Figure 1.
Flow diagram of the age structured model.
Susceptible individuals (S), which are structured into multiple age classes, can be colonized by CA- or HA-MRSA in the community or in the hospital. Colonized individuals, which are also structured by age, clear the pathogen either by treatment or through natural immune clearance. Individuals move between the hospital and the community at the same rate regardless of colonization status.
Figure 2.
Distribution of the US population over age classes, age dependency of hospitalizations, treatment rates, and durations of hospitalization in the US.
Data are shown for the 18 age classes used in the age-structured model.
Table 1.
Default model parameters of the basic model.
Figure 3.
Parameter range for which HA-MRSA and CA-MRSA coexist.
The blue area indicates the parameter-combinations for which HA-MRSA and CA-MRSA coexist. The dark grey region indicates the parameter-combinations in which HA-MRSA cannot be invaded by CA-MRSA. The light-grey region indicates parameter-combinations in which CA-MRSA cannot be invaded by HA-MRSA. The range between the two red lines corresponds to fitness costs for which selection in the hospital and community act in opposite directions (i.e. CA-MRSA is fitter in the community and HA-MRSA is fitter in the hospital). The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the absence of effective therapy. The y-axis corresponds to the average number of secondary infections caused by a single colonized individual admitted to a hospital containing only susceptible individuals (single-admission reproduction number R0HA,H [41], see Table 1).
Figure 4.
The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the basic model.
The red area indicates co-existence in the age-structured model. Axes and parameter values are the same as in Figure 3. Note that in order to assure comparable transmissibility measures as y-axes in the homogeneous and heterogeneous models, we measure transmissibility as the single-admission reproductive number R0HA,H – i.e. the dominant eigenvalue of the next-generation matrix of the hospital [41], [42] (see Table 1).
Figure 5.
The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the treatment-structured model.
The red area indicates coexistence in the treatment- and age-structured model. Axes and parameter values are the same as in Figure 3.
Figure 6.
A) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the basic model.
The red area indicates coexistence in the age-structured model. B) The blue area indicates the parameter combinations for which HA-MRSA and CA-MRSA coexist in the treatment-structured model. The red area indicates co-existence in the treatment- and age-structured model. The x-axis corresponds to the fitness disadvantage of HA-MRSA compared to CA-MRSA in the community in the absence of effective therapy. The y-axis corresponds to ratio between the fitness costs of HA-MRSA in hospital and community.
Figure 7.
Coexistence between HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA-infected host population in the treatment- and age-structured model (corresponding to the red area in Figure 5).
Colors indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (CA-MRSA): Blue indicates coexistence (i.e. both strains >5%), dark grey indicates HA-MRSA only, and light grey CA-MRSA only. The dashed orange line delimits the parameter region in which HA-MRSA can invade MSSA (criterion for invasion: frequency of MRSA >5%, 50 years after its introduction; see Figure S2).
Figure 8.
Coexistence between MSSA, HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA/MSSA-infected host population in the treatment- and age-structured model.
Colors (see legend) indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (MSSA/CA-MRSA).