Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-17 (of 17 Records) |
Query Trace: Sowers SB[original query] |
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Long-term neutralizing antibody levels against measles and rubella viruses among adults with 3 doses of measles-mumps-rubella vaccine
Alonge OD , Marin M , Hickman CJ , Sowers SB , Chen MH , Hao L , Mercader S , El-Badry E , McClure DL , Icenogle JP , Sugerman DE , Crooke SN , Nguyen HQ . Open Forum Infect Dis 2024 11 (1) ofad700 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. |
Performance Characteristics of Six Immunoglobulin M (IgM) ELISA Assays Used for Laboratory Confirmation of Measles (preprint)
Sowers SB , Anthony K , Mercader S , Colley H , Crooke SN , Rota PA , Latner DR , Hickman CJ . medRxiv 2022 04 Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles specific IgM in serum by enzyme linked immunosorbent assay (ELISA) is the most used method for confirming measles infection. ELISA formats vary as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false negative result, which can delay confirmation of measles cases. Interfering substances can yield a false positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against 5 commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; sensitivity and specificity for the commercial kits ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False positive results occurred in 2.0 to 13.1% of sera while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high quality measles surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Etiological analysis of discarded measles in the context of a measles outbreak among a highly immunized population
Torner N , Mercader S , Dominguez A , Martinez A , Costa J , Sowers SB , Abernathy ES , Bellini WJ , Hickman CJ . Pediatr Int 2022 65 (1) e15430 BACKGROUND: Measles can lead to serious complications and remains an important cause of morbidity and mortality worldwide. We aimed to assess the etiological diagnosis of discarded measles cases in the context of an outbreak among a highly immunized population. METHODS: We conducted a retrospective observational study of discarded measles cases from an outbreak that occurred from October 2006 to July 2007 in Catalonia. A confirmed case was defined as having a positive measles serum IgM result and/or a positive result by RT-PCR in urine and/or nasopharyngeal swab; or an epidemiological link to a confirmed case. Serum specimens were tested by a commercially available indirect-format and by an in-house capture-format measles IgM enzyme immunoassays. RESULTS: Testing of 89 samples discarded for measles determined the etiologies for 10 (11.2%), including 1 rubella, 3 human herpes virus 6, and 6 measles infections. Of 381 confirmed cases in the outbreak, 10% had received at least one dose of the measles-mumps-rubella vaccine versus 54% of the discarded for measles (OR=0.09: 95%CI 0.06, 0.14; p<0.001). CONCLUSIONS: Highly sensitive surveillance systems are critical to identifying cases, responding to outbreaks and verifying progress towards measles elimination. Molecular tools for measles detection and differential diagnosis, and collection of appropriate specimens for molecular and serologic testing are essential to correctly diagnose suspected measles infection. |
Performance characteristics of six immunoglobulin m enzyme-linked immunosorbent assays used for laboratory confirmation of measles
Sowers SB , Anthony K , Mercader S , Colley H , Crooke SN , Rota PA , Latner DR , Hickman CJ . J Clin Microbiol 2022 60 (12) e0122722 Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles-specific IgM in serum by enzyme-linked immunosorbent assay (ELISA) is the most common method used to confirm measles infection. ELISA formats vary, as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false-negative result, which can delay confirmation of measles cases. Interfering substances can yield a false-positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against five commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; the sensitivity and specificity for each commercial kit ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False-positive results occurred in 2.0 to 13.1% of sera, while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high-quality measles surveillance. |
Preservation of lymphocyte functional fitness in perinatally-infected and treated HIV+ pediatric patients displaying sub-optimal viral control
Khanolkar A , Muller WJ , Simpson BM , Cerullo J , Williams R , Sowers SB , Matthews K , Mercader S , Hickman CJ , D'Aquila RT , Liu G . Commun Med (Lond) 2022 2 BACKGROUND: Host-pathogen dynamics associated with HIV infection are quite distinct in children versus adults. We interrogated the functional fitness of the lymphocyte responses in two cohorts of perinatally infected HIV+ pediatric subjects with early anti-retroviral therapy (ART) initiation but divergent patterns of virologic control. We hypothesized that sub-optimal viral control would compromise immune functional fitness. METHODS: The immune responses in the two HIV+ cohorts (n = 6 in each cohort) were benchmarked against the responses measured in age-range matched, uninfected healthy control subjects (n = 11) by utilizing tests for normality, and comparison [the Kruskal-Wallis test, and the two-tailed Mann-Whitney U test (where appropriate)]. Lymphocyte responses were examined by intra-cellular cytokine secretion, degranulation assays as well as phosflow. A subset of these data were further queried by an automated clustering algorithm. Finally, we evaluated the humoral immune responses to four childhood vaccines in all three cohorts. RESULTS: We demonstrate that contrary to expectations pediatric HIV+ patients with sub-optimal viral control display no significant deficits in immune functional fitness. In fact, the patients that display better virologic control lack functional Gag-specific T cell responses and compared to healthy controls they display signaling deficits and an enrichment of mitogen-stimulated CD3 negative and positive lymphocyte clusters with suppressed cytokine production. CONCLUSIONS: These results highlight the immune resilience in HIV+ children on ART with sub-optimal viral control. With respect to HIV+ children on ART with better viral control, our data suggest that this cohort might potentially benefit from targeted interventions that might mitigate cell-mediated immune functional quiescence. |
Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity
Coughlin MM , Matson Z , Sowers SB , Priest JW , Smits GP , van der Klis FRM , Mitchell A , Hickman CJ , Scobie HM , Goodson JL , Alexander JPJr , Rota PA , Bankamp B . J Clin Microbiol 2021 59 (6) Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles whole virus antigen MBA (MeV WVA(L)) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole virus antigen (MeV WVA(C)) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVA(C) and MeV WVA(L) MBAs (R=0.962, R(2)=0.926). IgG concentrations from the MeV WVA(C) MBA showed strong correlation with PRN titers (R=0.846) with a linear relationship comparable to values obtained with the MeV WVA(L) MBA and PRN assay (R(2)=0.716 and R(2)=0.768, respectively). Receiver-operating characteristic (ROC) curve analysis of the MeV WVA(C) using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 84%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R=0.959 and R(2)=0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multi-antigen serosurveys assessing measles and rubella population immunity. |
Qualitative Variation Among Commercial Immunoassays to Detect Measles-Specific IgG.
Latner DR , Sowers SB , Anthony K , Colley H , Badeau C , Coates J , Wong P , Fakile Y , Interiano C , Pannell KB , Leung-Pineda V , Patel MM , Rota PA , Limbago BM , Hickman CJ . J Clin Microbiol 2020 58 (6) 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 was good agreement across platforms for IgG negative sera and for samples with intermediate to high levels of IgG. False negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody. |
Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood
Rasheed MAU , Hickman CJ , McGrew M , Sowers SB , Mercader S , Hopkins A , Grimes V , Yu T , Wrammert J , Mulligan MJ , Bellini WJ , Rota PA , Orenstein WA , Ahmed R , Edupuganti S . Proc Natl Acad Sci U S A 2019 116 (38) 19071-19076 In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine >/=10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity. |
Measles outbreak at a privately operated detention facility: Arizona, 2016
Venkat H , Briggs G , Brady S , Komatsu K , Hill C , Leung J , Patel M , Livar E , Su CP , Kassem A , Sowers SB , Mercader S , Rota PA , Elson D , Timme E , Robinson S , Fitzpatrick K , Franco J , Hickman C , Gastanaduy PA . Clin Infect Dis 2019 68 (12) 2018-2025 BACKGROUND: We describe a measles outbreak and control measures implemented at a privately operated detention facility housing US Immigration and Customs Enforcement detainees in 2016. METHODS: Case-patients reported fever and rash and were either laboratory-confirmed or had an epidemiological link to a laboratory-confirmed case-patient. Immunoglobulin G (IgG) avidity and plaque reduction neutralization tests distinguished between primary acute and reinfection case-patients. Measles-specific IgG was measured to assess detainee immunity levels. We compared attack rates (ARs) among detainees and staff, between IgG-negative and IgG-positive detainees, and by detainee housing units and sexes. RESULTS: We identified 32 measles case-patients (23 detainees, 9 staff); rash onsets were during 6 May-26 June 2016. High IgG avidity and neutralizing-antibody titers >40000 to measles (indicating reinfection) were identified in 18 (95%) and 15 (84%) of 19 tested case-patients, respectively. Among 205 unit A detainees tested for presumptive immunity, 186 (91%) had detectable IgG. Overall, the AR was 1.65%. ARs were significantly higher among detainees in unit A (7.05%) compared with units B-F (0.59%), and among male (2.33%) compared with female detainees (0.38%); however, ARs were not significantly different between detainees and staff or between IgG-negative and IgG-positive detainees. Control measures included the vaccination of 1424 of 1425 detainees and 190 of 510 staff, immunity verification for 445 staff, case-patient isolation, and quarantine of affected units. CONCLUSIONS: Although ARs were low, measles outbreaks can occur in intense-exposure settings, despite a high population immunity, underscoring the importance of high vaccination coverage and containment in limiting measles transmission. |
Development and use of an endpoint titration assay to characterize mumps IgG avidity following measles, mumps, and rubella vaccination and wild-type mumps infection
Mercader S , McGrew M , Sowers SB , Williams NJ , Bellini WJ , Hickman CJ . mSphere 2018 3 (5) Waning mumps IgG antibody and incomplete IgG avidity maturation may increase susceptibility to mumps virus infection in some vaccinees. To measure mumps IgG avidity, serum specimens serially diluted to the endpoint were incubated on a commercial mumps-specific IgG enzyme immunoassay and treated with the protein denaturant diethylamine (60 mM, pH 10). End titer avidity indices (etAIs [percent ratio of detected diethylamine-resistant IgG at endpoint]) were calculated. Unpaired serum specimens (n = 108) from 15-month-old children living in a low-incidence setting were collected 1 month and 2 years after the first measles, mumps, and rubella vaccine dose (MMR1) and tested for mumps avidity. Per the receiver operating characteristic curve, the avidity assay is accurate (area under the curve, 0.994; 95% confidence interval [CI], 0.956 to 1.000), 96.5% sensitive (95% CI, 87.9 to 99.6%), and 92.2% specific (95% CI, 81.1 to 97.8%) at an etAI of 30%. When 9 sets of paired serum specimens collected 1 to 60 months post-MMR1 were tested for mumps and measles IgG avidity using comparable methods, the mumps etAI increased from 11% to 40 to 60% in 6 months. From 6 to 60 months, avidity was sustained at a mean etAI of 50% (95% CI, 46 to 54%), significantly lower (P < 0.0001) than the mean measles etAI of 80% (95% CI, 74 to 86%). Mean etAIs in children 2 years post-MMR1 (n = 51), unvaccinated adults with distant mumps disease (n = 29), and confirmed mumps cases (n = 23) were 54, 62, and 57%, respectively. A mumps-specific endpoint avidity assay was developed and validated, and mumps avidity was determined to be generally sustained at etAIs of 40 to 60%, reaching etAIs of >80% in some individuals.IMPORTANCE Numerous outbreaks of mumps have occurred in the United States among two-dose measles-mumps-rubella (MMR)-vaccinated populations since 2006. The avidity of mumps-specific IgG antibodies may affect susceptibility to mumps virus infection in some vaccinated individuals. To accurately measure mumps avidity, we developed and validated a mumps-specific IgG avidity assay that determines avidity at the endpoint titer of serially diluted serum specimens, providing results that are independent of IgG concentration. At low antibody titers, endpoint methods are considered more accurate than methods that determine avidity at a single dilution. We determined that 6 months after the first MMR dose, mumps IgG avidity is high and generally sustained at avidity indices of 40 to 60%, reaching values of >80% in some individuals. Additionally, 4% (4/103) of individuals had avidity indices of </=30% (low avidity) 2 years after vaccination. Inadequate mumps avidity maturation may be one factor influencing susceptibility to mumps virus infection among previously vaccinated or naturally infected individuals. |
High concentrations of measles neutralizing antibodies and high-avidity measles IgG accurately identify measles reinfection cases
Sowers SB , Rota JS , Hickman CJ , Mercader S , Redd S , McNall RJ , Williams N , McGrew M , Walls ML , Rota PA , Bellini WJ . Clin Vaccine Immunol 2016 23 (8) 707-16 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. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. |
Immunity to Measles, Mumps, and Rubella in US Children With Perinatal HIV Infection or Perinatal HIV Exposure Without Infection
Siberry GK , Patel K , Bellini WJ , Karalius B , Purswani MU , Burchett SK , Meyer WA 3rd , Sowers SB , Ellis A , Van Dyke RB . Clin Infect Dis 2015 61 (6) 988-95 BACKGROUND: Children with perinatal human immunodeficiency virus (HIV) infection (PHIV) may not be protected against measles, mumps, and rubella (MMR) because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV-infected and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort. METHODS: PHIV and HEU children were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007 to 2009. At annual visits, demographic, laboratory, immunization, and clinical data were abstracted and serologic specimens collected. Most recent serologic specimen was used to determine measles seroprotection by plaque reduction neutralization assay and rubella seroprotection and mumps seropositivity by enzyme immunoassay. Sustained combination antiretroviral therapy (cART) was defined as taking cART for at least 3 months. RESULTS: Among 428 PHIV and 221 HEU PHACS participants, the prevalence was significantly lower in PHIV children for measles seroprotection (57% [95% confidence interval {CI}, 52%-62%] vs 99% [95% CI, 96%-100%]), rubella seroprotection (65% [95% CI, 60%-70%] vs 98% [95% CI, 95%-100%]), and mumps seropositivity (59% [95% CI, 55%-64%] vs 97% [95% CI, 94%-99%]). On multivariable analysis, greater number of vaccine doses while receiving sustained cART and higher nadir CD4 percentage between last vaccine dose and serologic testing independently improved the cumulative prediction of measles seroprotection in PHIV. Predictors of rubella seroprotection and mumps seropositivity were similar. CONCLUSIONS: High proportions of PHIV-infected children, but not HEU children, lack serologic evidence of immunity to MMR, despite documented immunization and current cART. Effective cART before immunization is a strong predictor of current seroimmunity. |
Outbreak of measles among persons with prior evidence of immunity, New York City, 2011
Rosen JB , Rota JS , Hickman CJ , Sowers SB , Mercader S , Rota PA , Bellini WJ , Huang AJ , Doll MK , Zucker JR , Zimmerman CM . Clin Infect Dis 2014 58 (9) 1205-10 BACKGROUND: Measles was eliminated in the United States through high vaccination coverage and a public health system able to rapidly respond to measles. Measles may occur among vaccinated individuals, but secondary transmission from such individuals has not been documented. METHODS: Suspected patients and contacts exposed during a measles outbreak in New York City in 2011 were investigated. Medical histories and immunization records were obtained. Cases were confirmed by detection of measles-specific immunoglobulin M and/or RNA. Tests for measles immunoglobulin G (IgG), IgG avidity, measurement of measles neutralizing antibody titers, and genotyping were performed to characterize the cases. RESULTS: The index patient had 2 doses of measles-containing vaccine; of 88 contacts, 4 secondary patients were confirmed who had either 2 doses of measles-containing vaccine or a past positive measles IgG antibody. All patients had laboratory confirmation of measles infection, clinical symptoms consistent with measles, and high-avidity IgG antibody characteristic of a secondary immune response. Neutralizing antibody titers of secondary patients reached >80 000 mIU/mL 3-4 days after rash onset and that of the index was <500 mIU/mL 9 days after rash onset. No additional cases of measles occurred among 231 contacts of secondary patients. CONCLUSIONS: This is the first report of measles transmission from a twice-vaccinated individual with documented secondary vaccine failure. The clinical presentation and laboratory data of the index patient were typical of measles in a naive individual. Secondary patients had robust anamnestic antibody responses. No tertiary cases occurred despite numerous contacts. This outbreak underscores the need for thorough epidemiologic and laboratory investigation of suspected cases of measles regardless of vaccination status. |
Estimates of mumps seroprevalence may be influenced by antibody specificity and serologic method
Latner DR , McGrew M , Williams NJ , Sowers SB , Bellini WJ , Hickman CJ . Clin Vaccine Immunol 2013 21 (3) 286-97 Neutralizing antibodies are assumed to be essential for protection against mumps virus infection, but their measurement is labor and time intensive. For this reason ELISA assays are typically used to measure mumps specific IgG. However, since there is poor correlation between mumps neutralization titers and ELISA assays that measure the presence of mumps specific IgG, ELISA assays that better correlate with neutralization are needed. To address this issue, we measured mumps antibody by plaque reduction neutralization, by a commercial ELISA (whole-virus antigen), and by ELISAs specific for the mumps nucleoprotein and hemagglutinin. The results indicate that differences in the antibody response to the individual mumps proteins could partially explain the lack of correlation among various serologic tests. Furthermore, the data indicate that some seropositive individuals have low levels of neutralizing antibody. If neutralizing antibody is important for protection, this suggests that previous estimates of immunity based on whole-virus ELISA may be overstated. |
Laboratory characterization of measles virus infection in previously vaccinated and unvaccinated individuals
Hickman CJ , Hyde TB , Sowers SB , Mercader S , McGrew M , Williams NJ , Beeler JA , Audet S , Kiehl B , Nandy R , Tamin A , Bellini WJ . J Infect Dis 2011 204 Suppl 1 S549-58 Waning immunity or secondary vaccine failure (SVF) has been anticipated by some as a challenge to global measles elimination efforts. Although such cases are infrequent, measles virus (MeV) infection can occur in vaccinated individuals following intense and/or prolonged exposure to an infected individual and may present as a modified illness that is unrecognizable as measles outside of the context of a measles outbreak. The immunoglobulin M response in previously vaccinated individuals may be nominal or fleeting, and viral replication may be limited. As global elimination proceeds, additional methods for confirming modified measles cases may be needed to understand whether SVF cases contribute to continued measles virus (MeV) transmission. In this report, we describe clinical symptoms and laboratory results for unvaccinated individuals with acute measles and individuals with SVF identified during MeV outbreaks. SVF cases were characterized by the serological parameters of high-avidity antibodies and distinctively high levels of neutralizing antibody. These parameters may represent useful biomarkers for classification of SVF cases that previously could not be confirmed as such using routine laboratory diagnostic techniques. |
Two case studies of modified measles in vaccinated physicians exposed to primary measles cases: high risk of infection but low risk of transmission
Rota JS , Hickman CJ , Sowers SB , Rota PA , Mercader S , Bellini WJ . J Infect Dis 2011 204 Suppl 1 S559-63 In 2009, measles outbreaks in Pennsylvania and Virginia resulted in the exposure and apparent infection of 2 physicians, both of whom had a documented history of vaccination with >2 doses of measles-mumps-rubella vaccine. These physicians were suspected of having been infected with measles after treating patients who subsequently received a diagnosis of measles. The clinical presentation was nonclassical in regard to progression, duration, and severity. It is hypothesized that the 2 physicians mounted vigorous secondary immune responses typified by high avidity measles immunoglobulin G antibody and remarkably high neutralizing titers in response to intense and prolonged exposure to a primary measles case patient. Both of the physicians continued to see patients, because neither considered that they could have measles. Despite surveillance for cases among contacts, including unvaccinated persons, no additional cases were identified. |
Investigation of a mumps outbreak among university students with two measles-mumps-rubella (MMR) vaccinations, Virginia, September-December 2006
Rota JS , Turner JC , Yost-Daljev MK , Freeman M , Toney DM , Meisel E , Williams N , Sowers SB , Lowe L , Rota PA , Nicolai LA , Peake L , Bellini WJ . J Med Virol 2009 81 (10) 1819-1825 Following the clinical diagnosis of the first case of mumps on September 22, 2006 at the University of Virginia (UVA), 52 suspected cases were identified through active surveillance for mumps by the end of December 2006. Samples were collected from 47 students who presented with parotitis despite a documented history of two doses of measles, mumps, and rubella (MMR) vaccine. Six of 47 serum samples (13%) were positive for mumps IgM, and 46/47 specimens were positive for mumps IgG. Endpoint titration of acute phase serum samples from laboratory-confirmed cases did not provide evidence that elevated serum IgG is a consistent marker for infection among cases due to secondary vaccine failure. Buccal swab samples from 39 of the 47 students were tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) and/or viral culture. Mumps virus or mumps RNA was detected in 12 of 39 buccal samples (31%). Genetic analysis of the virus from the outbreak at UVA indicated that the outbreak was not linked to the large mumps outbreak in the Midwestern US that occurred earlier in 2006. Our findings support the use of viral detection to improve laboratory diagnosis of mumps among persons who have received two doses of MMR. J. Med. Virol. 81:1819-1825, 2009. (c) 2009 Wiley-Liss, Inc. |
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