2. INTRODUCTION
• Malaria is a mosquito-borne infectious disease caused by intracellular
protozoan parasite, Plasmodium.
• Characterized by febrile paroxysms, which occur with definite
intermittent periodicity.
• Affects 214 million and kills 0.5 million people each year.
• In India, 1.13 million cases and 287 malarial deaths (2015).
4. Lifecycle of Plasmodium
2 stages
1) Sexual phase in the mosquito
2) Asexual phase in humans
• Exoerthrocytic (Pre-erythrocytic)
schizogony
• Erythrocytic schizogony
• The infectious stage of malaria –
Sporozoite (found in the salivary
glands of female mosquitoes).
5. Asexual cycle (Human cycle)
• Human infection is initiated when sporozoites are injected with the
saliva during mosquito feeding.
• The sporozoites enter the blood stream, where many are destroyed
by phagocytes, but some reach the liver and enter the hepatocytes.
6. Exoerythrocytic stage
• After invading the hepatocyte, the parasite undergoes an asexual
replication. This replicative stage is called exoerythrocytic (or pre-
erythrocytic) schizogony.
• After 1-2 weeks of development, they become hepatic schizonts,
which eventually burst giving rise to thousands of merozoites.
• In P. vivax and P. ovale some of the sporozoites do not immediately
undergo asexual replication, but enter a dormant phase known as the
hypnozoite. This hypnozoite can reactivate and undergo schizogony at
a later time resulting in a relapse.
7. Erythrocytic stage
• Merozoites released from the infected liver cells invade erythrocytes.
The merozoites recognize specific proteins on the surface of the
erythrocyte and actively invade the cell.
• After entering the erythrocyte the parasite undergoes a trophic
period followed by an asexual replication.
• During the trophic period the parasite ingests the host cell cytoplasm
and breaks down the hemoglobin into amino acids.
• A by-product of the hemoglobin digestion is the malaria pigment, or
hemozoin, which are golden-brown to black.
8. • Appearance of malaria pigment varies in different species:
• P vivax: Numerous fine golden-brown dust-like particles.
• P falciparum: Few 1-3 solid blocks of black pigment.
• The young trophozoite is often called a ring form due to its
morphology in Giemsa-stained blood smears.
• As the parasite increases in size this 'ring' morphology disappears
and it is called a trophozoite.
9. • Nuclear division marks the end of the trophozoite stage and the
beginning of the schizont stage.
• Erythrocytic schizogongy consists of 3-5 rounds (depending on
species) of nuclear replication followed by a budding process.
• The host erythrocyte ruptures and releases the merozoites. These
merozoites invade new erythrocytes and initiate another round of
schizogony.
• The rupture of mature schizont releases large quantities of pyrogens.
This is responsible for the febrile paroxysms characterizing malaria.
10. Gametogeny
• As an alternative to schizogony some of the parasites develop into
sexually differentiated forms, micro- or macrogametocytes.
• Gametocytes do not cause pathology in the human host, but are
essential for transmission of the infection.
• Female anopheles mosquito ingests the gametocytes during its blood
meal.
11. Sexual cycle (Mosquito cycle)
• The highly mobile microgametes will seek out and fuse with a
macrogamete, to produce the zygote.
• Within 12-24 hours, the resulting zygote develops into an
ookinete.
• The ookinete is a motile invasive stage which transverses both
the peritrophic matrix and the midgut epithelium of the
mosquito.
12. Sporogony:
• On reaching the outer surface of stomach, the ookinete develops into
an oocyst.
• The oocysts undergo an asexual replication, called sporogony, which
culminates in the production of several thousand sporozoites within
them.
• This generally takes 10-28 days depending on species and
temperature.
• Upon maturation the oocyst ruptures and releases the sporozoites
which cross the basal lamina into the hemocoel (body cavity) of the
mosquito.
• Many of the sporozoites migrate to the salivary glands, and the
mosquito becomes infective to man.