Although routine infant vaccination with rubella vaccine has had profound effects on the incidence of both acquired and congenital rubella, mass vaccination rapidly stops circulation of the virus and prevents paradoxical increases in susceptibility of women that might result from decreased exposure in childhood. Whereas routine rubella vaccination has eliminated the infection from many developed countries, mass vaccination has rapidly accomplished the same goal in Latin America and the Caribbean, and is being applied in other developing country areas.

Rubella and measles seroprevalence among women of childbearing age, Argentina, 2002.

To assess rubella and measles susceptibility among women of childbearing age we conducted a cross-sectional seroprevalence study in four cities and one rural area in Argentina. A convenience sample of women aged 15-49 years seeking care in public health-care institutions was selected (n=2804). Serum specimens were tested for rubella and measles IgG antibody titres. The overall susceptibility to rubella and measles was 8.8 and 12.5% respectively. Seroprevalence differences were found for both rubella (P<0.001) and measles (P=0.002) across sites. Rubella seroprevalence was higher in women aged >or=40 years than in younger women (P=0.04). Measles seroprevalence tended to increase with age (P<0.001). Approximately 15% of women aged 15-29 years were not immune to measles. No risk factors were associated with rubella seronegativity; however, age (P<0.001) and having less than four pregnancies (P<0.001) were factors associated with measles seronegativity. Our findings support the introduction of supplemental immunization activities targeting adolescents and young adults to prevent congenital rubella syndrome and measles outbreaks over time.

[Congenital rubella syndrome in Costa Rica: importance of active surveillance]. / Síndrome de rubéola congénita en Costa Rica: importancia de reforzar la vigilancia activa.

OBJECTIVE: To identify cases of congenital rubella syndrome (CRS) and their form of presentation in children aged < 3 months in the National Children's Hospital of Costa Rica between 1996 and 2000. METHODS: Between 1996 and 2000, patients aged 1 day to 3 months with positive IgM serology for rubella, identified by means of the computerized database of the National Children's Hospital Laboratory, were selected. Their corresponding medical records were reviewed and the characteristics of these patients were analyzed. RESULTS: Sixty-six children with positive serology were identified, of which 49 had a complete medical record that allowed review. Of these, 29 (60 %) were boys. The mean age at which IgM serology was requested was 33 days. The principal manifestations leading to serology were hepatosplenomegaly, microcephaly and multiple congenital anomalies. The initial diagnosis was TORCH infection. Of the 49 patients, 45 were classified as CRS and four as infection with rubella. CONCLUSIONS: The present study highlights the need to increase active surveillance of CRS. Greater vigilance in applying the criteria for clinical diagnosis is required to allow an adequate degree of suspicion and early reporting of cases.

Síndrome de rubéola congénita en Costa Rica: importancia de reforzar la vigilancia activa / Congenital rubella syndrome in Costa Rica: importance of active surveillance

Objetivo: Identificar los casos de síndrome de rubéola congénita(SRC) y su forma de presentación en niños menores de3 meses atendidos en el Hospital Nacional de Niños de1996 a 2000. Métodos: En el período de 1996 a 2000 se seleccionaron los pacientes de un día de edad a 3 meses, con un positivo de serologíaI gM por rubéola, identificados por medio del registro computarizado del laboratorio. Se revisó la historia clínica correspondiente, analizando las características delos pacientes. Resultados: Se identificaron 66 niños con serología positiva, 49 tenían historia clínica completa que permitió la revisión. De éstos, 29 (60 %) eran varones. La edad media en que se solicitó la serología fue de 33 días. La hepatosplenomegalia, la microcefalia y las polimalformaciones fueron las tres principales manifestaciones por las cuales se solicitó la serología. El diagnóstico inicial que predominó fue el TORCHS (toxoplasmosis, rubéola, citomegalovirus, herpes,sífilis). Tras la revisión final de los 49 casos, 45 pacientes se clasificaron como SRC y cuatro como infección por rubéola. Conclusiones: El presente estudio pone de manifiesto la necesidad dereforzar la vigilancia activa permanente del SRC. Se debe reforzar la búsqueda de signos y síntomas, así como los antecedentes maternos que permitan la sospecha adecuada y la comunicación oportuna de los casos de SRC

Objective: To identify cases of congenital rubella syndrome (CRS)and their form of presentation in children aged < 3 months in the National Children’s Hospital of Costa Rica between1996 and 2000.MethodsBetween 1996 and 2000, patients aged 1 day to 3 months with positive IgM serology for rubella, identified by means of the computerized database of the National Children’s Hospital Laboratory, were selected. Their corresponding medical records were reviewed and the characteristics of these patients were analyzed. Results: Sixty-six children with positive serology were identified, of which 49 had a complete medical record that allowed review. Of these, 29 (60 %) were boys. The mean age at which IgM serology was requested was 33 days. The principal manifestations leading to serology were hepatospleno megaly, microcephaly and multiple congenital anomalies. The initial diagnosis was TORCH infection. Of the 49 patients, 45 were classified as CRS and four as infection with rubella. Conclusions: The present study highlights the need to increase active surveillance of CRS. Greater vigilance in applying the criteria for clinical diagnosis is required to allow an adequate degree of suspicion and early reporting of cases

A large rubella outbreak, Romania--2003.

Romania experienced a large rubella outbreak in 2002-03, with more than 115,000 reported cases nationwide, and an incidence of 531 reported cases per 100,000 population. The incidence was highest in children of school age. The cohorts of adolescent girls vaccinated in 1998 and 2002 (when a rubella-containing vaccine was available) had significantly lower incidence rates (p<0.001) compared with those in boys in the same age groups who were not vaccinated. In 2003, of the 150 suspected congenital rubella syndrome (CRS) cases reported, seven (4.6%) were confirmed by positive rubella IgM antibodies. In the absence of available rubella containing vaccine for outbreak control, an outbreak response plan to improve the detection of cases and to limit rubella virus transmission was developed. The following activities were conducted: surveillance of pregnant women with suspected rubella or history of exposure to rubella virus was implemented, with follow up of pregnancy outcomes; surveillance for CRS was strengthened; existing infection control guidelines to prevent disease transmission within healthcare facilities were reinforced; and a communication plan was developed. In May 2004, Romania is introducing measles, mumps and rubella (MMR) vaccine for routine vaccination of children aged 12 to 15 months, while continuing vaccination of girls in the 8th grade of school (13-14 years of age) with rubella-only vaccine.

Incidence of congenital rubella syndrome at a hospital serving a predominantly Hispanic population, El Paso, Texas.

OBJECTIVE: The current epidemiology of rubella reveals an increase in the number of cases among adult Hispanics and an increase in the number of congenital rubella syndrome (CRS) cases among infants of Hispanic mothers. Recent rubella outbreaks have occurred primarily among adult Hispanics, many of whom are foreign-born natives of countries where rubella vaccination is not routine or has only recently been implemented. The objective of this study was to estimate the incidence of CRS in a hospital serving a predominantly Hispanic population. METHODS: Hospital charts of infants <1 year old discharged between January 1, 1994 and December 31, 1996 with International Classification of Diseases, Ninth Revision (ICD-9) discharge codes consistent with CRS were reviewed; we looked for cataracts, deafness, congenital heart defects, dermal erythropoiesis, microcephaly, meningoencephalitis, and other defects associated with CRS. We abstracted data on maternal and infant ethnicity, maternal age, gestational age, infants' birth weight, infants' clinical characteristics, and laboratory evaluation. Cases were categorized according to the Council of State and Territorial Epidemiologists' case classification for CRS. RESULTS: Of the 182 infants with 1 or more ICD-9 codes consistent with CRS, 6 (3.3%) met either the confirmed or probable case definition for CRS. Two infants met the definition for confirmed CRS. Although laboratory tests for rubella immunoglobulin M antibodies were positive for both of these infants, only 1 of the cases had been reported to the state health department. Four other infants had clinical presentations that met the definition for a probable case. One of these had been tested for rubella immunoglobulin M antibodies, and the test was negative. The other 3 had not been tested. The rate of infants meeting the definition of confirmed and probable CRS was 3.1 per 10 000 hospital births. All confirmed and probable cases were among infants born to Hispanic mothers. Maternal country of origin was Mexico for the 2 confirmed cases and 1 of the probable cases, and unknown for the remaining 3 probable cases. CONCLUSION: The rate of confirmed and probable CRS among infants in this predominantly Hispanic population is higher than the reported rate in the United States in the vaccine era, which has been reported to range from approximately 0.01-0.08 per 10 000 live births. These findings indicate a need for heightened awareness of CRS among physicians who serve populations at risk for rubella. Physicians should report all confirmed and probable CRS cases to the state health department. The lack of appropriate laboratory testing in 3 infants with probable CRS indicates that physicians should consider a diagnosis of CRS in infants with some signs consistent with CRS, particularly in areas serving high numbers of individuals at risk for rubella.

A large rubella outbreak with spread from the workplace to the community.

CONTEXT: Childhood vaccination has reduced rubella disease to low levels in the United States, but outbreaks continue to occur. The largest outbreak in the past 5 years occurred in Nebraska in 1999. OBJECTIVES: To examine risk factors for disease, susceptibility of the risk population, role of vaccine failure, and the need for new vaccination strategies in response to the Nebraska rubella outbreak. DESIGN, SETTING, AND PATIENTS: Investigation of 83 confirmed rubella cases occurring in Douglas County, Nebraska, between March 23 and August 24, 1999; serosurvey of 413 pregnant women in the outbreak locale between October 1998 and March 1999 (prior to outbreak) and April and November 1999 (during and after outbreak). MAIN OUTCOME MEASURES: Case characteristics, compared with that of the general county population; area childhood rubella vaccination rates; and susceptibility among pregnant women before vs during and after the outbreak. RESULTS: All 83 rubella cases were unvaccinated or had unknown vaccination status and fell into 3 groups: (1) 52 (63%) were young adults (median age, 26 years), 83% of whom were born in Latin American countries where rubella vaccination was not routine. They were either employed in meatpacking plants or were their household contacts. Attack rates in the plants were high (14.4 per 1000 vs 0. 19 per 1000 for general county population); (2) 16 (19%), including 14 children (9 of whom were aged <12 months) and 2 parents, were US-born and non-Hispanic, who acquired the disease through contacts at 2 day care facilities (attack rate, 88.1 per 1000); and (3) 15 (18%) were young adults (median age, 22 years) whose major disease risk was residence in population-dense census tracts where meatpacking-related cases resided (R(2) = 0.343; P<.001); 87% of these persons were born in Latin America. Among pregnant women, susceptibility rates were 13% before the outbreak and 11% during and after the outbreak. Six (25%) of 24 susceptible women tested were seropositive for rubella IgM. Rubella vaccination rates were 90.2% for preschool children and 99.8% for school-aged children. CONCLUSIONS: A large rubella outbreak occurred among unvaccinated persons in a community with high immunity levels. Crowded working and living conditions facilitated transmission, but vaccine failure did not. Workplace vaccination could be considered to prevent similar outbreaks. JAMA. 2000;284:2733-2739.

Unseen blindness, unheard deafness, and unrecorded death and disability: congenital rubella in Kumasi, Ghana.

OBJECTIVES: Although rubella serosusceptibility among women of reproductive age in West Africa ranges from 10% to 30%, congenital rubella syndrome has not been reported. In Ghana, rubella immunization and serologic testing are unavailable. Our objectives were to identify congenital rubella syndrome cases, ascertain rubella antibody seroprevalence during pregnancy, and recommend strategies for congenital rubella syndrome surveillance. METHODS: Congenital rubella syndrome cases were identified through prospective surveillance and retrospective surveys of hospital records. A rubella serosurvey of pregnant urban and rural women was performed. RESULTS: Eighteen infants born within a 5-month period met the congenital rubella syndrome case definitions, coinciding with a 9-fold increase in presentation of infantile congenital cataract. The congenital rubella syndrome rate for this otherwise unrecorded rubella epidemic was conservatively estimated to be 0.8 per 1000 live births. A postepidemic rubella immunity rate of 92.6% was documented among 405 pregnant women; susceptibility was significantly associated with younger age (P = .000) and ethnicity (northern tribes, P = .024). CONCLUSIONS: Congenital rubella syndrome occurs in Ghana but is not reported. Information about congenital rubella syndrome and rubella in sub-Saharan Africa is needed to evaluate inclusion of rubella vaccine in proposed measles control campaigns.

Preparing for elimination of congenital Rubella syndrome (CRS): summary of a workshop on CRS elimination in the United States.

The goal of eliminating indigenous rubella and congenital rubella syndrome (CRS) in the United States in the near future is now within reach, because rubella incidence has been sustained at record-low levels since the mid-1990s. Effective prevention strategies to eliminate CRS and rubella require improvement in the surveillance of CRS and congenital rubella infection (CRI). The purpose of the workshop was to review rubella and CRS epidemiology, as well as current clinical, diagnostic, and laboratory practices, to determine whether new strategies are needed to achieve and document CRS elimination. Workshop participants agreed that surveillance for CRS must be strengthened, particularly through augmented laboratory capabilities, and the case definition for CRS must be revised to reflect the current scientific information available. Further studies of methods are needed to identify high-risk populations and geographic areas for rubella and CRS and to enhance identification of infants with CRS.