Characteristics of Large Mumps Outbreaks in the United States, July 2010-December 2015.

BACKGROUND: Mumps is an acute viral illness that classically presents with parotitis. Although the United States experienced a 99% reduction in mumps cases following implementation of the 2-dose vaccination program in 1989, mumps has resurged in the past 10 years. METHODS: We assessed the epidemiological characteristics of mumps outbreaks with ≥20 cases reported in the United States electronically through the National Notifiable Diseases Surveillance System and from supplemental outbreak data through direct communications with jurisdictions from July 2010 through December 2015. Mumps cases were defined using the 2012 Council of State and Territorial Epidemiologists case definition. RESULTS: Twenty-three outbreaks with 20-485 cases per outbreak were reported in 18 jurisdictions. The duration of outbreaks ranged from 1.5 to 8.5 months (median, 3 months). All outbreaks involved close-contact settings; 18 (78%) involved universities, 16 (70%) occurred primarily among young adults (median age, 18-24 years), and 9 (39%) occurred in highly vaccinated populations (2-dose measles-mumps-rubella vaccine coverage ≥85%). CONCLUSIONS: During 2010-2015, multiple mumps outbreaks among highly vaccinated populations in close-contact settings occurred. Most cases occurred among vaccinated young adults, suggesting that waning immunity played a role. Further evaluation of risk factors associated with these outbreaks is warranted.

Antibody Levels at 3-Years Follow-Up of a Third Dose of Measles-Mumps-Rubella Vaccine in Young Adults.

Mumps outbreaks and breakthrough infections of measles and rubella have raised concerns about waning of vaccine-induced immunity after two doses of measles-mumps-rubella (MMR) vaccination. In the present follow-up study, serum IgG antibodies against mumps, measles and rubella, as well as the functional neutralizing antibodies against both the mumps vaccine strain and mumps outbreak strains were measured longitudinally in young adults that received a third MMR (MMR3) dose. The mumps-specific IgG and virus neutralizing antibody levels at 3 years after vaccination were still elevated compared to pre-vaccination antibody levels, although the differences were smaller than at earlier timepoints. Interestingly, subjects with low antibody levels to mumps before vaccination benefited the most as they showed the strongest antibody increase after an MMR3 dose. Three years after an MMR3 dose, all subjects had antibody levels to measles and rubella above the internationally agreed antibody cutoff levels for clinical protection. Our data support the recommendation that an MMR3 dose may provide additional protection for those that have become susceptible to mumps virus infection during outbreaks. MMR3 also resulted in an increase in anti-measles and rubella antibody levels that lasted longer than might have been expected.

Mumps-specific IgG, IgG subclasses and neutralization titres to the vaccine and outbreak mumps strains differ in vaccinated healthy controls, breakthrough mumps infection cases and naturally infected individuals.

BACKGROUND: Despite widespread use of the mumps vaccine resulting in significant reduction in the incidence of symptomatic mumps infection, large outbreaks continue to occur in highly vaccinated populations. OBJECTIVES: We examined the mumps-specific IgG, IgG subclasses and neutralization titres to the outbreak Genotype G5 and Jeryl Lynn vaccine (Genotype A) mumps strains. STUDY DESIGN: Sera from 207 individuals were classified into five distinct cohorts: healthy controls and mumps cases of 5-17 years and 18-25 years, and naturally infected individuals of 50+ years. Mumps specific IgG and IgG subclass levels were measured using modified ELISA assays with lysates and nucleoprotein antigens from both the mumps vaccine and circulating Genotype G5 strains. All sera were investigated for in vitro neutralizing antibody titres (GMT) using focus reduction neutralization assays. Data was analysed using the Kruskal-Wallis test and pairwise Wilcoxon tests. RESULTS: Mumps cases had higher mumps IgG levels compared to controls, to both the vaccine and outbreak strains, however levels decreased with age. Mumps IgG3 levels were significantly raised in mumps cases (p < 0.001). Neutralization titres were lower to the outbreak strain in all cohorts with titres markedly lower in the mumps cohorts compared to healthy controls. Mean GMT to the vaccine strain increased with age. The naturally infected group displayed the highest GMT to the JL vaccine and the lowest GMT to the outbreak strain. CONCLUSIONS: Antigenic differences between mumps vaccine strain and circulating mumps viruses decrease the cross-neutralization capacity of vaccine-induced antibodies which may play a role in breakthrough infection.

Mumps Outbreaks in Vaccinated Populations-Is It Time to Re-assess the Clinical Efficacy of Vaccines?

History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vaccinated individuals, demonstrating a benefit of this vaccine. Therefore, the question of what constitutes a good mumps vaccine and how its impact is assessed in this modern era remains to be addressed. Epidemiology of the individuals most affected by the outbreaks (predominantly young adults) and variance in the circulating MuV genotype have been well-described alluding to a collection of influences such as vaccine hesitancy, heterogeneous vaccine uptake, primary, and/or secondary vaccine failures. This review aims to discuss in detail the interplay of factors thought to be contributing to the current mumps outbreaks seen in highly vaccinated populations. In addition, how mumps diagnoses has progressed and impacted the understanding of mumps infection since a mumps vaccine was first developed, the limitations of current laboratory tests in confirming protection in vaccinated individuals and how vaccine effectiveness is quantified are also considered. By highlighting knowledge gaps within this area, this state-of-the-art review proposes a change of perspective regarding the impact of a vaccine in a highly vaccinated population from a clinical, diagnostic and public perspective, highlighting a need for a paradigm shift on what is considered vaccine immunity.

Presence of low mumps-specific IgG in oral fluids is associated with high mumps viral loads.

BACKGROUND: Mumps outbreaks continue to occur in highly vaccinated populations. Although the diagnosis of mumps is primarily based on clinical symptoms, other viral infections such as parainfluenza can manifest in a similar manner. Therefore, laboratory confirmation of mumps virus infection is important. OBJECTIVES: The aims of this study were to examine mumps cases during the January 2018 to March 2019 period in Ireland as well as to evaluate the association between mumps RNA viral loads, mumps IgG levels, age and gender among patients with laboratory-confirmed mumps virus infection. STUDY DESIGN: Oral fluid samples requested for mumps RNA testing (n = 1296) were included in the study. The mumps N gene was detected by real time PCR and reported as Ct values. RESULTS: The proportion of samples received monthly with detectable mumps RNA increased from 10.26%-70.3% during the recent outbreak. Acute mumps cases occurred predominantly in the 16-25 years old age cohort (67.5 %) and in males (55.9 %). Mumps RNA viral loads were significantly higher in females (p < 0.001). During the outbreak, a significantly higher proportion of samples had Ct <30 (p < 0.05). A significant correlation was observed between mumps IgG levels and Ct values in oral fluid samples (p < 0.0001). CONCLUSIONS: The presence of low mumps virus-specific IgG in oral fluids is significantly associated with high mumps viral loads. Our findings show that mumps virus is maintained in circulation in the non-outbreak period and acute mumps cases occur predominantly in the MMR vaccinated young adult male population.

Mumps outbreaks in a highly vaccinated population: Investigation of a neutralization titre against the current circulating wildtype genotype G5 mumps virus.

BACKGROUND: Mumps outbreaks continue to occur globally, despite high levels of uptake of the mumps vaccine. OBJECTIVES: In order to address immunity to the current circulating wildtype virus, we sought to determine a mumps G5 specific IgG quantitative value which correlates with genotype G5 specific neutralization ability in vitro. STUDY DESIGN: Sera from 199 individuals including controls and acute mumps cases were assessed for mumps specific IgG titres using five different enzyme immunoassays coated with antigen from different mumps virus strains. A subset of 66 sera was also assessed for in vitro neutralizing antibody against a contemporary circulating genotype G5 mumps virus. RESULTS: For all the different antigenic targets, mumps specific IgG titres were higher in patients following acute mumps infection compared to controls. In acute mumps infected patients, females showed significantly higher serum titres of anti-G5 IgG compared to males (p<0.05). Furthermore, control males did not show any change in G5 specific IgG with increasing age whereas females show a progressive rise in titre. Linear regression analysis revealed a significant association between the mumps G5 specific IgG levels in the EIA and the in vitro neutralization titres (r(2)=0.59). CONCLUSIONS: Specific IgG to the current circulating genotype G5 mumps strain showed significantly lower titres in males which supports our previous observation that there is a male gender bias in cases of acute mumps infection. Furthermore, in this preliminary study, the data indicate that genotype G5 specific IgG levels of >40 RU/ml are required for neutralization capability to be observed in vitro.