Malaria parasites—discovery of the early liver form

Abstract

Infections of mammalian malaria parasites start when sporozoites from an infected anopheline mosquito are injected into the bloodstream of the host. The sporozoites enter the hepatocytes and become transformed into exoerythrocytic schizonts. Since the discovery of the primate parasite Plasmodium cynomolgi in monkey hepatocytes¹ and the rodent parasite Plasmodium berghei in hamster hepatocytes², the ultrastructure of these stages has been extensively studied both in primate^3,4 and rodent plasmodia^5–10. These observations relate only to the development of the exoerythrocytic schizont 25 h⁸ after sporozoite injection until the final maturation (of P. berghei) 50 h post-inoculation. Recently, we have studied the route of entry of sporozoites across the cellular lining of liver sinusoids and invasion of the liver parenchymal cells^11–13 by using transmission electron microscopy. The results of these studies in combination with other physiological experiments^14–17 strongly suggested that the sporozoite was initially harboured by the Kupffer cell, from which the parasite escaped into the neighbouring hepatocyte. The migration of sporozoites from liver sinusoids to hepatocytes can be achieved within a few minutes¹⁸. We present here the first ultrastructural observations on the natural transformation of intrahepatocytic sporozoites into exoerythrocytic forms in vivo, using the rodent malaria parasite P. berghei in a laboratory host, the Brown Norway rat. These observations complete the search for the final link in the life cycle of malaria parasites.