Plasmodium vivax - Life Cycle, Host Immunity

Life Cycle of Plasmodium vivax

Plasmodium vivax is transmitted by the bite of a female Anopheles mosquito during a blood meal. The hypnozoites of this parasite are present in the liver parenchyma of the human host.

Human Cycle

• A bite by an infected female Anopheles mosquito during the blood meal injects the Plasmodium vivax sporozoites into the capillaries of the skin

• these parasitic sporozoites enter the blood circulation and within less than 30 minutes, they enter the host tissue cells

Exo-erythrocytic schizogony

• after a period of seven days, the sporozoites infecting the liver cells transform into exo-erythrocytic schizonts.

• the exo-erythrocytic schizonts are oval, 40μm length morphological forms that have blue-stained cytoplasm and lightly stained nucleus

• each schizont may contain around 1000

• the schizonts rupture to release the vast number of merozoites

• some merozoites are killed by the host immune system while most invade the host erythrocytes to begin erythrocytic schizogony

• some Plasmodium vivax remains in the liver cells as hypnozoites, which are responsible for relapse of the malaria disease

• hypnozoites, which are a dormant form of the parasite, are 4μm to 6μm in diameter with a single nucleus

• after the hypnozoites activate after a certain amount of time (may range from 6 months to 12 months), they transform into tissue schizonts within the time period of 12 to 17 days after re-infection

• as a result, relapse occurs which may take place upto 3 years or more after the initial malaria infection

Erythrocytic schizogony

• all stages of erythrocytic schizogony take place in the peripheral blood

• the merozoites of Plasmodium vivax, released from schizonts, invade only young erythrocytes and reticulocytes but rarely infect old erythrocytes

• around 2% of erythrocytes are infected by the Plasmodium vivax parasite

• Once inside the erythrocytes, the merozoites develop into trophozoites and eventually into erythrocytic schizonts – all within 42 to 44 hours of the invasion

• each mature erythrocytic schizont contains up to 24 or more merozoites

• once the Plasmodium vivax erythrocytic schizonts rupture, the merozoites are released

• these merozoites infect new erythrocytes to form erythrocytic schizonts and then into new merozoites for a few cycles

• After a few cycles of merozoites to erythrocytic schizonts to merozoites, some of the merozoites develop into gametocytes- the macrogametocytes and the microgametocytes

• these gametocytes take about four days to mature and more macrogametocytes are formed in number when compared to microgametocytes

Mosquito cycle

The sporogony or sexual life cycle of Plasmodium vivax takes place in the female Anopheles mosquitoes and is completed in 9 days to 10 days.

• both the macrogametocytes and microgametocytes are ingested by the female Anopheles mosquito during a blood meal from infected humans

• after reaching the mid-gut (stomach) of the mosquito, the male gametocyte (microgametocyte) undergoes exflagellation, which is the transformation by rapid division

  exflagellation involves microgametocytes becoming extra cellular followed by repeated division of nuclei within 10-12 minutes to form 6-8 daughter nuclei

  eventually, each nuclei becomes surrounded by a developing axoneme

  finally, the microgametocyte rupture to release 6-8 daughter nuclei- with each nuclei containing an axoneme bud which later becomes microgametes

• these Plasmodium vivax microgametes are highly motile sperm-like organisms with a single flagella

• the female gametocyte (macrogametocyte) matures by a single process of nuclear reduction and extension of polar bodies

• each macrogametocyte can only give rise to only one macrogamete

• the male gametocyte nucleus fuses with the female gametocyte nucleus through the process of fertilization and a zygote is produced

• the zygote is formed within 20 to 120 minutes from the blood meal by the vector mosquito

• the zygote then lengthens and extends to form a motile ookinete which is more slender in Plasmodium vivax than in other Plasmodium spp

• these ookinetes penetrate the gut wall of the mosquito host, secrets a thin wall, and grow into a sphere (6μm to 12 μm in diameter) which is termed an oocyst

• the oocyst contains a number of sporoblasts (haploid nucleated masses)

• these sporoblasts then divide repeatedly to form sporozoites which are in turn released into the hemocele of the mosquito after rupturing of oocyst – the process called sporogony

• the Plasmodium vivax sporozoites, which are infectious to humans, migrate to the salivary glands

• sporozoites are injected into the human host when the mosquito takes a blood meal from a healthy human and the life cycle of Plasmodium vivax is continued

Host Immunity of Plasmodium vivax

Haemoglobin E provides natural protection against Plasmodium vivax

Pathogenesis and infection of Plasmodium vivax depend on the ability of merozoites to attach to specific receptors present on the surface of erythrocytes. These receptor sites are called Duffy sites and people who genetically possess them are called Duffy blood group and Duffy-positive persons. The Duffy blood group expresses two alleles called Fya and Fyb which are glycoprotein receptors.

The Duffy negative people are most common in Africa. Since they lack the Fya and Fyb receptors in their erythrocytes, the merozoites cannot invade the RBCs and cause malaria.