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Clostridium difficile surveillance in England

(IASR Vol. 41 p39-41: March, 2020)

From 2002, the emergence of a previously uncommon but more virulent strain, known as Clostridium difficile North American pulsed field type 1 (NAP1) or ribotype 027, fundamentally changed the epidemiology of C. difficile infection (CDI). These marked changes in epidemiology occurred first in North America and then in Northern Europe.1,2 In 2007-08, more than 55 000 CDI cases were reported in England, of which almost a quarter were in younger people who had previously not been considered to be at high risk for this antibiotic associated infection. Furthermore, the number of death certificates including the term ‘C. difficile’ increased each year in England and Wales, from 2238 in 2004 to 8324 in 2007.3

In response to the changing epidemiology of CDI, and because of concern surrounding large outbreaks associated with severe disease and poor outcomes, from 2007, every acute National Health Service (NHS) hospital in England was mandated to report all of the cases of CDI in patients aged ≥2 years. Notably at this time, mandatory reduction targets for CDIs were established,4 and figures for reported CDIs were made publically available, on a month by month basis, and according to either the hospital or community setting. This surveillance system entails each hospital/trust (approximately n=150 across England) having to report all the cases of CDI that are diagnosed by its laboratory (which usually cover both hospitalised and community patients. Cases of CDI are defined according to a NHS testing algorithm (combination of tests), which must include a toxin assay. Each year since 2007, hospitals have been set mandatory maximum allowable target numbers of CDIs, with fines potentially applicable for institutions that fail to meet these.

The incidence of CDI has declined strikingly in England (and throughout the UK) over the past decade. Similarly, the incidence of large outbreaks of CDI associated with considerable morbidity and mortality, often due to C. difficile ribotype 027, declined markedly. The initial target to reduce CDIs in England by 30% was far exceeded; in fact, an ~75% reduction in CDIs has been achieved to date.4 Between 2007/08 and 2012/13 rates of CDI fell rapidly. Since 2012/13 rates have continued to decline, but much less quickly. The decline in the rate of all cases of CDI was mirrored by falls in hospital-onset cases. However, the fall in community-onset cases has not been so rapid. Indeed, community-onset cases now represent approximately two-thirds of all cases. Many of the infection prevention and antimicrobial prescribing interventions in England over the past decade were focussed on the reduction of CDI rates in the hospital setting, which likely explains the relative changes seen in hospital- versus community-onset cases. However, the division of cases into hospital-onset and community-onset cases does not take into account whether patients had experienced prior hospital admissions. Consequently, and to align surveillance in England with that performed by ECDC and CDC, categorisation of CDIs according to prior trust exposure was introduced from April 2017.4

A second key component of the NHS response to the CDI threat was the establishment in 2007 (centrally funded by the Health Protection Agency, later to become Public Health England) of the Clostridium difficile Ribotyping Network (CDRN) for England, as part of an enhanced surveillance program for C. difficile.5 CDRN consists of several regional microbiology laboratories in England, which aim to provide timely access (i.e. results within 1-2 weeks of sample submission) to C. difficile culture and ribotyping, using standardized criteria for the submission of diarrhoeal faecal samples. Enhanced fingerprinting using multi-locus variable repeat analysis (MLVA), for isolates linked in time and place that share the same ribotype, was also introduced from the start of CDRN. CDRN is recognised as one of the leading strain-based C. difficile surveillance systems. Importantly, knowledge of the epidemiology of C. difficile has increased considerably over the last decade, including via the use of ground breaking studies incorporating the use of whole genome sequencing.6-18

In the first 3 years of its operation, CDRN received 12 603 faecal specimens, comprising significantly (p<0.05) increasing numbers and proportions of national CDI cases in 2007-08 (n=2109, 3.8%), 2008-09 (n=4774, 13.2%), and 2009-10 (n=5720, 22.3%).6 The C. difficile recovery rate from samples submitted to CDRN was 90%, yielding 11 294 isolates for ribotyping in the first 3 years. Rates of 9 of the 10 most common ribotypes changed significantly (p<0.05) during 2007-10. Although C. difficile ribotype 027 predominated, this decreased markedly from 55% to 36% and 21% in 2007-08, 2008-09 and 2009-10, respectively. Mortality data were subject to potential reporting bias, but there was a significant decrease in CDI-associated deaths during 2007-10, which may have been due to multiple factors, including reduced prevalence of ribotype 027.

In summary, a comprehensive surveillance system was established in England in 2007 at the height of the epidemic of CDIs, in particular driven by ribotype 027. Mandatory CDI targets and access to ribotyping/MLVA have helped to bring marked reductions in cases and dramatic changes in the prevalence of the virulent ribotpye 027 clones. Reports of deaths associated with CDI also started to decrease the year after CDRN commenced, which is likely due to enhanced control of the epidemic ribotype C. difficile 027. These experiences demonstrate the value of a comprehensive national surveillance programme, noting that the levels of reduction in CDI seen in England have rarely been achieved in other countries.

 

References
  1. Kuijper EJ, et al., Clin Microbiol Infect 12(suppl 6): 2-18, 2006
  2. Warny M, et al., Lancet 366: 1079-1084, 2005
  3. Health Protection Agency and Department of Health, Clostridium difficile infection: how to deal with the problem
    http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1232006607827, Accessed 4 February 2020
  4. Public Health England, Clostridioides difficile: guidance, data and analysis
    https://www.gov.uk/government/collections/clostridium-difficile-guidance-data-and-analysis epidemiology, Accessed 4 February 2020
  5. Public Health England, Clostridioides difficile ribotyping network(CDRN)report
    https://www.gov.uk/government/publications/clostridium-difficile-ribotyping-network-cdrn-report. Accessed 4 February 2020
  6. Wilcox MH, et al., Clin Infect Dis 55: 1056-1063, 2012
  7. WN Fawley, et al., J Clin Microbiol 49: 4333-4337, 2011
  8. Walker AS, et al., PLoS Med 9(2): e1001172, 2012
  9. Didelot X, et al., Genome Biol 13: R118, 2012 http://doi.org/10.1186/gb-2012-13-12-r118
  10. Eyre DW, et al., PLoS One 8(5): e63540, 2013
  11. Eyre DW, et al., New Eng J Med 369: 1195-1205, 2013
  12. Eyre DW, et al., J Clin Microbiol 51: 4141-4149, 2013
  13. Mawer DPC, et al., Clin Infect Dis 64: 1163-1170, 2017
  14. Dingle KE, et al., Lancet Infect Dis 17: 411-421, 2017
  15. Stoesser N, et al., PLoS One 12: e0182307, 2017
  16. Eyre DW, et al., Clin Infect Dis 65: 433-441, 2017
  17. Martin JSH, et al., Clin Infect Dis, doi: 10.1093/ cid/ciy302, 2018
  18. Eyre DW, et al., Clin Infect Dis, doi: 10.1093/cid/ciy252, 2018
  
Leeds Teaching Hospitals, University of Leeds and Public Health England.
 Mark H. Wilcox

Copyright 1998 National Institute of Infectious Diseases, Japan

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