Measles, Mumps, and Rubella Antibody: Patterns of Persistence and Rate of Decline Following the Second Dose of the MMR Vaccine
Open Forum Infectious Diseases
Background Antibodies to measles, mumps, and rubella decline an estimated average of 3% per year,... more Background Antibodies to measles, mumps, and rubella decline an estimated average of 3% per year, and have a high degree of variation among individuals. Yet, this variation and differences in individual-level response to the 3 antigens are not well understood. To better understand potential implications on individual and population-level susceptibility, we reanalyzed existing longitudinal data to identify patterns of seropositivity and antibody persistence. Methods Wisconsin children given the second dose of measles, mumps, and rubella vaccine (MMR2) at age 4–6 years were followed up to 12 years postvaccination. The rate of antibody decline and factors associated with the rate of decline were assessed using regression models that accounted for differences between and among 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 me...
Qualitative Variation Among Commercial Immunoassays to Detect Measles-Specific IgG
Journal of Clinical Microbiology
Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity amon... more Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary re-vaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization (PRN), the gold standard method and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there ...
Notes from the Field: Absence of Asymptomatic Mumps Virus Shedding Among Vaccinated College Students During a Mumps Outbreak - Washington, February-June 2017
Mumps Virus Nucleoprotein and Hemagglutinin-Specific Antibody Response Following a Third Dose of Measles Mumps Rubella Vaccine
Open forum infectious diseases, 2017
Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised qu... more Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised questions regarding the potential benefits of a third dose of vaccine (MMR3). If MMR3 provides a sustained elevation in mumps antibody, it may be beneficial for certain at-risk groups or as an outbreak control measure. Sera were collected immediately prior to MMR3 and at 1 month and 1 year post-MMR3 from 656 healthy adults aged 18-28 years in a nonoutbreak setting. Immunoglobulin G (IgG) was measured by enzyme-linked immunosorbent assay (ELISA) using whole mumps virus (commercial ELISA), hemagglutinin (HN; major neutralizing target), and nucleoprotein (NP; immunodominant) antigens. ELISA measurements were compared with in vitro plaque reduction neutralization (PRN) titers, and baseline antibody was compared with post-MMR3 levels. There were modest but statistically significant (P < .05) increases in mumps antibody at 1 month post-MMR3 by all 3 ELISA methods and by PRN titer. At 1 year p...
Measles, mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine
Vaccine, Jan 6, 2018
Antibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree ... more 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. Children vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4-6 years of age were followed up to 12 years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects. 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 ...
High concentrations of measles neutralizing antibodies and high avidity measles IgG accurately identify measles reinfection cases
Clinical and Vaccine Immunology, 2016
In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred i... more In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis...
Measles Outbreak Associated with Low Vaccine Effectiveness among Adults — Pohnpei State, Federated States of Micronesia, 2014
Open Forum Infectious Diseases, 2016
Background. A measles outbreak in Pohnpei State, Federated States of Micronesia in 2014 affected... more Background. A measles outbreak in Pohnpei State, Federated States of Micronesia in 2014 affected many persons who had received ≥1 dose of measles-containing vaccine (MCV). A mass vaccination campaign targeted persons aged 6 months to 49 years, regardless of prior vaccination. Methods. We evaluated vaccine effectiveness (VE) of MCV by comparing secondary attack rates among vaccinated and unvaccinated contacts after household exposure to measles. Results. Among 318 contacts, VE for precampaign MCV was 23.1% (95% confidence interval [CI], −425 to 87.3) for 1 dose, 63.4% (95% CI, −103 to 90.6) for 2 doses, and 95.9% (95% CI, 45.0 to 100) for 3 doses. Vaccine effectiveness was 78.7% (95% CI, 10.1 to 97.7) for campaign doses received ≥5 days before rash onset in the primary case and 50.4% (95% CI, −52.1 to 87.9) for doses received 4 days before to 3 days after rash onset in the primary case. Vaccine effectiveness for most recent doses received before 2010 ranged from 51% to 57%, but it...
Measles Virus Neutralizing Antibody Response, Cell-Mediated Immunity, and Immunoglobulin G Antibody Avidity Before and After Receipt of a Third Dose of Measles, Mumps, and Rubella Vaccine in Young Adults
Seroprevalence of Mumps Antibody in the U.S. Population, 1999-2004
Background: The US has set the goal of mumps elimination by 2010. In 2006, however, the largest m... more Background: The US has set the goal of mumps elimination by 2010. In 2006, however, the largest mumps outbreak in 20 years occurred. We describe the mumps antibody prevalence using data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population, conducted during 1999-2004. Methods: A mumps-specific enzyme immunoassay was used to measure the presence of mumps IgG antibody (Ab) in sera from NHANES participants 6-49 years of age. For analysis, participants were grouped by ten-year birth cohort. Prevalence estimates and 95% Confidence Interval (CI) were age-adjusted and calculated using SUDAAN. Logistic regression was performed to identify the independent predictors. Results: Overall mumps IgG Ab seroprevalence in the US population 6-49 years of age was 90.0% (95% CI 88.8-91.1%). Age-adjusted mumps Ab seroprevalence was higher among non-Hispanic blacks (NHB) (96.4% [95% CI 95.5-97.1%]) and Mexican-Americans (MA) (92.1% [95...
Etiologic Investigation of Sporadic Cases of Parotitis
Background: The etiology of sporadic parotitis cases is often undetermined. Mumps cannot be exclu... more Background: The etiology of sporadic parotitis cases is often undetermined. Mumps cannot be excluded based on negative serologic or viral test results, especially in vaccinees. Other viruses known to cause parotitis are not routinely assessed. This project examined the frequency of viruses identified from patients with parotitis, but without a known exposure to mumps virus. Methods: Eight participating states submitted specimens from parotitis cases that occurred in 2009 through 2011. According to routine practice, cases of parotitis were investigated on the assumption they were mumps (swelling of the parotid or other salivary gland for ≥2 days). Buccal and throat swabs were collected. If the patient was not epidemiologically linked to a confirmed or probable case of mumps, the swab was sent to CDC, where it was tested for the presence of viral nucleic acids for mumps virus (MuV), enteroviruses (EV), human parechovirus (HPeV), human herpesviruses 6A & 6B (HHV-6A & HHV-6B), Epstein-B...
Measles, Mumps, and Rubella Antibody: Patterns of Persistence and Rate of Decline Following the Second Dose of the MMR Vaccine
Open Forum Infectious Diseases
Background Antibodies to measles, mumps, and rubella decline an estimated average of 3% per year,... more Background Antibodies to measles, mumps, and rubella decline an estimated average of 3% per year, and have a high degree of variation among individuals. Yet, this variation and differences in individual-level response to the 3 antigens are not well understood. To better understand potential implications on individual and population-level susceptibility, we reanalyzed existing longitudinal data to identify patterns of seropositivity and antibody persistence. Methods Wisconsin children given the second dose of measles, mumps, and rubella vaccine (MMR2) at age 4–6 years were followed up to 12 years postvaccination. The rate of antibody decline and factors associated with the rate of decline were assessed using regression models that accounted for differences between and among 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 me...
Qualitative Variation Among Commercial Immunoassays to Detect Measles-Specific IgG
Journal of Clinical Microbiology
Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity amon... more Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary re-vaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization (PRN), the gold standard method and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there ...
Notes from the Field: Absence of Asymptomatic Mumps Virus Shedding Among Vaccinated College Students During a Mumps Outbreak - Washington, February-June 2017
Mumps Virus Nucleoprotein and Hemagglutinin-Specific Antibody Response Following a Third Dose of Measles Mumps Rubella Vaccine
Open forum infectious diseases, 2017
Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised qu... more Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised questions regarding the potential benefits of a third dose of vaccine (MMR3). If MMR3 provides a sustained elevation in mumps antibody, it may be beneficial for certain at-risk groups or as an outbreak control measure. Sera were collected immediately prior to MMR3 and at 1 month and 1 year post-MMR3 from 656 healthy adults aged 18-28 years in a nonoutbreak setting. Immunoglobulin G (IgG) was measured by enzyme-linked immunosorbent assay (ELISA) using whole mumps virus (commercial ELISA), hemagglutinin (HN; major neutralizing target), and nucleoprotein (NP; immunodominant) antigens. ELISA measurements were compared with in vitro plaque reduction neutralization (PRN) titers, and baseline antibody was compared with post-MMR3 levels. There were modest but statistically significant (P < .05) increases in mumps antibody at 1 month post-MMR3 by all 3 ELISA methods and by PRN titer. At 1 year p...
Measles, mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine
Vaccine, Jan 6, 2018
Antibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree ... more 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. Children vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4-6 years of age were followed up to 12 years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects. 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 ...
High concentrations of measles neutralizing antibodies and high avidity measles IgG accurately identify measles reinfection cases
Clinical and Vaccine Immunology, 2016
In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred i... more In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis...
Measles Outbreak Associated with Low Vaccine Effectiveness among Adults — Pohnpei State, Federated States of Micronesia, 2014
Open Forum Infectious Diseases, 2016
Background. A measles outbreak in Pohnpei State, Federated States of Micronesia in 2014 affected... more Background. A measles outbreak in Pohnpei State, Federated States of Micronesia in 2014 affected many persons who had received ≥1 dose of measles-containing vaccine (MCV). A mass vaccination campaign targeted persons aged 6 months to 49 years, regardless of prior vaccination. Methods. We evaluated vaccine effectiveness (VE) of MCV by comparing secondary attack rates among vaccinated and unvaccinated contacts after household exposure to measles. Results. Among 318 contacts, VE for precampaign MCV was 23.1% (95% confidence interval [CI], −425 to 87.3) for 1 dose, 63.4% (95% CI, −103 to 90.6) for 2 doses, and 95.9% (95% CI, 45.0 to 100) for 3 doses. Vaccine effectiveness was 78.7% (95% CI, 10.1 to 97.7) for campaign doses received ≥5 days before rash onset in the primary case and 50.4% (95% CI, −52.1 to 87.9) for doses received 4 days before to 3 days after rash onset in the primary case. Vaccine effectiveness for most recent doses received before 2010 ranged from 51% to 57%, but it...
Measles Virus Neutralizing Antibody Response, Cell-Mediated Immunity, and Immunoglobulin G Antibody Avidity Before and After Receipt of a Third Dose of Measles, Mumps, and Rubella Vaccine in Young Adults
Seroprevalence of Mumps Antibody in the U.S. Population, 1999-2004
Background: The US has set the goal of mumps elimination by 2010. In 2006, however, the largest m... more Background: The US has set the goal of mumps elimination by 2010. In 2006, however, the largest mumps outbreak in 20 years occurred. We describe the mumps antibody prevalence using data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population, conducted during 1999-2004. Methods: A mumps-specific enzyme immunoassay was used to measure the presence of mumps IgG antibody (Ab) in sera from NHANES participants 6-49 years of age. For analysis, participants were grouped by ten-year birth cohort. Prevalence estimates and 95% Confidence Interval (CI) were age-adjusted and calculated using SUDAAN. Logistic regression was performed to identify the independent predictors. Results: Overall mumps IgG Ab seroprevalence in the US population 6-49 years of age was 90.0% (95% CI 88.8-91.1%). Age-adjusted mumps Ab seroprevalence was higher among non-Hispanic blacks (NHB) (96.4% [95% CI 95.5-97.1%]) and Mexican-Americans (MA) (92.1% [95...
Etiologic Investigation of Sporadic Cases of Parotitis
Background: The etiology of sporadic parotitis cases is often undetermined. Mumps cannot be exclu... more Background: The etiology of sporadic parotitis cases is often undetermined. Mumps cannot be excluded based on negative serologic or viral test results, especially in vaccinees. Other viruses known to cause parotitis are not routinely assessed. This project examined the frequency of viruses identified from patients with parotitis, but without a known exposure to mumps virus. Methods: Eight participating states submitted specimens from parotitis cases that occurred in 2009 through 2011. According to routine practice, cases of parotitis were investigated on the assumption they were mumps (swelling of the parotid or other salivary gland for ≥2 days). Buccal and throat swabs were collected. If the patient was not epidemiologically linked to a confirmed or probable case of mumps, the swab was sent to CDC, where it was tested for the presence of viral nucleic acids for mumps virus (MuV), enteroviruses (EV), human parechovirus (HPeV), human herpesviruses 6A & 6B (HHV-6A & HHV-6B), Epstein-B...
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