Hashemite University
Faculty of Medicine, 2nd year
Hematopoietic and Lymphoid system
Dr Mohammad Al-Tamimi, MD, PhD
Parasitology
The plasmodia are sporozoa in which the sexual and
asexual cycles of reproduction are completed in different
host species
The sexual phase occurs within the gut of mosquitoes that
subsequently transmit the parasite while feeding on a
vertebrate host
Within the red blood cells (RBCs) of the vertebrate, the
plasmodia reproduce asexually; they eventually burst from
the erythrocyte and invade other uninvolved RBCs. This
event produces periodic fever and anemia in the host, a
disease process known as malaria
Of the many species of plasmodia, four are known to infect
humans and will be considered here: Plasmodium vivax, P.
ovale, P. malariae, and P. falciparum
Life Cycle
1. The sexual cycle
1. Begins when a female Anopheles mosquito ingests
circulating male and female gametocytes while feeding
on a malarious human
2. In the gut of the mosquito, the gametocytes mature and
effect fertilization. The resulting zygote penetrates the
mosquito’s gut wall, lodges beneath the basement
membrane, and vacuolates to form an oocyst
3. Within this structure, thousands of sporozoites are
formed. The enlarging cyst eventually ruptures, releasing
the sporozoites into the body cavity of the mosquito
4. Some penetrate the salivary glands, rendering the
mosquito infectious for humans
2. The asexual cycle
1. Occurs in the human and begins when the infected
Anopheles takes a blood meal from another individual
2. Sporozoites from the mosquito’s salivary glands are
injected into the human’s subcutaneous capillaries and
circulate in the peripheral blood
3. Within 1 hour they attach to and invade liver cells
(hepatocytes)
4. Each sporozoites producing about 2000 to 40,000
daughter cells, or merozoites
5. One to two weeks later, the infected hepatocytes rupture,
releasing merozoites into the general circulation
3. The erythrocytic phase
1. Starts with the attachment of merozoite to a specific
receptor on the RBC surface
2. After attachment, the merozoite invaginates the cell
membrane and is slowly endocytosed. The intracellular
parasite initially appears as a ring-shaped trophozoite,
which enlarges and becomes more active and irregular
3. Within a few hours, nuclear division occurs, producing
the multinucleated schizont
4. Cytoplasm eventually condenses around each nucleus of
the schizont to form an intraerythrocytic cluster of
merozoite daughter cells
5. Infected erythrocytes rupture, releasing the merozoites
and producing the first clinical manifestations of disease
6. Other daughter cells are transformed into sexual forms or
gametocytes, continue to circulate in the peripheral
vasculature until ingested by an appropriate mosquito
Morphology
The morphology of the stained intraerythrocytic
parasites shows three characteristic features:
1. red nuclear chromatin
2. blue cytoplasm
3. brownish-black malarial pigment, or hemozoin
The change in the shape of the cytoplasm and the
division of the chromatin at different stages of parasite
development are obvious
Gametocytes can be differentiated from the asexual
forms by their large size and lack of nuclear division
Epidemiology
Malaria has a worldwide distribution . P. vivax is the
most widely distributed of the four species, and
together with the uncommon P. malariae, is found
primarily in temperate and subtropical areas. P.
falciparum is the dominant organism of the tropics. P.
ovale is rare and found principally in Africa
In hyperendemic areas transmission is usually
constant, and disease manifestations are moderated by
the development of immunity
Mortality is largely restricted to infants and to
nonimmune adults who migrate into the region
Pathogenesis
1. Fever
The hallmark of malaria, appears to be initiated by the
process of RBC rupture that leads to the liberation of a
new generation of merozoites (sporulation)
The resulting fever is irregular and periodic. Because
temperatures in excess of 40° C destroy mature
parasites, a single population eventually emerges,
sporulation is synchronized, and fever occurs in
distinct paroxysms at 48hour or, in the case of P.
malariae, 72-hour intervals
2. Anemia
Parasitized erythrocytes are phagocytosed by a
stimulated reticuloendothelial system or are destroyed
at the time of sporulation
Depression of marrow function, sequestration of
erythrocytes within the enlarging spleen, and
accelerated clearance of nonparasitized cells all appear
to contribute to the anemia
Intravascular hemolysis, although uncommon, may
occur, particularly in falciparum malaria. When
hemolysis is massive, hemoglobinuria develops,
resulting in the production of dark urine. This process
in conjunction with malaria is known as blackwater
fever
3. Circulatory Changes
The high fever results in significant vasodilatation. In
falciparum malaria, vasodilatation leads to a decrease
in the effective circulating blood volume and
hypotension
The intense parasitemias P. falciparum is capable of
producing adhesion of infected RBCs to the
endothelium of visceral capillaries can impair the
microcirculation and precipitate tissue hypoxia, lactic
acidosis, and hypoglycemia. Although all deep tissues
are involved, the brain is the most intensely affected
4. Thrombocytopenia
Is common in malaria and appears to be related to
both splenic pooling and a shortened platelet lifespan
5. Acute transient glomerulonephritis in falciparum
malaria and progressive renal disease in chronic P.
malariae malaria. These phenomena probably result
from the host immune response, with deposition of
immune complexes in the glomeruli
Immunity
Once infected, the host quickly mounts a species- and
strain-specific immunologic response that typically
limits parasite multiplication and moderates the
clinical manifestations of disease
Without eliminating the infection. A prolonged
recovery period marked by recurrent exacerbations in
both symptoms and number of erythrocytic parasites
follows
With time, these recrudescences become less severe
and less frequent, eventually stopping altogether
Clinical Manifestations
The incubation period between the bite of the mosquito and the onset
of disease is approximately 2 weeks
The clinical manifestations vary with the species but typically include
chills, fever, splenomegaly, and anemia
The hallmark of disease is the malarial paroxysm. This manifestation
begins with a cold stage, which persists for 20 to 60 minutes. During
this time, the patient experiences continuous rigors and feels cold. With
the consequent increase in body temperature, the rigors cease and
vasodilatation commences, ushering in a hot stage. The temperature
continues to rise for 3 to 8 hours, reaching a maximum of 40 to 41.7° C
before it begins to fall. The wet stage consists of a decrease in fever and
profuse sweating. It leaves the patient exhausted but otherwise well
until the onset of the next paroxysm
In falciparum malaria, capillary blockage can lead to
several serious complications
When the central nervous system is involved (cerebral
malaria), the patient may develop delirium,
convulsions, paralysis, coma, and rapid death
When splanchnic capillaries are involved, the patient
may experience vomiting, abdominal pain, and
diarrhea with or without bloody stools
Jaundice and acute renal failure are also common in
severe illness
Most deaths occur within 3 days
Diagnosis
Malarial parasites can be demonstrated in stained smears of
the peripheral blood in virtually all symptomatic patients.
Blood are stained with Wright or Giemsa stain and examined
for the presence of erythrocytic parasites. Thick smears,
where erythrocytes are lysed with water concentrate the
parasites and allow detection of mild parasitemia
Simple, specific card antigen detection procedures are now
available. The most widely used test, ParaSight F, detects a
protein (HRP2) excreted by P. falciparum within minutes.
The test can be performed under field conditions and has a
sensitivity more than 95%. A second rapid test, OptiMAL,
detects parasite lactate dehydrogenase, and, unlike ParaSight
F, can distinguish between P. falciparum and P. vivax
Serologic tests are offered at large reference laboratories but
are used primarily for epidemiologic purposes
Treatment
The indications for treatment rest on two factors:
1. The first is the infecting species of Plasmodium
2. The second is the immune status of the afflicted patient
Falciparum malaria is potentially lethal in nonimmune
individuals such as new immigrants or travelers to a
malarious area and immunosuppressed indigenous
individuals such as pregnant women. These individuals
must be treated emergently
The complete treatment of malaria requires the
destruction of the erythrocytic schizont, the hepatic
schizont, and the erythrocytic gametocyte
Termination of Acute Attack
1. Several agents can destroy asexual erythrocytic
parasites. Chloroquine, has been the most commonly
used
2. Chloroquine-resistant strains of P. falciparum are
now widespread in Africa and Southeast Asia
3. Other agents include quinine/quinidin
Radical Cure
In P. vivax and P. ovale infections, hepatic schizonts
persist and must be destroyed to prevent reseeding of
circulating erythrocytes with consequent relapse.
Primaquine, is used for this purpose
Prevention
1. Personal Protection
In endemic areas, mosquito contact can be minimized
with the use of house screens, insecticide within
rooms, and/ or insecticide-impregnated mosquito
netting around beds. Those who must be outside from
dusk to dawn, the period of mosquito feeding, should
apply insect repellent and wear clothing with long
sleeves and pants. In addition, it is possible to suppress
clinical manifestations of infection with a weekly dose
of chloroquine
2. General
Malaria control measures have been directed toward
reducing the infected human and mosquito
populations to below the critical level necessary for
sustained transmission of disease. The techniques
employed include those mentioned previously,
treatment of febrile patients with effective antimalarial
agents, chemical or physical disruption of mosquito
breeding areas, and use of residual insecticide sprays
3. Chemoprophylaxis: anti-malria prophylaxis before
travelling to endemic area
4. Vaccines
Advances in the last decade have produced the hope
that an effective malaria vaccine might be within reach
of medical science for the first time
