1. Plasmodium 1- Most important parasitic disease affecting human.
Introduction
1- Most important parasitic disease affecting human.
2- Most common in Tropic –Subtropics mostly Africa, Asia & S. America
3- It is estimated that more than 300 million people suffer annually.
4- Number of Deaths more than 2 million per year mostly among children
5- Transmission of the disease is mainly by bite of female Anopheles.
6- Transmission in an area depends upon: infected cases “Gametocytes
carriers” – Anopheles mosquito Vector (which require an optimum
condition of humidity & temperature ºC) –rainfall provides
breeding places.
7- Inhabitants in hyperendemic areas are repeatedly inoculated by
Sporozoites through mosquito’s bite
8- Children are more susceptible in areas of high transmission than Adults
9- “Premunition” a form of immunity sufficient to control but not to
prevent infection develops which control infection in elders.
10- P. falciparum malaria infection is severe in immune & non-immune
pregnant females.
DR. RAAFAT T. MOHAMED

2. Plasmodium
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3. Plasmodium Causes Human Malaria Mal: bad aria: air P.vivax:
vivax or benign tertian malaria
Most predominant
P.ovale:
ovale or ovale tertian malaria
Tropics
P.malariae:
malariae or quartan malaria
Temperate zones
P.falciparum:
falciparum or subtertian or malignant malaria
Tropics
Geographical Distribution
Presence of Malaria = Presence of Anopheline mosquito
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4. Malaria Distribution all over the world
Areas where malaria has disappeared or never existed Ø
Areas with limited risk +
Areas where malaria transmission occurs ++
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5. Life Cycle of Plasmodium
I- Development in Man
Infective female Anopheles
I- Liver phase
sporozoites
40 min
Liver merozoites
P.vivax P.ovale
hypnozoite
Trophozoite
Schizont
Rupture
II- Blood phase ♂
Blood merozoites
P.v. 3rd d
P.o. 3rd d ♀
haemozoin
P.m. 4th d
Ring
Trophozoite
Schizont
Rupture
P.f. irreg.
gametocyte
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6. II- Development in Anopheles Mosquito gut
Sporozoites in salivary gland
♂ and ♀ gametocytes
Reduction division
♂ and ♀ gametes
Sporogony
Sporocyst
Oocyst
exflagellation
Ookinete
fusion
Zygote
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7. Plasmodium life cycle Mode of infection:
Man (Intermediate Host) – Asexual cycle (Schizogony)
♀Anopheles (Definitive Host)
Sexual Cycle (Sporogony)
Mode of infection:
1- Bite of ♀Anopheles (common)
2- Blood transfusion – common syringes.
3- Congenital transmission.
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8. Plasmodium life cycle
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9. Plasmodium life cycle 2 1
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10. Some Stages of Malaria in Anopheles
Feeding female Anopheles
Exflagellation showing microgametes
Sporozoites from salivary gland
Oocysts on outside of mosquito stomach
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11. Exoerythrocytic Cycle
Schizonts take 5-7 days to develop
formation of >10,000 merozoites
upon rupture of hepatocyte, released
merozoites will invade R.B.Cs.
The final step involves the release of merozoites (green) into the bloodstream. The signal(s) that trigger the release remain unknown. Plasmodium merozoites are released by the formation of merozoite-filled vesicles (merosomes), which bud off from the infected hepatocytes into the sinusoidal lumen.
Nature Reviews Microbiology (2006): 4-849
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12. Plasmodium (Ring form)
Accolè form
P. falciparum
Early Trophozoite (Ring stage):
Thin loop of cytoplasm & a small chromatin dot enclosing a pale central vacuole (signet form).
In P falciparum it appears like a pair of stereo-head phones. Also more than one ring in the
Same RBCs (multiple infection). Accolè form (marginal ring).
ovale
falciparum
vivax
P malariae
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13. Plasmodium (Late Trophozoite)
falciparum
vivax
ovale
malariae
Mature Trophozoite (late trophozoite):
The parasite develops by increasing the amount of cytoplasm. Digested haemoglobin gives rise to malaria pigments (haemozoin). Parasitised cells become osmotically fragile.
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14. Plasmodium (E. Schizont)
ovale
falciparum
vivax
malariae
Erythroytic Schizont:
The chromatin & cytoplasm break into fragments merozoites .
The pigments remains as a single mass in the center.
 The Schizont (mature stage of the parasite) eventually occupies the entire R.B.C
Rupture of E. Schizonts merozoites - malaria pigments - toxins into the blood stream: *Merozoites attack new R.B.Cs repeating the cycle. *Pigments (haemozoin) are engulfed by R.E.Cs. *Toxins (immunogenic) induce malarial paroxysm.
Merozoites attack clean RBCs repeating the cycle
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15. Plasmodium (Gametocytes)
vivax
falciparum
malariae
ovale
Following repeated cycles Merozoites invade RBCs - develop into: *Microgametocytes (male gametocytes) & * Macrogametocytes ( female gametocyte).
Gametocytes are infective to the female Anopheles .
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16. Pathogenesis and Clinical Picture
1- Destruction of osmotically fragile infected R.B.C.s intra & extra-vascular
haemolysis HAEMOLYTIC ANAEMIA.
2-Toxins activate the macrophage / monocyte series of cells which will stimulate
sensitized T -lymphocytes to produce Cytokines FEVER.
3- Merozoites - parasitized R.B.C.s -lysed R.B.C.s - toxins - pigments are cleared
from the circulation by stimulation of the R.E.S SPLENOMEGALY
besides HEPATOMEGALY.
4-Destruction of immature Reticulocyte together with suppressed erythropoiesis
decreased production of R.B.C.s ANAEMIA.
5- Enlarged spleen early destruction of RBCs (activation of the
complement system) ANAEMIA
6- Large number of circulating immune complexes 'C.LC.s' (takes place with
P.malariae & P falciparum infections) deposit in the glomerular capillaries
acute glomerulopathy NEPHROTIC syndrome.
7- Parasite feeds on haemoglobin depletion of iron stores
inappropriate haemoglobin metabolism ANAEMIA.
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17. Pathogenesis and Clinical Picture
8- Haemolysis of R.B.C.s JAUNDICE
9- Parasitised erythrocytes of P falciparum Cytoadhere to the endothelial surface of capillaries occludes the microcirculatory blood flow
PERNICIOUS syndrome as a result of Tissue Anoxia - Focal Necrosis -
Hemorrhage - Oedema of vital organs 'multiorgan involvement‘.
1- Paroxysms are repeated for few weeks or longer with decreasing intensity.  
The disease is self-limited (due to cytokine activity & Premunition). In between attacks the patient may be exhausted but generally feels well.
2- Relapse of the infection may occur in both P. vivax & P.ovale after resolution of the primary infection (mainly due to Hypnozoites).
3- Recrudescence of the infection may occur in both P.malariae & P falciparum (due to persistent low grade undetectable parasitaemia) flare up of the infection with recurrence of the clinical attack.
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18. Pathogenesis and Clinical Picture
All species of Plasmodium will give rise to the following Clinical Picture:
1- FEVER
2- SPLENOMEGALY
3- HEPATOMEGALY
5- JAUNDICE.
4- ANAEMIA
1- FEVER (PAROXYSM)
three successive stages: Cold - Hot - Sweat
Cold stage : Shivering "chills"(O hr.) followed by sharp rise in the temperature.
Hot stage : High fever- headache - flushed face - rapid pulse (1 - 4 hrs.).
Sweat stage : Sweat with drop of temperature (1- 4 hrs.).
paroxysms associated with synchrony of merozoites release
between paroxysms temperature is normal and patient feels well
falciparum may not exhibit classic paroxysms (continuous fever)
Subtertian malaria
tertian malaria
quartan malaria
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19. Pathogenesis and Clinical Picture
2- ANAEMIA
Haemolytic anaemia - multifactorial due to rupture of R.B.C.s- deficient Hb.metabolism - suppressed erythropoiesis - early R.B.C.s destruction.
*Severe in P falciparum (high parasitaemia "young & old RBCs" are infected).
*Moderate in P vivax & P.ovale (moderate parasitaemia "young RBCs" are infected).
*Mild in Pimalariae (mild parasitaemia "old RBCs" are infected).
3- SPLENOMEGALY
The Spleen: is enlarged - soft - tender
*Mild to moderate "P vivax & P ovale".
*Marked enlargement "P malariae"(prolonged duration of infection "chronic" with repeated
attacks that end up by hypersplenism).
*Marked enlargement "P falciparum" (cytoadherence phenomenon).
4- JAUNDICE
*Mild "P. vivax – P ovale – P malariae" (haemolysis of RBC).
*Severe "P .falciparum'' (liver involved by cytoadherence)
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