UKNEQAS Parasitology
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Malaria life cycle

  There are four generally recognized species of malaria parasites of humans;

Plasmodium malariae

Plasmodium vivax

Plasmodium falciparum

Plasmodium ovale

The life cycle of all species of human malaria parasites is essentially the same. It comprises an exogenous sexual phase (sporogony) with multiplication in certain Anopheles mosquitoes and an endogenous asexual phase (schizogony) with multiplication in the vertebrate host.

The latter phase includes the development cycle in the red cells (erythrocytic schizogony) and the phase taking place in the parenchyma cells in the liver (pre-erythrocytic schizogony).

 When a female Anopheles mosquito ingests the blood of a human host with malaria parasites in the circulation the asexual parasites are digested together with the red cells while the mature sexual cells (gametocytes) undergo a series of developments in the stomach of the mosquito which result in the production of motile sporozoites. The sporozoites migrate from the body cavity of the mosquito to the salivary glands and the mosquito now becomes infective. When the mosquito feeds on blood after piercing the skin the sporozoites are injected into the wound and pass into the bloodstream of the vertebrate host. Following the inoculation of sporozoites there is a brief period of about 30 minutes when the blood is infected. Later the sporozoites disappear from the blood. Many are destroyed by phagocytes but some enter the paranchymal cells of the liver (hepatocytes) directly or via the Kupffer cells and undergo a process of development and multiplication known as pre-erythrocytic schizogony. Within 40-48 hours the sporozoites have developed into tiny parasites 3µm in diameter and consist of a single nucleus with a narrow cytoplasmic ring (merozoites). In P. vivax and P. ovale the sporozoites differentiate into hypnozoites as well as merozoites.The hypnozoites remain dormant in hepatocytes for considerable periods of time. The mechanism of activating the growth of these parasites remains a mystery. When they are "reactivated" they grow and undergo exo-erythrocytic schizogony forming a wave of merozoites that invade the blood and produce a clinical relapse. In P. falciparum and P. malariae hypnozoites are not formed and the parasite develops directly into pre-erythrocytic schizonts.

 At the end of the pre-erythrocytic stage, 6-16 days after the time of infection, the envelope of the cell containing the schizont ruptures; the merozoites are set free into the surrounding tissue and thence into the blood circulation. Most of them invade the red cells present in the sinusoids of the liver but some are phagocytosed.

 The interval between the date of the infection and the time when the malaria parasites are detectable in the peripheral blood is known as the pre-patent period. This should be distinguished from the incubation period which is related to the first appearance of clinical symptoms of the disease.

The merozoites released from the liver schizont invade the red cells and develop in to trophozoites. In the course of their development they absorb the haemoglobin of the red cells leaving as the product of digestion a pigment called haemozoin, a combination of haematin with protein. This iron-containing pigment is seen in the body of the parasite in the form of dark granules, which are more obvious in the later stages of development.

 After a period of growth the trophozoite undergoes an asexual dividing process of erythrocytic schizogony. The nucleus divides 3-5 times into a variable number of small nuclei. This is soon followed by the division of cytoplasm forming a schizont. Mature schizonts are fully developed forms in which, as a result of segmentation of the nucleus and the cytoplasm a number of small rounded merozoites are produced. When the process of schizogony is completed the red cell bursts and the merozoites are released into the blood stream. The merozoites then invade fresh red cells in which another generation of parasites is produced by the same process. This erythrocytic cycle of schizogony is repeated over and over again in the course of infection, leading to a progressive increase of parasitaemia until the process is slowed down by the immune response of the host.

It is usually only after several rounds of blood schizogony that a proportion of the merozoites develop in to the sexual stages of the parasites - the gameteocytes. The precise mechanism for this differentiation remains unknown but it is thought that the development of host antibodies may play a large part in the process.

 Stages of the malaria parasite seen in the blood

 The trophozoite stage.

This stage is the most commonly seen; it is often referred to as the ring stage, although it sometimes takes the form of an incomplete ring.

Because the trophozoite form is a growing stage, the parasite within the red cell may vary in size from small to quite large. Pigment appears as the parasites grows. Malaria pigment - haemozoin, is a metabolic by-product of the parasite. It does not stain, but has a colour of its own, which may range from pale yellow to dark brown or black.

 The schizont stage.

At the schizont stage the parasite starts to divide. This is referred to as schizogony and takes place in the liver and in the peripheral blood.

The parasite reproduces by simple division. There are several obvious phases in this stage, ranging from parasites with two chromatin pieces to parasites with a number of chromatin dots and definite cytoplasm - merozoites.

 The gametocyte stage.

The gametocyte stage is sexual in that the parasites become either male or female in preparation for the next stage, which takes place in the stomach of the female Anopheline mosquito. Gametocytes may be either rounded or banana/crescent in shape, depending on the species. The way in which the parasite takes up the stain is usually an indication of which sex the gametocytes are. Male gametocytes appear to stain more of a "pink" colour than do the female gametocytes.

 

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