- © 2005 Canadian Medical Association or its licensors
Jacques Pépin and associates1 have reported an epidemic of Clostridium difficile-associated diarrhea (CDAD) associated with an increased case-fatality rate. They hypothesize the presence of a more virulent strain.
The genus Clostridium consists of gram-positive, anaerobic, spore-forming rods and is notorious for causing human and animal diseases by producing various extracellular toxins. C. difficile exerts its effects through toxin A, an enterotoxin, and toxin B, a cytotoxin, which result in colitis and pseudomembranes.2 The development of a more virulent circulating strain could occur, in part, through the acquisition of a novel gut-specific toxin, possibly from another clostridial species.
The manifestations of severe CDAD described by Pépin and associates1 (i.e., megacolon, perforation, shock or rapid death) resemble those of another clostridial-related disease, enteritis necroticans. This condition, also referred to as pigbel or Darmbrand (“fire belly”), is an often-fatal intestinal illness characterized by hemorrhagic, inflammatory or ischemic necrosis with pseudomembranes, although it preferentially involves the small bowel.3 It is caused by the β-toxin of Clostridium perfringens type C. This toxin is encoded by a plasmid-borne gene, cpb2, and is potentially transferable to other clostridial species.4 In certain developing countries (e.g., Papua New Guinea), enteritis necroticans has been controlled by immunization against β-toxin,5 which underscores the importance of this protein in intestinal disease. In developed countries, the condition is limited to adults with chronic illnesses and malnutrition. Reduced gastric acidity is a known risk factor, possibly because the toxin is not destroyed under these conditions.3 Interestingly, proton pump inhibitors and decreased gastric acidity may also be associated with an increased risk for severe CDAD in Quebec.6
Diagnostic tests for CDAD have been available for years and are based on detection of toxin B (cytotoxin assay) or toxins A and B (immunoassay). The current epidemic strongly favours consideration that increased virulence may be due to elaboration of another toxin not detected by standard tests. A search for such toxins might be worthwhile in accounting for the more severe CDAD seen in Quebec.