Large, non-pigmented schizonts manifestly different from the classical schizonts found in erythrocytes have been observed in some strains of P. relictum, P. gallinaceum, P. cathemerium, P. circumflexum, and (one unconfirmed report) P. nucleophilum, but not in several other species of avian and simian malaria examined. Although human malarial infections have not yet been extensively studied, forms similar to those seen in avian malarias have been reported in infections with P. vivax and P. falciparum.
The identification of infected cells has usually not been made by specialists, but infections are reported in endothelial cells and various cells of the lymphoid-macrophage system (rarely in granulocytes).
In infections with P. elongatum schizonts occurring in all blood and blood-forming cells are morphologically identical; the large schizonts mentioned above have not been described.
That the exo-erythrocytic schizonts are a part of the malarial life cycle and not a contaminant is indicated principally by the facts that they have not been separated from malaria nor shown to occur apart from it, that they differ characteristically in different species of malaria, and that their immunological specificity parallels that of the associated malaria. Miscellaneous other evidence supports this view. They clearly differ from both avian and mammalian types of toxoplasmas in morphology and transmissibility.
The exo-erythrocytic stages are not appreciably affected by schizonticidal drugs, but their number is reduced by plasmochin.
Various evidence that the sporozoite development does not occur in circulating erythrocytes, together with the fact that the exo-erythrocytic schizonts appear earlier and more numerously after sporozoite inoculation than after the injection of infected blood, suggests that the exo-erythrocytic schizonts are the early developmental stages of sporozoites. Evidence is inconclusive on this question, though exo-erythrocytic schizonts have been found 16 hours after the inoculation of sporozoites.
Other ideas on the significance of the exo-erythrocytic stages include theories that they reflect an unfavorable condition of the blood as a medium, or reduced digestive activity of tissue phagocytes, and the theory that they represent stages in the evolution of sporozoa of the sub-order Haemosporidiidea into strictly erythrocytic parasites. While they indicate a closer relationship between the Plasmodidae and the Haemoproteidae, adequate criteria for the separation of these families still exist.
In addition to their great biological significance, the newly discovered exo-erythrocytic stages are of vital practical importance, particularly in the study of chemotherapy of malaria.