Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-27 (of 27 Records) |
Query Trace: Coughlin M [original query] |
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shinyMBA: a novel R shiny application for quality control of the multiplex bead assay for serosurveillance studies
Matson Z , Cooley G , Parameswaran N , Simon A , Bankamp B , Coughlin MM . Sci Rep 2024 14 (1) 7442 The multiplex bead assay (MBA) based on Luminex xMAP technology can be used as a tool to measure seroprevalence as part of population immunity evaluations to multiple antigens in large-scale serosurveys. However, multiplexing several antigens presents challenges for quality control (QC) assessments of the data because multiple parameters must be evaluated for each antigen. MBA QC parameters include monitoring bead counts and median fluorescence intensity (MFI) for each antigen in plate wells, and performance of assay controls included on each plate. Analyzing these large datasets to identify plates failing QC standards presents challenges for many laboratories. We developed a novel R Shiny application, shinyMBA, to expedite the MBA QC processes and reduce the risk of user error. The app allows users to rapidly merge multi-plate assay outputs to evaluate bead count, MFI, and performance of assay controls using statistical process control charts for all antigen targets simultaneously. The utility of the shinyMBA application and its various outputs are demonstrated using data from 32 synthetic xPONENT files with 3 multiplex antigens and two population serosurveillance studies that evaluated 1200 and 3871 samples, respectively, for 20 multiplexed antigens. The shinyMBA open-source code is available for download and modification at https://github.com/CDCgov/shinyMBA . Incorporation of shinyMBA into Luminex serosurveillance workflows can vastly improve the speed and accuracy of QC processes. |
Hybrid immunity and SARS-CoV-2 antibodies: results of the HEROES-RECOVER prospective cohort study
Romine JK , Li H , Coughlin MM , Jones JM , Britton A , Tyner HL , Fuller SB , Bloodworth R , Edwards LJ , Etoule JN , Morrill TC , Newes-Adeyi G , Olsho LEW , Gaglani M , Fowlkes A , Hollister J , Bedrick EJ , Uhrlaub JL , Beitel S , Sprissler RS , Lyski Z , Porter CJ , Rivers P , Lutrick K , Caban-Martinez AJ , Yoon SK , Phillips AL , Naleway AL , Burgess JL , Ellingson KD . Clin Infect Dis 2024 BACKGROUND: There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (SARS-CoV-2 infection or COVID-19 vaccination). From a cohort of health care personnel, first responders, and other frontline workers in six US states, we examined heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. METHODS: Exposures included event-count (sum of infections and vaccine doses) and event-order, categorized into seven permutations of vaccination and/or infection. Outcome was level of serum binding antibodies against receptor binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding Ig), measured by enzyme-linked immunosorbent assay. Mean antibody levels were examined up to 365 days after each of the 1st-7th events. RESULTS: Analysis included 5,793 participants measured from August 7, 2020 to April 15, 2023. Hybrid immunity from infection before one or two vaccine doses elicited modestly superior antibody responses after the 2nd and 3rd events (compared to infections or vaccine-doses alone). This superiority was not evident after the 4th and 5th events (additional doses). Among adults infected before vaccination, adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (0.81-0.94), and 0.99 (0.85-1.15) after the 2nd-5th events, respectively. Post-vaccination infections elicited superior responses: adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were: 0.93 (0.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the 2nd-5th events, respectively. CONCLUSIONS AND RELEVANCE: Findings reflecting heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy. |
Neuroinvasive bacillus cereus infection in immunocompromised hosts: Epidemiologic investigation of 5 patients with acute myeloid leukemia
Little JS , Coughlin C , Hsieh C , Lanza M , Huang WY , Kumar A , Dandawate T , Tucker R , Gable P , Vazquez Deida AA , Moulton-Meissner H , Stevens V , McAllister G , Ewing T , Diaz M , Glowicz J , Winkler ML , Pecora N , Kubiak DW , Pearson JC , Luskin MR , Sherman AC , Woolley AE , Brandeburg C , Bolstorff B , McHale E , Fortes E , Doucette M , Smole S , Bunnell C , Gross A , Platt D , Desai S , Fiumara K , Issa NC , Baden LR , Rhee C , Klompas M , Baker MA . Open Forum Infect Dis 2024 11 (3) ofae048 BACKGROUND: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. METHODS: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. RESULTS: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. CONCLUSIONS: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen. |
Characterizing infection of B cells with wild-type and vaccine strains of measles virus
Melot L , Bankamp B , Rota PA , Coughlin MM . iScience 2023 26 (10) 107721 Acute infection with measles virus (MeV) causes transient immunosuppression often leading to secondary infections. MeV infection of B lymphocytes results in changes in the antibody repertoire and memory B cell populations for which the mechanism is unknown. In this study, we characterize the infection of primary B cells with wild-type and vaccine strains of MeV. Vaccine-infected B cells were characterized by a higher percentage of cells positive for viral protein, a higher level of viral transcription and reduced cell death compared to wild-type infected cells, regardless of B cell subtype. Vaccine-infected cells showed more production of TNF-α and IL-10 but less production of IL-8 compared to wild-type infected cells. IL-4 and IL-6 levels detected were increased during both vaccine and wild-type infection. Despite evidence of replication, measles-infected B cells did not produce detectable viral progeny. This study furthers our understanding of the outcomes of MeV infection of human B cells. |
Humoral immune response to messenger RNA coronavirus disease 2019 vaccination among children aged 5-11 years in a multisite prospective cohort study, September 2021-September 2022
Lyski ZL , Porter C , Uhrlaub JL , Ellingson KD , Jeddy Z , Gwynn L , Rivers P , Sprissler R , Hegmann KT , Coughlin M , Fowlkes A , Hollister J , LeClair L , Mak J , Beitel SC , Fuller S , Grant L , Newes-Adeyi G , Yoo YM , Olsho L , Burgess JL , Caban-Martinez A , Yoon S , Britton A , Gaglani M , Lutrick K . Open Forum Infect Dis 2023 10 (8) ofad431 BACKGROUND: The PROTECT study is a longitudinal cohort study initiated in July 2021 with weekly testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 4 states: Arizona, Florida, exas, and Utah. This study aims to examine vaccine-elicited antibody response against postvaccination SARS-CoV-2 infections. METHODS: Children aged 5-11 years had serum collected 14-59 days after their second dose of monovalent Pfizer-BioNTech coronavirus disease 2019 messenger RNA vaccine. Vaccine-elicited antibodies were measured using the area under the curve (AUC) and end-point titer using enzyme-linked immunosorbent assay (receptor-binding domain [RBD] and S2) and surrogate neutralization assays against ancestral (WA1) and Omicron (BA.2). RESULTS: 79 vaccinated participants (33 [41.7%] female; median age, 8.8 years [standard deviation, 1.9 years]), 48 (60.8%) were from Tucson, Arizona; 64 (81.0%) were non-Hispanic white; 63 (80.8%) attended school in person; 68 (86.1%) did not have any chronic conditions; and 47 (59.5%) were infected after vaccination. Uninfected children had higher AUCs against WA1 (P = .009) and Omicron (P = .02). The geometric mean and surrogate neutralization titer above the limit of detection was 346.0 for WA1 and 39.7 for Omicron, an 8.7-fold decrease (P < .001). After adjustment of covariates in the WA1-specific model, we observed a 47% reduction in the odds of postvaccination infection for every standard deviation increase in RBD AUC (aOR, 0.53 [95% confidence interval, .29-.97) and a 69% reduction in the odds of infection for every 3-fold increase in RBD end titer (0.31 [.06-1.57]). CONCLUSIONS: Children with higher antibody levels experienced a lower incidence of postvaccination SARS-CoV-2 infection. |
Estimates of SARS-CoV-2 seroprevalence and incidence of primary SARS-CoV-2 infections among blood donors, by COVID-19 vaccination status - United States, April 2021-September 2022
Jones JM , Manrique IM , Stone MS , Grebe E , Saa P , Germanio CD , Spencer BR , Notari E , Bravo M , Lanteri MC , Green V , Briggs-Hagen M , Coughlin MM , Stramer SL , Opsomer J , Busch MP . MMWR Morb Mortal Wkly Rep 2023 72 (22) 601-605 Changes in testing behaviors and reporting requirements have hampered the ability to estimate the U.S. SARS-CoV-2 incidence (1). Hybrid immunity (immunity derived from both previous infection and vaccination) has been reported to provide better protection than that from infection or vaccination alone (2). To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies (or both), data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 (April-June), an estimated 68.4% of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including 47.5% from vaccination alone, 12.0% from infection alone, and 8.9% from both. By the third quarter of 2022 (July-September), 96.4% had SARS-CoV-2 antibodies from previous infection or vaccination, including 22.6% from infection alone and 26.1% from vaccination alone; 47.7% had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years (36.9%), the group with the highest risk for severe disease if infected, and was highest among those aged 16-29 years (59.6%). Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.*(,)(†). |
Tetanus and diphtheria seroprotection among children younger than 15 years in Nigeria, 2018: Who are the unprotected children
Tohme RA , Scobie HM , Okunromade O , Olaleye T , Shuaib F , Jegede T , Yahaya R , Nnaemeka N , Lawal B , Egwuenu A , Parameswaran N , Cooley G , An Q , Coughlin M , Okposen BB , Adetifa I , Bolu O , Ihekweazu C . Vaccines (Basel) 2023 11 (3) Serological surveys provide an objective biological measure of population immunity, and tetanus serological surveys can also assess vaccination coverage. We undertook a national assessment of immunity to tetanus and diphtheria among Nigerian children aged <15 years using stored specimens collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey, a national cross-sectional household-based survey. We used a validated multiplex bead assay to test for tetanus and diphtheria toxoid-antibodies. In total, 31,456 specimens were tested. Overall, 70.9% and 84.3% of children aged <15 years had at least minimal seroprotection (≥0.01 IU/mL) against tetanus and diphtheria, respectively. Seroprotection was lowest in the north west and north east zones. Factors associated with increased tetanus seroprotection included living in the southern geopolitical zones, urban residence, and higher wealth quintiles (p < 0.001). Full seroprotection (≥0.1 IU/mL) was the same for tetanus (42.2%) and diphtheria (41.7%), while long-term seroprotection (≥1 IU/mL) was 15.1% for tetanus and 6.0% for diphtheria. Full- and long-term seroprotection were higher in boys compared to girls (p < 0.001). Achieving high infant vaccination coverage by targeting specific geographic areas and socio-economic groups and introducing tetanus and diphtheria booster doses in childhood and adolescence are needed to achieve lifelong protection against tetanus and diphtheria and prevent maternal and neonatal tetanus. |
Experiences with COVID-19 case investigation and contact tracing: A qualitative analysis
DeLuca N , Caruso E , Gupta R , Kemmerer C , Coughlin R , Chan O , Vohra D , Oeltmann JE , Taylor MM , Moonan PK , Thorpe PG , Loosier PS , Haile G . SSM Qual Res Health 2023 3 100244 Case investigation and contact tracing (CI/CT) is a critical part of the public health response to COVID-19. Individuals' experiences with CI/CT for COVID-19 varied based on geographic location, changes in knowledge and guidelines, access to testing and vaccination, as well as demographic characteristics including age, race, ethnicity, income, and political ideology. In this paper, we explore the experiences and behaviors of adults with positive SARS-CoV-2 test results, or who were exposed to a person with COVID-19, to understand their knowledge, motivations, and facilitators and barriers to their actions. We conducted focus groups and one-on-one interviews with 94 cases and 90 contacts from across the United States. We found that participants were concerned about infecting or exposing others, which motivated them to isolate or quarantine, notify contacts, and get tested. Although most cases and contacts were not contacted by CI/CT professionals, those who were reported a positive experience and received helpful information. Many cases and contacts reported seeking information from family, friends, health care providers, as well as television news and Internet sources. Although participants reported similar perspectives and experiences across demographic characteristics, some highlighted inequities in receiving COVID-19 information and resources. |
Lessons learned from the implementation of integrated serosurveillance of communicable diseases in the Americas
Saboyá-Díaz MI , Castellanos LG , Morice A , Ade MP , Rey-Benito G , Cooley GM , Scobie HM , Wiegand RE , Coughlin MM , Martin DL . Rev Panam Salud Publica 2023 47 e53 OBJECTIVE: Systematize the experience and identify challenges and lessons learned in the implementation of an initiative for integrated serosurveillance of communicable diseases using a multiplex bead assay in countries of the Americas. METHODS: Documents produced in the initiative were compiled and reviewed. These included concept notes, internal working papers, regional meetings reports, and survey protocols from the three participating countries (Mexico, Paraguay, and Brazil) and two additional countries (Guyana and Guatemala) where serology for several communicable diseases was included in neglected tropical diseases surveys. Information was extracted and summarized to describe the experience and the most relevant challenges and lessons learned. RESULTS: Implementing integrated serosurveys requires interprogrammatic and interdisciplinary work teams for the design of survey protocols to respond to key programmatic questions aligned to the needs of the countries. Valid laboratory results are critical and rely on the standardized installment and roll-out of laboratory techniques. Field teams require adequate training and supervision to properly implement survey procedures. The analysis and interpretation of serosurveys results should be antigen-specific, contextualizing the responses for each disease, and triangulated with programmatic and epidemiological data for making decisions tailored to specific population socioeconomic and ecologic contexts. CONCLUSIONS: Integrated serosurveillance as a complementary tool for functional epidemiological surveillance systems is feasible to use and key components should be considered: political engagement, technical engagement, and integrated planning. Aspects such as designing the protocol, selecting target populations and diseases, laboratory capacities, anticipating the capacities to analyze and interpret complex data, and how to use it are key. |
Performance of SARS-CoV-2 Antigens in a Multiplex Bead Assay for Integrated Serological Surveillance of Neglected Tropical and Other Diseases.
Gwyn S , Abubakar A , Akinmulero O , Bergeron E , Blessing UN , Chaitram J , Coughlin MM , Dawurung AB , Dickson FN , Esiekpe M , Evbuomwan E , Greby SM , Iriemenam NC , Kainulainen MH , Naanpoen TA , Napoloen L , Odoh I , Okoye M , Olaleye T , Schuh AJ , Owen SM , Samuel A , Martin DL . Am J Trop Med Hyg 2022 107 (2) 260-7 Serosurveillance can provide estimates of population-level exposure to infectious pathogens and has been used extensively during the COVID-19 pandemic. Simultaneous, serological testing for multiple pathogens can be done using bead-based immunoassays to add value to disease-specific serosurveys. We conducted a validation of four SARS-CoV-2 antigens-full-length spike protein, two receptor binding domain proteins, and the nucleocapsid protein-on our existing multiplex bead assay (MBA) for enteric diseases, malaria, and vaccine preventable diseases. After determining the optimal conditions for coupling the antigens to microsphere beads, the sensitivity and specificity of the assay were determined on two instruments (Luminex-200 and MAGPIX) when testing singly (monoplex) versus combined (multiplex). Sensitivity was assessed using plasma from 87 real-time reverse transcription polymerase chain reaction (rRT-PCR) positive persons collected in March-May of 2020 and ranged from 94.3% to 96.6% for the different testing conditions. Specificity was assessed using 98 plasma specimens collected prior to December 2019 and plasma from 19 rRT-PCR negative persons and ranged from 97.4% to 100%. The positive percent agreement was 93.8% to 97.9% using 48 specimens collected > 21 days post-symptom onset, while the negative percent agreement was ≥ 99% for all antigens. Test performance was similar using monoplex or multiplex testing. Integrating SARS-CoV-2 serology with other diseases of public health interest could add significant value to public health programs that have suffered severe programmatic setbacks during the COVID-19 pandemic. |
Descriptive Evaluation of Antibody Responses to SARS-CoV-2 Infection in Plasma and Gingival Crevicular Fluid in a Nursing Home Cohort-Arkansas, June-August 2020.
Brown NE , Lyons AK , Schuh AJ , Stumpf MM , Harcourt JL , Tamin A , Rasheed MAU , Mills L , Lester SN , Thornburg NJ , Nguyen K , Costantini V , Vinjé J , Huang JY , Gilbert SE , Gable P , Bollinger S , Sabour S , Beshearse E , Surie D , Biedron C , Gregory CJ , Clemmons NS , Whitaker B , Coughlin MM , Seely KA , Garner K , Gulley T , Haney T , Kothari A , Patil N , Halpin AL , McDonald LC , Kutty PK , Brown AC . Infect Control Hosp Epidemiol 2021 43 (11) 1-24 OBJECTIVE: Characterize and compare SARS-CoV-2-specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection. DESIGN: Prospective cohort. SETTING: Nursing home. PARTICIPANTS: SARS-CoV-2-infected nursing home residents. METHODS: A convenience sample of 14 SARS-CoV-2-infected nursing home residents, enrolled 4-13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. Post diagnosis, plasma SARS-CoV-2-specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 timepoints and GCF SARS-CoV-2-specific IgG and IgA were measured at 4 timepoints. RESULTS: All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12, neutralizing antibodies in 11, IgM in 10, and IgA in 9. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 and IgA in 12. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response was similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive through this evaluation's end 46-55 days post-diagnosis. All participants were viral culture negative by the first detection of antibodies. CONCLUSIONS: Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Non-invasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized. |
Infectious Period of Severe Acute Respiratory Syndrome Coronavirus 2 in 17 Nursing Home Residents-Arkansas, June-August 2020.
Surie D , Huang JY , Brown AC , Gable P , Biedron C , Gilbert SE , Garner K , Bollinger S , Gulley T , Haney T , Lyons AK , Beshearse E , Gregory CJ , Sabour S , Clemmons NS , James AE , Tamin A , Reese N , Perry-Dow KA , Brown R , Harcourt JL , Campbell D , Houston H , Chakravorty R , Paulick A , Whitaker B , Murdoch J , Spicer L , Stumpf MM , Mills L , Coughlin MM , Higdem P , Rasheed MAU , Lonsway D , Bhatnagar A , Kothari A , Anderson K , Thornburg NJ , Breaker E , Adamczyk M , McAllister GA , Halpin AL , Seely KA , Patil N , McDonald LC , Kutty PK . Open Forum Infect Dis 2021 8 (3) ofab048 BACKGROUND: To estimate the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adults with underlying conditions, we assessed duration of coronavirus disease 2019 (COVID-19) symptoms, reverse-transcription polymerase chain reaction (RT-PCR) positivity, and culture positivity among nursing home residents. METHODS: We enrolled residents within 15 days of their first positive SARS-CoV-2 test (diagnosis) at an Arkansas facility from July 7 to 15, 2020 and instead them for 42 days. Every 3 days for 21 days and then weekly, we assessed COVID-19 symptoms, collected specimens (oropharyngeal, anterior nares, and saliva), and reviewed medical charts. Blood for serology was collected on days 0, 6, 12, 21, and 42. Infectivity was defined by positive culture. Duration of culture positivity was compared with duration of COVID-19 symptoms and RT-PCR positivity. Data were summarized using measures of central tendency, frequencies, and proportions. RESULTS: We enrolled 17 of 39 (44%) eligible residents. Median participant age was 82 years (range, 58-97 years). All had ≥3 underlying conditions. Median duration of RT-PCR positivity was 22 days (interquartile range [IQR], 8-31 days) from diagnosis; median duration of symptoms was 42 days (IQR, 28-49 days). Of 9 (53%) participants with any culture-positive specimens, 1 (11%) severely immunocompromised participant remained culture-positive 19 days from diagnosis; 8 of 9 (89%) were culture-positive ≤8 days from diagnosis. Seroconversion occurred in 12 of 12 (100%) surviving participants with ≥1 blood specimen; all participants were culture-negative before seroconversion. CONCLUSIONS: Duration of infectivity was considerably shorter than duration of symptoms and RT-PCR positivity. Severe immunocompromise may prolong SARS-CoV-2 infectivity. Seroconversion indicated noninfectivity in this cohort. |
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. |
Shedding of culturable virus, seroconversion, and 6-month follow-up antibody responses in the first 14 confirmed cases of COVID-19 in the United States.
Killerby ME , Ata Ur Rasheed M , Tamin A , Harcourt JL , Abedi GR , Lu X , Kujawski S , Shah MM , Kirking HL , Gold JAW , Salvatore PP , Coughlin MM , Whitaker B , Tate JE , Watson JT , Lindstrom S , Hall AJ , Fry AM , Gerber SI , Midgley CM , Thornburg NJ . J Infect Dis 2021 224 (5) 771-776 We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to six months post-onset, among 14 early US COVID-19 patients. We isolated viable SARS-CoV-2 from rRT-PCR-positive respiratory specimens collected during days 0-8 post-onset, but not after. All 13 patients with two or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at six months post-onset; all retained detectable anti-spike IgG, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at six months. |
Rapid Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Detention Facility, Louisiana, USA, May-June, 2020.
Wallace M , James AE , Silver R , Koh M , Tobolowsky FA , Simonson S , Gold JAW , Fukunaga R , Njuguna H , Bordelon K , Wortham J , Coughlin M , Harcourt JL , Tamin A , Whitaker B , Thornburg NJ , Tao Y , Queen K , Uehara A , Paden CR , Zhang J , Tong S , Haydel D , Tran H , Kim K , Fisher KA , Marlow M , Tate JE , Doshi RH , Sokol T , Curran KG . Emerg Infect Dis 2021 27 (2) 421-429 To assess transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a detention facility experiencing a coronavirus disease outbreak and evaluate testing strategies, we conducted a prospective cohort investigation in a facility in Louisiana, USA. We conducted SARS-CoV-2 testing for detained persons in 6 quarantined dormitories at various time points. Of 143 persons, 53 were positive at the initial test, and an additional 58 persons were positive at later time points (cumulative incidence 78%). In 1 dormitory, all 45 detained persons initially were negative; 18 days later, 40 (89%) were positive. Among persons who were SARS-CoV-2 positive, 47% (52/111) were asymptomatic at the time of specimen collection; 14 had replication-competent virus isolated. Serial SARS-CoV-2 testing might help interrupt transmission through medical isolation and quarantine. Testing in correctional and detention facilities will be most effective when initiated early in an outbreak, inclusive of all exposed persons, and paired with infection prevention and control. |
Decline in SARS-CoV-2 Antibodies After Mild Infection Among Frontline Health Care Personnel in a Multistate Hospital Network - 12 States, April-August 2020.
Self WH , Tenforde MW , Stubblefield WB , Feldstein LR , Steingrub JS , Shapiro NI , Ginde AA , Prekker ME , Brown SM , Peltan ID , Gong MN , Aboodi MS , Khan A , Exline MC , Files DC , Gibbs KW , Lindsell CJ , Rice TW , Jones ID , Halasa N , Talbot HK , Grijalva CG , Casey JD , Hager DN , Qadir N , Henning DJ , Coughlin MM , Schiffer J , Semenova V , Li H , Thornburg NJ , Patel MM . MMWR Morb Mortal Wkly Rep 2020 69 (47) 1762-1766 Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline. The percentage of participants who experienced seroreversion, defined as an antibody signal-to-threshold ratio >1.0 at baseline and <1.0 at the follow-up visit, was assessed. Overall, 194 (6.0%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline (1). Upon repeat testing approximately 60 days later (range = 50-91 days), 146 (93.6%) of 156 participants experienced a decline in antibody response indicated by a lower signal-to-threshold ratio at the follow-up visit, compared with the baseline visit, and 44 (28.2%) experienced seroreversion. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response. Whether decay in these antibodies increases risk for reinfection and disease remains unanswered. However, these results suggest that serology testing at a single time point is likely to underestimate the number of persons with previous SARS-CoV-2 infection, and a negative serologic test result might not reliably exclude prior infection. |
Change in Antibodies to SARS-CoV-2 Over 60 Days Among Health Care Personnel in Nashville, Tennessee.
Patel MM , Thornburg NJ , Stubblefield WB , Talbot HK , Coughlin MM , Feldstein LR , Self WH . JAMA 2020 324 (17) 1781-1782 This study examines the duration of antibody response to SARS-CoV-2 in health care personnel over a 60-day period in Nashville, Tennessee. |
Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network - 13 Academic Medical Centers, April-June 2020.
Self WH , Tenforde MW , Stubblefield WB , Feldstein LR , Steingrub JS , Shapiro NI , Ginde AA , Prekker ME , Brown SM , Peltan ID , Gong MN , Aboodi MS , Khan A , Exline MC , Files DC , Gibbs KW , Lindsell CJ , Rice TW , Jones ID , Halasa N , Talbot HK , Grijalva CG , Casey JD , Hager DN , Qadir N , Henning DJ , Coughlin MM , Schiffer J , Semenova V , Li H , Thornburg NJ , Patel MM . MMWR Morb Mortal Wkly Rep 2020 69 (35) 1221-1226 Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission. |
Perspective on global measles epidemiology and control and the role of novel vaccination strategies
Coughlin MM , Beck AS , Bankamp B , Rota PA . Viruses 2017 9 (1) Measles is a highly contagious, vaccine preventable disease. Measles results in a systemic illness which causes profound immunosuppression often leading to severe complications. In 2010, the World Health Assembly declared that measles can and should be eradicated. Measles has been eliminated in the Region of the Americas, and the remaining five regions of the World Health Organization (WHO) have adopted measles elimination goals. Significant progress has been made through increased global coverage of first and second doses of measles-containing vaccine, leading to a decrease in global incidence of measles, and through improved case based surveillance supported by the WHO Global Measles and Rubella Laboratory Network. Improved vaccine delivery methods will likely play an important role in achieving measles elimination goals as these delivery methods circumvent many of the logistic issues associated with subcutaneous injection. This review highlights the status of global measles epidemiology, novel measles vaccination strategies, and describes the pathway toward measles elimination. |
Effect of jet injection on infectivity of measles, mumps, and rubella vaccine in a bench model
Coughlin MM , Collins M , Saxon G , Jarrahian C , Zehrung D , Cappello C , Dhere R , Royals M , Papania M , Rota PA . Vaccine 2015 33 (36) 4540-7 Disposable-syringe jet injectors (DSJIs) with single-use, auto disable, needle-free syringes offer the opportunity to avoid hazards associated with injection using a needle and syringe. Clinical studies have evaluated DSJIs for vaccine delivery, but most studies have focused on inactivated, subunit, or DNA vaccines. Questions have been raised about possible damage to live attenuated viral vaccines by forces generated during the jet injection process. This study examines the effect of jet injection on the integrity of measles, mumps, and rubella vaccine (MMR), measured by viral RNA content and infectivity. Three models of DSJIs were evaluated, each generating a different ejection force. Following jet injection, the RNA content for each of the vaccine components was measured using RT-qPCR immediately after injection and following passage in Vero cells. Jet injection was performed with and without pig skin as a simulation of human skin. There was little to no reduction of RNA content immediately following jet injection with any of the three DSJIs. Samples passaged in Vero cells showed no loss in infectivity of the measles vaccine following jet injection. Mumps vaccine consistently showed increased replication following jet injection. Rubella vaccine showed no loss after jet injection alone but some infectivity loss following injection through pig skin with two of the devices. Overall, these data demonstrated that forces exerted on a live attenuated MMR vaccine did not compromise vaccine infectivity. The bench model and protocol used in this study can be applied to evaluate the impact of jet injection on other live virus vaccines. |
Contribution of dendritic cells to measles virus induced immunosuppression
Coughlin MM , Bellini WJ , Rota PA . Rev Med Virol 2012 23 (2) 126-38 Measles virus (MV) remains an important pathogen in children worldwide. The morbidity and mortality of MV is associated with severe immune suppression. Dendritic cells (DCs) were identified as initial target cells in vivo, and DCs were efficiently infected by MV in vitro. MV infection of DCs likely contributes to functional deficiency in these cells; therefore playing a role in MV-induced immunosuppression. DCs appeared to mature phenotypically; however, the ability of infected cells to stimulate T cells was compromised. Phenotypic maturation of infected immature DCs was partially controlled by IFN production; however, infected DCs also maintained markers of an immature phenotype such as the continued uptake of antigen and lack of expression of chemokine receptor CCR7. Furthermore, mature DCs did not appear to maintain phenotypic maturation following infection demonstrated by decreased MHC and co-stimulatory molecule expression. Several mechanisms of MV-induced DC dysfunction have been suggested, each likely contributing to the immunosuppressive effect of MV-infected DCs. Infected DCs responded aberrantly to secondary maturation stimuli such as CD40L or TLR4 stimulation. MV infection resulted in apoptosis in DC/T-cell cocultures, which may contribute to a reduced T-cell response. Additionally, the immunological synapse between infected DCs and T cells was compromised resulting in reduced T-cell interaction times and activation signaling. The mechanisms of MV contribution to DC dysfunction appear multifaceted and central to MV-induced immunosuppression. Copyright (c) 2012 John Wiley & Sons, Ltd. |
Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing
Elshabrawy HA , Coughlin MM , Baker SC , Prabhakar BS . PLoS One 2012 7 (11) e50366 Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses. |
Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential
Coughlin MM , Prabhakar BS . Rev Med Virol 2011 22 (1) 2-17 The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) led to a rapid response not only to contain the outbreak but also to identify possible therapeutic interventions, including the generation of human monoclonal antibodies (hmAbs). hmAbs may be used therapeutically without the drawbacks of chimeric or animal Abs. Several different methods have been used to generate SARS-CoV specific neutralizing hmAbs including the immunization of transgenic mice, cloning of small chain variable regions from naive and convalescent patients, and the immortalization of convalescent B cells. Irrespective of the techniques used, the majority of hmAbs specifically reacted with the receptor binding domain (RBD) of the spike (S) protein and likely prevented receptor binding. However, several hmAbs that can bind to epitopes either within the RBD, located N terminal of the RBD or in the S2 domain, and neutralize the virus with or without inhibiting receptor binding have been identified. Therapeutic utility of hmAbs has been further elucidated through the identification of potential combinations of hmAbs that could neutralize viral variants including escape mutants selected using hmAbs. These results suggest that a cocktail of hmAbs that can bind to unique epitopes and have different mechanisms of action might be of clinical utility against SARS-CoV infection, and indicate that a similar approach may be applied to treat other viral infections. Copyright (c) 2011 John Wiley & Sons, Ltd. |
Fecal occult blood testing beliefs and practices of U.S. primary care physicians: serious deviations from evidence-based recommendations
Nadel MR , Berkowitz Z , Klabunde CN , Smith RA , Coughlin SS , White MC . J Gen Intern Med 2010 25 (8) 833-9 BACKGROUND: Fecal occult blood testing (FOBT) is an important option for colorectal cancer screening that should be available in order to achieve high population screening coverage. However, results from a national survey of clinical practice in 1999-2000 indicated that many primary care physicians used inadequate methods to implement FOBT screening and follow-up. OBJECTIVE: To determine whether methods to screen for fecal occult blood have improved, including the use of newer more sensitive stool tests. DESIGN: Cross-sectional national survey of primary care physicians. PARTICIPANTS: Participants consisted of 1,134 primary care physicians who reported ordering or performing FOBT in the 2006-2007 National Survey of Primary Care Physicians' Recommendations and Practices for Cancer Screening. MAIN MEASURES: Self-reported data on details of FOBT implementation and follow-up of positive results. RESULTS: Most physicians report using standard guaiac tests; higher sensitivity guaiac tests and immunochemical tests were reported by only 22.0% and 8.9%, respectively. In-office testing, that is, testing of a single specimen collected during a digital rectal examination in the office, is still widely used although inappropriate for screening: 24.9% of physicians report using only in-office tests and another 52.9% report using both in-office and home tests. Recommendations improved for follow-up after a positive test: fewer physicians recommend repeating the FOBT (17.8%) or using tests other than colonoscopy for the diagnostic work-up (6.6%). Only 44.3% of physicians who use home tests have reminder systems to ensure test completion and return. CONCLUSIONS: Many physicians continue to use inappropriate methods to screen for fecal occult blood. Intensified efforts to inform physicians of recommended technique and promote the use of tracking systems are needed. |
Too much of a good thing? Physician practices and patient willingness for less frequent pap test screening intervals
Meissner HI , Tiro JA , Yabroff KR , Haggstrom DA , Coughlin SS . Med Care 2010 48 (3) 249-259 BACKGROUND: Recent guidelines recommend longer Pap test intervals. However, physicians and patients may not be adopting these recommendations. OBJECTIVES: Identify (1) physician and practice characteristics associated with recommending a less frequent interval, and (2) characteristics associated with women's willingness to adhere to a 3-year interval. RESEARCH DESIGN: We used 2 national surveys: (1) a 2006/2007 National Survey of Primary Care Physicians for physician cervical cancer screening practices (N = 1114), and (2) the 2005 Health Information Trends Survey for women's acceptance of longer Pap intervals (N = 2206). MEASURES AND METHODS: Physician recommendation regarding Pap intervals was measured using a clinical vignette involving a 35-year-old with no new sexual partners and 3 consecutive negative Pap tests; associations with independent variables were evaluated with logistic regression. In parallel models, we evaluated women's willingness to follow a 3-year Pap test interval. RESULTS: A minority of physicians (32%) have adopted-but more than half of women are willing to adopt-3-year Pap test intervals. In adjusted models, physician factors associated with less frequent screening were: serving a higher proportion of Medicaid patients, white, non-Hispanic race, fewer years since medical school graduation, and US Preventive Services Task Force being very influential in physician clinical practice. Women were more willing to follow a 3-year interval if they were older, but less willing if they had personal or family experiences with cancer or followed an annual Pap test schedule. CONCLUSIONS: Many women are accepting of a 3-year interval for Pap tests, although most primary care physicians continue to recommend shorter intervals. |
Breast cancer as a global health concern
Coughlin SS , Ekwueme DU . Cancer Epidemiol 2009 33 (5) 315-8 Public health data indicate that the global burden of breast cancer in women, measured by incidence, mortality, and economic costs, is substantial and on the increase. Worldwide, it is estimated that more than one million women are diagnosed with breast cancer every year, and more than 410,000 will die from the disease. In low- and middle-income countries (LMCs), the infrastructure and resources for routine screening mammography are often unavailable. In such lower resource settings, breast cancers are commonly diagnosed at late stages, and women may receive inadequate treatment, pain relief, or palliative care. There have been an increasing number of global health initiatives to address breast cancer including efforts by Susan G. Komen for the Cure((c)), the Breast Health Global Initiative (BHGI), the U.S. Centers for Disease Control and Prevention (CDC), the American Cancer Society, the National Cancer Institute (NCI), and ongoing work by leading oncology societies in different parts of the world. To support such initiatives, and to provide a scientific evidence base for health policy and public health decision making, there is a need for further health services research and program evaluations. Cancer registries can be invaluable in ascertaining the magnitude of cancer disease burden and its distribution in these countries. Additional data are needed for various geographic areas to assess resources required, cost-effectiveness, and humane approaches for preventing or controlling breast cancer in low resource settings in developing countries. |
Development of a spiritually based educational program to increase colorectal cancer screening among African American men and women
Holt CL , Roberts C , Scarinci I , Wiley SR , Eloubeidi M , Crowther M , Bolland J , Litaker MS , Southward V , Coughlin SS . Health Commun 2009 24 (5) 400-12 This study describes the development of a spiritually based intervention to increase colorectal cancer screening through African American churches by framing the health message with spiritual themes and scripture. The intervention development phase consisted of ideas from an advisory panel and core content identified in focus groups. In the pilot-testing phase, prototypes of the intervention materials were tested for graphic appeal in additional focus groups, and content was tested for acceptability and comprehension in cognitive interviews. Participants preferred materials showing a variety of African Americans in real settings, bright color schemes, and an uplifting message emphasizing prevention and early detection. Spiritual themes such as stewardship over the body, being well to serve God, and using faith to overcome fear, were well received. The materials were then finalized for implementation and will be used by community health advisors to encourage screening. |
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