A Canadian farm-to-fork quantitative microbial risk assessment of ciprofloxacin-resistant Campylobacter spp.
Creators: Tschritter, Dana
Publisher: name: University of Alberta Library
Year: 2022

<p>Antimicrobial resistance (AMR) is one of the largest public health threats of the 21st century with 4.95 million global deaths associated with bacterial AMR in 2019. Continued spread of bacterial AMR threatens the possibility of a post-antimicrobial era, where humans and animals may succumb from previously treatable illnesses. Widespread and persistent ciprofloxacin-resistant (CIPR) Campylobacter has been noted in humans and food-producing animals, especially broiler chickens (chickens raised for meat). Campylobacter itself is an extremely prevalent foodborne bacteria causing over 95 million global cases of gastroenteritis annually. Ciprofloxacin-resistant Campylobacter illnesses may have an elevated probability of more intense symptomology with increased risk of treatment failure in immunocompromised or vulnerable patients. </p>

<p>The objective of this thesis was to model transmission of CIPR Campylobacter along the farm-to-fork pathway of broiler chicken and estimate incidence of consequent CIPR illness in Canada. The quantitative microbial risk assessment (QMRA) framework was adopted, and four principal tasks were accomplished: an exposure assessment, a dose-response model (DRM), a risk characterization, and model analysis.</p>

<p>The exposure assessment was constructed with nine nodes tracing the broiler farm-to-fork pathway and modeled using stochastic processes and Monte Carlo simulations. At each node, the prevalence among all chickens with external Campylobacter and CIPR Campylobacter was estimated, and the corresponding concentrations per bird. Changes to prevalence and concentration at each node were modeled from peer-reviewed literature and federal surveillance data. The final estimate was the probability distribution of consuming a serving of broiler meat with Campylobacter or CIPR Campylobacter and how much Campylobacter and CIPR Campylobacter was ingested.</p>

<p>A novel AMR dose-response model was constructed, adapted from a recently proposed framework. In cases of no prior ciprofloxacin use or in cases of CIPR Campylobacter exposure in the presence of ciprofloxacin, the traditional beta-Poisson DRM was used with parameters determined by a previous QMRA. The novel model was used in cases of prior ciprofloxacin use and exposure to ciprofloxacin-susceptible Campylobacter, for which new shape parameters were determined using pharmacodynamic data. An inequality comparing survival probabilities of CIPS Campylobacter versus CIPR Campylobacter was used to predict if an infection would be resistant to ciprofloxacin. A conditional probability was used to further estimate the probability of symptomatic illness given an infection. </p>

<p>The risk characterization had two major metrics, estimated for both overall Campylobacter and CIPR Campylobacter: probability of illness from one random serving of chicken and the incidence of illness in Canada per 100,000 population. The former was completed through pairing the exposure assessment outputs with the DRM to determine the probability of illness from a serving. Multiplying this probability of illness per serving by the total number of servings consumed annually and scaling by Canadian population yielded the estimated incidence illnesses.</p>

<p>Lastly, sensitivity and scenario analyses were performed on the model described above. The sensitivity analysis used conditional medians to determine which data inputs were most influential in determining the final probabilities of overall and CIPR Campylobacter illness per one serving. Additionally, seven hypothetical scenarios were independently applied to the baseline model to simulate potential procedure changes and resulting incidences were compared to the baseline to determine intervention efficacy.</p>

<p>The estimated probabilities of total and CIPR Campylobacter illness from any serving of chicken were 0.015% (90% CrI: 0.000082-3.1%) and 0.002% (90% CrI: 0.000012-0.44%), respectively. The estimated incidence per 100,000 population for total and CIPR illness were 1,101 (90% CrI: 6-223,000) and 143 (90% CrI: 1-31,500), respectively. </p>

<p>The sensitivity analysis revealed that the temperature during cooking, within-flock spread during transportation to the abattoir, and within-flock contamination during evisceration were most influential in determining probability of overall illness per serving. The fraction of flocks colonized with CIPR Campylobacter was most critical in determining if an illness from a serving would be CIPR. Reducing the prevalence of contaminated birds leaving the abattoir, limiting flock colonization, and reducing consumer mishandling were most effective at reducing overall incidence. No scenario significantly altered CIPR illness incidence. </p>

<p>Additionally, this thesis compares our findings with published literature to assess the validity of the model. Knowledge gaps in the field are identified and directions of future work are discussed. Ultimately, this model provides unparalleled insight on transmission of CIPR Campylobacter to the Canadian public and guidance for risk managers and policy makers.</p>