Plasmodium vivax- Life Cycle in Man and in Mosquito

Plasmodium vivax is a protozoal parasite that infects humans and causes malaria, a life-threatening disease that is transmitted by some types of mosquitoes. It is the most common and widely distributed cause of recurring malaria, which means that it can cause repeated episodes of fever and illness in the infected person.

Plasmodium vivax is mainly found in Asia, Latin America, and some parts of Africa. It is believed to have originated in Asia, but recent studies have shown that it is closely related to parasites that infect wild chimpanzees and gorillas in central Africa.

Plasmodium vivax has a complex life cycle that involves two hosts: humans and female Anopheles mosquitoes. In humans, it undergoes asexual reproduction by multiple fission in the liver cells and red blood cells, causing damage to these organs and symptoms such as fever, chills, headache, and anemia. In mosquitoes, it undergoes sexual reproduction by fusion of male and female gametes, forming a zygote that develops into infective sporozoites that can be injected into a new human host when the mosquito bites.

Plasmodium vivax is less virulent than Plasmodium falciparum, the deadliest malaria parasite, but it can still cause severe disease and death, especially in children under 5 years, pregnant women, travelers, and people with HIV or AIDS. Plasmodium vivax can also form dormant stages in the liver called hypnozoites, which can reactivate months or years after the initial infection and cause relapses.

Plasmodium vivax can be prevented by avoiding mosquito bites and taking antimalarial drugs. It can be diagnosed by microscopic examination of blood smears or rapid diagnostic tests. It can be treated by a combination of drugs that target both the blood and liver stages of the parasite. However, there are challenges such as drug resistance, lack of effective vaccines, and limited access to health services that hinder the control and elimination of this parasite.

Schizogony is the process of asexual reproduction by which Plasmodium undergoes multiple fission in liver cells and red blood cells (RBCs) of humans. It occurs in two phases: liver schizogony and erythrocytic schizogony.

Liver schizogony

Liver schizogony is the first phase of asexual multiplication that takes place in the liver cells of humans. It begins when sporozoites, the infective stage of Plasmodium, are inoculated into the bloodstream by an infected female Anopheles mosquito during a blood meal. The sporozoites are spindle-shaped, motile, and uninucleated parasites that measure about 11 to 12 µm in length and 0.5 to 1 µm in width. They have an elastic pellicle with contractile microtubules, a single vesicular nucleus, a single mitochondrion, and secretory organelles at the anterior end that help them penetrate the liver cells.

The sporozoites disappear from the bloodstream within half an hour and enter the parenchymatous cells of the liver, where they grow in size and become large and spherical schizonts. The nucleus of each schizont divides asexually by multiple fission to form thousands of merozoites, which are small, oval-shaped, and uninucleated parasites. The schizonts rupture and release the merozoites into the sinusoids or venous passages of the liver. These merozoites are also called cryptozoites or cryptomerozoites because they are immune to medicines and host resistance. The formation of cryptozoites from sporozoites in the liver cells is called pre-erythrocytic schizogony. It is completed in 8 to 10 days and does not produce any symptoms in humans.

Some of the cryptozoites enter fresh liver cells and undergo another round of asexual multiplication, forming more merozoites. These merozoites are called metacryptozoites or phanerozoites because they are visible under a microscope. They are of two types: micro metacryptozoites and macro metacryptozoites. The micro metacryptozoites are smaller and more numerous, and they enter the RBCs to start the erythrocytic phase. The macro metacryptozoites are larger and less numerous, and they infect fresh liver cells to continue the exo-erythrocytic phase. The formation of metacryptozoites from cryptozoites in the liver cells is called exo-erythrocytic schizogony. It can last for several weeks or months and can cause relapses of malaria.

Erythrocytic schizogony

Erythrocytic schizogony is the second phase of asexual multiplication that takes place in the RBCs of humans. It starts when the micro metacryptozoites enter the RBCs, especially the young and immature ones. Inside the RBCs, they pass through different stages: trophozoite stage, signet ring stage, amoeboid stage, and schizont stage.

The trophozoite stage is when the metacryptozoite grows in size by ingesting hemoglobin from the RBC. It has a large nucleus and a dense cytoplasm.

The signet ring stage is when a large vacuole appears in the cytoplasm of the trophozoite, pushing the nucleus to the periphery and forming a ring-like structure. This stage is about one-third to one-half the size of an RBC.

The amoeboid stage is when the vacuole disappears and the trophozoite develops pseudopodia-like processes in its cytoplasm. It also secretes digestive enzymes that break down hemoglobin into protein and hematin. The protein is used as food by the parasite, while hematin is deposited as hemozoin, a brownish-black pigment that is toxic to humans.

The schizont stage is when the nucleus of the amoeboid trophozoite divides asexually by multiple fission to form 12 to 24 merozoites. The merozoites are arranged around hemozoin at the center, forming a rosette-like structure. This stage also produces yellowish granules in the cytoplasm of the RBC, called Schuffner`s dots, which are antigens excreted by the parasite.

The erythrocytic schizogony cycle takes about 48 hours to complete. At the end of this cycle, the RBC ruptures and releases merozoites into the plasma. These merozoites infect new RBCs and repeat the cycle. Some of the merozoites differentiate into sexual forms called gametocytes, which are of two types: male (microgametocytes) and female (macrogametocytes). The gametocytes do not divide but remain in the blood for several weeks, waiting to be ingested by a mosquito. The erythrocytic schizogony cycle is responsible for the clinical manifestations of malaria, such as fever, chills, anemia, and splenomegaly.

The infection of a human host by Plasmodium vivax begins when an infected female Anopheles mosquito bites the person and injects saliva containing sporozoites into the bloodstream. Sporozoites are the infective stage of the parasite that can invade the liver cells and initiate the asexual cycle or schizogony.

Sporozoites are spindle-shaped, slightly curved or sickle-shaped, and uninucleated organisms that measure about 11 to 12 µm in length and 0.5-1 µm in width. They are covered by an elastic, firm pellicle that has longitudinally arranged contractile microtubules that help in their wriggling movements. They also have an apical cap at their anterior end that contains secretory organelles that secrete enzymes to facilitate their penetration into the liver cell. They have a single vesicular nucleus, a single mitochondrion with tubular cristae, and a Golgi complex.

Sporozoites are capable of gliding movements and can disappear from the bloodstream within half an hour after inoculation. They reach the liver parenchyma through the hepatic sinusoids and enter the hepatocytes by forming a parasitophorous vacuole. Inside the liver cells, they undergo asexual multiplication by schizogony to produce thousands of merozoites that can infect the red blood cells and cause the clinical symptoms of malaria.

However, some sporozoites of P. vivax can remain dormant in the liver cells as hypnozoites, which can persist for weeks or even years and cause relapses of malaria by invading the bloodstream later. These hypnozoites are resistant to most antimalarial drugs and require specific treatment to prevent recurrent infections.

The duration between the initial sporozoite infection and the first appearance of parasites in the blood is called the pre-patent period, which is about 8 days in P. vivax. The period between infection and appearance of the first malarial symptoms is called the incubation period, which is about 10-17 days (average 14 days) in P. vivax.

Liver schizogony is the first phase of asexual multiplication of Plasmodium vivax in the human host. It occurs in the liver cells, where the sporozoites that were injected by the mosquito during a blood meal invade and grow into schizonts. Liver schizogony has two sub-phases: pre-erythrocytic and exo-erythrocytic.

Pre-erythrocytic phase: This phase begins when the sporozoites enter the liver cells, also called hepatocytes, and transform into trophozoites. The trophozoites then undergo multiple fission, producing thousands of merozoites. The liver cell ruptures and releases the merozoites into the bloodstream. Some of these merozoites will infect the red blood cells and start the erythrocytic schizogony, while others will remain dormant in the liver cells as hypnozoites. The pre-erythrocytic phase is completed in 8-10 days and is asymptomatic. The blood remains sterile during this phase and cannot transmit the infection to another mosquito.
Exo-erythrocytic phase: This phase occurs when some of the hypnozoites in the liver cells reactivate and resume their development into schizonts. The schizonts then produce merozoites, which are released into the bloodstream as metacryptozoites or phanerozoites. These merozoites can either infect new red blood cells or new liver cells, continuing the exo-erythrocytic phase. The exo-erythrocytic phase can last for several weeks or months, depending on the strain of P. vivax and the host immunity. It is responsible for the relapses of malaria that can occur after a primary infection. The exo-erythrocytic phase is resistant to most anti-malarial drugs, except for primaquine, which can eliminate the hypnozoites.

Liver schizogony is an important stage of P. vivax life cycle, as it allows the parasite to evade the host immune system and persist in the liver for long periods of time. It also contributes to the transmission of malaria by increasing the number of merozoites that can infect red blood cells and produce gametocytes. Understanding the molecular mechanisms and host factors involved in liver schizogony could help to develop new strategies to prevent and treat P. vivax malaria.

The pre-patent period is the time between the initial infection by the sporozoites and the first appearance of parasites in the blood. The incubation period is the time between the infection and the onset of clinical symptoms. Both periods depend on the species of Plasmodium, the number of sporozoites inoculated, and the immune status of the host.

For Plasmodium vivax, the pre-patent period is usually about 8 days, but it can vary from 6 to 30 days. The incubation period is typically 10 to 17 days, with an average of 14 days. However, some strains of P. vivax can cause relapses from dormant liver stages (hypnozoites) that can prolong the incubation period for months or even years.

The pre-patent and incubation periods are important for diagnosis, treatment, and prevention of malaria. A blood test can detect parasites in the blood during the pre-patent period, before symptoms appear. This can help to identify asymptomatic carriers and prevent further transmission. Treatment with antimalarial drugs can also be initiated early to reduce the severity and duration of symptoms. However, some drugs may not be effective against the liver stages of P. vivax, so a radical cure may require additional drugs that target the hypnozoites.

The incubation period determines the risk of malaria for travelers who visit endemic areas. Travelers should take prophylactic drugs before, during, and after their trip to prevent infection or relapse. They should also be aware of the possibility of delayed onset of malaria symptoms after leaving the endemic area, and seek medical attention if they develop fever or other signs of malaria within a year of their travel.

The third phase of asexual multiplication occurs in the red blood cells (RBCs) of the human host and is known as erythrocytic schizogony. This cycle begins when the micro metacryptozoites, which are the smaller and more numerous merozoites produced in the liver schizogony, enter the RBCs. Plasmodium vivax preferentially infects young and immature RBCs, also called reticulocytes.

Inside the RBCs, the micro metacryptozoites grow and transform into different stages of trophozoites, which are the feeding and growing forms of the parasite. The first stage is called the signet ring stage, because the parasite appears as a small ring-shaped structure with a large vacuole that pushes the nucleus to the periphery of the cytoplasm. The signet ring stage is about one-third to one-half the size of an RBC.

The signet ring trophozoites ingest the hemoglobin of the RBCs and form a food vacuole, where they digest the protein component and release hematin, a toxic by-product. Hematin is converted into hemozoin, a brownish pigment that accumulates in the cytoplasm of the parasite. The parasite also secretes some antigens into the cytoplasm of the RBCs, which form small granules called Schuffner`s dots. These dots are characteristic of Plasmodium vivax infection and can be seen under a microscope.

As the trophozoites grow in size, they lose their vacuole and become more amoeboid, extending pseudopodia into the cytoplasm of the RBCs. This stage is called the amoeboid stage, and it is more active and invasive than the signet ring stage. The amoeboid trophozoites then mature into erythrocytic schizonts, which are large spherical structures that undergo multiple fission to produce 12 to 24 merozoites. The merozoites are arranged around a central mass of hemozoin, forming a rosette-like pattern.

The erythrocytic schizonts rupture the RBCs and release the merozoites into the bloodstream, along with hemozoin and other toxic substances. This causes fever, chills, anemia, and other symptoms of malaria. The merozoites then invade new RBCs and repeat the erythrocytic schizogony cycle every 48 hours. Some of the merozoites differentiate into male and female gametocytes, which are the sexual forms of the parasite that can be taken up by a mosquito during a blood meal.

The erythrocytic schizogony cycle is responsible for most of the clinical manifestations of malaria, as well as for its transmission from human to human via mosquitoes. It is also the target of most anti-malarial drugs that aim to kill or inhibit the growth of the parasites in the blood.

Post-erythrocytic schizogony
Post-erythrocytic schizogony is a process that occurs in some cases of P. vivax infection, where some merozoites produced by erythrocytic schizogony do not invade new red blood cells, but instead return to the liver and infect new hepatocytes.
This process can lead to relapses of malaria symptoms, as the liver merozoites can re-enter the bloodstream and initiate another cycle of erythrocytic schizogony.
Post-erythrocytic schizogony is also known as pre-erythrocytic schizogony, as it resembles the first phase of liver schizogony that occurs after the initial infection by sporozoites.
The merozoites that undergo post-erythrocytic schizogony are called hypnozoites, as they can remain dormant in the liver cells for weeks, months or even years, depending on the strain of P. vivax .
The hypnozoites are resistant to most antimalarial drugs that target the blood stages of the parasite, and require a specific treatment with primaquine or tafenoquine to prevent relapses .
The mechanism and triggers of hypnozoite activation are not fully understood, but some factors that may influence it include environmental changes, host immunity, hormonal cycles and co-infections.
Post-erythrocytic schizogony is a major challenge for malaria elimination, as it contributes to the persistence and transmission of P. vivax in endemic areas.

Formation of gametocytes

After several cycles of erythrocytic schizogony, some of the merozoites that are released from the ruptured red blood cells do not undergo further asexual multiplication, but instead differentiate into sexual forms called gametocytes. Gametocytes are the precursors of male and female gametes, which are essential for the sexual reproduction of Plasmodium vivax in the mosquito vector. Gametocytes can be distinguished from schizonts by their elongated shape and their lack of internal division.

There are two types of gametocytes: macrogametocytes and microgametocytes. Macrogametocytes are the female gametocytes, which have a large, compact nucleus and a dark blue cytoplasm. Microgametocytes are the male gametocytes, which have a small, central nucleus and a pale cytoplasm. Both types of gametocytes contain hemozoin, the brown pigment that results from the digestion of hemoglobin by the parasite. Gametocytes also enlarge the infected red blood cells and cause them to display Schuffner`s dots, which are antigenic granules that stain with eosin.

Gametocytes appear in the peripheral blood at variable intervals after the onset of fever, depending on the strain of P. vivax and the immune status of the host. They can persist in the blood for several weeks, but they remain inactive until they are ingested by a female Anopheles mosquito during a blood meal. Only then they undergo further development and maturation into gametes. Therefore, gametocytes are the transmissible stage of P. vivax from humans to mosquitoes.

Life cycle in mosquito or Sexual Cycle in mosquito

The sexual cycle of Plasmodium vivax takes place in the female Anopheles mosquito, which acts as the definitive host and vector of the parasite. The sexual cycle involves the following stages:

Ingestion by mosquito: When a female Anopheles mosquito bites an infected person, it ingests the gametocytes (sexual forms) of P. vivax along with the blood. The gametocytes are the only stage of the parasite that can survive in the mosquito`s gut, while the other stages are digested.
Gametogenesis/Gametogony (Formation of gametes): In the mosquito`s gut, the gametocytes undergo gametogenesis or gametogony, which is the process of forming gametes (sex cells). The male gametocytes (microgametocytes) undergo exflagellation, which means they produce flagella-like structures called microgametes or sperms. Each microgametocyte can produce 6-8 microgametes by nuclear division and cytoplasmic elongation. The female gametocytes (macrogametocytes) undergo maturation, which means they expel two polar bodies and form a receptive cone on one side. The female gametes or macrogametes are larger and less motile than the male gametes.
Fertilization: The microgametes are attracted to the macrogametes by chemotaxis and penetrate them through the receptive cone. The fusion of the nuclei and cytoplasm of the male and female gametes results in the formation of a diploid zygote or synkaryon. This process is called syngamy and it is anisogamous, meaning that the gametes are unequal in size and shape.
Ookinete: The zygote remains spherical and inactive for about 24 hours, then it elongates and becomes motile. The elongated zygote is called an ookinete or vermicule. It has a spindle-shaped body with pointed ends and measures about 15-22 µm in length and 3 µm in width. It has a single nucleus, dense cytoplasm, brown pigment granules, mitochondria, and ribosomes. It also has a pellicle with contractile fibrils that help it move.
Encystment: The ookinete penetrates the wall of the mosquito`s midgut with the help of lytic enzymes and settles under the basal lamina that separates the midgut from the hemocoel (body cavity). There it becomes spherical again and forms a cyst wall around itself. This stage is called an oocyst or sporont. The cyst wall is partly secreted by the ookinete and partly derived from the midgut tissue. The oocyst grows in size and can be seen as a white spot on the midgut wall. Many oocysts (<500) can be formed by a single mosquito. The ookinetes that fail to penetrate the midgut wall are excreted with the fecal matter.
Sporogony: Each oocyst undergoes a phase of asexual multiplication called sporogony, which is the process of forming sporozoites (infective forms) from the zygote nucleus by multiple fission. The nucleus of the oocyst divides first by meiosis and then by mitosis, forming thousands of haploid nuclei. These nuclei are surrounded by cytoplasmic buds that elongate into slender sporozoites. Each oocyst can produce up to 10 thousand sporozoites, which are arranged around vacuoles inside the oocyst. The sporozoites are sickle-shaped and measure about 11-12 µm in length and 0.5-1 µm in width. They have an apical cap with secretory organelles that help them invade host cells. They also have a single nucleus, a single mitochondrion, and a pellicle with contractile fibrils that help them move. The process of sporogony takes about 10-20 days from the time the gametocytes are ingested by the mosquito, depending on the temperature. When the oocyst matures, it ruptures and releases thousands of sporozoites into the hemocoel of the mosquito.
Migration to salivary glands: The sporozoites are very active and motile, and they migrate to the salivary glands of the mosquito through the hemolymph (blood). They enter the ducts of the salivary glands and accumulate in the acini (secretory units). There they remain until the mosquito bites another person, and they are injected along with the saliva into the bloodstream. The sporozoites are the stage that initiates the infection in humans and completes the life cycle of P. vivax.

Ingestion by mosquito and Gametogenesis/Gametogony (Formation of gametes)

When a female Anopheles mosquito bites an infected person, it ingests the blood containing the gametocytes of Plasmodium vivax along with other stages of the parasite. The gametocytes are the sexual forms of the parasite that can undergo further development in the mosquito. The other stages are digested by the mosquito`s enzymes and do not survive.

The gametocytes are of two types: male (microgametocytes) and female (macrogametocytes). They are inactive and non-dividing in the human blood, but they become activated and differentiate into gametes in the mosquito`s stomach. This process is called gametogenesis or gametogony.

The microgametocytes undergo a process called exflagellation, in which they produce six to eight flagellated microgametes or sperms by multiple fission of their nuclei. The first division is meiotic, followed by mitotic divisions. The microgametes are motile and seek out the female gametes for fertilization.

The macrogametocytes undergo a process called maturation, in which they expel two polar bodies and become macrogametes or eggs. The macrogametes are non-motile and develop a cytoplasmic projection called the fertilization cone or the cone of reception on one side, where they receive the microgametes.

The formation of gametes from gametocytes takes about 15 to 30 minutes after ingestion by the mosquito. The gametes are haploid and have half the number of chromosomes as the gametocytes. The gametes are ready to fuse and form a diploid zygote, which is the next stage of the life cycle.

Fertilization and Ookinete

After the ingestion of gametocytes by the female Anopheles mosquito, the microgametocytes undergo exflagellation and produce eight flagellated microgametes each. The microgametes then fertilize the macrogametes, forming diploid zygotes. The zygotes are initially spherical and non-motile, but soon elongate and become motile ookinetes. The ookinetes are spindle-shaped, uninucleated cells that measure about 15-22 µm in length and 3 µm in width. They have a central nucleus, dense cytoplasm, brown pigment granules, many mitochondria, and ribosomes. They also have a pellicle with contractile fibrils that enable them to glide through the blood meal and penetrate the midgut wall of the mosquito.

The ookinetes are the invasive stage of the parasite that can cross the peritrophic matrix and the epithelial cells of the midgut. They secrete lytic enzymes that help them to breach these barriers. The ookinetes reach the basal lamina of the midgut, where they stop moving and encyst. The process of encystment involves the formation of a cyst wall around the ookinete, which protects it from the host immune system and environmental factors. The cyst wall is partly secreted by the ookinete and partly derived from the midgut tissue of the mosquito. The encysted ookinetes are called oocysts, and they are the site of sporogony, the next phase of the parasite`s life cycle.

The ookinete stage is a critical target for transmission-blocking interventions, as it is exposed to both host and vector immune responses, as well as to drugs and antibodies in the blood meal. The ookinetes express surface proteins that are involved in their attachment, invasion, and survival in the midgut. One of these proteins is Pvs25, a candidate for a transmission-blocking vaccine against P. vivax. Pvs25 is a 25-kDa protein with four epidermal growth factor-like domains and 11 disulfide bonds. It is highly conserved among P. vivax isolates from different regions of the world. Pvs25 is recognized by transmission-blocking antibodies that can inhibit ookinete development and prevent oocyst formation.

Encystment and Sporogony

After penetrating the midgut wall, the ookinetes develop into spherical structures called oocysts .
The oocysts are enclosed by a thin, elastic and permeable cyst wall, which is partly secreted by the ookinete and partly derived from the mosquito tissue.
The oocysts grow in size and sometimes are called sporonts.
Inside the oocysts, a phase of asexual multiplication occurs, known as sporogony .
Sporogony is the process of formation of sporozoites from the zygote nucleus by multiple fission.
The nucleus of the oocyst divides first by meiosis and then by mitosis, forming a large number of haploid nuclei.
These nuclei are surrounded by cytoplasm and form sporoblasts, which elongate to form slender or sickle-shaped sporozoites.
Each oocyst may contain up to 10 thousand sporozoites, which are arranged around vacuoles within the oocyst.
The process of sporogony takes about 10 to 20 days from the time the gametocytes are ingested by the mosquito, depending on the temperature.
When the oocysts mature, they rupture and release thousands of sporozoites into the body cavity (hemocoel) of the mosquito .
The sporozoites are very active and motile, and they migrate to the salivary glands of the mosquito, where they enter the ducts of the hypopharynx .
The sporozoites are now ready to infect a new human host when the mosquito bites them, thus completing the life cycle of Plasmodium vivax .

The sexual cycle of Plasmodium vivax takes place in the female Anopheles mosquito, which acts as the definitive host and vector of the parasite. The sexual cycle involves the following stages:

Ingestion by mosquito: When a female Anopheles mosquito bites an infected person, it ingests the gametocytes (sexual forms) of P. vivax along with the blood. The gametocytes are the only stage of the parasite that can survive in the mosquito`s gut, while the other stages are digested.
Gametogenesis/Gametogony (Formation of gametes): In the mosquito`s gut, the gametocytes undergo gametogenesis or gametogony, which is the process of forming gametes (sex cells). The male gametocytes (microgametocytes) undergo exflagellation, which means they produce flagella-like structures called microgametes or sperms. Each microgametocyte can produce 6-8 microgametes by nuclear division and cytoplasmic elongation. The female gametocytes (macrogametocytes) undergo maturation, which means they expel two polar bodies and form a receptive cone on one side. The female gametes or macrogametes are larger and less motile than the male gametes.
Fertilization: The microgametes are attracted to the macrogametes by chemotaxis and penetrate them through the receptive cone. The fusion of the nuclei and cytoplasm of the male and female gametes results in the formation of a diploid zygote or synkaryon. This process is called syngamy and it is anisogamous, meaning that the gametes are unequal in size and shape.
Ookinete: The zygote remains spherical and inactive for about 24 hours, then it elongates and becomes motile. The elongated zygote is called an ookinete or vermicule. It has a spindle-shaped body with pointed ends and measures about 15-22 µm in length and 3 µm in width. It has a single nucleus, dense cytoplasm, brown pigment granules, mitochondria, and ribosomes. It also has a pellicle with contractile fibrils that help it move.
Encystment: The ookinete penetrates the wall of the mosquito`s midgut with the help of lytic enzymes and settles under the basal lamina that separates the midgut from the hemocoel (body cavity). There it becomes spherical again and forms a cyst wall around itself. This stage is called an oocyst or sporont. The cyst wall is partly secreted by the ookinete and partly derived from the midgut tissue. The oocyst grows in size and can be seen as a white spot on the midgut wall. Many oocysts (<500) can be formed by a single mosquito. The ookinetes that fail to penetrate the midgut wall are excreted with the fecal matter.
Sporogony: Each oocyst undergoes a phase of asexual multiplication called sporogony, which is the process of forming sporozoites (infective forms) from the zygote nucleus by multiple fission. The nucleus of the oocyst divides first by meiosis and then by mitosis, forming thousands of haploid nuclei. These nuclei are surrounded by cytoplasmic buds that elongate into slender sporozoites. Each oocyst can produce up to 10 thousand sporozoites, which are arranged around vacuoles inside the oocyst. The sporozoites are sickle-shaped and measure about 11-12 µm in length and 0.5-1 µm in width. They have an apical cap with secretory organelles that help them invade host cells. They also have a single nucleus, a single mitochondrion, and a pellicle with contractile fibrils that help them move. The process of sporogony takes about 10-20 days from the time the gametocytes are ingested by the mosquito, depending on the temperature. When the oocyst matures, it ruptures and releases thousands of sporozoites into the hemocoel of the mosquito.
Migration to salivary glands: The sporozoites are very active and motile, and they migrate to the salivary glands of the mosquito through the hemolymph (blood). They enter the ducts of the salivary glands and accumulate in the acini (secretory units). There they remain until the mosquito bites another person, and they are injected along with the saliva into the bloodstream. The sporozoites are the stage that initiates the infection in humans and completes the life cycle of P. vivax.