Dataset Information

Pet Ownership Protects Against Recurrence of Clostridioides difficile Infection.

ABSTRACT: Background:Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated and health care-associated diarrhea in humans. Recurrent CDI (R-CDI) occurs in ~20%-30% of patients with CDI and results in increased morbidity, mortality, and hospital costs. Genomic analyses have shown overlap of C. difficile isolates from animals and people, suggesting that a zoonotic reservoir may contribute to recurrence. The objective of this study was to determine whether pet ownership is a risk factor for recurrence of CDI. Methods:We conducted a case-control study among patients with recurrent CDI (cases; n?=?86) and patients with nonrecurrent CDI (controls; n?=?146). Multivariable logistic regression modeling was used to determine the association between recurrence of CDI and pet ownership while accounting for patient-level risk factors. Results:Pet ownership was not significantly associated with recurrence of CDI (odds ratio [OR],?1.02; 95% confidence interval [CI],?0.38-2.72; P?=?0.965) among all patients (n?=?232). However, among the subset of patients with community-associated or community-onset health care facility-acquired CDI (n?=?127), increasing contact with pets was increasingly protective against recurrence: for every point increase in a pet contact score (out of 7 possible points), the odds of recurrence decreased by 14% (OR,?0.86; 95% CI,?0.74-1.00; P?=?0.051). Conclusions:Close interactions with pets appear protective against the recurrence of community-acquired CDI. A potential mechanism may involve beneficial contributions to the microbiota of pet owners afflicted with CDI, as has been observed for other conditions such as atopy, obesity, and food allergies. However, more research is needed to understand the interactions between pets, owners, and their microbiota.

SUBMITTER: Redding LE

PROVIDER: S-EPMC6969483 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Pet Ownership Protects Against Recurrence of <i>Clostridioides difficile</i> Infection.

Redding Laurel E LE Kelly Brendan J BJ Stefanovski Darko D Lautenbach John K JK Tolomeo Pam P Cressman Leigh L Gruber Eli E Meily Paige P Lautenbach Ebbing E

Open forum infectious diseases 20200118 1

<h4>Background</h4><i>Clostridioides difficile</i> infection (CDI) is the leading cause of antibiotic-associated and health care-associated diarrhea in humans. Recurrent CDI (R-CDI) occurs in ~20%-30% of patients with CDI and results in increased morbidity, mortality, and hospital costs. Genomic analyses have shown overlap of <i>C. difficile</i> isolates from animals and people, suggesting that a zoonotic reservoir may contribute to recurrence. The objective of this study was to determine whethe ...[more]

PMID: 31976354

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Project description:The symptoms of Clostridioides difficile infection (CDI) are largely attributed to two C. difficile toxins, TcdA and TcdB. Significant efforts have been devoted to developing vaccines targeting both toxins through parenteral immunization routes. Recently, we generated a novel chimeric protein (designated Tcd169), comprised of the glucosyltransferase domain (GT), the cysteine protease domain (CPD), and the receptor binding domain (RBD) of TcdB, and the RBD of TcdA. Parenteral immunizations with Tcd169 provide mice effective protection against infection with a ribotype (RT) 027 C. difficile strain. In this study, we expressed Tcd169 in a nontoxigenic C. difficile CCUG37785 strain (designated NTCD), resulting in strain NTCD_Tcd169 to develop an oral vaccine that can target both C. difficile toxins and colonization/adhesion factors. Oral immunizations with NTCD_Tcd169 spores induced systematic and mucosal antibody responses against, not only both toxins, but also C. difficile flagellins (FliC/FliD). Intriguingly yet importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2). Oral immunizations with NTCD_Tcd169 spores provided mice effective protection against infection with a hypervirulent RT027 C. difficile strain R20291and significantly reduced R20291spore numbers in feces compared with NTCD or PBS immunized mice. These results imply that the genetically modified, nontoxigenic C. difficile strain expressing Tcd169 may represent a novel mucosal vaccine candidate against CDI. IMPORTANCE Clostridioides difficile is an enteric pathogen, and symptoms of C. difficile infection (CDI) are mainly by two exotoxins TcdA and TcdB. Active vaccination is cost-effective approach to prevent CDI and high rates of recurrence. Ideally, vaccines should target both C. difficile toxins and cell/spore colonization. In this study, we expressed immunodominant fragments of TcdA and TcdB (i.e., Tcd169) in a nontoxigenic C. difficile CCUG37785 strain, generating a promising oral/mucosal vaccine candidate against CDI, by targeting both toxins and colonization of pathogenic C. difficile strains. Importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2), and all of which are involved in C. difficile adhesion/colonization in vitro and in vivo.

Dataset Information

Pet Ownership Protects Against Recurrence of Clostridioides difficile Infection.

Publications

Pet Ownership Protects Against Recurrence of <i>Clostridioides difficile</i> Infection.

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