Malaria

• Malaria is a protozoan infection of red blood

cells transmitted by the bite of a blood-
feeding female anopheline mosquito.
• It is the most important parasitic disease of
humans and
often the most common cause of fever in the
tropics.
 Malaria is caused by four plasmodia:
• falciparum, P. vivax, P. malariae, P. ovale

and also by the simian parasite P. knowlesi.

The vector and definitive host for plasmodia is
the female Anopheles mosquito.
There are two phases in the life cycle:
a)Sexual cycle, which occurs primarily in
mosquitoes.
b)Asexual cycle, which occurs in humans, the
intermediate hosts.
Life cycle:
The sexual cycle is called sporogony because
sporozoites are produced.
The asexual cycle is called schizogony because
schizonts are made.
Humans are infected through the bite of an
infected female Anopheles mosquito that
inoculates spindle shaped sporozoites into
the bloodstream.
The sporozoites of all Plasmodium species
reach the liver in the bloodstream and infect
hepatocytes, in which asexual multiplication
takes place.
In this process, the sporozoite develops into a
multinuclear, large schizont described as a
tissue schizont.
Following cytoplasmic division of schizonts,
merozoites are produced.
Shortly thereafter, the tissue schizonts release
the merozoites, which then infect
erythrocytes.
In infections with P. vivax and P. ovale,
sporozoites develop into tissue schizonts, but
some remain dormant as so-called
hypnozoites, which may develop into
schizonts following activation after months or
years causing relapses of the disease.
The merozoites produced in the liver are
released into the bloodstream where they
infect erythrocytes, in which they reproduce
asexually.
The merozoites attach to receptor molecules
on the erythrocyte surface.
These receptors are speices-specific, which
explains why certain Plasmodium species
prefer certain cell types:
P. malariae infects mainly older erythrocytes,
P. vivax and P. ovale prefer reticulocytes, and
P. falciparum infects younger and older
erythrocytes.
Plasmodium that has recently infected an
erythrocyte appears ring-shaped in a Giemsa-
stained blood smear.
The ring forms develop into schizonts, which
feed on glucose and hemoglobin.
The schizont undergoes multiple divisions to
produce merozoites, in different numbers
depending on the Plasmodium species.
The merozoites enter the blood plasma when
the erythrocyte is destroyed, they infect other
erythrocytes and begin a new asexual cycle.
A cycle takes 48 hours with P. vivax, P.ovale,
and P. falciparum and 72 hours with P.
malariae.
Fever is induced when the schizonts burst and
when many red blood cells are destroyed at
once, causing the typical, intermittent fever
attacks (“malarial paroxysm”).
After one or more schizogonic generations,
some of the plasmodia develop into sexual
forms, the male microgamonts
(microgametocytes), and female
macrogamonts (macrogametocytes).
These sexual forms (gametocytes) persist for a
certain period in the blood (P. vivax one day, P.
falciparum up to 22 days), after which those
not taken up by bloodsucking Anopheles
females die.
Pathogenesis:
Most of the pathologic findings of malaria
result from the destruction of red blood cells.
Red cells are destroyed by :
1.The release of the merozoites. ( the RBCs
ruptured ).
2.The action of the spleen (sequester infected
red cells are lyses in spleen).
Disease caused by P. malariae is called quartan
malaria because it recurs every fourth day.
Malaria caused by the others is called tertian
malaria because it recurs every third day.
Tertian malaria is subdivided into malignant
malaria, caused by P. falciparum, and benign
malaria, caused by P. vivax and P. ovale.
P. falciparum causes a high level of
parasitemia, because:
It can infect red cells of all ages. In contrast, P.
vivax infects only reticulocytes and P. malariae
infects only mature red cells.
Clinical Findings:
1. fever followed sweats and chills.
2. headache,
3.myalgias
4. arthralgias.
5. nausea.
6.vomiting,
7. abdominal pain.
8.Splenomegaly is seen in most patients
9 .hepatomegaly .
10. Anemia.

Patients usually feel well between the febrile

episodes.
Untreated malaria caused by P. falciparum is
life-threatening as a result of :
1.cerebral malaria.
2.blackwater fever.

Malaria caused by the other three plasmodia

is usually self-limited, with a low mortality
rate.
Diagnosis:
Microscopic examination of blood, using both
thick and thin Giemsa-stained smears.
The thick smear is used to screen for the
presence of organisms, and the thin smear is
used for species identification.
It is important to identify the species, because
the treatment of different species can differ.
Ring-shaped trophozoites can be seen within
infected red blood cells.
Plasmodium falciparum—Ring-shaped
trophozoite.
The gametocytes of P. falciparum are crescent-
shaped ("banana-shaped"), whereas those of
the other plasmodia are spherical .
Plasmodium falciparum—Gametocyte. Arrow
points to a "banana-shaped" gametocyte of
Plasmodium falciparum
If blood smears do not reveal the diagnosis,
then a PCR-based test for Plasmodium nucleic
acids or an ELISA test for a protein specific for
P. falciparum can be useful.
Treatment
artemethinie derivatives
mefloquine or a combination of quinine and
doxycycline is used.
In severe cases, especially of falciparum
malaria,use intravenous quinidine (or
quinine) plus another antimalarial drug such
as doxycycline or clindamycin .