Download Microbiology

Malaria
What is malaria?
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Name means “bad air”-
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Malaria is a serious and sometimes fatal disease
caused by a parasite. Patients with malaria typically
are very sick with high fevers, shaking chills, and flulike illness.
History
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One of the oldest known diseases- 50,000
years.
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First advances in malaria were made in 1880
by a French army doctor named Charles
Laveran.
He looked into infected red blood cells and
discovered the parasite was a protist. This
was the first time a protist was discovered to
cause a disease.
Alphonse Laveran
History
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Ronald Ross discovered that mosquitoes
transmitted malaria in 1898.
First effective medicine was discovered
by Pierre Pelletier and Joseph Caventou.
This medicine is called quinine, which
comes from the bark of cinchona trees in
Peru.
No effective vaccine: only immunity is a
result of multiple infections.
Sir Ronald Ross
AGENT
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Malaria is caused by species of Plasmodium.
The genus Plasmodium contains 172 species
 only four species are known to infect humans.
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Plasmodium falciparum
Plasmodium malariae
Plasmodium ovale
Plasmodium vivax
Plasmodium parasites are highly
specific with female Anopheles mosquitoes
Salient features
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Plasmodium species belong to phylum Apicomplexa.
Resistant stage called spore is present. Hence also
called Sporozoa.
They live intracellularly at least during part of their life
cycle.
Alteration of generations: sexual phase and asexual
phase.
Alteration of hosts: Definitive host and intermediate
host.
Types of Malaria
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Falciparum: Almost 80% of cases and 90% of malaria
deaths. Primarily found in South America and Africa.
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Ovale: Rarest form. Found in West Africa.
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Malariae: Found in Africa and SE Asia: Can infect
other mammals
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Vivax: 20% of infections. Widest geographic
distribution.
Malaria
Transmission

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Transmitted from one person to another by the bite of a
female anopheles mosquito.
The female mosquito bites during dusk and dawn and
needs a blood meal to feed her eggs.
Male mosquitoes do not transmit malaria as they feed on
plant juices and not blood.
About 380 species of anopheles mosquito, but only 60
are able to transmit malaria.
Life cycle
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Parasite completes its life cycle in two hosts– MAN &
MOSQUITO
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The asexual cycle occurs in MAN (Intermediate host)
The sexual cycle occurs in MOSQUITO (definitive host)
Exo – erythrocytic stage
ASEXUAL CYCLE
(Schizogony)
SEXUAL CYCLE
(Gametogony)
Erythrocytic stage
Exo-erythrocytic cycle

Developmental stage in the liver cells.

The sporozoites enter the hepatocytes through the
Kupffer cells with the help of the apical complex.
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Within the hepatocytes, the parasites undergo multiple
rounds of nuclear division without cytoplasmic division
followed by budding or segmentation to form progeny
called MEROZOITES.
Exo-erythrocytic cycle
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The merozoites are released into the circulatory system
followed by the rupture of hepatocytes.
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The number of merozoites differ from spp to spp
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Neither
clinical
manifestations
nor
changes are seen during this stage.
any
pathological
Persistence of malaria
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Persistence of dormant asexual parasitic forms seen in
some spp (P.vivax & P.ovale) – HYPNOZOITES
CAUSES FOR PERSISTANCE: 2 theories put forward
1.Cyclic Theory
2. Hypnozoite Theory
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Once the host immunity fails these hypnozoites can
reactivate & undergo schizogony at a later time
resulting in Relapse & Recrudescence
In P.falciparum there is no relapse as all the intrahepatic schizonts rupture almost simultaneously.
Hepatic Schizont
Erythrocytic cycle
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Merozoites released from the hepatocytes invade the
RBC
The merozoites recognize specific proteins on the
surface of the RBC & actively invade the cell. After
entering the RBC the parasite undergoes a trophic
period followed by an asexual replication.
Erythrocytic cycle contd…
 After the parasite enters the
RBC, it grows rapidly utilizing
host nutrients.
 As it grows, the parasite
takes on different shapes &
sizes. The nucleus then
divides into several portions to
form multinucleated Schizont
Erythrocytic cycle contd…
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1.
2.
3.
The RBC becomes more spherical and finally ruptures
releasing newly formed merozoites into the blood stream.
These merozoites have 3 fates:
They invade fresh RBC to initiate a new erythrocytic
cycle.
They die due to inactivation by Igs or by phagocytosis.
After a few erythrocytic cycle, some merozoites develop
into sexual forms – male and female gametocytes.
Erythrocytic cycle contd…
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The duration of Erythrocytic cycle is constant for
each spp of malarial parasite.
P.falciparum – 48 hrs
P.vivax
- 48 hrs
P.ovale
- 48 hrs
P.malariae
- 72 hrs
The newly formed merozoites do not invade the
liver cells again.
Gametogony
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As an alternative to schizogony some of the merozoites
develop into sexual forms – male & female gametocytes
The immature gametocytes develop in the blood vessels
of spleen, bone marrow & enter the blood after attaining
maturity (4days)
P.vivax gametocytes grow in the peripheral blood unlike
P.falciparum, which grow in capillaries of internal organs
and thus are found in circulation before they are
completely developed.
Gametogony
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Gametocytes do not cause any clinical symptoms
They disappear from the circulation if not taken
up by appropriate vector.
The individuals who harbor the gametocytes are
known as CARRIERS
Gametocyte - Plasmodium
falciparum: The gametocytes of P.
falciparum have a crescent or
banana shape
Gametocyte - Plasmodium
malariae: The gametocytes of P.
malariae have a round shape about
the size of red blood cells. They
have a fine granular appearance
Gametocyte - Plasmodium ovale: A
round gametocyte that is larger than
normal red blood cells. It has a
granular appearance as well as
Schuffner's dots
Sexual life cycle
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Occurs in the Definitive host – the Female
Anopheles mosquito.
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When a female anopheles mosquito bites an infected
host, both asexual & sexual forms enter.
In the stomach of the mosquito, the asexual forms are
destroyed but the gametocytes survive & undergo
further development.
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The microgametocyte undergoes 3 rounds of nuclear
replication to form 8 nuclei which then becomes
associated with flagella that emerge from the body of
microgametocyte.
This process is called as EX-FLAGELLATION. And the
micro gametocytes are matured into micro-gametes.
 The female gametocyte undergoes reduction division to get
converted into single MACROGAMETE.
 By chemotaxis, the highly motile microgamete fertilizes the
macrogamete to form the ZYGOTE.
 The zygote then lengthens first to a banana-shaped form & later
matures into vermiform OOKINETE , which is motile and
invasive.
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The ookinite matures to form oocyst
Oocyst later develops to form sporocyst which
contains large number of sporozoites.
Sporozoites have predilection for salivary glands,
hence migrate to get concentrated in salivary
glands of mosquito.
These sporozoites during a blood meal are
injected into a new host
Comparative Features of Plasmodium spp:
Duration of
asexual phase
Duration of
sporogony in
mosquito
P.vivax
P.falciparum
P.malariae
P.ovale
48 hrs
48 hrs
72 hrs
48 hrs
10 – 12 days at 10 days at 25 - 25 – 28 days at
27˚C
30˚C
22 - 27˚C
Forms found in
blood smear
Ring forms &
gametocytes
Trophozoites –
Ring forms
Cytoplasm
opp the
nucleus is
thicker
Trophozoites,
schizonts &
gametocytes
Trophozoites,
schizonts &
gametocytes
14 days at
27˚C
Trophozoites,
schizonts &
gametocytes
Cytoplasm fine Same as P.vivax Same as P.vivax
& regular in
outline. Often
with 2 nuclei.
Form vacuole.
Multiple
infections seen
P.vivax
P.falciparum
P.malariae
P.ovale
Growing
forms
•Irregular
with vacuole.
•Actively
amoeboid.
•Assumes a
compact form.
•Pigment
collects into a
single mass.
•Band like.
•Slightly
amoeboid
• Vacuole
disappears
early
• No ribbon shape.
• Slightly amoeboid.
Schizonts
(Mature)
Regular,
almost
completely
fills an
enlarged RBC
Fills two-thirds
of a red cell
which is not
enlarged.
Regular
,almost fills a
normal sized
red blood
cell.
Fills about threequarters of a red
blood cell ,which is
enlarged.
Arranged in a
grape like
cluster
Arranged
around a
central mass
of pigment
like a “daisy”
or a
”rosette”
Irregularly arranged.
Merozoites Arranged in
an irregular
grape like
cluster
P.vivax
Malarial
pigments
Yellowish
brown; fine
granules
P.falciparum
P.malariae
P.ovale
Dark brown
or blackish;
one or two
solid blocks
Dark brown.
Coarse
granules
Dark yellowish
brown.
Coarser than
P.vivax
Infected RBC’s Enlarged pale
Schuffner’s
dots present
Crenated,
reddish violet
color and
Maurer’s dots
Not much
change.
Zeimann’s dots
on prolonged
staining
Slightly
enlarged, oval
shape,
fimbriated.
James’s dots
appear early
Gametocytes
Crescenteric.
Larger than a
RBC. Host cell
hardly
recognizable
Round or oval.
Size of a RBC.
Host cell not
enlarged.
Oval. Size of a
RBC. Host cell
slightly
enlarged with
James’s dots
Spherical or
globular. Much
larger than a
RBC. Host cell
enlarged with
Schuffner’s
dots.
1. Malaria is transmitted to humans by the Anopheles
mosquito, which injects the _______ stage of the
organism Plasmodium.
A) Oocyst
B) Gametocyte
C) Schizont
D) Merozoite
E) Sporozoite
2. Arrange the following in the proper order in which
they occur during the human-phase of the
Plasmodium life cycle.
1. Formation of schizont
2. Invasion of the liver
3. Invasion of red blood cells
A)1, 2, 3 B)2, 1, 3 C)2, 3, 1 D)3, 2, 1 E)3, 1, 23.
3. Arrange the following in the proper order in which
they occur during the mosquito-phase of the
Plasmodium life cycle.
1. Formation of zygote
2. Formation of oocyst
3. Formation of sporozoites
A)1, 2, 3 B)2, 1, 3 C)2, 3, 1 D)3, 2, 1 E)3, 1, 2
4. Plasmodium gametocytes are capable of producing
gametes in mosquitoes, but not in human hosts.
A) True
B) False
5. The liver cells of people infected with malaria contain
the ring trophozoite form of Plasmodium
A) True
B) False