Dataset Information

Comparison of Clostridioides difficile Stool Toxin Concentrations in Adults With Symptomatic Infection and Asymptomatic Carriage Using an Ultrasensitive Quantitative Immunoassay.

ABSTRACT: Background:We used an ultrasensitive, quantitative single molecule array (Simoa) immunoassay to test whether concentrations of Clostridioides (formerly Clostridium) difficile toxins A and/or B in the stool of adult inpatients with C. difficile infection (CDI) were higher than in asymptomatic carriers of toxinogenic C. difficile. Methods:Patients enrolled as CDI-NAAT had clinically significant diarrhea and a positive nucleic acid amplification test (NAAT), per US guidelines, and received CDI treatment. Potential carriers had recently received antibiotics and did not have diarrhea; positive NAAT confirmed carriage. Baseline stool samples were tested by Simoa for toxin A and B. Results:Stool toxin concentrations in both CDI-NAAT (n = 122) and carrier-NAAT (n = 44) cohorts spanned 5 logs (0 pg/mL to >100000 pg/mL). Seventy-nine of 122 (65%) CDI-NAAT and 34 of 44 (77%) carrier-NAAT had toxin A + B concentration ≥20 pg/mL (clinical cutoff). Median toxin A, toxin B, toxin A + B, and NAAT cycle threshold (Ct) values in CDI-NAAT and carrier-NAAT cohorts were similar (toxin A, 50.6 vs 60.0 pg/mL, P = .958; toxin B, 89.5 vs 42.3 pg/mL, P = .788; toxin A + B, 197.2 vs 137.3 pg/mL, P = .766; Ct, 28.1 vs 28.6, P = .354). However, when CDI/carrier cohorts were limited to those with detectable toxin, respective medians were significantly different (A: 874.0 vs 129.7, P = .021; B: 1317.0 vs 81.7, P = .003, A + B, 4180.7 vs 349.6, P = .004; Ct, 25.8 vs 27.7, P = .015). Conclusions:Toxin concentration did not differentiate an individual with CDI from one with asymptomatic carriage. Median stool toxin concentrations in groups with CDI vs carriage differed, but only when groups were defined by detectable stool toxin (vs positive NAAT).

SUBMITTER: Pollock NR

PROVIDER: S-EPMC6293008 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Comparison of Clostridioides difficile Stool Toxin Concentrations in Adults With Symptomatic Infection and Asymptomatic Carriage Using an Ultrasensitive Quantitative Immunoassay.

Pollock Nira R NR Banz Alice A Chen Xinhua X Williams David D Xu Hua H Cuddemi Christine A CA Cui Alice X AX Perrotta Matthew M Alhassan Eaman E Riou Brigitte B Lantz Aude A Miller Mark A MA Kelly Ciaran P CP

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190101 1

<h4>Background</h4>We used an ultrasensitive, quantitative single molecule array (Simoa) immunoassay to test whether concentrations of Clostridioides (formerly Clostridium) difficile toxins A and/or B in the stool of adult inpatients with C. difficile infection (CDI) were higher than in asymptomatic carriers of toxinogenic C. difficile.<h4>Methods</h4>Patients enrolled as CDI-NAAT had clinically significant diarrhea and a positive nucleic acid amplification test (NAAT), per US guidelines, and re ...[more]

PMID: 29788296

Similar Datasets

Project description:Background: We employed DNA microarray technology to investigate the host response to Streptococcus pneumoniae in a mouse model of asymptomatic carriage. Over a period of six weeks, we profiled transcript abundance and complexity in the Nasal Associated Lymphoid Tissue (NALT) to identify genes whose expression differed between pneumococcal-colonized and uncolonized states. Results: Colonization with S. pneumoniae altered the expression of hundreds of genes over the course of the study, demonstrating that carriage is a dynamic process characterized by increased expression of a set of early inflammatory responses, including induction of a Type 1 Interferon response, and the production of several antimicrobial factors. Subsequent to this initial inflammatory response, we observed increases in transcripts associated with T cell development and activation, as well as wounding, basement membrane remodeling, and cell proliferation. Our analysis suggests that microbial colonization induced expression of genes encoding components critical for controlling JAK/STAT signaling, including stat1, stat2, socs3, and mapk1, as well as induction of several Type 1 Interferon-inducible genes and other antimicrobial factors at the earliest stages of colonization. Conclusions: Examining multiple time points over six weeks of colonization demonstrated that asymptomatic carriage stimulates a dynamic host response characterized by temporal waves with distinct biological programs. Our data suggest that the usual response to the presence of the pneumocccus is an initial controlled inflammatory response followed by activation of host physiological processes such as response to wounding, basement membrane remodeling, and increasing cellular numbers that ultimately allow the host to maintain an intact epithelium and eventually mount a preventive adaptive immune response. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied.

Project description:Laboratory tests for Clostridioides difficile infection (CDI) rely on the detection of free toxin or molecular detection of toxin genes. The Singulex Clarity C. diff toxins A/B assay is a rapid, automated, and ultrasensitive assay that detects C. difficile toxins A and B in stool. We compared CDI assays across two prospective multicenter studies to set a cutoff for the Clarity assay and to independently validate the performance compared with that of a cell culture cytotoxicity neutralization assay (CCCNA). The cutoff was set by two sites testing fresh samples from 897 subjects with suspected CDI and then validated at four sites testing fresh samples from 1,005 subjects with suspected CDI. CCCNA testing was performed at a centralized laboratory. Samples with discrepant results between the Clarity assay and CCCNA were retested with CCCNA when the Clarity result agreed with that of at least one comparator method; toxin enzyme immunoassays (EIA), glutamate dehydrogenase (GDH) detection, and PCR were performed on all samples. The cutoff for the Clarity assay was set at 12.0?pg/ml. Compared to results with CCCNA, the Clarity assay initially had 85.2% positive agreement and 92.4% negative agreement. However, when samples with discrepant results between the Clarity assay and CCCNA in the validation study were retested by CCCNA, 13/17 (76.5%) Clarity-negative but CCCNA-positive samples (Clarity+/CCCNA-) became CCCNA-, and 5/26 (19.2%) Clarity+/CCCNA- samples became CCCNA+, resulting in a 96.3% positive agreement and 93.0% negative agreement between Clarity and CCCNA results. The toxin EIA had 59.8% positive agreement with CCCNA. The Clarity assay was the most sensitive free-toxin immunoassay, capable of providing CDI diagnosis in a single-step solution. A different CCCNA result was reported for 42% of retested samples, increasing the positive agreement between Clarity and CCCNA from 85.2% to 96.3% and indicating the challenges of comparing free-toxin results to CCCNA results as a reference standard.

Dataset Information

Comparison of Clostridioides difficile Stool Toxin Concentrations in Adults With Symptomatic Infection and Asymptomatic Carriage Using an Ultrasensitive Quantitative Immunoassay.

Publications

Comparison of Clostridioides difficile Stool Toxin Concentrations in Adults With Symptomatic Infection and Asymptomatic Carriage Using an Ultrasensitive Quantitative Immunoassay.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets