Updated by: Arabinda Naik
Life cycle of Plasmodium vivax is digenetic i.e., they complete their life cycle in two hosts:
Man: Secondary host or intermediate host: human is the secondary host. Human contains asexual phase of the parasite and develops symptoms of disease due to the presence of parasite and is termed as secondary host. the asexual phase is completed in human beings.
Mosquito: Primary host or definitive host: Female Anopheles mosquito is the primary host. The organism which contains sexual phase of the parasite and is regarded as definitive host. The sexual phase of the life cycle is completed in the female Anopheles mosquito. Mosquito is also called as the vector as it transmits the parasite from one person to another.
In the life cycle of the plasmodium the asexual life cycle alternates with the sexual life cycle. This phenomenon is called as alternation of generations. Plasmodium vivax is the most common of the human infecting malaria fever parasites. It is an intracellular parasite in man. It lives in the red blood corpuscles and liver cells in man. While extracellular in mosquitoes, living in its alimentary canal and salivary glands.
a) Part of Lifecycle of P. Vivax in Man (Asexual Cycle):
Asexual cycle or Schizogony in man
Schizogony is the process of asexual reproduction by which Plasmodium undergoes asexual multiplication in liver cell and RBCs of man. It occurs in human liver cell (liver schizogony) and in RBC (erythrocytic schizogony). When an infected female Anopheles mosquito bites a healthy person, it injects thousands of sporozoites along with saliva into the bloodstream. Inside liver and RBC different form of sporozoite cause infection.
1. Infection (Inoculation):
When an infected female Anopheles bites a man to suck his blood, The mosquito punctures the host’s skin with proboscis and introduced some saliva in the bloodstream first. Along with saliva, it inoculates thousands of sporozoites into the bloodstream. The parasite remains always in the body of one of the two hosts, hence, the sporozoites do not possess any protective covering.
Inoculation
When an infected female Anopheles mosquito bites a healthy person it sucks his/her blood for meal, she injects saliva containing sporozoites into the wound through its needle like mouth parts. This is called inoculation.
2. Sporozoite:
These are infective forms of parasites. It is minutes measures about 11 to 12 µ in length and 0.5-1 µ in width. It is a spindle-shaped, slightly curved, or sickle-shaped, and uninucleated organism. They are covered externally by an elastic; firm pellicle having longitudinally arranged contractile microtubules. The microtubules help in their wriggling movements. Its anterior end is the apical cap, made of 3 or more concentric rings, into which opens the secretory paired organelles. These secretory organelles are supposed to secrete some secretion which helps its penetration into the liver cell. It contains a single and vesicular nucleus having a nucleolus in its center. It contains a single mitochondrion with tubular cristae.
3. Schizogony in Liver Cells:
The sporozoites are capable of slight gliding movements. In about a half hour sporozoites disappear from bloodstreams and enter the parenchymatous cells of the liver where they multiply asexually by schizogony. Inside the liver and RBC different forms of sporozoite cause infection. Liver schizogony has 2 phases, pre-erythrocytic and exo-erythrocytic.
a) Pre-erythrocytic phase:
In the liver cells, Sporozoites grow and become large and spherical in shape called schizonts. The nucleus of schizont multiply asexually (multiple fission) and forms thousands of merozoites. The schizonts ruptures and merozoites are liberated into the sinusoids or venous passage of the liver in the form of Cryptozoites or cryptomerozoites. These cryptozoites are immune to medicines and the resistance of the host. It is completed in 8-10 days. The process of formation of many cryptozoites from single sporozoites in the liver cells is called pre-erythrocytic schizogony. During this stage, the blood remains sterile, and inoculation does not produce infection.
b) Exo-erythrocytic phase:
The second phase of asexual multiplication known as the exo-erythrocytic phase in which cryptomerozoites enter fresh liver cells and grow into schizonts, the schizonts divide to form merozoites, and merozoites of 2nd generation are termed as metacryptozoites or phanerozoites. The same process is repeated several times in liver cells to form a reservoir of merozoites and each time new liver cells are infected. It has been reported that metacryptozoites which are smaller in size and numerous called micro metacryptozoites and some are larger and less numerous in size called macro metacryptozoites. The micro metacryptozoites enter the red blood cells to start the erythrocytic phase while the macro metacryptozoites infect the fresh liver cells to continue the exo-erythrocytic phase. The exo-erythrocytic phase of parasites remain immune to the resistance of the host and parasites are not susceptible to the action of any kind of anti-malarial drug.
c) Pre patent and Incubation periods:
The pre-patent period is the duration between the initial sporozoite infection and the first appearance of parasite in the blood. In case of P. vivax, it is about 8 days on an average. The incubation period is the time taken from the infection of man by sporozoites till the appearance of first malarial symptom. In case of P. vivax, it is about 14 days on an average ranging from 10 to 17 days. Of course, during the incubation period the host shows no symptoms of malaria.
4. Schizogony in Erythrocytes:
3rd multiplication phase of schizogony occurs in the erythrocytes known as erythrocytic schizogony. This cycle starts when the micro metacryptozoites enter erythrocytes. Single metacryptozoites enter single RBC and pass through the trophozoite stage, signet ring stage, amoeboid stage, and schizont stage.
a) Trophozoite stage: When metacryptozoites invade the RBC, it becomes rounded with a large nucleus and grows by ingesting hemoglobin of corpuscles. This stage of the parasite is called the trophozoite stage.
b) Signet ring stage: As the trophozoites grow in a size, a large non-contractile vacuole appears which pushes the nucleus towards the periphery and forms a ring-like structure known as the signet ring stage. The signet ring stage is 1/3 to ½ the size of an erythrocyte. The signet ring trophozoites ingest a large portion of the cytoplasm of RBC forming a food vacuole into which it secretes digestive enzymes. The enzyme brings about the proteolysis of blood haemoglobin, which breaks down the protein component into hematin. Protein is used as food by the trophozoite, while unused hematin is deposited in the form of hemozoin (toxic malarial pigment).
c) Amoeboid stage: The signet ring trophozoites enlarge, and vacuole starts disappearing and develops pseudopodial processes in the cytoplasm and changed into the amoeboid stage. This stage is called the amoeboid stage. Currently, small red eosinophilic granules appear in the cytoplasm of the host corpuscle which are known as Schuffner’s granules.
d) Schizont: The amoeboid trophozoites after feeding becomes rounded grow and become erythrocytic schizont. Asexual multiplication takes place in schizont to from 12 to 24 nuclei which get arranged at the periphery and cytoplasmic masses surrounding them. Each cytoplasmic mass with one nucleus becomes an oval-shaped merozoites. This phase is known as erythrocytic schizogony. The haemozoin granules are gathered at the centre. The arrangement is just like the arrangement of petals in rose flowers. So, this stage is called the rosette stage.
With the rupture of the red blood corpuscle, the merozoites are liberated into the plasma in the form of erythrocytic merozoites. The merozoites invade fresh corpuscles to repeat the erythrocytic cycle. One complete erythrocytic cycle takes 48 hours.
d) Post-erythrocytic Schizogony:
Sometimes, some merozoites which are produced in erythrocytic schizogony reach the liver cell and undergo schizogonic development in liver cells. This is known as post-erythrocytic schizogony.
5. Formation of Gametocytes:
After many generations of schizogony in the blood, some of the merozoites invade the new RBC and do not change into schizonts but they grow and transformed into 2 types of gametocytes called macrogametocytes and microgametocytes. Gametocytes appear in the peripheral blood at various intervals after the onset of fever, they remain inactive while in the human blood.
Macrogametocytes or female gametocytes: are large (10-12µ) and numerous in number. They have a small compact peripheral nucleus. They have reserved food materials and the cytoplasm is dark in colour.
Microgametocytes or male gametocytes: are smaller (9-10 µ) motile and few. They have large centrally placed nuclei. They lack reserved food and stains faintly hence the cytoplasm is light in colour and clear. Both gametocytes contain a large amount of hemozoin; they enlarge the erythrocytes. The gametocytes do not divide but remain in human blood corpuscles for several weeks. It is necessary for them to be taken into the body of Anopheles for further development, if this does not happen, they will either degenerate or die.
Many species of Anopheles, but not all species, act as intermediate hosts. If the gametocytes are sucked up along with human blood by a female Anopheles, then they reach the stomach where corpuscles are dissolved, and the gametocytes are set free.
1. Ingestion by Mosquito:
When female Anopheles mosquito sucks the blood of the infected persons, containing the gametocytes and other stages of the erythrocytic cycle. They reach the stomach where all the stages along with RBCs are digested except gametocytes.
2. Gametogony:
a) Microgametes: The process of the formation of gametes from the gametocytes is called gametogenesis or gametogony. Like gametocytes, the gametes are also of 2 types i.e., microgametes and macro-gametes. Microgametocytes undergo the ex-flagellation process in the mid-gut of the mosquito. The drop in temperature, due to transfer from warm blooded human host to cold blooded insect, provides the stimulation for the process. The nucleus of microgametocytes divides to form 6-8 daughter nuclei, by meiotic division. These nuclei move to the periphery along with the cytoplasm, forming flagella like structure. Thus 6-8 flagella-like male gametes are formed from each microgametocyte. The elongated structure is called microgametes or sperms. These microgametes measures about 20-25 microns in length. The movement of flagella causes the gametes to separate and move actively in the stomach of the mosquito in search of female gametes.
b) Megagametes: On the other hand, the macro gametocytes undergo maturation process, thereby two polar bodies are pushed out and a female gamete or macrogamete is formed. The female gamete is non-motile and develops a cytoplasmic or receptive cone.
3. Fertilization: The nucleus of the female gamete comes to lie near its receptive cone. If microgametes happen to reach the macrogametes, then it enters the female gamete at the point of the cytoplasmic cone and finally completes the fusion of nucleus and cytoplasm of 2 gametes occurs, resulting in the formation of a diploid zygote or synkaryon. The fertilization takes place known as syngamy. Syngamy is anisogamous as the uniting male and female gametes are dissimilar. Zygotes form in the stomach of mosquitoes about 9 to 10 days after the blood meal.
4. Ookinete: For some period, about 24 hours zygote remains rounded and motionless but soon it becomes elongated to become worm-like having pointed ends and motile. The zygotes are now called ookinetes. It measures about 15-22 µ in length and 3 µ in width. It penetrates the wall of the stomach with the help of lytic secretion. It settles into the inner portion of the stomach wall. Ookinetes has shown the presence of a central irregular nucleus, dense cytoplasm, brown pigment granules, many mitochondria, and ribosomes. The ookinetes are motile due to the presence of ectoplasmic contractile fibrils.
5. Encystment:
Ookinetes penetrate the wall of the midgut to settle down just under the thin membranes that separate the midgut from the hemocoel. The ookinete then changes into a spherical shape, takes nutrition from the wall of the stomach, and gets enclosed in a thin, elastic, and permeable cyst wall, such stage is called the oocyst stage. The oocyst grows, and they are now be seen on the outside of the midgut or stomach as transparent rounded structure. The cyst wall is secreted partly by ookinete and partly derived from the stomach tissue of the mosquito. Many oocysts 50 or more are seen on the stomach wall of an infected mosquito.
6. Sporogony:
Each oocyst enters a phase of asexual multiplication know as sporogony. It is the process of the formation of sporozoites from the zygote nucleus by asexual multiple fission. Oocysts mature and develop. The nucleus of oocyst divides first by meiosis and then by mitosis, forming many haploid nuclei (2-3 days) and forms sporozoites forming cells known as sporoblasts. The nuclei of sporoblast again multiply and the cytoplasm gets constricted around them. Thus, the resultant structures in the sporoblasts elongate to form slender or sickle-shaped sporozoites. Each sporozoite has tapering ends and a broad middle part containing a single nucleus. Each oocyst may have 10 thousand sporozoites, and a group of sporozoites gets arranged around the vacuoles. The process of formation of sporozoites is known as sporogony which is completed in 10-20 days from the time the gametocytes are taken by the mosquito, the time depending on the temperature. Therefore, each oocyst fills with numerous sporozoites. Now, these give pressure to the oocyst, and due to which the oocyst burst or rupture, and thousands of sporozoites are released in the body cavity (hemocoel) of the mosquito. The sporozoites are very active and motile, then they reach the salivary glands of the mosquito and enter the duct of the hypopharynx. Then the sporozoites are ready to infect the healthy person when the mosquito bites each bite. And the life cycle is repeated.