title: Emergence of Clostridium difficile-associated disease in North America and Europe.
abstract: The clinical spectrum of Clostridium difficile-associated disease (CDAD) ranges from diarrhoea to severe life-threatening pseudomembranous colitis. Although not always associated with previous antibiotic exposure, it is in the majority of cases. CDAD is recognised increasingly in a variety of animal species and in individuals previously not considered to be predisposed. C. difficile can be transmitted via personal contact or environmentally. The role of patients and healthcare workers who are symptom-free but colonised with C. difficile in the intestinal tract is unclear. C. difficile, with more than 150 PCR ribotypes and 24 toxinotypes, has a pathogenicity locus (PaLoc) with genes encoding enterotoxin A (tcdA) and cytotoxin B (tcdB). Genes for the binary toxin are located outside the PaLoc, but the role of this toxin is unclear. The recently completed genome sequence of C. difficile 630 revealed a large proportion of 11% of mobile genetic elements, mainly in the form of conjugative transposons. Diagnostic assays include tests for the detection of C. difficile products or genes and culture methods for isolation of a toxin-producing bacterium. Enzyme immunoassays to detect toxin in faeces are widely available, with varying sensitivities and specificities. Despite practical drawbacks and sensitivity less than 100%, the cell cytototoxicity assay is still considered to be the standard. Rapid diagnostic assays are available on a limited scale and require much improvement. Molecular tests enable the detection of carriers of toxigenic and non-toxigenic strains, as does culture. It is highly recommended to culture C. difficile from toxin-positive faeces samples and to store isolates for future characterisation and typing. The financial impact of CDAD on the healthcare system is substantial (5-15,000 euro/case in England and $1.1 billion/year in the USA). Assuming a European Union population of 457 million, the potential cost of CDAD can be estimated to be 3000 million euro/year, and is expected to almost double over the next four decades. In North America, increasing rates of CDAD have been reported in Canada and the USA since March 2003, involving a more severe course, higher mortality, increased risk of relapse and more complications. This increased virulence is presumably associated with higher levels of toxin production by fluoroquinolone-resistant strains belonging to PCR ribotype 027, pulsed-field gel electrophoresis (PFGE) type NAP1, REA (restriction endonuclease analysis) type BI and toxinotype III. In Europe, outbreaks of CDAD due to the new, highly virulent strain of C. difficile PCR ribotype 027, toxinotype III have been recognised in 75 hospitals in England, 16 hospitals in The Netherlands, 13 healthcare facilities in Belgium and nine healthcare facilities in France. These outbreaks are very difficult to control, and preliminary results from case-control studies indicate a correlation with fluoroquinolones and cephalosporins. Information concerning community-acquired cases of ribotype 027 is lacking, and data concerning its incidence in nursing homes are limited. European countries should first develop early-warning and response capabilities at a national level. Depending on the nature of the notifications received, countries should implement laboratory-based or patient-based surveillance systems in specific, targeted populations.
authors.affiliation: Leiden University, Leiden, The Netherlands. ejkuijper@gmail.com
authors.forename: E J
authors.initials: EJ
authors.lastname: Kuijper
authors.forename: B
authors.initials: B
authors.lastname: Coignard
authors.forename: P
authors.initials: P
authors.lastname: Tüll
mesh_terms: D000818:Animals; D016360:Clostridioides difficile; D021821:Communicable Diseases, Emerging / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology* / Q000628:therapy; D004761:Enterocolitis, Pseudomembranous / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D005060:Europe / Q000453:epidemiology; D006801:Humans; D009656:North America / Q000453:epidemiology; D000091402:Prohibitins