LIFE CYCLE OF PLASMODIUM PARASITES (MALARIA AND MOSQUITO)

The life cycle of the human malaria species consists of two phases. The sexual phase (Sporogony/Exogenous) which involves the development and multiplication on the female anopheles mosquito. The Asexual phase (Schizogony/Endogenous) which involves multiplication in man divided into two parts:
 THE ARE:
a). Pre-erythrocytic schizogony in the liver cells.
b). The erythrocytic-schizogony in the red blood cells.   


Endogenous phase in human which is the asexual cycle schizogony involves exo-erythrocytic multiplication in liver parenchyma cells to merozites, the merozoites enters red cells inform of ring trophozoite then matured trophozoites to immature. Schizonts to mature schizonts. The ring trophozoites differentiate into micro and macro gametocyte, which is the gametogony cycle of the parasite. The gameto cytes in the human blood enter the mosquito and fertilization forming the zygote which Ookinate the motile zygote emerges.

These motile zygotes penetrate the outer lager of stomach wall of mosquito and encyst. The oocyst grows by multiple divisions. Then the cyst burst to release sporozoites, this pass through the body cavity of the mosquito to reach the salivary gland of the mosquito and it is known as the exogenous phase in mosquito, which is sexual cycle (Sporogony). The sporozoites in saliva of the mosquito can be re-injected into human host and another cycle begins. 

ASEXUAL PHASE IN MAN
Human infection result from the bite of an infected female anopheles mosquito in which the sporozoites, resulting from the sexual and subsequent sporogonic cycle of development in the mosquito are injected into the human blood steam. The sporozoites rapidly (usually within one hour) enter the parenchymal cells of the liver, where the first stage development in human takes place (Pre-erythrocytic phase of the life cycle). They multiply in the liver and are later liberated as merozoites from mature schizont. The merozoites rupture and leave the liver cells, enter the blood stream and invade erythrocytes (Erythrocytic phase of the life cycle).

Parasites in the red blood cells multiply in species characteristic fashion, breaking out of their host cells at the same time. To enter the cells, the merozoites bind to glycophorine the major erythrocytic glycoprotein that is specific for a particular species of the parasite. The apex of the merozites release substances that forms a deep pit on the surface of the red blood cells and maintain contact by forming a ring. The merozoites are enveloped by Red blood cells on a vacuole known as parasitophorous vacuole. 

        In the Red blood cells, the merozoites develop into rings forms that grow in size to trophozoite absorbing haemoglobin leaving a pigment known as heamatin or heamazoin (a combination of Hb in protein which can be seen as dark granules). The trophozites multiply by schizogony dividing into a number of small merozoites varying with the species to form the mature schizontes. The erythrocytic cycle is with successive broods of merozoites appearing at 48 hours intervals for (P. vivax, P. ovale and P. falciparum) or every 72 hours for p. malariae.
        There is no return of merozoites from Red blood cells to liver cells without treatment; falciparum infection ordinarily will terminate spontaneously in less than one year unless it ends  fatally. The other three species continue to multiply in the liver cells long after the initial blood stream invasion or there may be delayed multiplication in the liver. These pre-erythrocytic cycle coexist with erythrocytic cycles and in P. vivax and P. ovale, may persist as non growing resting forms or hyprozoites, after the parasite have disappeared from the peripheral blood.

        Resurface of an erythrocytic infections (relapse) occurs when merozoites from hyprozoites in the liver breakout are not phagocytize in the blood stream and succeeded in re-establishing a red blood cell infection. During the erythrocytic cycles certain merozoites enter red cells and become sexually differentiated as male or female gametocyte (Gametogony). The male is known as micro gametocyte while the female is known as macro gametocyte which differ in morphology in the species of the parasite.                        
                
SEXUAL PHASE IN MOSQUITO
        The gametocytes are taken up by female anopheline mosquito and undergo further development. These gametocytes develop into gametes in the gut of he mosquito, macrogametocyte formd marogamete while the microgametocyte form microgamete. The microgamete divide to form  long slender thread like structures known asex-flagellations, then macrogametes developing with nuclei shifted to the periphery where projections are formed. Fertilization occurs when a microgamete penetrates this projection and the fertilized macrogamete is called a zygote. The zygote gives rise to the Ookinate as the ookinate grows, it penetrates the epithelial cell of the mid gut. 

After a period of 1-15 days after injection of gametocytes by mosquito, the oocyst mature with multiplication of nuclei and transforms which is temperature dependent. The oocyst burst and sporozoites are released throughout the insect body. The sporozoites that came in contact with the salivaryd gland are injected into a healthy  man after blood meal. Their shape vary from narrow, slightly curved as in P. vivax,  thick as in P. malariae  and sickle shaped in P. falciparum. Malaria is always a  accompanied by haemmolysis and in a severe to prolonged attack anaema may be found. The haemolysis is most severe with P. falciparum, which invades red blood cells of all ages, including the erythropoietic sterm cells in bone marrow.
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