Proposed relationship of toxemia-defined progression with clinical staging.

The triphasic (TP) kinetics of anthrax toxemia with slow progression in non-human primates mirrors the clinical staging algorithm. A brief incubation period is followed by 1) the early-prodromal stage 1 with the onset of non-specific symptoms which coincides with the early rise in toxemia to the end-of-phase-1 (EOP1). This is followed by 2) the intermediate-progressive stage which coincides with the plateau/decline in toxemia that continues to the end-of-phase-2 (EOP2) when the critical toxemic thresholds are exceeded, which coincides with entry to 3) the late-fulminant stage with a rapid decline in clinical stability and rapid rise in toxemia/bacteremia. Fast progression occurs over a compressed timeline during which the phase-2 plateau may (fast triphasic-TP) or may not be observed (fast monophasic-MP) kinetics. The dependence of progression on toxemia can be seen with the shorter time-to-threshold for fast progression than slow and the similar time from threshold-to-terminal for both. Progression may be reoriented from time/clinical-dependent staging to toxin/clinical-dependent staging.