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 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.
Plasmodium
 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
 Malaria Distribution all over the world

Areas where malaria has disappeared or never existed Ø

Areas with limited risk +
Areas where malaria transmission occurs ++
 Life Cycle of Plasmodium
I- Development in Man
Infective
I- Liver 40 min sporozoites female
phase Anopheles

Liver merozoites
P.vivax
P.ovale
hypnozoite Trophozoite Schizont Rupture
II- Blood ♂
phase Blood merozoites
P.v. 3rd d
P.o. 3rd d ♀
P.m. 4th d haemozoin
Ring Trophozoite Schizont Rupture
P.f. irreg. gametocyte
 II- Development in Anopheles Mosquito gut

Sporozoites ♂ and ♀ gametocytes

in salivary Reduction division
gland ♂ and ♀ gametes
Sporogony
Sporocyst

Oocyst
exflagellation

Ookinete
fusion

Zygote
 Plasmodium life cycle
♀Anopheles (Definitive Host) Man (Intermediate Host) – Asexual cycle (Schizogony)
Sexual Cycle (Sporogony)

Mode of infection:
1- Bite of ♀Anopheles (common)
2- Blood transfusion – common syringes.
3- Congenital transmission.
Plasmodium life cycle
 Some Stages of Malaria in Anopheles

Feeding female Anopheles Exflagellation showing microgametes

Sporozoites from salivary gland Oocysts on outside of mosquito stomach

 Plasmodium life cycle

2 1

28a_malaria_life_cycle_of_plasodium.swf plasmodium.swf
 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

 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

vivax falciparum

P malariae
 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
 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
 Plasmodium (Gametocytes)

falciparum vivax

malariae
ovale

Following repeated cycles Merozoites invade RBCs -

develop into: *Microgametocytes (male gametocytes)
.& * Macrogametocytes ( female gametocyte)
. Gametocytes are infective to the female Anopheles
 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.
Merozoites - parasitized R.B.C.s -lysed R.B.C.s - toxins - pigments are cleared -3
from the circulation by stimulation of the R.E.S. SPLENOMEGALY
besides HEPATOMEGALY.

Destruction of immature Reticulocyte together with suppressed erythropoiesis-4

decreased production of R.B.C.s ANAEMIA.
5- Enlarged spleen early destruction of RBCs (activation of the
complement system) ANAEMIA
Large number of circulating immune complexes 'C.LC.s' (takes place with -6
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.
 Pathogenesis and Clinical Picture
8- Haemolysis of R.B.C.s JAUNDICE
Parasitised erythrocytes of P falciparum Cytoadhere to the endothelial surface -9
of capillaries occludes the microcirculatory blood flow
- PERNICIOUS syndrome as a result of Tissue Anoxia - Focal Necrosis
Hemorrhage - Oedema of vital organs 'multiorgan involvement‘.

.Paroxysms are repeated for few weeks or longer with decreasing intensity -1
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.
 Pathogenesis and Clinical Picture
All species of Plasmodium will give rise to the following Clinical Picture:
1- FEVER 2- SPLENOMEGALY 3- HEPATOMEGALY
4- ANAEMIA 5- JAUNDICE.
JAUNDICE

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
 Pathogenesis and Clinical Picture
ANAEMIA -2

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).

SPLENOMEGALY -3

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).

JAUNDICE -4

*Mild "P. vivax – P ovale – P malariae" (haemolysis of RBC).

Severe "P .falciparum'' (liver involved by cytoadherence)*