Conrad P Quinn | Centers for Disease Control and Prevention (original) (raw)

Papers by Conrad P Quinn

This article cites 28 articles, 11 of which can be accessed free

L'invention concerne une methode de traitement de l'hypersecretion de mucus, facteur caus... more L'invention concerne une methode de traitement de l'hypersecretion de mucus, facteur causal de la bronchopneumopathie chronique obstructive (COPD), de l'asthme et d'autres etats cliniques impliquant la COPD. Ladite methode consiste a administrer un compose qui inhibe l'exocytose dans les cellules secretant le mucus ou les neurones qui commandent ou dirigent la secretion de mucus. L'invention porte egalement sur un compose a utiliser dans le traitement de l'hypersecretion de mucus, qui inhibe la secretion de mucus en inhibant la secretion de mucus par les cellules secretant le mucus, et/ou en inhibant la liberation de neurotransmetteur des cellules neuronales commandant ou dirigeant la secretion de mucus.

Emerging Infectious Diseases, Oct 1, 2002

, the first inhalational anthrax case in the United States since 1976 was identified in a media c... more , the first inhalational anthrax case in the United States since 1976 was identified in a media company worker in Florida. A national investigation was initiated to identify additional cases and determine possible exposures to Bacillus anthracis. Surveillance was enhanced through health-care facilities, laboratories, and other means to identify cases, which were defined as clinically compatible illness with laboratory-confirmed B. anthracis infection. From October 4 to November 20, 2001, 22 cases of anthrax (11 inhalational, 11 cutaneous) were identified; 5 of the inhalational cases were fatal. Twenty (91%) case-patients were either mail handlers or were exposed to worksites where contaminated mail was processed or received. B. anthracis isolates from four powder-containing envelopes, 17 specimens from patients, and 106 environmental samples were indistinguishable by molecular subtyping. Illness and death occurred not only at targeted worksites, but also along the path of mail and in other settings. Continued vigilance for cases is needed among health-care providers and members of the public health and law enforcement communities.

PLOS Pathogens

Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive, and late... more Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive, and late-fulminant. We report the comprehensive characterization of anthrax toxins, including total protective antigen (PA), total lethal factor (LF), total edema factor (EF), and their toxin complexes, lethal toxin and edema toxin in plasma, during the course of inhalation anthrax in 23 cynomolgus macaques. The toxin kinetics were predominantly triphasic with an early rise (phase-1), a plateau/decline (phase-2), and a final rapid rise (phase-3). Eleven animals had shorter survival times, mean±standard deviation of 58.7±7.6 hours (fast progression), 11 animals had longer survival times, 113±34.4 hours (slow progression), and one animal survived. Median (lower–upper quartile) LF levels at the end-of-phase-1 were significantly higher in animals with fast progression [138 (54.9–326) ng/mL], than in those with slow progression [23.8 (15.6–26.3) ng/mL] (p = 0.0002), and the survivor (11.1 ng/mL). The...

Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive and late-... more Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive and late- fulminant. The toxins produced during infection exert pathologic effects leading to death, but they have not been comprehensively characterized throughout the course of infection. Mass spectrometry methods for anthrax toxins, total-protective antigen (PA), total-lethal factor (LF), total-edema factor (EF), and toxin complexes, lethal toxin and edema toxin were used to characterize the stages of inhalation anthrax in 23 cynomolgus macaques. The target aerosol dose was 200 LD50B. anthracis Ames spores. 22 animals died during the study. Different patterns of toxemia and bacteremia were observed in 11 animals with the shortest survival times (fast progression), the 11 animals with longer survival (slow progression), and the one survivor. Toxemia and bacteremia were predominantly triphasic with an early rise (phase-1), a plateau/decline (phase-2), and a final rapid rise (phase-3). The patter...

Application of in vivo induced antigen technology (IVIAT) to Bacillus anthracis.

L'invention concerne l'isolement, la caracterisation et la synthese d'oligosaccharide... more L'invention concerne l'isolement, la caracterisation et la synthese d'oligosaccharides HF-PS et BcIA-OS du bacillus anthracis. Des anticorps qui se lient a de telles fractions de saccharide et divers procedes d'utilisation pour de tels fractions et anticorps de saccharide sont egalement presentes.

Journal of Biological Chemistry, 1991

Linker insertion mutagenesis was employed to create structural disruptions of the lethal factor (... more Linker insertion mutagenesis was employed to create structural disruptions of the lethal factor (LF) protein of anthrax toxin to map functional domains. A dodecameric linker was inserted at 17 blunt end restriction enzyme sites throughout the gene. Paired MluI restriction sites within the linker allowed the inserts to be reduced from four to two amino acids. Shuttle vectors containing the mutated genes were transformed into the avirulent Bacillus anthracis UM23C1-1 for expression and secretion of the gene products. Mutations at five sites in the central one-third of the sequence made the protein unstable, and purified protein could not be obtained. Mutated LF proteins with insertions at the other sites were purified and assessed for toxic activity in a macrophage lysis assay and for their ability to bind to the protective antigen (PA) component of anthrax toxin, the receptor binding moiety. Most insertions located in the NH2-terminal one-third of the LF protein eliminated both toxicity and binding to PA, while all four insertions in the COOH-terminal one-third of the protein eliminated toxicity without affecting binding to PA. These data support the hypothesis that the NH2-terminal domain contains the structures required for binding to PA and the COOH-terminal domain contains the putative catalytic domain of LF.

Analytical and Bioanalytical Chemistry, 2019

Inhalation of Bacillus anthracis spores can cause a rapidly progressing fatal infection. B. anthr... more Inhalation of Bacillus anthracis spores can cause a rapidly progressing fatal infection. B. anthracis secretes three protein toxins: lethal factor (LF), edema factor (EF), and protective antigen (PA). EF and LF may circulate as free or PA-bound forms. Both free EF (EF) and PA-bound-EF (ETx) have adenylyl cyclase activity converting ATP to cAMP. We developed an adenylyl cyclase activitybased method for detecting and quantifying total EF (EF+ETx) in plasma. The three-step method includes magnetic immunocapture with monoclonal antibodies, reaction with ATP generating cAMP, and quantification of cAMP by isotope-dilution HPLC-MS/MS. Total EF was quantified

Biologicals, 2019

Despite wide spread vaccination, the public health burden of pertussis remains substantial. Curre... more Despite wide spread vaccination, the public health burden of pertussis remains substantial. Current acellular pertussis vaccines comprise upto five Bordetella pertussis (Bp) antigens. Performing an ELISA to quantify antibody for each antigen is laborious and challenging to apply to pediatric samples where serum volume may be limited. We developed a microsphere based multiplex antibody capture assay (MMACA) to quantify antibodies to five pertussis antigens; pertussis toxin, pertactin, filamentous hemagglutinin and fimbrial antigens 2/3, and adenylate cyclase toxin in a single reaction (5-plex) with a calibrated reference standard, QC reagents and SAS ® based data analysis program. The goodness of fit (R 2) of the standard curves for five analytes was ≥0.99, LLOQ 0.04-0.15 IU or AU/mL, accuracy 1.9%-23.8% (%E), dilutional linearity slopes 0.93-1.02 and regression coefficients r 2 = 0.91-0.99. MMACA had acceptable precision within a median CV of 16.0%-22.8%. Critical reagents, antigen conjugated microsphere and reporter antibody exhibited acceptable (< 12.3%) lot-lot variation. MMACA can be completed in < 3 h, requires low serum volume (5μL/multiplex assay) and has fast data turnaround time (< 1 min). MMACA has been successfully developed and validated as a sensitive, specific, robust and rugged method suitable for simultaneous quantification of anti-Bp antibodies in serum, plasma and DBS.

Analytical biochemistry, Jan 7, 2017

Anthrax lethal factor (LF) is a zinc-dependent endoprotease and a critical virulence factor for B... more Anthrax lethal factor (LF) is a zinc-dependent endoprotease and a critical virulence factor for Bacillus anthracis, the causative agent of anthrax. The mass spectrometry (MS) method for total-LF quantification includes three steps; 1) LF specific antibody capture/concentration, 2) LF-specific hydrolysis of a peptide substrate, and 3) detection and quantification of LF-cleaved peptides by isotope-dilution MALDI-TOF/MS. Recombinant LF spiked plasma was used for calibration and quality control (QC) materials. Specificity was 100% from analysis of serum and plasma from 383 non-infected humans, 31 rabbits, and 24 rhesus macaques. Sensitivity was 100% from 32 human clinical anthrax cases including infections by inhalation, ingestion, cutaneous and injection exposures and experimental infections for 29 rabbits and 24 rhesus macaques with inhalation anthrax. Robustness evaluation included sample storage, serum and plasma, antimicrobial and antitoxin effects and long-term performance. Data f...

PloS one, 2017

Bacillus anthracis (Ba) and human infection-associated Bacillus cereus (Bc) strains Bc G9241 and ... more Bacillus anthracis (Ba) and human infection-associated Bacillus cereus (Bc) strains Bc G9241 and Bc 03BB87 have secondary cell wall polysaccharides (SCWPs) comprising an aminoglycosyl trisaccharide repeat: →4)-β-d-ManpNAc-(1→4)-β-d-GlcpNAc-(1→6)-α-d-GlcpNAc-(1→, substituted at GlcNAc residues with both α- and β-Galp. In Bc G9241 and Bc 03BB87, an additional α-Galp is attached to O-3 of ManNAc. Using NMR spectroscopy, mass spectrometry and immunochemical methods, we compared these structures to SCWPs from Bc biovar anthracis strains isolated from great apes displaying "anthrax-like" symptoms in Cameroon (Bc CA) and Côte d'Ivoire (Bc CI). The SCWPs of Bc CA/CI contained the identical HexNAc trisaccharide backbone and Gal modifications found in Ba, together with the α-Gal-(1→3) substitution observed previously at ManNAc residues only in Bc G9241/03BB87. Interestingly, the great ape derived strains displayed a unique α-Gal-(1→3)-α-Gal-(1→3) disaccharide substitution at som...

Emerging infectious diseases, 2017

We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009-2010 outbreak of Bacillus... more We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009-2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0-5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6-11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak.

Vaccine, 2016

Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administratio... more Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administration (FDA) for a post-exposure prophylaxis (PEP) indication in adults 18-65 years of age. The schedule is three doses administered subcutaneous (SC) at 2-week intervals (0, 2, and 4 weeks), in conjunction with a 60-day course of antimicrobials. The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) developed an animal model to support assessment of a shortened antimicrobial PEP duration following Bacillus anthracis exposure. A nonhuman primate (NHP) study was completed to evaluate the efficacy of a two dose anthrax vaccine absorbed (AVA) schedule (0, 2 weeks) aerosol challenged with high levels of B. anthracis spores at week 4-the time point at which humans would receive the third vaccination of the approved PEP schedule. Here we use logistic regression models to combine the survival data from the NHP study along with serum anthrax lethal toxin neutralizing activity (TNA) and anti-PA IgG measured by enzyme linked immunosorbent assay (ELISA) data to perform a cross-species analysis to estimate survival probabilities in vaccinated human populations at this time interval (week 4 of the PEP schedule). The bridging analysis demonstrated that high levels of NHP protection also yield high predicted probability of human survival just 2 weeks after the second dose of vaccine with the full or half antigen dose regimen. The absolute difference in probability of human survival between the full and half antigen dose was estimated to be at most approximately 20%, indicating that more investigation of the half-antigen dose for vaccine dose sparing strategies may be warranted.

Expert Review of Vaccines, 2016

Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved... more Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the vaccine&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s PEP application.