Abstract
Clostridium difficile associated disease is fundamentally associated with dysbiosis of the gut microbiome as a consequence of antibiotic use. This is because this sporulating, obligate anaerobe germinates and proliferates rapidly in the dysbiotic gut, which is an indirect consequence of their use. During its growth, C. difficile produces two toxins, toxin A (TcdA) and toxin B (TcdB), which are responsible for the majority of clinical symptoms associated with the disease. Three parenterally delivered vaccines, based on detoxified or recombinant forms of these toxins, have undergone or are undergoing clinical trials. Each offers the opportunity to generate high titres of toxin neutralising antibodies. Whilst these data suggest these vaccines may reduce primary symptomatic disease, they do not in their current form reduce the capacity of the organism to persist and shed from the vaccinated host. The current progress of vaccine development is considered with advantages and limitations of each highlighted. In addition, several alternative approaches are described that seek to limit C. difficile germination, colonisation and persistence. It may yet prove that the most effective treatments to limit infection, disease and spread of the organism will require a combination of therapeutic approaches. The potential use and efficacy of these vaccines in low and middle income countries will be depend on the development of a cost effective vaccine and greater understanding of the distribution and extent of disease in these countries.
Highlights
Clostridium difficile associated disease is fundamentally associated with dysbiosis of the gut microbiome as a consequence of antibiotic use
This is because this sporulating, obligate anaerobe germinates and proliferates rapidly in the dysbiotic gut, which is an indirect consequence of their use
C. difficile produces two toxins, toxin A (TcdA) and toxin B (TcdB), which are responsible for the majority of clinical symptoms associated with the disease
Summary
Clostridium difficile is the leading cause of healthcare-associated diarrhoeal disease in the developed world [1], and a major cause of community-associated infection (CAI) [2]. A small but clinically relevant number of strains encode a third toxin, commonly referred to as C difficile binary toxin (CDT) [18] This toxin is composed of two domains, an enzymatically active A component (CDTa), which causes ADPribosylation of G-actin, and a cell-binding and translocation B component, CDTb. CDT alone does not induce severe disease in a hamster [19] or mouse model of CDI [20] but appears to enhance colonisation [21] and contribute to virulence [22] the biological role of CDT in infection appears to be adjunctive, enhanced protection in preclinical vaccine trials following inclusion of this antigen was seen [23]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have