Fig 1.
A schematic diagram of the resolution of an infectious disease system into the three sub-systems.
(a) The host sub-system which consists of seven main levels (i) the cell level, (ii) the tissue level, (iii) the organ level, (iv) the microecosystem level, (v) the host/organism level, (vi) the community level, and (vii) the macroecosystem level. (b) The environmental sub-system which consists of two main levels of organization which are the inside-host environmental level and the outside-host environmental level (or community level). The outside-host environmental level (or community level) has three sub-levels which are (i) the local community level, (ii) the territorial community level, and (iii) the regional community level. (c) The pathogen sub-system which in its functional role consists of two main levels of organization, with each level being the same as a scale which are (i) the single pathogen species/strain level/scale and (ii) the multiple pathogen species/strains level/scale. However, in circumstances where there is horizontal gene transfer, the pathogen sub-system would consist of (i) the single pathogen species/strain level and (ii) the multiple pathogen species/strains level. In this Figure, we did not illustrate this structural role of the pathogen sub-system in order keep it simple.
Fig 2.
The schematic diagram of the seven main hierarchical levels of organization of an infectious disease system and the associated scales and the four main biological linking mechanisms of the levels and scales: [a.] linked through exchange of single pathogen species/strain, [b.] linked through exchange of multiple pathogen species/strains, [c.] linked through exchange of single infected host species/host species products, and [d.] linked through exchange of infected multiple host species/host species products.
The linkage of the scales of an infectious disease system through mobile genetic elements such phage or plasmids is not shown in this Figure in order to keep it simple.
Fig 3.
The schematic diagram of the four-stage research and development process for multiscale models of infectious disease systems which are as follows.
Stage I: define the infectious disease problem to be addressed by multiscale modeling, Stage II: formulate the multiscale model of the infectious disease system, Stage III: assess the quality of the multiscale model of the infectious disease system, and Stage IV: use the multiscale model of the infectious disease system in decision support with four steps for each of the four stages. The arrows in this Figure indicate the iterative process of moving from one development stage of the multiscale model to another.
Fig 4.
A conceptual diagram of the integration of knowledge from the four different multiscale modelling approaches of infectious disease systems: [2.1] empirical-based multiscale model (E-MSM), [2.2] mathematical-based multiscale model (M-MSM), [2.3] computational-based multiscale model (C-MSM), and [2.4] data-based multiscale model (D-MSM) and the interplay between the four different multiscale modelling approaches when considered in pairs.
[a.] interplay between M-MSMs and C-MSMs, [b.] interplay between D-MSMs and C-MSMs, [c.] interplay between M-MSMs and D-MSMs, [d.] interplay between M-MSMs and E-MSMs, [e.] interplay between C-MSMs and E-MSMs, and [f.] interplay between D-MSMs and E-MSMs.