Discovery of the pre-erythrocytic stages of a saurian malaria parasite, hypnozoites, and a possible mechanism for the maintenance of chronic infections throughout the life of the host

Re-examination of tissue sections from four Takydromus tachydromoides (Sauria: Lacertidae) naturally infected with Plasmodium sasai found liver parenchymal cells, containing uninucleate parasites which may correspond to the hypnozoite stage of primate malaria parasites, schizonts and segmenters in parenchymal cells, and hepatic macrophages which contained numerous schizonts. Following destaining of the original H&E and prolonged restaining with warm Giemsa stain, encysted schizonts, protected by a hyaline wall, were discovered in the connective tissue or capillary endothelium of lung, liver, brain, heart, pancreas, kidney, intestine wall, testis, and both intra- and intermuscularly in the femoral muscles. Unencysted schizonts in the pulmonary endothelium apparently represent the phanerozoic stages, which, following encystment in the various tissues, are recognized as a new stage in the life cycle of reptilian malarial parasites, the chronozoic schizonts. A hypothesis is presented to describe the life cycle of P. sasai, which may be characteristic of other saurian malaria parasites. It interprets the sequence of pre-erythrocytic stages found as follows: sporozoites enter hepatic parenchymal cells where some may become dormant as hypnozoites, and others form cryptozoic schizonts. The cryptozoites parasitize hepatic macrophages and form metacryptozoic schizonts. Metacryptozoites produce phanerozoic schizonts in the capillary endothelium and connective tissue of the lung and other organs. Phanerozoites and possibly metacryptozoites then invade the erythrocytes to begin the erythrocytic cycle. Some of the phanerozoites in endothelium, connective tissue and skeletal muscle become encysted as chronozoic schizonts, and their progeny, chronozoites, renew the erythrocytic cycle throughout the life of the host and produce seasonal relapses of gametocytemia, in spring, at the end of hibernation by the lizard.