Life Cycle of Plasmodium | Protozoa | Microorganisms | Zoology

Life-cycle of Plasmodium is complicated. It comprises several stages and requires two hosts for completion—a primary, definitive or principal host i.e. man and a secondary, intermediate or vector host. i.e. female Anopheles mosquitoes.

According to modern researches, the following four stages are met within the life cycle of plasmodium:

1. Asexual Cycle and Shizogony in Man: 

i. Pre-Erythrocytic Cycle

ii. Exo-Erythrocytic Cycle

iii. Erythrocytic Cycle

2. Life-Cycle of Plasmodium in Mosquito (Sexual Cycle)

1. Asexual Cycle and Shizogony in Man:

i. Pre-Erythrocytic Cycle:

Only female Anopheles is capable of sucking the blood. The male lives upon the sap and juice etc. of the plants. The impregnated female needs the blood of man or other warm blooded animal for the nourishment of its eggs. Before piercing the skin to suck the blood the female Anopheles injects a little of its saliva into the blood of the host.

The enzymes present in its saliva prevent the coagulation of blood. Innumerable sporozoites reach the blood of the host along with the saliva. Each sporozoite is a very minute and narrow sickle-shaped structure. Its length is about 10 to 15 microns. The cuticle of sporozoite is touch and elastic due to which it is able to maintain the definite shape of its body.

Transmission of infection through bite of mosquito is by inoculative method. There are other methods of transmission possible. Transfusion malaria occurs is blood of donors with latent infection is used for blood transfusion. Congenital malaria may occur by transmission of infection from mother’s blood to the foetus in vitro due to some placental defect.

Therapeutic malaria can be induced artificially, for treatment of neurosyphilis, by injecting an emulsion of salivary glands containing sporozoites, or inoculating blood of an infected donor or biting of recipient by laboratory-bred infected mosquitoes. Accidental malaria can develop by the use of the same syringe for persons one of whom might be infected.

Previously, it was thought that soon after reaching the blood of man, the sporozoites enter the red blood corpuscles and start the erythrocytic schizogony, but according to recent researches this does not happen. After about half an hour, the sporozoites completely disappear from the blood circulation.

All the sporozoites reach the liver and enter its cells where they multiply rapidly to form preerythrocytic schizonts. As a result of its division about 1,000 pre-erythrocytic merozoites or crytomerozoites are produced. After the rupture of schizont they reach other liver cells. This asexual cycle is called pre­-erythrocytic cycle.

Pre-Patent Period:

The pre-erythrocytic phase lasts for about 8 days in P. vivax. The duration between the initial sporozoite infection and the first appearance of the parasites in the blood is termed the pre-patent period. It is the time in which the pre-erythrocytic phase of liver schizogony is completed. It ranges from 5 to 15 days according to the species being of about 8 days in P. vivax.

ii. Exo-Erythrocytic Cycle:

After re-entering a liver cell, each cryto-merozoite becomes a trophozoite known as a metacryptozoite or phanerozoite. As a result of schizogony it may produce several thousand metacrypto-merozoites. Of these some are smaller in size but more numerous and called as the micro- metacrypto-merozoites.

They enter the red blood corpuscies to start the erythrocytic cycle. Others are larger in size but less numerous and called as the macro-metacrypto-merozoites. They attack fresh liver cells to continue the exoerythrocytic cycle, which may be repeated several times. No exoerythrocytic phase occurs in P. falciparum.

The pre-and exo-erythrocytic stages of the parasite remain immune to the resistance of the host or to the therapeutic action of any anti-malarial drug. Little or no damage occurs to the host’s tissues during these phases and haemozoin pigments are absent. Moreover, in case of P. vivax and P. malariae, the parasite may continue to live for years without causing clinical symptoms, in the liver cells serving a reservoir.

From this reservoir, the parasite may re-infect the blood and cause a malaria relapse, whenever the immunity or the resistance of the host has fallen down. Such relapses may occur repeatedly for at least two years in case of P. vivax, and for several years in case of P. malariae.

iii. Erythrocytic Cycle:

This cycle occurs in RBCs and begins when a cryptomerozoite or micro metacryptomerozoite enters into an RBC.

It is divisible into 4 stages:

(a) Signet-Ring Stage:

After entering into an erythrocyte, a merozoite soon becomes a rounded, disc-like young trophozoite. As it grows, a large non-contractile vacuole appears in its centre, pushing the cytoplasm and nucleus to a thin peripheral layer and giving a signet-ring appearance to the trophozoite. Rarely, two or more such vacuoles may form.

(b) Amoeboid Stage and Growth Period:

Soon, the vacuole disappears, and the trophozoite becomes somewhat amoeboid. Now, the trophozoite starts feeding more actively upon cytoplasm of host RBC. It secretes out digestive enzymes (lysolecithin) which liquefy the cytoplasm of RBCs by its partial digestion. It then absorbs the liquefied cytoplasm by diffusion through its surface, or by active pinocytosis. Digestion is completed in pinocytic vesicles and food vacuoles.

During its growth period of a few hours, the trophozoite acquires brownish-black haemozoin granules, formed due to proteolysis of the haemoglobin of host cell. Haemoglobin breaks down into its component protein, the globin, and the red pigment, hematin. Globin is digested for nutrition, while hematin accumulates in trophozoite’s cytoplasm.

In 1^1/2 of 2^1/2 days (depending upon the species), the young trophozoite grows into an adult, occupying almost the entire RBC. Besides plasmalemma, endoplasmic reticulum, mitochondria, food vacuoles, Golgi complex, nucleus, etc., a concentric structure of unknown significance has been recently observed in this trophozoite by electron microscopy. The host RBC gets somewhat enlarged and irregular in shape. A number of orange or yellow eosinophilic granules of unknown nature, called Schuffner’s dots or granules appear in its cytoplasm.

(c) Erythrocytic Schizogony and Incubation:

As the trophozoite is fully grown, its nucleus undergoes repeated mitotic divisions, forming 8 to 26 daughter nuclei and preparing the trophozoite for schizogony. The multinucleate organism, thus formed, is erythrocytic schizont.

Its daughter nuclei migrate close to its periphery. Most of its cytoplasm, now, segregates into small masses, each around a nucleus, forming 8 to 26 small (1.5 µ in diameter) and oval, uninucleate merozoites or schizozoites. A small amount of residual cytoplasm, heavily laden with hemozoin granules, is left in the centre of the schizont.

On completion of schizogony, both schizont and host RBC burst due to the pressure of merozoites. Hence, the merozoites and the residual cytoplasm of schizont are released into host’s blood. Liberated merozoites invade fresh RBCs to repeat the erythrocytic cycles. Accumulation of hemozoin granules, and probably also some other toxic substances in blood, causes the characteristic attack of malarial fever, initially after about four erythrocytic cycles and, then, after each cycle.

The ruptured RBCs and schizonts, referred to as “ghost cells”, are destroyed in the spleen. The interval between inoculation of sporozoites into human blood and first attack of the fever is called incubation period.

Completion of an erythrocytic cycle in a fixed time of 48 to 72 hours according to different species of Plasmodium, indicates operation of some sort of a “Biological Clock”. Repeated erythrocytic cycles result, not only in intermittent attack of fever, but also in a larger-scale destruction RBCs, weakening the patient to a considerable extent.

(d) Development of Gametocytes:

After a number of erythrocytic cycles, some merozoites, invading fresh RBCs grow, not into normal schizonts, but into a different kind of rounded forms called gametocytes (cell that marry) or gamonts.

Growth of merozoites into gametocytes is rather fast. It is characterized by the absence of a signet-ring stage. Also, the gametocytes have a larger, central nucleus and denser cytoplasm due to more numerous hemozoin granules. Even the host RBCs exhibits more numerous Schuffner’s dots.

For reasons not fully realized, some merozoites, instead of undergoing the usual schizogony, develop into the sexual forms. They grow into compact rounded bodies known as gametocytes or gamonts. The infected corpuscles, containing young gametocytes, do not circulate in the blood stream but reach the blood vessels of the spleen or marrow. Within 96 hours the gametocytes become full grown and reach the superficial vessels. They contain even more haemozoin than a schizont.

Fully formed gametocytes are dimorphic:

(a) Smaller male, or microgametocytes with larger nucleus and light brown cytoplasm because of scattered hemozoin granules and no reserve food, and

(b) Larger female or macrogametocytes with smaller nucleus, but dark brown cytoplasm due to reserve food granules and more numerous, centrally aggregated hemozoin granules.

2. Life-Cycle of Plasmodium in Mosquito (Sexual Cycle):

The further development of gametocytes does not take place in human body. It at this time a female Anopheles sucks the blood of the malarial patient, the gametocytes and also merozoites reach its stomach along with the blood. Here except gametocytes all others are digested. The gametocytes now come out of the red blood corpuscles.

The gametocytes so liberated in the lumen of mosquito’s stomach, form sex cell or gametes by gametogenesis. The male, microgametocytes undergo spermatogenesis. The nucleus of each rapidly divides by meiosis (reduction division), into 6 to 8 haploid nuclei. The latter move close to the surface of the microgametocyte.

Now, the cytoplasm of the microgametocyte mostly segregates around these nuclei. Suddenly each cytoplasmic mass, together with its nucleus, shoots out from the surface of the microgametocyte in the form of a 20 µ to 25 µ long, whip-like microgamete or sperm. This process is termed ex-flagellation. By their vigorous lashings, the microgametes soon detach from the parent gametocyte and wriggle about in the lumen of the stomach of the host.

The female, macrogametocytes undergo oogenesis. Each divides twice by meiosis, throwing out two small polar bodies, and itself becoming a haploid macrogamete or ovum.

Fertilization:

A small cytoplasmic bulge; called cone of reception or fertilization cone, forms on one side of an ovum. The nucleus moves into this cone. As a wriggling sperm happens to come in contact with the cone, it sticks to it and, eventually, enters into the ovum by its vigorous lashings. Soon, the cytoplasm of the sperm mixes with that of the ovum and the nuclei of the two fuses to form a diploid zygotic nucleus or synkaryon. Zygotes form in the stomach of mosquito about 9 or 10 days after the blood meal.

Ookinete:

The zygote remains rounded and motionless for some time, but soon it becomes elongated, vermiform and motile. It performs writhing or gliding movements and is known as vermicule or ookinete (active egg). It measures about 12-22µ length and 3µ in width. By its tapered end, it pierces through the epithelial lining of the mosquito stomach.

First, it comes to lie against the peritrophic membrane, pushes aside the brush border, enters the cell and later rests against the basement membrane of the stomach. Here it stops to move, becomes spherical and begins to encyst.

Electron Microscope Study of Ookinete:

The electron microscope study of the ookinete by Garnham, Bird and Baker (1962) reveals a complex structure. The pellicle includes an outer corrugated and an inner smooth layer, containing 55 to 65 microtubules responsible for active movements.

Anterior end shows a slit like cytostome through which proteolytic substances are secreted which bring about the lysis of gut cells of mosquito. There is a single granular nucleus with a single nucleolus. Cytoplasmic inclusions represent mitochondria, lysosomes, crystalline ribosomes, irregular masses of black pigment granules in vacuoles, etc.

Oocyst and Sporogony:

Encysted zygote is called oocyst. Just one or two days after fertilization, 20 to 500 oocysts appear upon the surface of the stomach of an infected female Anopheles, bulging as tiny nodules. By actively absorbing nourishment from stomach wall, the oocysts soon grow 5 to 6 times larger. After a day or two, these stop absorbing nourishment; yet continue to grow in size due to formation of several large and irregular, non-contractile vacuoles in them.

Eventually, the encysted zygote in each oocyst, now called a sporont, undergoes asexual multiplication by sporogony. Its nucleus divides repeatedly by mitosis, forming about 10,000 minute daughter nuclei within 2-3 days. The tiny nuclei are arranged at the margins of the vacuoles. The cytoplasm segregates into tiny masses, each around a nucleus. Within next 2 or 3 days, each cytoplasmic mass becomes elongated and spindle-shaped.

Together with its nucleus, it now projects into the adjacent vacuole. These spindle-shaped bodies are called sporozoites. Eventually, all sporozoites become free from the residual cytoplasm of sporont and fill into the vacuoles. By their pressure, the oocyst ruptures.

Hence, the sporozoites get liberated into the haemocoel of the host. Floating freely in haemocoelomic fluid, these reach the salivary glands of the host and become lodged in its common salivary duct in large numbers, ready to be inoculated into human blood, time and again.