Vaccines against Clostridium difficile infection (CDI) are in development, with potential to directly protect those vaccinated and to mitigate transmission by reducing environmental contamination caused by prevented symptoms. For a vaccine that may or may not alter susceptibility to acquiring colonization, its projected transmission-reduction effect may depend on the contribution of symptomatic CDI to overall transmission, which remains uncertain. Mathematical models can help project population effects of vaccine administration under assumptions consistent with existing data.
We designed a simulation model of CDI among patients in a network of 10 short- and long-term acute care hospitals and nursing homes. Model calibration relied on published infection and carriage data and whole genome sequencing studies that estimated the fraction of CDI attributable to transmission from other CDI patients in healthcare settings. The modeled vaccine effectiveness for reducing the rate of progression to CDI among carriers was set at 75%, achieved after completing a vaccine course. We then simulated initiation of this vaccine course to a random subset of patients at transfer or live discharge and tallied direct and indirect CDI-reduction effects per vaccinated patient over 5 years.
Model calibration found that data are consistent with higher infectivity of CDI patients over other carriers by a factor of 30-85, depending on assumed rates of initial carriage importation. Vaccine simulations produced an average reduction of 36 CDI cases per 1000 vaccinated patients, with 25 of those cases prevented among those vaccinated and 11 prevented among unvaccinated patients. These results were robust across transmission and carriage rates supported by data.
Our findings demonstrate potential for a vaccine against CDI to reduce transmissions in healthcare facilities, even if it does not decrease acquisition of carriage per exposure among those receiving it. The finding is robust to the remaining uncertainty around the relative prevalence and infectivity of CDI patients among all carriers. The vaccine will have maximal impact if received by individuals likely to experience future infections in settings where environmental contamination poses risk to others.
K. Khader, None
J. O'Hagan, None
H. Yu, Pfizer, Inc: Employee and Shareholder , Salary .
A. Quintana, Pfizer, Inc: Employee and Shareholder , Salary .
D. L. Swerdlow, Pfizer Inc: Employee and Shareholder , Salary .