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Epidemiology of Clostridioides difficile infection in Canada: A six-year review to support vaccine decision-making.

ABSTRACT: Background:Two vaccines against Clostridioides difficile infections (CDI) are currently in phase III trials. To enable decision-making on their use in public health programs, national disease epidemiology is necessary. Objectives:To determine the epidemiology of hospital-acquired CDI (HA-CDI) and community-associated CDI (CA-CDI) in Canada using provincial surveillance data and document discrepancies in CDI-related definitions among provincial surveillance programs. Methods:Publicly-available CDI provincial surveillance data from 2011 to 2016 that distinguished between HA-CDI and CA-CDI were included and the most common surveillance definitions for each province were used. The HA-, CA-CDI incidence rates and CA-CDI proportions (%) were calculated for each province. Both HA- and CA-CDI incidence rates were examined for trends. Types of disparities were summarized and detailed discrepancies were documented. Results:Canadian data were analyzed from nine provinces. The HA-CDI rates ranged from 2.1/10,000 to 6.5/10,000 inpatient-days, with a decreasing trend over time. Available data on CA-CDI showed that both rates and proportions have been increasing over time. Discrepancies among provincial surveillance definitions were documented in CDI case classifications, surveillance populations and rate calculations. Conclusion:In Canada overall, the rate of HA-CDI has been decreasing and the rate of CA-CDI has been increasing, although this calculation was impeded by discrepancies in CDI-related definitions among provincial surveillance programs. Nationally-adopted common definitions for CDI would enable better comparisons of CDI rates between provinces and a calculation of the pan-Canadian burden of illness to support vaccine decision-making.

SUBMITTER: Xia Y

PROVIDER: S-EPMC6615439 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Epidemiology of <i>Clostridioides difficile</i> infection in Canada: A six-year review to support vaccine decision-making.

Xia Y Y Tunis M C MC Frenette C C Katz K K Amaratunga K K Rose S Rhodenizer SR House A A Quach C C

Canada communicable disease report = Releve des maladies transmissibles au Canada 20190704 7-8

<h4>Background</h4>Two vaccines against <i>Clostridioides difficile</i> infections (CDI) are currently in phase III trials. To enable decision-making on their use in public health programs, national disease epidemiology is necessary.<h4>Objectives</h4>To determine the epidemiology of hospital-acquired CDI (HA-CDI) and community-associated CDI (CA-CDI) in Canada using provincial surveillance data and document discrepancies in CDI-related definitions among provincial surveillance programs.<h4>Meth ...[more]

PMID: 31355824

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Project description:Background:To understand the clinical burden of Clostridioides difficile infection (CDI), we analyzed health outcome data from Ontario, Canada for CDI associated with and manifested in acute care hospitals (ACH), long-term care facilities (LTCF), the community, or ACH-associated with community-onset. Methods:We performed a retrospective analysis using individual-level data from Ontario databases (April 1, 2005 to March 31, 2015), identifying CDI cases ?18 years requiring hospitalization, and stratifying into cohorts based on association and onset location. Cohort members were matched to controls on demographics and medical conditions at onset, for outcomes including 30- and 180-day all-cause mortality and rehospitalization. Results:We stratified 22 617 individuals hospitalized with CDI during the study period: 13 152 (58.1%) ACH-associated/ACH-onset, 7116 (31.5%) community-associated/community-onset, 1847 (8.2%) ACH-associated/community-onset, and 502 (2.2%) LTCF-associated/LTCF-onset. Compared with controls, unadjusted 30-day rehospitalization rates were significantly higher (P < .0001) for ACH-associated/ACH-onset CDI (9.5% vs 0.4%), LTCF-associated/LTCF-onset (7.2% vs 1.1%), community-associated/community-onset (7.8% vs 0.8%), and ACH-associated/community-onset (10.9% vs 0.7%). One hundred eighty-day mortality rates were higher in the community-associated/community-onset and the LTCF-associated/LTCF-onset cohorts than controls: 66.3% vs 12.3% (P < .0001) and 30.9% vs 3.1% (P < .0001), respectively. All differences remained significant after adjusting for patient factors. Conclusions:Clostridioides difficile infection is associated with higher rates of 30-day rehospitalization compared with controls. In addition, mortality rates within 180-days of hospital discharge are significantly higher for community-associated/community-onset and LTCF-associated/LTCF-onset CDI cohorts than controls. Clostridioides difficile infection warrants increased prevention and monitoring efforts.

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

Epidemiology of Clostridioides difficile infection in Canada: A six-year review to support vaccine decision-making.

Publications

Epidemiology of <i>Clostridioides difficile</i> infection in Canada: A six-year review to support vaccine decision-making.

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