Development of a WHO International Standard for anti-Clostridioides difficile toxin neutralising serum (human)

Summary 

Clostridioides difficile infection, termed CDI, is caused by colonisation of the human intestine by a bacterium. Normally the millions of bacteria in the gut prevent disease-causing bacteria like C. difficile from causing a problem. However, antibiotics that we may take for an infection elsewhere (e.g., a chest infection) can damage these defences, allowing C. difficile to move in, grow and produce toxins (poisons) that affect the gut lining, resulting in diarrhoea. This ability to take over and invade the intestines when other bacteria are missing makes C. difficile an ‘opportunistic’ pathogen. Hospitals diagnose CDI by detecting toxin in faeces (poo). It is important to detect the toxin rather than the bacteria because it can be present without producing toxin or causing symptoms (asymptomatic carriage). CDIs are considered an emerging health treat worldwide. Uptake of C. difficile bacterial spores through ingestion (swallowing) can result in asymptomatic carrier status or lead to CDI that could range from mild diarrhoea, eventually developing into inflammation of the bowel, and in some cases, a grossly distended bowel (toxic megacolon) that often results in high mortality. Several potential vaccines have been studied in clinical trials for CDI but there is a lack of standard or reference reagents to standardise immune, functional, or cytotoxic (toxic to cells) assays necessary for the evaluation of efficacy and quality of these vaccines. Hence the development of a human serum reference is essential. Human sera containing defined units of anti C. difficile toxins antibodies would enhance vaccine development and assist in disease surveillance.