Total numbers of malaria parasites in the bodies of two adults (logarithmic scale; vertical axis) with similar rapidly expanding infections who develop hyperparasitaemia (>5% parasitaemia) are shown against time since their infecting mosquito bites on the horizontal axis. The horizontal dotted line is the pyrogenic density (the density threshold for fever). The most likely mitotic division to give rise to de-novo resistance is the one immediately preceding peak parasitaemia. The most likely (i.e. modal) number of resistant parasites present therefore is one. There are correspondingly lower probabilities of there being much larger numbers of de-novo resistant parasites. The inset triangles represent the much rarer situation of earlier de-novo appearance of resistant mutants and the corresponding greater numbers of resistant parasites that would occur at presentation with hyperparasitaemia. In the example on the left the fitness and thus multiplication factor of the mutant parasites is unaffected by the resistance mechanism, whereas on the right their fitness and thus multiplication is reduced relative to their drug sensitive siblings.