Bulletin of Mathematical Biology

, Volume 79, Issue 10, pp 2242–2257 | Cite as

Healthcare-Associated Clostridium difficile Infections are Sustained by Disease from the Community

  • Angus McLure
  • Archie C. A. Clements
  • Martyn Kirk
  • Kathryn Glass
Original Article


Clostridium difficile infections (CDIs) are some of the most common hospital-associated infections worldwide. Approximately 5% of the general population is colonised with the pathogen, but most are protected from disease by normal intestinal flora or immune responses to toxins. We developed a stochastic compartmental model of CDI in hospitals that captures the condition of the host’s gut flora and the role of adaptive immune responses. A novel, derivative-based method for sensitivity analysis of individual-level outcomes was developed and applied to the model. The model reproduced the observed incidence and recurrence rates for hospitals with high and moderate incidence of hospital-acquired CDI. In both scenarios, the reproduction number for within-hospital transmission was less than 1 (0.67 and 0.44, respectively), but the proportion colonised with C. difficile at discharge (7.3 and 6.1%, respectively) exceeded the proportion colonised at admission (5%). The transmission and prevalence of CDI were most sensitive to the average length of stay and the transmission rate of the pathogen. Recurrent infections were most strongly affected by the treatment success rate and the immune profile of patients. Transmission within hospitals is substantial and leads to a net export of colonised individuals to the broader community. However, within-hospital transmission alone is insufficient to sustain endemic conditions in hospitals without the constant importation of colonised individuals. Improved hygiene practices to reduce transmission from symptomatic and asymptomatic individuals and reduced length of stay are most likely to reduce within-hospital transmission and infections; however, these interventions are likely to have a smaller effect on the probability of recurrence. Immunising inpatients against the toxins produced by C. difficile will reduce the incidence of CDI but may increase transmission.


Clostridium difficile Mathematical model Sensitivity analysis Nosocomial infection 



AM is supported by an Australian Government Research Training Program Scholarship. ACAC is funded by a National Health and Medical Council Research Fellowship (#1058878). We thank Luis Furuya-Kanamori for suggested reading and Thomas Riley for a valuable discussion.

Supplementary material

11538_2017_328_MOESM1_ESM.pdf (214 kb)
Supplementary material 1 (pdf 213 KB)


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Copyright information

© Society for Mathematical Biology 2017

Authors and Affiliations

  1. 1.Research School of Population HealthAustralian National UniversityCanberraAustralia

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