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...

Recent outbreaks of Clostridium difficile-associated diarrhoea (CDAD) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America, Japan and Europe. Definitions have been proposed by the European Centre of Disease Prevention and Control (ECDC) to identify severe cases of CDAD and to differentiate community-acquired cases from nosocomial CDAD (http://www.ecdc.europa.eu/documents/pdf/Cl_dif_v2.pdf). CDAD is mainly known as a healthcare-associated disease, but it is also increasingly recognised as a community-associated disease. The emerging strain is referred to as North American pulsed-field type 1 (NAP1) and PCR ribotype 027. Since 2005, individual countries have developed surveillance studies to monitor the spread of this strain. C. difficile type 027 has caused outbreaks in England and Wales, Ireland, the Netherlands, Belgium, Luxembourg, and France, and has also been detected in Austria, Scotland, Switzerland, Poland and Denmark. Preliminary data indicated that type 027 was already present in historical isolates collected in Sweden between 1997 and 2001.

Clostridium difficile-associated diarrhoea (CDAD) presents mainly as a nosocomial infection, usually after antimicrobial therapy. Many outbreaks have been attributed to C. difficile, some due to a new hyper-virulent strain that may cause more severe disease and a worse patient outcome. As a result of CDAD, large numbers of C. difficile spores may be excreted by affected patients. Spores then survive for months in the environment; they cannot be destroyed by standard alcohol-based hand disinfection, and persist despite usual environmental cleaning agents. All these factors increase the risk of C. difficile transmission. Once CDAD is diagnosed in a patient, immediate implementation of appropriate infection control measures is mandatory in order to prevent further spread within the hospital. The quality and quantity of antibiotic prescribing should be reviewed to minimise the selective pressure for CDAD. This article provides a review of the literature that can be used for evidence-based guidelines to limit the spread of C. difficile. These include early diagnosis of CDAD, surveillance of CDAD cases, education of staff, appropriate use of isolation precautions, hand hygiene, protective clothing, environmental cleaning and cleaning of medical equipment, good antibiotic stewardship, and specific measures during outbreaks. Existing local protocols and practices for the control of C. difficile should be carefully reviewed and modified if necessary.

Summary The prevalence of storage mite allergy was investigated in an epidemiological study of respiratory symptoms in farmers on Gotland, an island in the Baltic Sea. A questionnaire concerning work‐related and chronic symptoms from the airways and eyes was completed by 2578 farmers. A sample of 440 farmers subsequently underwent examination comprising skin‐prick tests (animal danders, pollens, moulds and house dust mite), blood sampling for RAST against four storage mites (Acarus siro, Lepidoglyphus destructor. Tyrophagus putrescentiae and Glycyphagus domesticus) and total IgE analyses. Immediate onset hypersensitivity reactions in the airways and eyes were very common among active farmers on Gotland, the prevalence being as high as 40.0%. The prevalence of atopic allergy was 15.6%. Allergy to storage mites was diagnosed, from the case history and a positive RAST to at least one of the four storage mites, in fifty‐two of 440 studied farmers (12%), corresponding to a calculated prevalence of storage mite allergy in the whole farming population of Gotland of 6.2%. The corresponding prevalence among farmers with hypersensitivity symptoms was 15.4%and among those with possibly IgE‐mediated symptoms it was as high as 37.8%. The present study clearly demonstrates a high prevalence of allergy to storage mites among farmers with respiratory symptoms.

BackgroundBecause they can generate comparable predictions, mathematical models are ideal tools for evaluating alternative drug or vaccine allocation strategies. To remain credible, however, results must be consistent. Authors of a recent assessment of possible influenza vaccination strategies conclude that older children, adolescents, and young adults are the optimal targets, no matter the objective, and argue for vaccinating them. Authors of two earlier studies concluded, respectively, that optimal targets depend on objectives and cautioned against changing policy. Which should we believe?Methods and FindingsIn matrices whose elements are contacts between persons by age, the main diagonal always predominates, reflecting contacts between contemporaries. Indirect effects (e.g., impacts of vaccinating one group on morbidity or mortality in others) result from off-diagonal elements. Mixing matrices based on periods in proximity with others have greater sub- and super-diagonals, reflecting contacts between parents and children, and other off-diagonal elements (reflecting, e.g., age-independent contacts among co-workers), than those based on face-to-face conversations. To assess the impact of targeted vaccination, we used a time-usage study's mixing matrix and allowed vaccine efficacy to vary with age. And we derived mortality rates either by dividing observed deaths attributed to pneumonia and influenza by average annual cases from a demographically-realistic SEIRS model or by multiplying those rates by ratios of (versus adding to them differences between) pandemic and pre-pandemic mortalities.ConclusionsIn our simulations, vaccinating older children, adolescents, and young adults averts the most cases, but vaccinating either younger children and older adults or young adults averts the most deaths, depending on the age distribution of mortality. These results are consistent with those of the earlier studies.