Recurrence of Clostridium difficile infection

M. Alfayyadh1,2, D. A. Collins3, S. Tempone4, R. McCann4, P. K. Armstrong4, A. Cook1 and T. V. Riley3,5,6

1School of Population and Global Health, The University of Western Australia, Crawley, Australia; 2Thi-Qar Public Health Division, Ministry of Health, Iraq; 3School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia; 4Communicable Disease Control Directorate, Western Australian Department of Health, East Perth, Australia; 5Department of Microbiology, PathWest Laboratory Medicine (WA), Nedlands, Australia and 6School of Veterinary and Life Sciences, Murdoch University, Murdoch, Australia

Clostridium difficile is the most common cause of hospital-associated diarrhoea in high-income countries and an emerging cause of community-acquired infection, and thus presents a major public health challenge. The high clinical and economic burden from C. difficile infection (CDI) relates largely to the high frequency of recurrent infections caused by either the same or different strains of C. difficile. However, how recurrent infections are classified is problematic. Recommendations for determining CDI classification suggest that an interval of 8 weeks or less after the onset of a previous episode (provided that symptoms from the index episode resolve with or without therapy) indicates recurrent CDI. We assessed strains of C. difficile in a sample of patients with recurrent CDI in Western Australia from October 2011 to July 2017. The performance of different intervals between initial and subsequent episodes of CDI was investigated. Of 4612 patients with CDI, 1471 (32%) were identified with recurrence. PCR ribotyping data were available for initial and recurrent episodes for 551 patients. Relapse (recurrence with same ribotype (RT) as index episode) was found in 350 (64%) patients and reinfection (recurrence with new RT) in 201 (36%) patients. Our analysis indicates that 8- and 20-week intervals failed to adequately distinguish reinfection from relapse. Where molecular epidemiological data are not available, we suggest that applying an 8-week interval to define recurrent CDI requires more consideration. Many factors impact whether a CDI case will get a recurrence of disease, either a relapse or re-infection. One of these is the presence of endogenous antibodies against C. difficile toxins which may protect against recurrence of CDI. Higher endogenous antibody titres against toxin B, but not toxin A, are associated with protection against recurrent CDI. Indeed, colonization with toxigenic C. difficile in infants is associated with a humoral immune response against toxins A and B. Further work is required looking at the role of immunity in recurrent CDI, and the possibility of preventing recurrence through vaccination either actively or passively.

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