Active and passive immunization against Clostridium difficile diarrhea and colitis

Clostridium difficile, a gram-positive bacterium, is the major cause of hospital-acquired infectious diarrhea and colitis in industrialized nations. C difficile colonization results from antibiotic administration and subsequent loss of protection provided by intestinal flora. C difficile induced-colitis is caused by the release of two exotoxins, toxin A and B. Host factors including advanced age, pre-existing severe illness and weakened immune defenses predispose individuals to symptomatic infection. The generation of antibody responses to toxin A through natural exposure is associated with protection from disease. In addition, an inability to acquire immunity to toxin A puts individuals at risk for recurrent and/or severe disease. Immunological approaches for the management of this disease are being developed which could reduce the reliance on antibiotics for treatment and allow for re-establishment of the natural barrier provided by an intact commensal flora. An active vaccine and various immunotherapeutic strategies under evaluation may prove to be effective against severe or relapsing C difficile infection. (C) 2003 Elsevier Ltd. All rights reserved.