Proposed mechanism and sequence of Plasmodium vivax relapse activation in a malaria endemic area. In an illustrated example, at the time of infection (sporozoite inoculation) the individual already has hypnozoites of two different genotypes acquired from two previous inoculations which are latent in the liver. The different genotypes are denoted by different colours (red and white). Half the newly acquired infection sporozoites (blue) develop into preerythrocytic schizonts and half become dormant as hypnozoites (the estimated proportions for tropical "strains") [59, 69]. Illness associated with the blood stage infection activates a small fraction of the hypnozoites (inset shows a "classic" P. vivax fever pattern in relation to asexual parasite development). In this example there is one hypnozoite of each genotype and each is activated by the illness and each develops into a pre-erythrocytic schizonts. By chance the progeny of one of the preexisting latent hypnozoites reach pyrogenic densities before the progeny of the recently inoculated hypnozoite (inset shows the logarithmic growth of the three genotypically different infections-vertical axis shows number of parasites in the body). The consequent febrile illness then suppresses further multiplication of the blood stage infection so that the progeny of the other two prerythrocytic schizonts may not reach transmissible densities. The ensuing illness activates some of the remaining hypnozoites (the same fraction as were activated initially) and relapses continue until either the number of hypnozoites is exhausted or some fail to be activated. If there are some hypnozoites which fail to be activated these may be activated at a later date by a subsequent malaria infection.