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Please read this section first
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DIFFERENTIAL SLIDES LEGEND
CYCLE 45 SLIDE 1 – AUGUST 2014
MALARIA
Malaria is a mosquito-borne infectious disease caused by a eukaryotic protist of the genus Plasmodium. It is
widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year,
there are approximately 350–500 million cases of malaria, killing between one and three million people, the
majority of whom are young children in sub-Saharan Africa. Ninety percent of malaria-related deaths occur
in sub-Saharan Africa. Malaria is commonly associated with poverty, but is also a cause of poverty and a
major hindrance to economic development.
Five species of the plasmodium parasite can infect humans; the most serious forms of the disease are caused
by Plasmodium falciparum. Malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae
causes milder disease in humans that is not generally fatal. A fifth species, Plasmodium knowlesi, is a zoonosis
that causes malaria in macaques but can also infect humans.
Transmission
Malaria is naturally transmitted by the bite of a female Anopheles mosquito. Only female mosquitoes feed on
blood, thus males do not transmit the disease. The females of the Anopheles genus of mosquito prefer to
feed at night. Malaria parasites can also be transmitted by blood transfusions, although this is rare. When a
mosquito bites an infected person, a small amount of blood is taken, which contains malaria parasites. These
develop within the mosquito, and about one week later, when the mosquito takes its next blood meal, the
parasites are injected with the mosquito's saliva into the person being bitten. After a period of between two
weeks and several months (occasionally years) spent in the liver, the malaria parasites start to multiply within
the red blood cells causing symptoms.
Pathogenesis
A mosquito infects a person by taking a blood meal. First, sporozoites enter the bloodstream, and migrate to
the liver. They infect liver cells (hepatocytes), where they multiply into merozoites, rupture the liver cells,
and escape back into the bloodstream. Within the red blood cells, the parasites multiply further, again
asexually, periodically breaking out of their hosts to invade fresh red blood cells. Several such amplification
cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites
escaping and infecting red blood cells. The merozoites in the red blood cells, develop into ring forms or
trophozoites (a feeding stage), then schizonts (a reproduction stage), then back into merozoites. Sexual
forms called gametocytes are also produced which, if taken up by a mosquito, will infect the insect and
continue the life cycle. Some P. vivax and P. ovale sporozoites do not immediately develop into
exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging
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from several months (6–12 months is typical) to as long as three years. After a period of dormancy, they
reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in these
two species of malaria. The parasite is relatively protected from attack by the body's immune system
because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to
immune surveillance. However, circulating infected blood cells are destroyed in the spleen.
To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood
cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite
from passage through the general circulation and the spleen. This "stickiness" is the main factor giving rise
to haemorrhagic complications of malaria. High endothelial venules (the smallest branches of the circulatory
system) can be blocked by the attachment of masses of these infected red blood cells. The blockage of
these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria the
sequestrated red blood cells can breach the blood brain barrier possibly leading to coma.
Diagnosis - Microscopic examination of blood films
The most economic, preferred, and reliable diagnosis of malaria is microscopic examination of blood films
because each of the four major parasite species has distinguishing characteristics. Some degree of
haemolysis is seen in all types of malarial infection. The most severe abnormalities are found in Plasmodium
falciparum infections.
In worst cases DIC occurs and intravascular haemolysis is marked with
haemoglobinuria. This may be associated with quinine therapy (“blackwater fever”). Thrombocytopenia is
commonly found in acute malaria. Patients with chronic malaria have an anaemia of chronic disorders;
hypersplenism may contribute to the anaemia and result in moderate thrombocytopenia and neutropenia.
Tropical splenomegaly is probably a chronic immune reaction to malaria.
Diagnostic Points
1) Red Cells are normal.
2) Rings appear fine and delicate and there may be
several in one cell.
3) Some rings may have two chromatin dots.
4) Presence of marginal or applique forms.
5) It is unusual to see developing forms in
peripheral blood films.
6) Gametocytes have a characteristic crescent
shape appearance. However, they do not usually
appear in the blood for the first four weeks of
infection.
7) Maurer's dots may be present
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1) Red cells containing parasites are
usually enlarged.
2) Schuffner's dots are frequently
present in the red cells as shown above
3) The mature ring forms tend to be large
and coarse.
4) Developing forms are frequently
present.
P.O. Box 131375, Bryanston, 2074
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Tel: +27 (011) 463-3260
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Diagnostic Points
1) Ring forms may have a squarish appearance.
2) Band forms are a characteristic of this species.
3) Mature schizonts may have a typical daisy head
appearance with up to ten merozoites.
4) Red cells are not enlarged
5) Chromatin dot may be on the inner surface of
the ring.
1)
2)
3)
4)
Red cells enlarged.
Rings large and coarse.
Comet forms common (top right).
Schuffner's dots, when present, may be
prominent.
5) Mature schizonts similar to those of
P. malariae but larger and coarser.
Treatment
Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Use of
prophylactic drugs is seldom practical for full-time residents of malaria-endemic areas, and their use is
usually restricted to short-term visitors and travellers to malarial regions. Modern drugs used preventively
include mefloquine (Lariam), doxycycline (available generically), and the combination of atovaquone and
proguanil hydrochloride (Malarone). The choice of which drug to use depends on which drugs the parasites in
the area are resistant to, as well as side-effects and other considerations. Quinine is used to treat
chloroquine resistant Plasmodium falciparum, as well as severe and cerebral stages of malaria, but is not
generally used for prophylaxis.
References
1. Essential Haematology – Hoffbrand, Pettit and Moss 4th Edition
2. http//en.wikipedia.org/wiki/Malaria
Questions
1. Discuss the diagnostic points of the four species of Plasmodium.
2. What are the symptoms of malaria?
3. Discuss the transmission and pathogenesis of malaria.
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