Mathematical models of Clostridium diffcile transmission
Creators: name: McLure, Angus
Publisher: name: The Australian National University
Year: 2018
Subjects: mathematical models
Clostridium difficile
hospital-acquired infections
zoonoses
asymptomatic carriage

description: Clostridium difficile infections (CDIs) are some of the most common hospital-acquired infections and the most common cause of antibiotic-associated diarrhoea. CDIs lead to great loss of life, severe health outcomes, and incur very high financial costs through treatment, extended hospital stays, and readmissions. Despite extensive research and many resources committed to the prevention and treatment CDIs in hospitalised patients, hospitals continue to be hotspots for this disease. Meanwhile, there is an emerging awareness of the burden this disease places on the broader community including patients who have not recently been hospitalised. In the community approximately 5% of adults and a higher proportion of infants are asymptomatically colonised. Colonisation is also common in livestock and the pathogen has been isolated from meat and vegetables. However, the various sources of transmission in the community and the consequences for infections within and beyond hospitals are not well understood. This thesis develops and employs mathematical models of C. difficile transmission to explore three themes: improving models to capture the complex epidemiology of C. difficile, populations that sustain C. difficile transmission, and the classifi cation of CDIs as hospital or community-acquired. Addressing the fi rst theme, I argue that the essential epidemiology of C. difficile is captured by modelling the interactions of three key factors: pathogen, immunity, and gut flora. I argue that modelling transmission in an integrated model of adults and infants across hospitals and communities provides insights that hospital-only and adult-only models cannot. By incorporating seasonality into these models, I argue that seasonal variation of antibiotic prescription rates is more likely to be the main driver of CDI seasonality than seasonal transmission. In the second theme, I argue that most hospitals -- though hotspots for transmission -- are not disease sustaining populations. Instead, transmission outside hospitals maintains the disease in the hospital and community. I argue that reducing transmission in the hospital cannot eliminate the disease in the broader population, but that reducing transmission from adults or infants in the community could interrupt transmission in the human population. Similarly, I argue that C. difficile in the community may be driven by transmission from animal reservoirs if as few as 3.5-26.0% of human infections are acquired from animal or food sources. In the final theme, I argue that an illusion of hospital-driven disease is in part perpetuated by surveillance defi nitions that systematically misclassify many community-acquired cases as hospital-acquired. The incubation period for C. difficile infections often exceeds the two-day or three-day cut-offs commonly used to classify patients recently admitted to hospital. I argue that many patients who acquire the pathogen prior to admission develop symptoms after the cut-off and are therefore incorrectly classifi ed as having acquired the infection during their hospital stay. Furthermore, I argue that time since hospital discharge is a poor indicator of whether a CDI is hospital or community-acquired.