Plasmodium

1
Plasmodium
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 20-30 ºC)
rainfall provides breeding places.
7- Inhabitants in hyperendemic areas are
repeatedly inoculated by Sporozoites
through mosquitos 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.
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Plasmodium
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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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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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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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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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Plasmodium life cycle
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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Plasmodium life cycle
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Plasmodium life cycle
1
2
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Some Stages of Malaria in Anopheles
Feeding female Anopheles
Exflagellation showing microgametes
Oocysts on outside of mosquito stomach
Sporozoites from salivary gland
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Exoerythrocytic Cycle

• Schizonts take 5-7 days to develop
• formation of gt10,000 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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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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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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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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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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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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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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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.5 - 1 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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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)