Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-14 (of 14 Records) |
Query Trace: Steward-Clark E[original query] |
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Genomic Insights on Variation Underlying Capsule Expression in Meningococcal Carriage Isolates From University Students, United States, 2015-2016.
Whaley MJ , Vuong JT , Topaz N , Chang HY , Thomas JD , Jenkins LT , Hu F , Schmink S , Steward-Clark E , Mathis M , Rodriguez-Rivera LD , Retchless AC , Joseph SJ , Chen A , Acosta AM , McNamara L , Soeters HM , Mbaeyi S , Marjuki H , Wang X . Front Microbiol 2022 13 815044 In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen. |
Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016-2018
Mercado-Reyes M , Gilboa SM , Valencia D , Daza M , Tong VT , Galang RR , Winfield CM , Godfred-Cato S , Benavides M , Villanueva JM , Thomas JD , Daniels J , Zaki S , Reagan-Steiner S , Bhatnagar J , Schiffer J , Steward-Clark E , Ricaldi JN , Osorio J , Sancken CL , Pardo L , Tinker SC , Anderson KN , Rico A , Burkel VK , Hojnacki J , Delahoy MJ , González M , Osorio MB , Moore CA , Honein MA , Ospina Martinez ML . Trop Med Infect Dis 2021 6 (4) Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May-November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia's existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy. |
Epidemiologic, immunologic, and virus characteristics in patients with paired SARS-CoV-2 serology and reverse transcription polymerase chain reaction testing.
Shragai T , Smith-Jeffcoat SE , Koh M , Schechter MC , Rebolledo PA , Kasinathan V , Wang Y , Hoffman A , Miller H , Tejada-Strop A , Jain S , Tamin A , Harcourt JL , Thornburg NJ , Wong P , Medrzycki M , Folster JM , Semenova V , Steward-Clark E , Drobenuic J , Biedron C , Stewart RJ , da Silva J , Kirking HL , Tate JE . J Infect Dis 2021 225 (2) 229-237 BACKGROUND: The natural history and clinical progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can be better understood using combined serological and reverse transcription polymerase chain reaction (RT-PCR) testing. METHODS: Nasopharyngeal swabs and serum were collected at a single time-point from patients at an urban, public hospital August - November 2020 and tested for SARS-CoV-2 using RT-PCR, viral culture, and anti-Spike pan-Ig antibody testing. Participant demographics and symptoms were collected through interview. Chi-squared and Fisher's exact tests were used to identify associations between RT-PCR and serology results with presence of viable virus and frequency of symptoms. RESULTS: Among 592 participants, 129 (21.8%) had evidence of SARS-CoV-2 infection by RT-PCR or serology. Presence of SARS-CoV-2 antibodies was strongly associated with lack of viable virus (p-value=0.016). COVID-19 symptom frequency was similar for patients testing RT-PCR positive/seronegative and patients testing RT-PCR positive/seropositive. Patients testing RT-PCR positive/seronegative reported headaches, fatigue, diarrhea and vomiting at rates not statistically significantly different from those testing RT-PCR negative/seropositive. CONCLUSIONS: While patients testing SARS-CoV-2 seropositive were unlikely to test positive for viable virus and were therefore low-risk for forward transmission, COVID-19 symptoms were common. Paired SARS-CoV-2 RT-PCR and antibody testing provides more nuanced understanding of patients' COVID-19 status. |
Serologic testing of U.S. blood donations to identify SARS-CoV-2-reactive antibodies: December 2019-January 2020.
Basavaraju SV , Patton ME , Grimm K , Rasheed MAU , Lester S , Mills L , Stumpf M , Freeman B , Tamin A , Harcourt J , Schiffer J , Semenova V , Li H , Alston B , Ategbole M , Bolcen S , Boulay D , Browning P , Cronin L , David E , Desai R , Epperson M , Gorantla Y , Jia T , Maniatis P , Moss K , Ortiz K , Park SH , Patel P , Qin Y , Steward-Clark E , Tatum H , Vogan A , Zellner B , Drobeniuc J , Sapiano MRP , Havers F , Reed C , Gerber S , Thornburg NJ , Stramer SL . Clin Infect Dis 2020 72 (12) e1004-e1009 BACKGROUND: SARS-CoV-2, the virus that causes COVID-19 disease, was first identified in Wuhan, China in December 2019, with subsequent worldwide spread. The first U.S. cases were identified in January 2020. METHODS: To determine if SARS-CoV-2 reactive antibodies were present in sera prior to the first identified case in the U.S. on January 19, 2020, residual archived samples from 7,389 routine blood donations collected by the American Red Cross from December 13, 2019 to January 17, 2020, from donors resident in nine states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at CDC for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan Ig) enzyme linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor binding domain / Ace2 blocking activity assay. RESULTS: Of the 7,389 samples, 106 were reactive by pan Ig. Of these 106 specimens, 90 were available for further testing. Eighty four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor binding domain / Ace2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all nine states. CONCLUSIONS: These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to January 19, 2020. |
Performance of InBios ZIKV Detect(TM) 2.0 IgM Capture ELISA in two reference laboratories compared to the original ZIKV Detect(TM) IgM Capture ELISA
Basile AJ , Ao J , Horiuchi K , Semenova V , Steward-Clark E , Schiffer J . J Virol Methods 2019 271 113671 ZIKV Detect 2.0 IgM Capture ELISA (InBios International, Seattle, WA) recently replaced the ZIKV Detect IgM Capture ELISA and a number of significant changes have been made to the original version. This study compares data generated from the ZIKV Detect 2.0 IgM Capture ELISA, to data generated using the original version of the kit. The same sample sets were used in this comparison, and reference test results for these samples were used to assess sensitivity, specificity, accuracy and concordance of results across two laboratories. Average sensitivity increased from 90.4% to 92.5% with the updated kit where the increase was not statistically different, and specificity increased from 79.5% to 97.4%, a statistically-significant difference. Accuracy of the ZIKV Detect 2.0 IgM Capture ELISA was 89% compared to 63.9% for the original version of the kit, and agreement across the laboratories increased from 79.5% to 97.4%. With secondary dengue virus infections, specificity increased from 9.3% to 82.6% with the updated kit, primarily due to the change in interpretation criteria that no longer includes "Possible Zika positive." |
Multi-laboratory comparison of three commercially available Zika IgM enzyme-linked immunosorbent assays
Basile AJ , Goodman C , Horiuchi K , Sloan A , Johnson BW , Kosoy O , Laven J , Panella AJ , Sheets I , Medina F , Mendoza EJ , Epperson M , Maniatis P , Semenova V , Steward-Clark E , Wong E , Biggerstaff BJ , Lanciotti R , Drebot M , Safronetz D , Schiffer J . J Virol Methods 2018 260 26-33 Zika virus (ZIKV) is an enveloped, positive-sense RNA virus in the family Flaviviridae, genus Flavivirus. It was first discovered in rhesus monkeys in 1947 in the Zika Forest of Uganda (Dick et al., 1952) and historically of unclear importance given the rarity of reported cases and to relatively mild symptoms in humans. The virus is chiefly transmitted by Aedes mosquitoes, the carrier of other flaviviruses of medical importance such as the dengue viruses (DENVs) and yellow fever virus (YFV). Little research had been conducted on ZIKV prior to a 2007 outbreak in Yap, Federated States of Micronesia (Duffy et al., 2009), at which point the virus was sequenced and molecular and serological tests were developed (Lanciotti et al., 2008). |
Meningococcal Carriage Following a University Serogroup B Meningococcal Disease Outbreak and Vaccination Campaign with MenB-4C and MenB-FHbp - Oregon, 2015-2016.
McNamara LA , Thomas JD , MacNeil J , Chang HY , Day M , Fisher E , Martin S , Poissant T , Schmink SE , Steward-Clark E , Jenkins LT , Wang X , Acosta A . J Infect Dis 2017 216 (9) 1130-1140 Background: Limited data exist on the impact of the serogroup B meningococcal (MenB) vaccines MenB-FHbp and MenB-4C on meningococcal carriage and herd protection. We therefore assessed meningococcal carriage following a MenB vaccination campaign in response to a university serogroup B meningococcal disease outbreak in 2015. Methods: A convenience sample of students recommended for vaccination provided oropharyngeal swabs and completed questionnaires during four carriage surveys over 11 months. Isolates were tested by real-time PCR, slide agglutination, and whole genome sequencing. Vaccination history was verified via university records and the state immunization registry. Results: A total of 4,225 oropharyngeal swabs were analyzed from 3,802 unique participants. Total meningococcal and genotypically serogroup B carriage prevalence among sampled students were stable at 11-17% and 1.2%-2.4% during each round, respectively; no participants carried the outbreak strain. Neither 1-3 doses of MenB-FHbp nor 1-2 doses of MenB-4C was associated with decreased total or serogroup B carriage prevalence. Conclusions: While few participants completed the full MenB vaccination series, limiting analytic power, these data suggest that MenB-FHbp and MenB-4C do not have a large, rapid impact on meningococcal carriage and are unlikely to provide herd protection in the context of an outbreak response. |
Validation of high throughput screening of human sera for detection of anti-PA IgG by Enzyme-Linked Immunosorbent Assay (ELISA) as an emergency response to an anthrax incident
Semenova VA , Steward-Clark E , Maniatis P , Epperson M , Sabnis A , Schiffer J . Biologicals 2016 45 61-68 To improve surge testing capability for a response to a release of Bacillus anthracis, the CDC anti-Protective Antigen (PA) IgG Enzyme-Linked Immunosorbent Assay (ELISA) was re-designed into a high throughput screening format. The following assay performance parameters were evaluated: goodness of fit (measured as the mean reference standard r2), accuracy (measured as percent error), precision (measured as coefficient of variance (CV)), lower limit of detection (LLOD), lower limit of quantification (LLOQ), dilutional linearity, diagnostic sensitivity (DSN) and diagnostic specificity (DSP). The paired sets of data for each sample were evaluated by Concordance Correlation Coefficient (CCC) analysis. The goodness of fit was 0.999; percent error between the expected and observed concentration for each sample ranged from -4.6% to 14.4%. The coefficient of variance ranged from 9.0% to 21.2%. The assay LLOQ was 2.6 mug/mL. The regression analysis results for dilutional linearity data were r2 = 0.952, slope = 1.02 and intercept = -0.03. CCC between assays was 0.974 for the median concentration of serum samples. The accuracy and precision components of CCC were 0.997 and 0.977, respectively. This high throughput screening assay is precise, accurate, sensitive and specific. Anti-PA IgG concentrations determined using two different assays proved high levels of agreement. The method will improve surge testing capability 18-fold from 4 to 72 sera per assay plate. |
Preexisting immunity, more than aging, influences influenza vaccine responses
Reber AJ , Kim JH , Biber R , Talbot HK , Coleman LA , Chirkova T , Gross FL , Steward-Clark E , Cao W , Jefferson S , Veguilla V , Gillis E , Meece J , Bai Y , Tatum H , Hancock K , Stevens J , Spencer S , Chen J , Gargiullo P , Braun E , Griffin MR , Sundaram M , Belongia EA , Shay DK , Katz JM , Sambhara S . Open Forum Infect Dis 2015 2 (2) ofv052 BACKGROUND: Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. METHODS: We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008-2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. RESULTS: Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers ≥ 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG+ and IgA+ memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50-59. CONCLUSIONS: Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers ≥40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age. |
Severe acute respiratory infections caused by 2009 pandemic influenza A (H1N1) among American Indians-southwestern United States, May 1-July 21, 2009
Suryaprasad A , Redd JT , Hancock K , Branch A , Steward-Clark E , Katz JM , Fry AM , Cheek JE . Influenza Other Respir Viruses 2013 7 (6) 1361-9 BACKGROUND: During April-July 2009, U.S. hospitalization rates for 2009 pandemic influenza A (H1N1) virus (H1N1pdm09) infection were estimated at 4.5/100 000 persons. We describe rates and risk factors for H1N1pdm09 infection among American Indians (AIs) in four isolated southwestern U.S. communities served by the Indian Health Service (IHS). METHODS: We reviewed clinical and demographic information from medical records of AIs hospitalized during May 1-July 21, 2009 with severe acute respiratory infection (SARI). Hospitalization rates were determined using denominator data provided by IHS. H1N1pdm09 infection was confirmed with polymerase chain reaction, rapid tests, or convalescent serology. Risk factors for more severe (SARI) versus milder [influenza-like illness (ILI)] illness were determined by comparing confirmed SARI patients with outpatients with ILI. RESULTS: Among 168 SARI-hospitalized patients, 52% had confirmed H1N1pdm09 infection and 93% had >1 high-risk condition for influenza complications. The H1N1pdm09 SARI hospitalization rate was 131/100 000 persons [95% confidence interval (CI), 102-160] and was highest among ages 0-4 years (353/100,000; 95% CI, 215-492). Among children, asthma (adjusted odds ratio [aOR] 3.2; 95% CI, 1.2-8.4) and age <2 years (aOR 3.8; 95% CI, 1.4-10.0) were associated with H1N1pdm09 SARI-associated hospitalization, compared with outpatient ILI. Among adults, diabetes (aOR 3.1; 95% CI, 1.5-6.4) was associated with hospitalization after controlling for obesity. CONCLUSIONS: H1N1pdm09 hospitalization rates among this isolated AI population were higher than reported for other U.S. populations. Almost all case patients had high-risk health conditions. Prevention strategies for future pandemics should prioritize AIs, particularly in isolated rural areas. |
Seropositivity for influenza A(H1N1)pdm09 virus among frontline health care personnel
Alagappan K , Silverman RA , Hancock K , Ward MF , Akerman M , Dawood FS , Branch A , De Cicco S , Steward-Clark E , McCullough M , Tenner K , Katz JM . Emerg Infect Dis 2013 19 (1) 140-3 Seroprevalence of antibodies to influenza A(H1N1)pdm09 virus among 193 emergency department health care personnel was similar among 147 non-health care personnel (odds ratio 1.4, 95% CI 0.8-2.4). Working in an acute care setting did not substantially increase risk for virus infection above risk conferred by community-based exposures. |
Quantitative assessment of anthrax vaccine immunogenicity using the dried blood spot matrix
Schiffer JM , Maniatis P , Garza I , Steward-Clark E , Korman LT , Pittman PR , Mei JV , Quinn CP . Biologicals 2012 41 (2) 98-103 The collection, processing and transportation to a testing laboratory of large numbers of clinical samples during an emergency response situation present significant cost and logistical issues. Blood and serum are common clinical samples for diagnosis of disease. Serum preparation requires significant on-site equipment and facilities for immediate processing and cold storage, and significant costs for cold-chain transport to testing facilities. The dried blood spot (DBS) matrix offers an alternative to serum for rapid and efficient sample collection with fewer on-site equipment requirements and considerably lower storage and transport costs. We have developed and validated assay methods for using DBS in the quantitative anti-protective antigen IgG enzyme-linked immunosorbent assay (ELISA), one of the primary assays for assessing immunogenicity of anthrax vaccine and for confirmatory diagnosis of Bacillus anthracis infection in humans. We have also developed and validated high-throughput data analysis software to facilitate data handling for large clinical trials and emergency response. |
Validation and long term performance characteristics of a quantitative enzyme linked immunosorbent assay (ELISA) for human anti-PA IgG
Semenova VA , Schiffer J , Steward-Clark E , Soroka S , Schmidt DS , Brawner MM , Lyde F , Thompson R , Brown N , Foster L , Fox S , Patel N , Freeman AE , Quinn CP . J Immunol Methods 2012 376 97-107 Accurate, reliable and standardized quantification of anti-protective antigen (PA) IgG antibody levels is essential for comparative analyses of anti-toxin immune responses in anthrax cases, recipients of PA-based anthrax vaccines and for evaluation of anti-PA based immunotherapies. We have previously reported the early performance characteristics and application of a quantitative anti-PA IgG enzyme linked immunosorbent assay. The principal application of this assay was in a Phase 4 human clinical trial of anthrax vaccine adsorbed (AVA, BioThrax), the central component of the CDC Anthrax Vaccine Research Program (AVRP) and in humans following bioterrorism associated Bacillus anthracis infection (Quinn et al., 2002; Quinn et al., 2004; Marano et al., 2008). The objective of the AVRP was to determine the feasibility of reducing the number of priming series and booster doses of the licensed Anthrax Vaccine Adsorbed (AVA) (BioThrax(R); Emergent BioSolutions, Lansing, MI) and changing the route of administration from subcutaneous (SC) to intramuscular (IM) (Marano et al., 2008). In this paper we report the validation and long term performance characteristics of the assay during its six year application in the AVRP (2002-2008). The critical features are 1) extensive validation of the assay using two standard reference sera; 2) long term stability and 3) consistency of the data for quantitative analysis of human long term anti-PA IgG responses. The reportable value (RV) of the assay was expressed as anti-PA IgG concentration (mcg/ml). Accuracy of the assay was high with a percent error (%ER) range of 1.6-11.4%. Overall intra-operator and intermediate precision were high with Coefficients of Variation (%CVs) of 2.5-15.4% and 6.3-13.2%, respectively. The assay demonstrated excellent dilutional linearity for human sera using log(10) transformed data with the slope=0.95 to 0.99, intercept=0.02 to 0.06 and r(2)=0.980-0.987. The assay was robust, tolerating changes in serum incubation temperatures from 35 to 39 degrees C, serum incubation times from 55 to 65min and changes in key reagents. The long-term assay stability over 6years using consecutive reference sera AVR414 and AVR801 demonstrated sustained high accuracy and precision for the assay, confirming its suitability for long term studies of PA protein-based anthrax vaccines. |
Sensitivity and specificity of serologic assays for the detection of human infection with 2009 pandemic H1N1 virus in U.S. populations
Veguilla V , Hancock K , Schiffer J , Gargiullo P , Lu X , Aranio D , Branch A , Dong L , Holiday C , Liu F , Steward-Clark E , Sun H , Tsang B , Wang D , Whaley M , Bai Y , Cronin L , Browning P , Dababneh H , Noland H , Thomas L , Foster L , Quinn CP , Soroka SD , Katz JM . J Clin Microbiol 2011 49 (6) 2210-5 Swine origin 2009 H1N1 influenza virus has spread globally to cause the first influenza pandemic of the 21(st) century. Serological studies can improve our understanding of the extent of human infection and risk factors associated with transmission of this pandemic virus. The "gold standard" for serodiagnosis of human influenza infection is the detection of seroconversion between acute and convalescent stage samples. However, timing of seroepidemiologic investigations often precludes collection of truly acute phase sera, requiring development of serologic criteria for evaluating convalescent phase sera that optimize detection of true positives and true negatives. To guide seroepidemiologic investigations into the spread of the novel 2009 pandemic H1N1 virus, we characterized serum antibody responses to 2009 H1N1 virus in 87 individuals with confirmed viral infection and 227 non-exposed U.S. individuals using microneutralization (MN) and hemagglutination-inhibition (HI) assays. Sensitivity and specificity were determined for each assay alone, and in combination, for detection of 2009 H1N1-specific antibodies in convalescent sera. Although the HI assay was more specific for detecting antibody to 2009 H1N1, the MN was more sensitive, particularly for detecting low titer seroconversions. A combination of titers (MN ≥40 and HI ≥20) provided highest sensitivity (90%) and specificity (96%) for individuals aged < 60 years and 92% specificity for adults aged ≥60 years for detection of serologically confirmed 2009 H1N1 infections in U.S. populations during the first pandemic waves. These studies provide an approach to optimize timely serologic investigations for future pandemics or outbreaks of novel influenza viruses among humans. |
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