C. difficile infection is the leading cause of antibiotic-associated diarrhoea in hospitals. Most C. difficile-associated disease (CDAD) cases involve elderly individuals who become infected in hospitals and long-term care facilities that have become reservoirs of these bacteria.
CDAD occurs in susceptible individuals following antibiotic therapy. A large variety of bacteria live in the colon of every healthy person that is collectively referred as the colonic flora. The colonic flora helps the digestive system to function effectively and apparently prevents colonization by C. difficile.
When antibiotics are administered to treat infection with harmful bacteria, they destroy the normal colonic flora and the patient becomes susceptible to C. difficile infection. Infection results from ingestion of C. difficile organisms present in the environment.
Hospitals and long-term care facilities have become reservoirs of C. difficile infection. Infected patients with diarrhoea release C. difficile organisms which produce microscopic spores that persist in the environment for years. There is currently no effective method to prevent the transmission of C. difficile spores in healthcare facilities. Consequently, C. difficile outbreaks are frequent and can lead to the temporary closure of hospital units.
The symptoms of CDAD vary according to the severity of the infection. Symptoms result from the production by C. difficile of two potent toxins (toxin A and toxin B) that cause inflammation of the colon (colitis). Mild infection is characterised by diarrhoea and abdominal pain while severe infection is associated with fever and dehydration. Pseudomembranous colitis is the most serious form of C. difficile infection and can be life-threatening.
Discontinuation of the causal antibiotic is sometimes sufficient to manage mild CDAD. However, in most cases, C. difficile infection is treated with antibiotics: oral metronidazole or vancomycin. Vancomycin is preferred when metronidazole is ineffective or not tolerated. The problem with this approach is that antibiotics keep patients susceptible to C. difficile infection. Consequently, relapsing infection is a frequent complication occurring when antibiotics are discontinued: about one patient out of five experiences one or more relapses (180,000 patients per year in both USA and Europe).
Acambis said, "A large number of studies in vivo and in humans indicate that immunity against C. difficile toxin A is a key defence mechanism against both initial episodes of CDAD as well as relapses. Recent clinical data indicate that toxin B is also responsible for disease manifestations, suggesting that immunity to both toxins A and B is desirable for broad-based prevention of primary C. difficile disease episodes as well as relapsing disease. Accordingly, a vaccine providing immune protection against toxins A and B could reduce the incidence of CDAD disease.
"We have successfully produced and tested a batch of an injectable vaccine containing inactivated C. difficile toxins A and B. Four doses of this toxoid vaccine was shown to be immunogenic and well tolerated in a Phase I clinical study on healthy young adults."
Commenting on the promising results of previous trials, Dr Thomas Monath, Chief Scientific Officer of Acambis, said, "The need for a vaccine to protect against C. difficile infection has grown with the emergence of a hypertoxic and epidemic C. difficile strain associated with severe disease, which has been reported in North America and the UK. These results are encouraging and show that subjects vaccinated with our C. difficile vaccine developed high levels of antibodies against toxins A and B, the toxins responsible for CDAD."
Today, no vaccine exists to protect individuals against CDAD and Acambis is the only company known to be developing a vaccine against it.
Volunteers are now preparing to take part in phase two trials of the vaccine at Cheltenham General Hospital and Gloucestershire Royal Hospital.
Hundreds of elderly and vulnerable patients will be given the jab to protect them from the infection and will then be monitored for their response, and any side effects, over a 12-month period.
Dr Sean Elyan, medical director at Gloucestershire Hospitals NHS Foundation Trust, said: "We have been chosen alongside a select number of trusts to pilot the vaccine. That will involve looking at blood tests and analysing the results.
'It's very exciting, but we are not going to relax and continue to take infection control very seriously."