Grant: Operating Grant: Antimicrobial Resistance

Clostridium difficile (C. diff) is the major cause of diarrhea in people in health care settings. It is considered a top priority pathogen for research by Canada and the USA. C. diff infection (CDI) usually happens after people ingest the bacteria spread from other patients and then receive antibiotics that deplete healthy gut bacteria, allowing C. diff to grow and produce two toxins, TcdA and TcdB. These toxins cause inflammation and damage to the lining of the colon, leading to diarrhea that can range from relatively mild to severe or even fatal, especially in older people. We have antibiotics to treat CDI, but 25-35% of people relapse and need multiple rounds of treatment, or eventually fecal microbial therapy (FMT or "stool transplant") to be cured. Newer treatments that reduce relapse risk are too expensive to be used routinely. If we can identify the patients who need them the most, we will be better able to use these treatments in a cost-effective way, and discover new ways to prevent CDI in vulnerable people. Our project is based on new tools we have developed to measure immune responses in people with CDI. In phase I we will study how natural immune responses to TcdA and TcdB develop and whether they can be used to predict relapses. First, we will measure these responses in people with recurrent CDI before and after FMT, and compare them to people with their first episode of CDI and to healthy volunteers who have never had CDI. We will do sophisticated studies with our funding partners to understand these responses on a basic, molecular level. Second, we will examine immune responses and clinical characteristics of patients with their first episode of CDI to build a scoring system that can predict relapses before they happen. If these studies are successful, in Phase II we will disseminate these tools to other centres to validate our results, and design rapid or point-of-care tests to easily identify patients at risk for recurrent CDI and its complications.