Rubini Strain Research Articles

Immunogenicity and persistence of trivalent measles, mumps, and rubella vaccines: a systematic review and meta-analysis

Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past two decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for the measles, mumps, and rubella components of MMR vaccines. In this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for randomised controlled trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published in English from database inception to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine, including different dosages and timepoints of vaccine administration. Studies featuring coadministration of MMR with other vaccines, maternal immunity to the MMR vaccine, or non-trivalent formulations of the vaccine were excluded. Pooled seroconversion and waning rates were estimated by random-effects meta-analyses. This study is registered with PROSPERO, CRD42019116705. We identified 3615 unique studies, 62 (1·7%) of which were eligible for analysis. Estimated overall seroconversion rates were 96·0% (95% CI 94·5-97·4; I2=91·1%) for measles, 93·3% (91·1-95·2; I2=94·9%) for mumps when excluding the Rubini strain, 91·1% (87·4-94·1; I2=96·6%) for mumps when including the Rubini strain, and 98·3% (97·3-99·2; I2=93·0%) for rubella. Estimated overall annual waning rates were 0·009 (95% CI 0·005-0·016; I2=85·2%) for measles, 0·024 (0·016-0·039; I2=94·7%) for mumps, and 0·012 (0·010-0·014; I2=93·3%) for rubella. Our meta-analysis provides estimates of primary and secondary vaccine failure, which are essential to improve the accuracy of mathematical and statistical modelling to understand and predict the occurrence of future measles, mumps, and rubella outbreaks in countries with high vaccine uptake. European Research Council.

Increasing mumps incidence rates among children and adolescents in the Republic of Korea: age–period–cohort analysis

To characterize the temporal dynamics of mumps epidemiology according to the different vaccine strains used, sex-specific trends were decomposed in an age-period-cohort (APC) analysis for mumps cases reported in South Korea. National surveillance data were used to describe the epidemiology of mumps cases from 2001 to 2015. An APC model was used to break down the reported mumps cases into the effects of age, period, and birth cohort. From 2001 to 2015, the incidence started to increase from fewer than 10 cases to more than 100 cases per 100 000. The incidence rate was highest among males aged 15-17 years during 2013-2015, reaching 508.7 per 100 000 persons. There was an increased incidence during the late teenage years in the 1998-2000 cohort. An age shift towards the earlier teenage years was observed across the 2001-2003 and 2004-2006 cohorts. The risk of mumps increased according to the birth cohort; the net drift from 2001 to 2015 was 27.67 (95% confidence interval 27.5.47-29.90) for males and 27.25 (95% confidence interval 24.91-29.65) for females. The increase in mumps seen in Korea may have been affected by the birth cohort exposed to the Rubini strain; however other factors may have contributed to the increase in non-exposed cohorts.

Mumps Outbreak among Highly Vaccinated Teenagers and Children in the Central Region of Portugal, 2012-2013.

Mumps vaccine was introduced in the National Immunization Program in Portugal in 1987, rapidly reaching a national coverage > 92%, with important reduction in the annual incidence of the disease. We report a mumps outbreak in the Central Region of Portugal, occurred in the winter 2012-13. Cases of salivary-gland swelling and other symptoms compatible with mumps were investigated. Geodemographics, clinical, laboratory and vaccination data were analyzed. Over six months, 148 outbreak-related cases were reported: 87.8% occurred in three of the 16 affected counties and 78.4% had a known epidemiological link. Median age was 14.5 years (2-62) and 70.3% were 11-20 years old; 61.5% were male. The mean duration of disease was seven days (2-20). The disease was generally mild; 80.4% had fever and in 55.4% there was unilateral involvement of the parotid gland. Seven cases had orchitis, one oophoritis and one had nephritis. Two cases were hospitalized. School transmission predominated and class attack rates were < 30%. Most of the cases occurred in vaccinated individuals (92%) of whom 86.8% had received 2 doses; 17.7% had received one dose of the vaccine containing the Rubini strain. Mumps virus genotype G was identified in 4 cases. This mumps outbreak among a highly vaccinated population, occurring mostly in teenagers at school, could be due to the partial effectiveness of the vaccine against the disease (particularly in the group vaccinated with Rubini strain), waning immunity overtime and genotype mismatch. This outbreak report shows the importance of discussion about the need of more booster dose of the actual vaccine or new vaccine including more genotypes to improve immunogenicity.

Resurgence of mumps in Korea.

Routine vaccination against mumps has markedly reduced its incidence. However, the incidence of mumps continuously has increased since 2007. In 2013, a large mumps epidemic occurred in Korea, and this epidemic is still an ongoing problem. This epidemic occurred primarily in school settings and affected vaccinated adolescents, predominantly male students. The recent resurgence of mumps is caused by multiple factors: suboptimal effectiveness of the current mumps vaccines, use of the Rubini strain vaccine, waning immunity in the absence of natural boosting due to the marked reduction in the mumps incidence, genotype mismatch between the vaccine and circulating mumps virus strains, and environmental conditions that foster intense exposures. Containment of mumps outbreaks is challenging because the sensitivity of diagnostic tests is low among vaccinees and control measures are less efficient because of the inherent nature of the mumps virus. Despite the suboptimal vaccine effectiveness in outbreak settings, maintaining the high vaccine coverage is an important strategy to prevent mumps outbreaks, given that the routine use of mumps vaccines has substantially reduced the incidence of mumps and its complications as compared with that in the pre-vaccine era. In order to control the current mumps epidemic and prevent further outbreaks, we need to better understand the dynamics of mumps among vaccinated populations and the changing epidemiology in Korea. Concerted efforts should be made to systematically monitor the immunization status of the Korean population and to improve diagnosis efficiency. Furthermore, more effective mumps vaccines need to be developed in the future.

Rebrote de parotiditis en la era vacunal. Factores implicados en un brote en Navarra, 2006–2007

We analysed a mumps outbreak that occurred in Navarre between August 2006 and December 2007, in which vaccinated persons were widely affected.Reports of mumps cases were completed by searching primary, emergency and hospital records and laboratory reports. Factors that could affect the occurrence of cases were analysed by birth cohort.A total of 2866 mumps cases were detected (attack rate 4.7/1000), with 61% of cases in men and a peak incidence at age 19 (inter-quartile range 16-25 years). 14% of cases were confirmed by laboratory: 59 by virus isolation, 14 by PCR and 333 by IgM. The G1 genotype was identified in 7 cases. 21% of cases had been born before 1980 (pre-vaccine cohorts), and 0.2% had not yet reached the vaccination age (15 months). In the cohorts born between 1980 and 2000 (with the opportunity for vaccination), 94.5% of cases had received at least one dose and 88.3%, two doses. 31% of cases occurred in cohorts vaccinated with a first (1995-1997) or second (1986-1988) dose of the Rubini strain. There was also a record of 772 cases who had received two doses of the Jeryl Lynn strain.This widespread outbreak is explained by the concurrence of various factors. The current vaccine has substantially reduced the incidence of mumps, but appears unable to totally eliminate virus circulation.

Mumps Outbreaks in Vaccinated Populations: Are Available Mumps Vaccines Effective Enough to Prevent Outbreaks?

Increased reports of mumps in vaccinated populations prompted a review of the performance of mumps vaccines. The effectiveness of prior vaccination with 1 dose of vaccine ranged from 72.8% to 91% for the Jeryl Lynn strain, from 54.4% to 93% for the Urabe strain, and from 0% to 33% for the Rubini strain. Vaccine effectiveness after 2 doses of mumps vaccine was reported in 3 outbreaks and ranged from 91% to 94.6%. There was evidence of waning immunity, which is a likely factor in mumps outbreaks, aggravated by possible antigenic differences between the vaccine strain and outbreak strains. Inadequate vaccine coverage or use of the Rubini vaccine strain accounted for the majority of outbreaks reviewed; however, some outbreaks could not be prevented, despite high vaccination coverage with 2 doses of the Jeryl Lynn vaccine strain. Our findings indicate the need for more-effective mumps vaccines and/or for review of current vaccination policies to prevent future outbreaks.

Brote de parotiditis vírica en un colegio de Bizkaia en 2006

Outbreaks of parotiditis have recently been recorded in Spain and in other developed countries. The possible reasons currently under consideration are the low degree of immunization coverage among the populations involved and/or the low degree of effectiveness of the vaccine strains employed. This study describes one outbreak of parotiditis having occurred in Bizkaia and assesses, the effectiveness of the vaccine strains and the usefulness of the diagnostic tests currently used. Those cases having compatible clinical symptoms and an epidemiological link within the period under study (February-May 2006) were labeled as cases. Blood samples were taken to study IgM and IgG and saliva for genotype and RNA detection. The immunization status and the strain used were found through the vaccine distribution records. A univariate analysis was conducted on the data and relative risks calculated according to the vaccine strains used. A total of 63 cases were detected, 52 being students from one school. Fifty percent were 9-13 years of age. A total of 88.5% of the cases detected at the school had been properly immunized. The IgM sensitivity was 9%, PCR sensitivity being 37%. The relative risk of those students immunized with an initial dose of Rubini strain as compared to those immunized with Jeryl-Lynn strain was 3.8 (95% CI:2.27-6.49). The high degree of immunization coverage does not prevent outbreaks from occurring in places having a high degree of exposure. The IgM reveals itself to be sensitive to a very small degree for the diagnosis of parotiditis. It seems necessary that the current immunization strategies and diagnostic methods be reconsidered.

Non-preventable mumps outbreaks in schoolchildren in Catalonia

Various doses of the combined MMR vaccine containing the Rubini mumps strain were distributed in Catalonia in 1994 and 1995. We studied outbreaks of mumps reported from 1997 to 2002 to determine the possible involvement of this vaccine in the appearance of non-preventable mumps outbreaks. A total of 17 mumps outbreaks were declared in the period 1997-2000, 14 of which were in schoolchildren. In 11, it was determined that children were correctly vaccinated. Of these, 10 were non-preventable outbreaks. 66% of cases investigated had ages which coincided with vaccination in the period 1994-1996, during which the MMR vaccine containing the Rubini mumps strain was administered. In Catalonia, during the period 1997-2000, at least two-thirds of mumps cases in schoolchildren could be explained by vaccination with the combined MMR vaccine containing the Rubini strain, which has also been associated with mumps outbreaks amongst vaccinated people in other countries.

Comparative efficacy of Rubini, Jeryl–Lynn and Urabe mumps vaccine in an Asian population

Objective The comparative efficacy of the three mumps vaccine strains (Jeryl–Lynn, Urabe and Rubini) was conducted in an Asian population from data arising from an epidemiological investigation of seven institutional outbreaks of mumps in Singapore. Methods Demographic information (gender, age, ethnic group), clinical presentation and vaccination history (date and place of mumps vaccination, type of mumps vaccine received) of all children who attended the six childcare centres and one primary school where outbreaks of 20 or more cases of mumps occurred in 1999 were collected. The attack rate of the unvaccinated group and the attack rates of the vaccine groups (for each vaccine strain) were determined and the vaccine efficacy of the three vaccines calculated. Results The vaccine efficacy of the Jeryl–Lynn strain, Urabe strain and Rubini strain mumps vaccine were 80.7, 54.4 and −55.3%, respectively. Conclusion Rubini strain mumps vaccine conferred no protection and has since been deregistered in Singapore.

Hemagglutinin-neuraminidase sequence and phylogenetic analyses of mumps virus isolates from a vaccinated population in Singapore.

During 1999-2000, a sustained mumps outbreak in the highly vaccinated population in Singapore was attributed to vaccine failure associated with the Rubini vaccine strain. To explain this phenomenon, the complete nucleotide and amino acid sequences of the hemagglutinin-neuraminidase (HN) gene of eight mumps virus isolates from patients with parotitis in Singapore were determined and compared with those of known vaccine strains. Phylogenetic trees constructed on the basis of HN nucleotide and amino acid sequences showed that the Singapore mumps virus isolates were more closely related to the Urabe strain and belonged to a different cluster from the Rubini and Jeryl-Lynn strains. The Rubini vaccine showed only approximately 93% nucleotide and approximately 96% amino acid sequence similarity to Urabe and Singapore isolates. Compared with the vaccine strains, six of the eight isolates lacked the extracellular glycosylation site at residues 400-402. Other significant amino acid disparities (e.g., at residue 354) may also affect the antigenic properties of the HN protein. These findings suggest that the evolution and adaptation of the currently circulating mumps virus strains in the community has led to the emergence of genetically distinct viral strains. The low vaccine efficacy of the Rubini strain represents a major reason for the recent mumps resurgence and failure of mumps immunization in Singapore.

Risk analysis of aseptic meningitis after measles-mumps-rubella vaccination in Korean children by using a case-crossover design.

Epidemiologic study of a vaccine's adverse events is not easy; so many countries have no reliable data. Vaccines containing the Urabe or Hoshino strain have been withdrawn from use in several countries. However, the data are not strong enough to form the basis of a recommendation not to use specific strains. The authors used a case-crossover design to estimate the relative risk of aseptic meningitis in children after receiving the measles-mumps-rubella vaccine in Korea. Study subjects were hospitalized children aged 8-36 months who had aseptic meningitis in 1998. Cases were confirmed by hospital chart reviews using previously defined criteria. Through a telephone survey, the authors obtained vaccination date and place information from parents' vaccination records. Study results showed that no significant risk was associated with the Jeryl Lynn or Rubini strain of the vaccine (relative risk = 0.6, 95% confidence interval (CI): 0.18, 1.97). For the Urabe or Hoshino strain, the relative risk was 5.5 (95% CI: 2.6, 11.8); the risk increased in the third week after vaccination (relative risk = 15.6, 95% CI: 5.9, 41.2) and was elevated until the sixth week. The case-crossover design was useful in confirming the risk of acute adverse events after receiving vaccines.

Mumps outbreak in vaccinated children in Gipuzkoa (Basque Country), Spain.

A mumps outbreak occurred in a group of vaccinated children aged 3-4 years in San Sebastián (Gipuzkoa, Basque Country, Spain) in 2000 during the same period as a revaccination campaign against measles-mumps-rubella (MMR) was performed. The clinical cases were confirmed by viral culture, detection of viral RNA and/or specific IgM. Eighty-eight percent of the children had been vaccinated with the Rubini strain and the remainder with the Jeryl-Lynn strain. The attack rate was 47.9% (35 cases in 73 school-attending children of this age). The outbreak was caused by an H genotype strain of mumps virus which was circulating at the same time as a D genotype strain that caused sporadic cases. By sequencing the small hydrophobic (SH) gene, the strains of the clinical cases were identified as wild-type mumps virus with heterologous genotypes in comparison to the vaccine strains used in our area.

Pediatric sentinel surveillance of vaccine-preventable diseases in Italy.

Planning and evaluating vaccination programs depend on reliable systems of monitoring disease incidence in the community. In Italy vaccine-preventable diseases are subject to statutory notification, but they are often unreported. In January, 2000, a pediatric sentinel network was launched, with the aim of monitoring in a timely and accurate way the geographic and temporal trends of vaccine-preventable diseases. The network consists of National Health System primary care pediatricians; participation is voluntary. The diseases under surveillance include measles, mumps, rubella, pertussis and varicella. Case definitions are based on specific clinical criteria, and pediatricians report cases on a monthly basis. Incidence rates are estimated and compared with those obtained by statutory notifications. The proportion of vaccinated cases is also computed. In 2000 an average of 468 pediatricians participated each month of a total of 7276 pediatricians under contract for primary care by the National Health System. The population under surveillance consisted of 371 670 children younger than 15 years (of a national total of 8.347.804 children of the same age). The annual national incidence per 100.000 children was estimated at 5345 for varicella, 1972 for mumps, 279 for pertussis, 108 for rubella and 62 for measles, although wide variations were observed among geographic areas. The national estimates are 3 to 7 times higher than those obtained through statutory notifications. For all of the diseases the ratio between the two sources of data was significantly higher in southern Italy, compared with the rest of the country. The proportion of vaccinated cases was similar for measles and rubella (21 and 17%) but was approximately 3 times higher for mumps (59%). Most (74%) of the vaccinated mumps cases had received the Rubini vaccine strain. The sentinel surveillance system is considerably more sensitive than statutory notifications, particularly in southern Italy. The high percentage of mumps cases vaccinated with the Rubini strain indicates a reduced effectiveness of this vaccine. Although further improvements are needed, pediatrician-based sentinel surveillance is a useful tool for evaluating vaccine-preventable disease trends.

Parotiditis en un área urbana de la Comunidad de Madrid. Estado vacunal, diagnóstico y medidas de intervención

To describe the epidemiological situation of an epidemic of mumps, to calculate the risk of catching the illness depending on the vaccine strain used and to evaluate the diagnostic performance of the serologic determination. Longitudinal observational study. The incidence of mumps between January 1999 and June 2000 was calculated. Case-control study of outbreaks evaluated the risk of catching the disease depending on the vaccine strain. Health Area 4 in the Community of Madrid. Residents and students from schools in the district.Interventions. Epidemiological vigilance. Serologic determination of IgM and titration of IgG. In outbreaks, people exposed were vaccinated after assessment of their vaccine status. The rate of incidence in the first 27 weeks of the year 2000 for the 1-4 year-old age group was 334.7/105, against 12.2 in 1999. In children under 5 vaccinated with the Rubini strain there was a significantly greater risk of suffering illness than in those vaccinated with the Jeryl-Lynn strain (OR, 6.28, 95% CI, 1.43-38.50). The amount of cases confirmed serologically (specific IgM positive) was 22.22%. The mean of the logarithms of the IgG titres was significantly higher (p < 0.001) in IgM-negative patients with epidemiological confirmation (4.05, 95% CI, 3.18-4.28) than in IgM-negative cases without any epidemiological link (2.58; 95% CI, 2.33-2.84). We emphasise the increase of mumps incidence in the school population (fundamentally in the under-5s), which parallels an increase in outbreaks. The results suggest that the Rubini strain is less efficacious. The possibility of using alternative methods to IgM detection (IgG titration) as a diagnostic tool in a population with high vaccination coverage is posed.

Two outbreaks of mumps in children vaccinated with the Rubini strain in Spain indicate low vaccine efficacy.

This paper reports a descriptive study of two outbreaks of mumps in Spanish towns in 1998 and an assessment of the efficacy of the vaccine used. It provides evidence of the low level of protection against the mumps virus that has been observed previously

Comparative efficacy of three mumps vaccines during disease outbreak in eastern Switzerland: cohort study

After the introduction of immunisation against measles, mumps, and rubella, numerous outbreaks of mumps were reported in the 1980s and ‘90s in Switzerland and southern Europe.1 2 The Rubini strain...

Efectividad comunitaria de las vacunas frente a la Parotiditis Infecciosa. Estudio de casos

BACKGROUND: In our country, there are two types of infectious mumps vaccines available. In recent times, doubts have been raised regarding the overall effectiveness of these vaccines and the comparative effectiveness of the two strains (Rubini strain and Jeryl Lynn strain). In the East Seville Primary Care district, 245 cases were reported in 1997 (90.1 cases per 100,000 inhabitants). This study is aimed at taking advantage of the outbreak of cases of mumps to evaluate affected populations and comparative incidence according to type of vaccines given during childhood. METHODS: Descriptive analysis of the cases (age, territorial spread, inoculation history ) and trend analysis (annual incident rates) within this health care district and the surrounding area. The overall effectiveness of the mumps vaccines. The case incidence rates among those inoculated with Rubini strain and those inoculated with Jeryl Lynn strain are also estimated. RESULTS: The highest rates of incidence are found among children in the 1-4 age range. Overall effectiveness rates for these vaccines have been estimated. A significantly higher rate of infection has been found among the children inoculated with Rubini strain than those inoculated with the Jeryl Lynn strain (relative risk of 6.5 with a Confidence Interval of 95% 3.6-11.8). CONCLUSIONS: The effectiveness which follows from this study does not seem as good as the theoretical effectiveness anticipated for the mumps vaccines. It thus seems advisable for other case studies to be conducted by types of vaccines used. The data to be furnished by means of sero-epidemiological studies are also of major interest.

Field evaluation of the clinical effectiveness of vaccines against pertussis, measles, rubella and mumps

Beginning in March 1995, in the adjacent provinces of Benevento and Campobasso in Southern Italy, we carried out a sentinal, paediatrician-based surveillance on pertussis, measles, rubella and mumps with the aim of evaluating the health impact of new vaccination programmes and the objectives of describing the time-space trends and estimating the effectiveness of new vaccinations. The study population consisted of 16500 children attended by 25 paediatricians. The estimated effectiveness of vaccines for pertussis, measles and rubella were close to the expected values, although a very low effectiveness was calculated for the mumps vaccine. The comparison among children vaccinated with various strains showed a diseases odds ration of 2.5 for the children vaccinated with Rubini strain. The effectiveness of this strain has to be verified in more rigorous settings.

An Outbreak of Mumps in a Population Partially Vaccinated with the Rubini Strain

Since 1991, 6 years after the recommendation of universal childhood triple vaccination against measles, mumps and rubella (M + M + R), Switzerland has been confronted with an increasing number of mumps cases affecting both vaccinated and unvaccinated children. The M + M + R vaccine mainly used in the Swiss population after 1986 contains the highly attenuated Rubini strain of mumps virus. We analysed an outbreak of 102 suspected mumps cases by virus isolation, determination of IgM antibodies to mumps virus in 27 acute phase sera, and verification of vaccination histories. Mumps was confirmed by virus isolation in 88 patients, of whom 72 had previously received the Rubini vaccine strain. IgM antibodies to mumps virus were detected in 24/27 acute phase serum samples. A group of 92 subjects from the same geographic area without signs of mumps virus infection served as controls. IgG antibodies to mumps virus and vaccination status were assessed in these children. The vaccination rate in these controls was 61%, with equal seropositivity for unvaccinated and Rubini-vaccinated subjects. These data support other recent reports which indicate an insufficient protective efficacy of current mumps vaccines.

Mumps epidemiology in Switzerland: results from the Sentinella surveillance system 1986-1993. Sentinella Work Group

Since 1990, there have been reports of an increasing number of mumps cases in Switzerland, in particular among vaccinated children, and of local outbreaks of mumps. Using data from the Sentinella reporting system, a network of voluntary participating doctors (general practitioners, internists and paediatricians, yearly average: n = 141), trends and factors influencing mumps incidence in the general population were assessed during the last seven years. Following an initial decline in mumps reports, since 1990, there has been a continuous and marked increase in reports from a minimum of 0.7 cases per physician and year in 1989/90 to a near five-fold increase of 3.3 cases in the last reporting period from June-December 1993 (calculated for one year). Half of this increase, which is reflected in a doubling of the number of cases reported in 1986/87, is explained by an increase in cases among vaccinated children. The trend in mumps cases contrasts with that of measles and rubella, where there has been a clear decline in these reports since 1986 (approximately 70-80%). Complications were reported in 75 (4.0%) of the total number of mumps patients (n = 1894); in 2/5 of the cases this was a meningitis, in 1/3 an orchitis. Based on available data on vaccination coverage, the estimated efficacy of the mumps vaccines against parotitis is between 47-77%; this is clearly lower than the corresponding figure for measles (91-97%) and rubella (89-97%) vaccines. The relatively low efficacy against parotitis is mainly due to a protective level of 13-73% of the vaccines containing the Rubini strain. The estimated efficacy of the Rubini vaccines against complications is 50-81%; it is nearly 60-90% if a possible reporting bias is taken into consideration. 1. The Rubini strain vaccines, which are the most commonly used in Switzerland, seem to have played an important role in the clear increase in mumps cases since 1990. 2. The situation seems more favourable concerning the efficacy against complications of the vaccines used. 3. Our data support the high efficacy of all measles and rubella vaccines. 4. The surveillance of MMR by the Sentinella reporting system provides a useful and effective manner to evaluate the MMR vaccination programme.