The lifecycle of Plasmodium, the parasite that causes malaria, involves both the mosquito and
human hosts 1 2.
1. Stages in the Mosquito:
• Mosquito Transmission Cycle: An uninfected Anopheles mosquito becomes infected by feeding
on a person who has malaria 1 2.
• Sporogony: Within the mosquito, sexual reproduction occurs, leading to the formation of
sporozoites. This process includes:
• Gametocyte Ingestion: The mosquito ingests male and female gametocytes during a blood mea
from an infected human 2.
• Zygote Formation: In the mosquito's gut, male microgametes fertilize female macrogametes to
form a zygote 2.
• Ookinete Development: The zygote transforms into a motile ookinete that penetrates the
mosquito's midgut wall 2.
• Oocyst Formation: The ookinete develops into an oocyst on the outer surface of the midgut wal
3.
• Sporozoite Development: Inside the oocyst, sporozoites develop through asexual reproduction
• Migration to Salivary Glands: The oocyst eventually ruptures, releasing sporozoites that migrate
to the mosquito's salivary glands, making the mosquito infectious 2.
2. Stages in the Human Host:
• Infection: When an infected mosquito bites a human, sporozoites are injected into the blood-
stream 1 2.
• Exoerythrocytic Stage (Liver Stage):
• Migration to Liver: Sporozoites travel to the liver and invade liver cells (hepatocytes) 4.
• Schizont Formation: Inside the liver cells, sporozoites undergo asexual reproduction, forming
schizonts 4.
• Merozoite Release: Each schizont ruptures, releasing thousands of merozoites into the blood
stream. This stage is asymptomatic 4.
• Erythrocytic Stage (Blood Stage):
• Invasion of Red Blood Cells: Merozoites invade red blood cells (erythrocytes), initiating the
erythrocytic stage 4.
• Trophozoite Formation: Inside the red blood cells, merozoites transform into trophozoites, which
feed on hemoglobin 4.
• Schizont Formation: Trophozoites undergo asexual reproduction, forming schizonts within the
red blood cells 4.
• Merozoite Release: The schizonts rupture, releasing more merozoites that infect new red blood
cells. This cycle repeats, causing the symptoms of malaria, such as fever, chills, and anemia 4
• Gametocyte Formation: Some merozoites differentiate into male and female gametocytes
within the red blood cells. These gametocytes do not cause symptoms in humans but are
essential for the parasite's sexual reproduction in the mosquito 5.
• Symptoms of Malaria: Symptoms typically develop within 10 days to 4 weeks after infection.
Common symptoms include shaking chills, high fever, profuse sweating, headache, nausea,
vomiting, abdominal pain, diarrhea, anemia, and muscle pain 6 7. Severe malaria can lead to
complications such as cerebral malaria, pulmonary edema, organ failure, and low blood sugar
7.
3. Sexual Reproduction:
• Gametocyte Ingestion: When a mosquito bites an infected human, it ingests the male and
female gametocytes present in the red blood cells 8.
• Exflagellation: In the mosquito's gut, the male gametocytes undergo exflagellation, a process
where they produce multiple motile microgametes 5.
• Fertilization: A microgamete fertilizes a female macrogamete, forming a zygote 2.
• Ookinete Formation: The zygote transforms into an ookinete, which penetrates the mosquito's
midgut wall to form an oocyst, completing the sexual reproduction phase 2.
4. Medicinal Impact:
• Liver Stage:
• Primaquine: This drug targets the hypnozoites of P. vivax and P. ovale in the liver, preventing
relapse. It also acts on the primary tissue forms of plasmodia 9 10 11. Primaquine may act by
generating reactive oxygen species or interfering with electron transport in the parasite 12.
• Erythrocytic Stage:
• Chloroquine: Effective against erythrocytic forms of P. vivax, P. ovale, and P. malariae, as well
as sensitive strains of P. falciparum 9 13 14. Chloroquine inhibits heme polymerase, leading to
the accumulation of toxic heme within the parasite 15.
• Quinine: Inhibits nucleic acid and protein synthesis and binds with hemazoin in parasitized
erythrocytes 9 13 16.
• Mefloquine: Effective against chloroquine-resistant strains. It may inhibit merozoite invasion and
interfere with parasite membrane lipid trafficking 9 13 17.
• Artesunate and Artemether: Rapidly acting blood schizonticides that produce free radicals,
killing the malarial parasite 9 13 18.
• Gametocytes:
• Primaquine: Has gametocytocidal activity against all Plasmodium species, including P. falci-
parum 9 3.
• Chloroquine and Quinine: Effective against gametocytes of P. vivax and P. malariae, but not P.
falciparum 9 13.
• Drug Resistance: Resistance to antimalarial drugs is a significant challenge. For example, P.
falciparum has developed resistance to chloroquine and pyrimethamine. Artemisinin-based
combination therapies (ACTs) are now widely used, but resistance to artemisinin is emerging
in some areas, necessitating the development of new drugs and treatment strategies 19 20.
5. Diagram or Visual Representation:
A lifecycle diagram of Plasmodium would effectively communicate this information. The diagram
should include:
•
Mosquito Stage: Illustrate the mosquito taking a blood meal, sporogony, oocyst formation, and
sporozoite migration to the salivary glands.
• Human Stage: Show the sporozoites entering the bloodstream, liver stage with schizont
formation and merozoite release, erythrocytic stage with merozoite invasion, trophozoite and
schizont formation, gametocyte formation, and the release of merozoites.
• Sexual Reproduction: Depict the mosquito ingesting gametocytes, exflagellation, zygote forma-
tion, ookinete development, and oocyst formation.
• Medicinal Impact: Indicate at which stages different antimalarial drugs are effective.
Such a diagram, supplemented with brief descriptions, would provide a comprehensive
overview of the Plasmodium lifecycle and the impact of antimalarial drugs.
