Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis

Androga, Grace O.; Hart, Julie; Foster, Niki F.; Charles, Adrian; Forbes, David; Riley, Thomas V.

doi:10.1128/jcm.01810-15

Cited by 40 publications

(26 citation statements)

References 13 publications

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“…Ribotypes 101 (40%; 6 of 15) and 137 (13Á3%; 2 of 15) were the two most prevalent RTs in lambs (Knight and Riley 2013b), RT 033 was the second most prevalent ribotype in both veal calves (19Á6%; 41 of 209; Knight et al 2013a) and piglets (13%;20/154;Knight et al 2015), while RT 237 is a pig strain unique to one piggery in WA (Knight et al 2015). All of these RTs of C. difficile have been isolated from human cases of CDI in Australia (Androga et al 2015;Furuya-Kanamori et al 2016;McGovern et al 2016).…”

Section: Discussionmentioning

confidence: 99%

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High prevalence ofClostridium difficileon retail root vegetables, Western Australia

et al. 2018

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Section: Discussionmentioning

confidence: 99%

“…All of these RTs of C. difficile have been isolated from human cases of CDI in Australia (Androga et al . ; Furuya‐Kanamori et al . ; McGovern et al .…”

Section: Discussionmentioning

confidence: 99%

High prevalence ofClostridium difficileon retail root vegetables, Western Australia

et al. 2018

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“…Experimental data have suggested that CDT results in the formation of microtubule-based protrusions on epithelial cells that might increase the adherence and colonization of C. difficile 142 . Importantly, the increasing presence of CDT in clinically relevant strain types commonly associated with severe CDI, such as PCR ribotypes 027 and 078, and the isolation of TcdA − TcdB − CDT + strains suggest that this toxin is likely to play an important but as yet undefined part in CDI 143,144 .…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Clostridium difficile infection

Smits

Lyras

Lacy

et al. 2016

Nat Rev Dis Primers

655

674

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Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis — the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.

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“…The symptomatic cohort was not used to establish the C 0 calculation as they may have included false negatives with CDI undetected by the TcdB PCR test alone. Two of these patients had positive MENSA and serum antibody responses against CDTa and/or CDTb but were negative for TcdB-CROP, suggesting they may have been infected with a binary toxin positive, TcdB negative CD strain (15, 41-43). CD strains positive for binary toxin and negative for TcdB have been recently described and would be missed in our symptomatic cohort since only TcdB PCR testing was performed.…”

Section: Discussionmentioning

confidence: 99%

Novel Immunoassay for Diagnosis of OngoingClostridioides difficileInfections Using Serum and Medium Enriched for Newly Synthesized Antibodies (MENSA)

Haddad¹,

Nozick²,

Kim³

et al. 2020

Preprint

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47BACKGROUND. Clostridioides difficile infections (CDI) have been a challenging and 48 increasing serious concern in recent years. While early and accurate diagnosis is crucial, available assays 49 have frustrating limitations 50 51 OBJECTIVE. Develop a simple, blood-based immunoassay to accurately diagnose patients 52 suffering from active CDI. 53 54 MATERIALS AND METHODS. Uninfected controls (n=95) and CDI patients (n=167) were 55 recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a 56 positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly 57 synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinant C. 58 difficile antigens. 59 60 RESULTS. Sixty-six percent of CDI patients produced measurable responses to C. difficile 61 antigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI 62 patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in 63 MENSA, and 27/167 (16%) were detectable only in serum. 64 65 DISCUSSION. We describe the results of a multiplex immunoassay for the diagnosis of ongoing 66 CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, 67 serum-positive only, MENSA-and serum-positive, and MENSA-and serum-negative. The MENSA 68 positive-only patients accounted for 30% and may be attributed to nascent antibody secretion in MENSA 69 prior to seroconversion. Conversely, the serum positive-only subset may have been more advanced in 70 5 5 their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI 71 patients who were not identified using MENSA or serum immunoassays. 72 73 IMPORTANCE. While there was considerable overlap between patients identified through 74 MENSA and serum, both methods detected additional, unique patients. The combined use of both 75 MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, 76 longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host 77 humoral immune responses in CDI patients. 78In this observational investigation, we present the results of a pilot study validating the use of a 127 multi-antigen immunoassay and its ability to measure antibody secretion reflecting ongoing CDI in 128 MENSA samples from a complex hospital population and compare its performance with results from sera. 129 130 RESULTS 131

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Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis

Cited by 40 publications

References 13 publications

High prevalence ofClostridium difficileon retail root vegetables, Western Australia

High prevalence ofClostridium difficileon retail root vegetables, Western Australia

Clostridium difficile infection

Novel Immunoassay for Diagnosis of OngoingClostridioides difficileInfections Using Serum and Medium Enriched for Newly Synthesized Antibodies (MENSA)

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