Plasmodium


PLASMODIUM – THE MALARIAL PARASITE

The genus Plasmodium (Sporozoa or Apicomplexa) includes species which cause malaria in man and animals. In humans malaria is caused by the following species:

Plasmodium vivax causes benign tertian malaria.

P. falciparum causes malignant malaria or cerebral malaria or pernicious malaria.

P. ovale causes mild tertian malaria or ovale malaria.

P. malariae causes quartan malaria as this species has 72 hr erythrocytic cycle while the other species have 48 hour cycle in RBCs.

Life cycle of Plasmodium is completed in two hosts. Man is considered to be the primary host in which schizogony occurs in liver and blood, and female Anopheles mosquito is the secondary or intermediate host in which gametogony and sporogony takes place.

HISTORY

McCuloch in 1827 proposed that malaria is caused due to foul air. Charles Laveran (1878) discovered for the first time malarial parasite in human blood. Camillo Golgi (1995) studied erythrocytic schizogony of Plasmodium malariae. But no one knew how it was transmitted to man. Ronald Ross (1897) discovered that malaria was transmitted by Anopheles mosquito. In 1898 McCullum studied gametogony in mosquito and Grassi studied sporogony on the stomach wall of mosquito. Short & Garnham (1948) studied schizogony in liver cells and wrote a monograph on this parasite.

LIFE CYCLE

Life cycle in man starts when thousands of sporozoites are injected by the bite of an infected Anopheles mosquito into blood stream. Sporozoites are minute spindle shaped organisms that measure 11-12 microns in length. Sporozoites that escape body’s immune system enter liver to start schizogony.

Schizogony in human liver

After penetrating the hepatic cells, each sporozoite becomes rounded and reproduces by multiple fission to produce schizont that ruptures and releases thousands of cryptozoites, which penetrate the healthy liver cells again to form schizonts. The secondary cryptozoites are called metacryptozoites or metacryptomerozoites. The cycle in liver is repeated for approximately 8 days in P. vivax, 6 days in P. falciparum and 9 days in P. ovale.

The smaller micrometacryptomerozoites enter the blood circulation and the larger ones (macrometacryptomerozoites) re-enter liver cells to produce schizonts.

Schizogony in human blood

After entering the blood stream the parasite invades erythrocytes (RBCs) and start erythrocytic schizogony. Inside RBC, the metacryptozoite modifies into a young trophozoite or nourishing stage. Signet-ring stage is formed when the trophozoite grows in size and a central vacuole develops so that the nucleus is pushed to one side into cytoplasm. Then amoeboid stage is formed when the parasite develops pseudopodia. At this time small red eosinophilic granules appear in the cytoplasm, called as Schuffner’s granules. The amoeboid trophozoite grows in size and becomes a schizont by undergoing multiple fission. With the rupture of RBCs, about two dozen merozoites are liberated in the blood stream where they invade fresh corpuscles to repeat the erythrocytic cycle. The parasite’s multiplication during the erythrocytic phase is responsible for bringing about the characteristic symptoms of malaria. Each cycle of erythrocytic schizogony lasts for 48 hours in P. vivax, P. ovale and P.falciparum and 72 hours in P. malariae.

Gametogony in mosquito stomach

After the parasites have undergone erythrocytic schizogony for some time, some of the merozoites, instead of developing into trophozoites and schizonts give rise to gametocytes which are capable of sexual reproduction after leaving the human host. Mature and inactive gametocytes are found in the peripheral blood of man and wait till they are sucked by mosquito along with blood.

A female Anopheles during its blood-meal from an infected person ingests both the sexual and asexual forms of parasite but it is only the mature sexual forms which are capable of development, the rest die off. The gamete formation occurs inside the stomach of mosquito. From one microgametocyte, 5 to 8 filamentous microgametes are formed, by way of ex-flagellation. The macrogametocyte does not show any flagellation and forms only one macrogamete. This phase is called gametogony.

The male gametes attach to the periphery of the female gamete at the site of a small protrusion and one of them penetrates inside for fusion of the two nuclei, resulting in fertilization and formation of a diploid zygote. In the next 24 hours, the zygote lengthens and matures to form a motile ookinete. It measures 15-22 microns in length and 3 microns in width, swims in blood and penetrates the stomach wall to form oocyst on the outer side of stomach wall.

Sporogony on the stomach wall

The encysted zygote is called oocyst or sporont. Each oocyst now enters a phase of asexual multiplication known as sporogony. As the oocyst matures, it increases in diameter and meiotic and mitotic divisions follow to form a large number of haploid sporozoites. When fully mature, the sporocyst ruptures, releasing the sporozoites in the body cavity of the mosquito.

Large numbers of sporozoites are present in the fluid surrounding the stomach. They penetrate and enter the salivary glands and wait for the mosquito to bite man and release them in human blood. The mosquito at this stage is capable of transmitting infection to man.

SYMPTOMS OF MALARIA

The clinical manifestations of malaria are a series of febrile paroxysms followed by anaemia and spleen enlargement. Febrile paroxysm shows a succession of 3 stages: the cold stage lasting 20 minutes to an hour, the hot stage lasting 1 to 4 hours and the sweating stage that lasts 2 to 3 hours. Thus, the total duration of the febrile cycle is from 6 to 10 hours.

Anaemia develops as a result of breaking down of red blood cells during schizogony of the parasite.

The falciparum infection often results in thrombosis of visceral capillaries. Death takes place when capillaries of brain become plugged with both the parasites and malarial pigment. It also results in black water fever that is characterized by massive destruction of RBC’s and excretion of blood in urine.

TREATMENT OF MALARIA

Various synthetic drugs, such as, Quinine, Chloroquine, Sulphadoxine and Pyrimethamine, Primaquine, Mefloquine, Artemicine etc. are used to kill various stages of the parasites.