A model-based analysis: what potential could there be for a S. aureus vaccine in a hospital setting on top of other preventative measures?

Abstract

Background: Over the past decade, there has been sustained interest and efforts to develop a S. aureus vaccine. There is a need to better evaluate the potential public health impact of S. aureus vaccination, particularly given that preventative measures exist to reduce infection. To our knowledge, there is no previous work to assess the potential of a S. aureus vaccine to yield additional MRSA infection reduction in a hospital setting, on top of other preventative measures that already proved efficient.

Methods: The main objectives were to propose a versatile simulation framework for assessing potential added benefits of a hypothetical S. Aureus vaccine in conjunction with other preventative measures, and to illustrate possibilities in a given hospital setting. To this end, we employed a recently published dynamic transmission modelling framework that we further adapted and expanded to include a hypothetical S. aureus vaccination component in order to estimate potential benefits of vaccinating patients prior to hospital admission.

Results: Model-based projections indicate that even with other hygiene prevention measures in place, vaccination of patients prior to hospital admission has the potential to provide additional reduction of MRSA infection. Vaccine coverage and vaccine efficacy are key factors that would ultimately impact the magnitude of this reduction. For example, in an average case scenario with 50% decolonization, 50% screening and 50% hygiene compliance level in place, S. aureus vaccination with 25% vaccine coverage, 75% vaccine efficacy against infection, and 0% vaccine efficacy against colonization, may lead to 12% model-projected additional reduction in MRSA infection prevalence due to vaccination, while this reduction could reach 37% for vaccination with 75% vaccine coverage and 75% vaccine efficacy against infection in the same average case scenario.

Conclusions: S. aureus vaccination could potentially provide additional reduction of MRSA infection in a hospital setting, on top of reductions from hygiene prevention measures. The magnitude of such additional reductions can vary significantly depending on the level of hygiene prevention measures in place, as well as key vaccine factors such as coverage and efficacy. Identifying appropriate combinations of preventative measures may lead to optimal strategies to effectively reduce MRSA infection in hospitals.

Figure 1

Structure of dynamic transmission model with vaccination for MRSA infection in a hospital setting. This model structure is following the model structure in [23]. Related parameter definitions and mathematical details can be found in Tables 1 and 2. This is a basic framework focused solely on transmission and infection at patient population level in a hospital setting, and not aiming to model dynamic feedback between hospital and community, patient history (pre- or post-hospitalization), etc. Patients are flowing into the hospital at a rate Λ defined as number of patients admitted per time unit (e.g., number of admissions per day), with corresponding fractions denoted by λ flowing in each of the Susceptible/Colonized (CA-MRSA/HA-MRSA)/Infected (CA-MRSA/HA-MRSA) states, unvaccinated and vaccinated, respectively, upon admission. We assume that vaccination takes place adequately prior to hospital admission, so that patients can mount a protective immune response; we do not consider in-hospital vaccination of current patients, under the assumption that the duration of the hospital stay is likely too short to enable a significant vaccine-induced immune response. We also do not consider vaccine protection waning for vaccinated patients while in the hospital, assuming the vaccine effects last at least for the duration of the current hospital stay. ^¥ “*” indicates additional potential benefits of vaccination that can be considered in this type of modelling framework: (1) potential faster clearance in the vaccinated patients; (2) potential faster recovery from infection in the vaccinated patients (milder infections); (3) lower death rates in the infected vaccinated patients (milder infections). In the analyses performed here, we did not consider such enhanced vaccination effects, and all the related parameters are similar in the Unvaccinated and Vaccinated model components. The possibility of a vaccine impacting colonization [26-30] is taken into account as a potential reduction in the force of infection.

Figure 2

Illustration of model-projected impact of bundle measures only (no vaccination) on MRSA infection prevalence reduction. All results shown here are at steady-state.

Figure 3

Illustration of simulated additional reduction in MRSA infection via vaccination on top of bundle measures. Model-projected relative (%) reduction in MRSA infection prevalence due to vaccination on top of bundle measures for an average case scenario with 50% decolonization and 50% screening. The top plots correspond to a 25% vaccine coverage scenario and the bottom plots to a 75% vaccine coverage scenario. The plots on the left were generated assuming that a potential vaccine would have no impact on colonization, while the corresponding plots on the right illustrate potential added benefits of a vaccine that would be 50% efficient at preventing colonization. All results shown are at steady-state.

Figure 4

Model-based projections, 25% vaccine coverage: annual number of cases averted and corresponding number of doses. Left panel: model-based projected reduction in the annual number of MRSA infections due to vaccination at 25% vaccine coverage on top of bundle measures, as a function of the hygiene compliance level, for an average case scenario with 50% decolonization and 50% screening. Right panel: annual number of vaccine doses necessary to achieve the corresponding levels of MRSA infection reduction, assuming one dose per patient. All results are shown at steady-state. The slight variations in the number of doses here for the same level of vaccine coverage reflect the corresponding differences in the number of daily admissions, which is allowed to vary in each instance to ensure full hospital occupancy at all times.

Figure 5

Model-based projections, 75% vaccine coverage: annual number of cases averted and corresponding number of doses. Left panel: model-based projected reduction in the annual number of MRSA infections due to vaccination at 75% vaccine coverage on top of bundle measures, as a function of the hygiene compliance level for an average case scenario with 50% decolonization and 50% screening. Right panel: annual number of vaccine doses necessary to achieve the corresponding levels of MRSA infection reduction, assuming one dose per patient. All results are shown at steady-state. The slight variations in the number of doses here for the same level of vaccine coverage reflect the corresponding differences in the number of daily admissions, which is allowed to vary in each instance to ensure full hospital occupancy at all times.