Abstract
Although the phenomenon of malarial relapse was known to the ancients, the mechanism has only recently been explained satisfactorily. The long-held hypothesis of a tissue "cycle" in primate malaria as a cause of relapse did not fit clinical and experimental observations. A latent stage for Plasmodium spp. in the liver, for which there is now extensive morphological and experimental confirmation, best explains both the relapse phenomenon and the long prepatent periods seen with some strains of Plasmodium vivax. These latent stages (hypnozoites) have been detected in three relapsing malarias and have been found to persist in the liver as uninucleate parasites for up to 229 days after sporozoite inoculation. They have been found in in vitro cultures of two species of Plasmodium, and their ultrastructure has been partially described.