1 MM Plasmodium

1.1 Classifications And Morphology

Malaria parasite belongs to

Phylum: Apicomplexa
Class: Sporozoa
Order: Haemosporida
Genus: Plasmodium.

The genus Plamodium is divided into 2 subgenera, P. vivax, P. malariae and P. ovale belong to the 
subgenus Plasmodium while P. falciparum is allocated to subgenus Laverania because it differs in a 
number of aspects from the other 3 species. 

P. vivax, P. malariae, and P. ovale are closely related to other primate malaria parasites. P. 
falciparum on the other hand, is more related to bird malaria parasites and appears to be a recent 
parasite of humans, in evolutionary terms. Perhaps for this reason, falciparum infection causes the 
severest form of malaria and is responsible for nearly all fatal cases. 

P. knowelsi, a parasite of long–tailed Macaque monkeys may also affect man. 

a. P. vivax has the widest geographical distribution, extending through the tropics, subtropics and 
temperate regions. It is believed to account for 80% of all malaria infections. It is the most common 
species of malaria parasite in Asia and America, but is much less common in Africa. It causes benign 
tertian malaria with frequent relapses. 

The sporozoites of P. vivax are narrow and slightly curved. On entering the liver cells, the sporozoites
initiate 2 types of infection. Some develop promptly into exoerythrocytic schizonts, while others 
persist in the dormant state for varying periods as hypnozoites. There may be 2 distinct types of 
sporozoites, the tachysporozoites (tachy: fast), which develops into the primary exoerythrocytic 
schizont and the bradysporozoite (brady: slow) which becomes the hypnozoite. 

The pre­erythrocytic schizogony lasts for 8 days and the average number of merozoites per tissue 
schizont is 10,000. 

Merozoites of P. vivax preferentially infect reticulocytes and young erythrocytes. 

All stages of erythrocytic schizogony can be seen in peripheral smears (Fig. 6.5). 

The degree of parasitization is not generally heavy, each infected red cell usually having only one 
trophozoite and not more than 2–5% of the red cells being affected. Reticulocytes are preferentially 
infected. 

The trophozoite is actively motile, as indicted by its name vivax. The ring form is well­defined, with a
prominent central vacuole. One side of the ring is thicker and the other side thin. Nucleus is situated 
on the thin side of the ring. The ring is about 2.5–3 μm in diameter, about a third of the size of an 
erythrocyte. The cytoplasm is blue and the nucleus red in stained films. The ring develops rapidly to 
the amoeboid form and accumulates malarial pigment (Figs 6.6 and 6.7). 

The infected erythrocytes are enlarged and show red granules known as Schffner’s dots on the 
surface. They become irregular in shape, lose their red color, and present a washed out appearance. A 
few of the parasitized erythrocytes retreat into the blood spaces of the internal organs. 

The schizont appears in about 36–40 hours. It occupies virtually the whole of the enlarged red cell. 
The schizont matures in the next 6–8 hours, with the development of merozoites, each with its central 
nucleus and surrounding cytoplasm. The pigment granules agglomerate into a few dark brown 
collections at the center, and with the merozoites around it, this stage presents a rosette appearance. 
There are about 12–24 (usually 16) merozoites per schizont. 

Erythrocytic schizogony takes approximately 48 hours. The red cell, which now measures about 10 
μm in diameter is heavily stippled and often distorted. It bursts to liberate the merozoites and pigment.
The pigment is phagocytosed by reticuloendothelial cells. 

The merozoites have no pigment. 

Gametocytes appear early, usually within 4 days after the trophozoites first appear. Both male and 
female gametocytes are large, nearly lling the enlarged red cell. The macrogametocyte has dense 
cytoplasm staining deep blue and a small compact nucleus. The microgametocyte has pale­staining 
cytoplasm and a large di use nucleus. Pigment granules are prominent in the gametocytes. 

b. P. falciparum

The name falciparum comes from the characteristic sickle shape of the gametocytes of this species 
(falx: sickle, parere: to bring forth). This is the highly pathogenic of all the plasmodia and hence, the 
name malignant tertian or pernicious malaria for its infection. 

The disease has a high rate of complications and unless treated, is often fatal. The species is 
responsible for almost all deaths caused by malaria. 

Schizogony: The sporozoites are sickle­shaped. The tissue phase consists of only a single cycle of 
pre­ erythrocytic schizogony. No hypnozoites occur. The mature liver schizont releases about 30,000
merozoites. 

They attack both young and mature erythrocytes and so the population of cells a ected is very large. 
Infected erythrocytes present a brassy coloration. 

Ring form: The early ring form in the erythrocyte is very delicate and tiny,measuring only a sixth 
(1/6) of the red cell diameter. Rings are often seen attached along the margin of the red cell, the so­
called form appliqué or accole. Binucleate rings (double chromatin) are common resembling stereo 
headphones in appearance. Several rings may be seen within a single erythrocyte. In course of time, 
the rings become larger, about a third of the size of the red cell and may have 1 or 2 grains of pigment
in its cytoplasm (Figs 6.8 and 6.9). 
The subsequent stages of the asexual cycle—late trophozoite, early and mature schizonts—are not 
ordinarily seen in peripheral blood, except in very severe or pernicious malaria. The presence of P. 
falciparum schizonts in peripheral smears indicates a grave prognosis. 

The infected erythrocytes are of normal size. They show a few (6–12) coarse brick­red dots which are 
called Maurer’s clefts. Some red cells show basophilic stippling. 

Gametogony: It begins after several generations of schizogony. Gametocytes are seen in circulation 
about 10 days after the ring stage rst appears. The early gametocytes seldom appear in peripheral 
circulation. The mature gametocytes, which are seen in peripheral smears are curved oblong 
structures, described as crescentic, sickle, sausage, or banana­shaped. They are usually referred to 
as crescents (Fig. 6.10). 

The male gametocytes are broad and sausage­ shaped or kidney­shaped, with blunt rounded ends as 
compared to the female gametocytes, which are thinner and more typically crescentic, with sharply 
rounded or pointed ends. The mature gametocyte is longer than the diameter of the red cell and so 
produces gross distortion and sometimes even apparent disappearance of the infected red cell. The red
cell is often seen as a rim on the concave side of the gametocyte. The cytoplasm in the female 
gametocyte is deep blue, while in the male it is pale blue or pink. The nucleus is deep red and 
compact in the female, with the pigment granules closely aggregated around it, while in the male, it is 
pink, large and di use, with the pigment granules scattered in the cytoplasm. 

Falciparum crescents can survive in circulation for up to 60 days, much longer than in other species. 
Gametocytes are most numerous in the blood of young children, 9 months to 2 years old. They, 
therefore serve as the most effective source of infection to mosquoties. 

c. P. malariae

This was the species of malaria parasite rst discovered by Laveran in 1880 and the name malariae is 
the one given by him. It causes quartan malaria, in which febrile paroxysms occur every fourth day, 
with 72 hours’ interval between the bouts. 

The disease is generally mild, but is notorious for its long persistence in circulation in undetectable 
levels, for 50 years or more. Recrudescence may be provoked by splenectomy or 
immunosuppression. The development of the parasite, in man and mosquito is much slower than with 
other species. Chimpanzees may be naturally infected with P. malariae and may constitute a natural 
reservoir for quartan malaria.

P. malariae occurs in tropical Africa, Sri Lanka, Burma, and parts of India, but its distribution is 
patchy.

The sporozoites are relatively thick. Pre­erythrocytic schizogony takes about 15 days, much longer 
than in other species. Each schizont releases about 15,000 merozoites. Hypnozoites do not occur. 
The long latency of the infection is believed to be due to persistence of small numbers of erythrocytic
forms in some internal organs. 
P.malaria epreferentially infects old ererythrocytes and the degree of parasitization is low.

The ring forms resembles those of P. vivax, although thicker and more intensely­stained. The old 
trophozoites are sometimes seen stretched across the erythrocyte as a broad band. These band forms
are a unique feature of P. malariae. Numerous large pigment granules are seen (Fig. 6.11). 

The schizonts appear in about 50 hours and mature during the next 18 hours. The mature schizont has 
an average of 8 merozoites, which usually present a rosette appearance. 

The infected erythrocytes may be of the normal size or slightly smaller. Fine stippling, called 
Ziemann’s stippling, may be seen with special stains. The degree of parasitization is lowest in P. 
malariae. 

Erythrocytic schizogony takes 72 hours.The gametocytes develop in the internal organs and appear in
the peripheral circulation when fully grown. Gametocytes occupy nearly the entire red cell. The male 
has pale blue cytoplasm with a large di use nucleus, while the female has deep blue cytoplasm and a 
small compact nucleus. 

c. P. ovale

This parasite produces a tertian fever resembling vivax malaria, but with milder symptoms, prolonged
latency and fewer relapses.It is the rarest of all plasmodia infecting humans and is seen mostly in 
tropical Africa, particularly along the West Coast.

The pre­erythrocytic stage extends for 9 days. 

Hepatocytes containing schizonts usually have enlarged nuclei. The mature liver schizont releases 
about 15,000 merozoites. Hypnozoites are present. 

The trophozoites resemble those in vivax malaria, but are usually more compact, with less amoeboid 
appearance. Schu ner’s dots appear earlier and are more abundant and prominent than in vivax 
infection (Fig. 6.12). The infected erythrocytes are slightly enlarged. In thin films, many of them 
present an oval shape with mbriated margins. This oval appearance of the infected erythrocyte is the 
reason for the name ovale given to this species. The schizonts resemble those of P. malariae, except 
that the pigment is darker and the erythrocyte is usually oval, with prominent Schuffner’s dots. 

1.2 Life Cycle
2. MM VEKTOR MALARIA

2.1 Classification

Kingdom : Animalia
Phylum : Arthropoda
Class : Insecta
Order : Diptera
Family : Culicidae
Subfam : Anophelinae
Genus : Anopheles

2.2 Life Cycle, Morphology

Like all mosquitoes, anophelines go through four stages in their life cycle: egg, larva, pupa, and adult.
The first three stages are aquatic and last 5-14 days, depending on the species and the ambient
temperature. The adult stage is when the female Anopheles mosquito acts as malaria vector. The adult
females can live up to a month (or more in captivity) but most probably do not live more than 1-2
weeks in nature.

Eggs

Adult females lay 50-200 eggs per oviposition. Eggs are laid singly directly on water and are unique
in having floats on either side. Eggs are not resistant to drying and hatch within 2-3 days, although
hatching may take up to 2-3 weeks in colder climates.

Larvae

Mosquito larvae have a well-developed head with mouth brushes used for feeding, a large thorax, and
a segmented abdomen. They have no legs. In contrast to other mosquitoes, Anopheles larvae lack a
respiratory siphon and for this reason position themselves so that their body is parallel to the surface
of the water.

Larvae breathe through spiracles located on the 8th abdominal segment and therefore must come to
the surface frequently.

Top: Anopheles Egg; note the lateral floats.

Bottom: Anopheles eggs are laid singly.
The larvae spend most of their time feeding on algae, bacteria, and other microorganisms in the
surface microlayer. They dive below the surface only when disturbed. Larvae swim either by jerky
movements of the entire body or through propulsion with the mouth brushes.

Larvae develop through 4 stages, or instars, after which they metamorphose into pupae. At the end of
each instar, the larvae molt, shedding their exoskeleton, or skin, to allow for further growth.

Anopheles Larva. Note the position, parallel to the water surface.

The larvae occur in a wide range of habitats but most species prefer clean, unpolluted water. Larvae
of Anopheles mosquitoes have been found in fresh- or salt-water marshes, mangrove swamps, rice
fields, grassy ditches, the edges of streams and rivers, and small, temporary rain pools. Many species
prefer habitats with vegetation. Others prefer habitats that have none. Some breed in open, sun-lit
pools while others are found only in shaded breeding sites in forests. A few species breed in tree holes
or the leaf axils of some plants.

Pupae

The pupa is comma-shaped when viewed from the side. The head and thorax are merged into a
cephalothorax with the abdomen curving around underneath. As with the larvae, pupae must come to
the surface frequently to breathe, which they do through a pair of respiratory trumpets on the
cephalothorax. After a few days as a pupa, the dorsal surface of the cephalothorax splits and the adult
mosquito emerges.

The duration from egg to adult varies considerably among species and is strongly influenced by
ambient temperature. Mosquitoes can develop from egg to adult in as little as 5 days but usually take
10-14 days in tropical conditions.

Anopheles Pupa

Anopheles Adults. Note (bottom row) the typical resting position.

Adults

Like all mosquitoes, adult anophelines have slender bodies with 3 sections: head, thorax and
abdomen.

The head is specialized for acquiring sensory information and for feeding. The head contains the eyes
and a pair of long, many-segmented antennae. The antennae are important for detecting host odors as
well as odors of breeding sites where females lay eggs. The head also has an elongate, forward-
projecting proboscis used for feeding, and two sensory palps.

The thorax is specialized for locomotion. Three pairs of legs and a pair of wings are attached to the
thorax.

The abdomen is specialized for food digestion and egg development. This segmented body part
expands considerably when a female takes a blood meal. The blood is digested over time serving as a
source of protein for the production of eggs, which gradually fill the abdomen.

Anopheles mosquitoes can be distinguished from other mosquitoes by the palps, which are as long as
the proboscis, and by the presence of discrete blocks of black and white scales on the wings.
Adult Anopheles can also be identified by their typical resting position: males and females rest with
their abdomens sticking up in the air rather than parallel to the surface on which they are resting.

Adult mosquitoes usually mate within a few days after emerging from the pupal stage. In most
species, the males form large swarms, usually around dusk, and the females fly into the swarms to
mate.

Males live for about a week, feeding on nectar and other sources of sugar. Females will also feed on
sugar sources for energy but usually require a blood meal for the development of eggs. After obtaining
a full blood meal, the female will rest for a few days while the blood is digested and eggs are
developed. This process depends on the temperature but usually takes 2-3 days in tropical conditions.
Once the eggs are fully developed, the female lays them and resumes host seeking.

The cycle repeats itself until the female dies. Females can survive up to a month (or longer in
captivity) but most probably do not live longer than 1-2 weeks in nature. Their chances of survival
depend on temperature and humidity, but also their ability to successfully obtain a blood meal while
avoiding host defenses.

2.3 Habitation and Behaviour

Mosquitoes will breed in practically any collection of water

that stands longer than five to seven days. Different kinds of mosquitoes vary in their
choice of breeding places. Some like sunlit places whereas others prefer the shade.
Some prefer fresh water to stagnant water. Others prefer the brackish water of salt
marshes. Common breeding sites are ponds, pools, slow-moving streams, inland
swamps and bogs, salt marshes, ditches, tree holes, rock holes, and manmade
containers of water. Manmade containers include wells, cisterns, rain barrels, roof
gutters, road gutters, cans, buckets, drains, cesspools, septic tanks, pit latrines,
excavation sites, road holes, bomb craters, and old tires that have been discarded.

Anopheles. Anopheles mosquitoes bite primarily during the period from

dusk to dawn. They may bite during the daylight hours in an area that is heavily shaded
or in a room that is dark. Most species will breed in any collection of water, but some
species breed only in tree holes. The larvae lie parallel to the surface of the water. The
adults usually rest and feed with the body at an angle of 45 to the surface (figure 5-2).

3. MM MALARIA

3.1 Definisi

3.2 Etiologi dan Epidemiologi

3.3 Klasifikasi (Including Clinical Manifestations)

Plamodium vivax: Benign Tertian Malaria 

Plasmodium falciparum: Malignant Tertian Malaria 

Plasmodium malariae: Benign Quartan Malaria 

Plasmodium ovale: Benign Tertian Malaria. 
3.3 Patogenesis