The potential value of Clostridium difficile vaccine: An economic computer simulation model

Abstract

Efforts are currently underway to develop a vaccine against Clostridium difficile infection (CDI). We developed two decision analytic Monte Carlo computer simulation models: (1) an Initial Prevention Model depicting the decision whether to administer C. difficile vaccine to patients at-risk for CDI and (2) a Recurrence Prevention Model depicting the decision whether to administer C. difficile vaccine to prevent CDI recurrence. Our results suggest that a C. difficile vaccine could be cost-effective over a wide range of C. difficile risk, vaccine costs, and vaccine efficacies especially when being used post-CDI treatment to prevent recurrent disease.

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

“…10,11 A recent computer simulation shows that vaccination could be the cost-effective approach in the prevention and treatment of CDI, especially the recurrent CDI. 12 It was initially reported that anti-TcdA antibodies were sufficient to protect the host against CDI. 13,14 However, recent studies demonstrated an even more important role of TcdB in the pathogenesis of CDI, [15][16][17][18] suggesting that an effective vaccine should target both toxins.…”

A Mixture of Functionally Oligoclonal Humanized Monoclonal Antibodies That Neutralize Clostridium difficile TcdA and TcdB with High Levels ofIn VitroPotency ShowsIn VivoProtection in a Hamster Infection Model

“…TcdB appears to be better evolved to catalyze the more long-lasting inflammatory events in the disease process by killing human gut and immune cells and eliciting or subverting local inflammatory responses by causing the local production of interleukin 1␤ (IL-1␤), tumor necrosis factor alpha (TNF-␣), IL-6, and IL-8 and being involved in systemic disease in a piglet model (21)(22)(23) Neutralizing and protective antibodies against TcdA and TcdB have been generated by both active and passive vaccination of animals (24,25). Vaccination offers the potential advantage of generating a polyclonal response, but the disadvantages relate to the timing of vaccine administration relative to the perceived risk of infection and variability in the strength and speed of a patient's immune response (26)(27)(28)(29). Parenteral administration of purified antibodies offers control over both timing and dose.…”

New and emerging therapies for Clostridium difficile infection

“…A previous model of CDI vaccination demonstrated cost-effectiveness even with wide-ranging risks of CDI and varied vaccine efficacies and costs. 44 A CDI vaccine is therefore an appealing goal, with the potential for substantial clinical impact in healthcare institutions across the world.…”