The gametocytes occur in the erythrocytes. Schizogony takes place in the erythrocytes and also in various other tissues, depending on the species. The exoerythrocytic ("e.e.") schizonts are solid or, at the most, vacuolated bodies. Members of this genus are parasites of mammals, birds and lizards. They are transmitted by mosquitoes, Anopheles transmitting the mammalian species, and culicines or sometimes Anopheles the avian and reptilian ones.
Members of this genus cause malaria, which is still the most important disease of man. They also cause a similar disease in birds. Coatney and Roudabush (1948) have cataloged the species of Plasmodium, and other species are discussed by Bray (1957). Man has 4 species, higher apes 4, lower apes and lemurs 7, rodents 2, and bats 1. Birds have 14 or 15 valid species (Hewitt, 1940; Bray, 1957; Laird and Lari, 1958).
The life cycle of Plasmodium vivax of man is representative. The sporozoites enter the blood thru a mosquito bite. They stay in the blood less than an hour, quickly entering liver parenchymal cells. Here they become schizonts (known as cryptozoites from their location), which enlarge and divide by multiple fission to form metacryptozoites (a type of merozoite). These enter new liver parenchymal cells, undergo multiple fission, and form new metacryptozoites. This process may go on indefinitely in P. vivax, but in another human species, P. falciparum, there is only a single generation of metacryptozoites.
The metacryptozoites break out of the liver cells, pass into the blood stream and enter the erythrocytes about a week to 10 days after infection. Here they round up and develop a large vacuole in their center. They are called ring stages because in Romanowsky stained smears they resemble a signet ring, with a red nucleus at one edge and a thin ring of blue cytoplasm around the vacuole. These grow and are now called schizonts or trophozoites.
The trophozoites were formerly thought to obtain their nutriment saprozoically, but Rudzinska and Trager (1957) showed in an electron microscope study of P. lophurae of the duck that they are holozoic as well. They form food vacuoles containing host cell cytoplasm by invagination. The hematin pigment granules are formed within these food vacuoles by digestion of the hemoglobin. This study, incidentally, settled once and for all the question which is raised perennially as to whether Plasmodium occurs within or on the surface of the host cell; it is within it.
The trophozoites undergo schizogony to produce merozoites, the number depending on the species. These break out of the erythrocytes, enter new ones, and repeat the cycle indefinitely.
The length of each cycle depends on the parasite species. It is 2 days in P. vivax and P. falciparum, and 3 days in another human species, P. malariae. Practically all the parasites are generally in the same stage of the cycle at the same time, so all the merozoites break out of the red cells and pass into the blood at the same time. Along with them go the hematin granules and other waste products produced by the parasites' metabolism. These are toxic, and cause a violent reaction or paroxysm in the host - the chills and fever characteristic of malaria.
After the infection has been present for some time and after an indefinite number of asexual generations, some merozoites entering the erythrocytes develop into macrogametes and others develop into microgametocytes. The former are customarily called macrogametocytes, but this name is incorrect since they are haploid from the start (see below). They remain in this stage until the blood is ingested by a mosquito.
In the stomach of the mosquito, microgametes are produced. The changes in the microgametocytes are striking. Within 10 to 15 minutes the nucleus divides, and 6 to 8 long, heavy flagellum-like microgametes are extruded. This process is known as exflagellation. The microgametes break off and swim freely until they find a macrogamete. Fertilization takes place, and a motile zygote (ookinete) is formed.
The ookinete penetrates into the stomach wall and grows into an oocyst, which forms a ball 50 to 60 u in diameter on the outer surface of the stomach. The oocyst nucleus divides repeatedly and a number of sporoblasts are formed. The nucleus of each sporoblast then divides repeatedly, and eventually each oocyst comes to contain 10,000 or more slender, spindle-shaped sporozoites about 15 u long with a nucleus in the center. These break out of the oocyst into the body cavity and migrate to the salivary glands. They are then injected into a new host when the mosquito bites again. The process of sporozoite development takes 10 days to 3 weeks or longer, depending on the species of Plasmodium, the species of mosquito and the temperature.
Once infected, a mosquito remains infected for life, and can transmit the parasites every time it bites. There is a case on record (James, 1927) of a mosquito which lived from August 5 to November 16 and infected more than 40 general paresis patients as part of their therapy.
In vivax and malariae malaria, relapses are common and may occur for a number of years after the individual has had his first attack. Between attacks the parasites are ordinarily not found in the blood. What apparently happens is that all the parasites do not leave the liver when the metacryptozoites emerge into the blood stream, but a few remain there and continue to multiply in secret until such time as the body's defenses have decreased sufficiently so that the parasites can again invade the blood.
There are several variations of the above general pattern. In P. falciparum of man, there is only a single generation of metacryptozoites in the liver, and relapses rarely occur. In addition, the schizonts and merozoites of this species are rarely seen in the peripheral blood. Instead, the infected red cells become viscid and clump together in the internal organs.
In the avian species, exoerythrocytic schizogony does not take place in the liver parenchyma, but either in the endothelial cells (P. gallinaceum, P. relictum, P. cathemerium, P. lophurae, P. fallax, P. circumflexum, P. durae, P. juxtanucleare, P. hexamerium) or largely in the haemopoietic cells (P. elongatum, P. vaughani and probably P. huffi and P. rouxi).
In bird malaria also, but not in mammalian malaria, some of the merozoites which have been formed in the erythrocytes are able to enter the tissue cells and develop exoerythrocytically. They are known as phanerozoites, but they do not differ morphologically from the forms derived from sporozoites.
Plasmodium, is haploid thruout its life cycle except for a brief period following fertilization and zygote formation. In a cytologic study of the early oocysts of 7 species of Plasmodium in mosquitoes, Bano (1959) found that the oocysts undergo meiosis 2 to 3 days after the infective blood meal, the time depending on the species. For P. vivax it was 48 hours, for P. gallinaceum 53 to 55 hours, and for P. inui 72 to 79 hours. After that, division is by mitosis.
The haploid number of chromosomes is 2 for P. falciparum, P. malariae, P. ovale, P. lophurae, P. relictum, P. floridense (Wolcott, 1955, 1957), P. vivax, P. knowlesi, P. berghei (Wolcott, 1955, 1957; Bano, 1959), and P. gallinaceum (Bano, 1959); it is 3 for P. gonderi and 4 for P. cynomolgi and P. inui (Bano, 1959).
Various species of Plasmodium have been cultivated in fluid media (Trager, 1947; Anfinsen et al., 1946; Geiman et al., 1946) and in avian embryos and tissue culture (see Pipkin and Jensen, 1958 for a review).