LEC.5 Protozoa (Sporozoa) Dr. Maysoon A.
Merdaw
Phylum Sporozoa referred to as Apicomplexa or Coccidia
Sporozoa undergo a complex life cycle with alternating sexual and asexual
reproductive phases. The human parasites Cryptosporidium, Toxoplasma and
the malarial parasites (Plasmodium species) are all intracellular parasites.
Plasmodium Species (Blood Sporozoa)
Malaria is the number one killer of all the parasitic diseases. It is estimated that
at least 1 million people die of malaria each year, mostly children under 5 years
of age. Transmission to humans is by the bite of female Anopheles mosquitoes.
Four species of Plasmodium cause malaria in humans: Plasmodium vivax, P.
falciparum, P. malariae, and P. ovale. The two most common species are P.
vivax and P. falciparum (account for 95% of infections), with falciparum being
the most pathogenic of all. P. vivax: 43% of total malarial cases in Iraq.
Life Cycle:
Malaria parasites exhibit a complex life cycle involving alternating cycles of
asexual division (schizogony) occurring in man (intermediate host) and sexual
development (sporogony) occurring in female Anopheles mosquito (definitive
host).
Human cycle
Primary exo-erythrocytic schizogony: Human infection results from the bite
of infected female Anopheles mosquito, through which the sporozoites are
injected into the bloodstream. The sporozoites rapidly (usually within 1 hour)
enter parenchymal cells of the liver, where the first stage of development in
humans takes place. Subsequently, numerous asexual progeny, the merozoites,
1
rupture and leave the liver cells, enter the bloodstream, and invade erythrocytes.
The merozoites do not return from red blood cells to liver cells.
Erythrocytic cycle: merozoites in the red cells multiply in a species-
characteristic fashion, breaking out of their host cells synchronously, with
successive broods of merozoites appearing at 48-hour intervals (P vivax, P
falciparum, and P ovale) or every 72 hours (P malariae). The digestion of red
cell hemoglobin, which is transformed into malaria pigment.
Gametogony: During the erythrocytic cycles, certain merozoites enter red cells
and become differentiated as male or female gametocytes.
Secondary exo-erythrocytic or dormant schizogony: P vivax and P ovale
may persist as dormant forms, or hypnozoites, after the parasites have
disappeared from the peripheral blood. Resurgence of an erythrocytic infection
(relapse) occurs when merozoites from hypnozoites in the liver break out, are
not phagocytosed in the bloodstream, and succeed in reestablishing a red cell
infection (clinical malaria). Without treatment, P vivax and P ovale infections
may persist as periodic relapses for up to 5 years.
2
Mosquito cycle
Sporogony: The gametocytes, male (microgametocytes) and female
(macrogametocytes), are ingested by an Anopheles mosquito during a blood
meal (only mature sexual forms are capable of further development and rest
die). In the mosquito's stomach, from one microgametocye eight microgametes
are formed by the process called exflagellation. The macrogametocyte does not
show exflagellation, it developes into a macrogamete.
Fertilization occur when the microgametes penetrate the macrogametes
generating zygotes. The zygotes in turn become motile and elongated
(ookinetes) which invade the midgut wall of the mosquito where they develop
into oocysts. The oocysts grow, rupture, and release millions of spindle-shaped
sporozoites, which make their way to the mosquito's salivary glands.
Inoculation of the sporozoites into cutaneous blood vessels and initiates
infection.
Plasmodium P falciparum P malariae P ovale
vivax (Benign (Malignant (Quartan (Ovale
Tertian Tertian Malaria) Malaria)
Malaria) Malaria)
Parasitized Enlarged, pale, Not enlarged. Not enlarged. Enlarged,
red cells (Schüffner (Maurer's clefts). No stippling pale.
dots). invades Invades all red (except with Schüffner
young red cells cells regardless special stains). dots. Cells
of age Primarily often oval, or
invades older crenated
red cells
Level of usual Up to May exceed Fewer than Fewer than
maximum 30,000/µL of 200,000/µL; 10,000/µL 10,000/µL
parasitemia blood commonly
50,000/µL
Ring stage Large rings Small rings (1/5 Large rings Large rings
trophozoites (1/3–1/2 red red cell (1/3 red cell (1/3 red cell
cell diameter). diameter). Often diameter). diameter).
Usually one two ring delicate, Usually one Usually one
3
Plasmodium P falciparum P malariae P ovale
vivax (Benign (Malignant (Quartan (Ovale
Tertian Tertian Malaria) Malaria)
Malaria) Malaria)
ring delicate may adhere to ring thick ring thick
red cells
Pigment in Fine; light Coarse; black; Coarse; dark Coarse; dark
developing brown; few clumps brown; yellow-
trophozoites scattered scattered brown;
clumps; scattered
abundant
Older Very Compact and Occasional Compact and
trophozoites pleomorphic rounded band forms rounded
Mature More than 12 Usually more Fewer than 12 Fewer than
schizonts merozoites than 12 merozoites. 12 large
(segmenters) (14–24) merozoites (8– Often in merozoites.
32). rosette Often in
rosette
Gametocyte Round or oval Crescentic Round or oval Round or
oval
distribution All forms Only rings and All forms All forms
in peripheral crescents
blood (gametocytes)
Some Characteristic Features of the Malarial Parasites of Humans
Only the sporozoite, merozoite and ookinete, which are designed for invasion of
the hepatocyte, erythrocyte or midgut epithelial cell of the mosquito
respectively, possess the invasion organelles (a specialized apical end
characteristic of Coccidia). Other stages of the life cycle, which are designed for
growth and development within the host cell, lack these.
Pathogenicity and symptoms:
1. Signs and symptoms are due to erythrocytic infection, not due to the Exo-
erythrocytic.
4
2. Destruction of RBCs due to rupture method by parasite and lysis of non-
parasitized cells due to debris and toxins metabolic byproducts of ruptured
cells cause anemia.
The number of RBCs in severe cases equal to half of normal number. As the
number of invaded RBCs increases and asexual cycles of parasite synchronized
the quantity of pyrogen becomes sufficient to produce the characteristic chills
and fever of malarial attack.
3. P. vivax and P. ovale infect youngest erythrocytes, while P. malariae infect
oldest one.
4. P. falciparum invades erythrocytes of all ages, so produces extensive
parasitemia and responsible for fatal infection.
5. In P. falciparum after 2-3 asexual cycles the number of infected RBCs
reaches a dangerous threshold without production of typical chills and fever.
6. Erythrocytes containing P. falciparum adhere to one another and to lining of
blood vessels causing blockage of blood capillaries in vital area such as brain,
lung, and kidney.
7. Toxin production interfere with oxygen utilization by the host cells, and
cause oxygen starvation of tissue followed by thrombosis in small blood
vessels and decrease in the volume of circulating blood.
8. Spleen is typically enlarged and congested (splenomegaly), its color get
darkened as amount of pigment increase and hard in chronic stage and soft
and hemorrhagic in acute stage.
9. The liver hypertrophic and congested in acute malaria and contains deposits
of pigments.
[Link] marrow undergoes the same changes as spleen. Kidneys are congested.
[Link] malaria cause glomerulonephritis and pulmonary congestion.
Febrile paroxysm:
It generally begins in the early afternoon and comprises of three successive
stages – cold stage, hot stage and sweating stage. In the cold stage, lasting for
5
15–60 minutes, the patient experiences intense cold and shivering. This is
followed by hot stage, lasting for 2– 6 hours, when the patient feels intense hot.
Patient develops high fever (40°–40.6°C), severe headache, nausea and
vomiting. Thereafter, fever ends by crisis accompanied by profuse sweating.
The periodicity of the attack varies with the species of the infecting parasite.
The periodicity is 48 hours in P. vivax (benign tertian) and P. ovale (ovale
tertian), and 72 hours in P. malariae (quartan). However, with P. falciparum,
the cycles of different broods (incubation period) of parasite do not become
synchronized as they do in other species. Therefore, typical tertian fever is not
usual in falciparum (malignant tertian) malaria.
Anaemia:
After a few paroxysms, anaemia develops as a result of: • Direct RBC lysis as a
result of life cycle of the parasite. • Splenic removal of both infected and
uninfected RBCs (coated with immune complexes). • Autoimmune lysis of
coated infected and uninfected RBCs. • Decreased incorporation of iron into
heme. • Increased fragility of RBCs. • Decreased RBC production from bone
marrow.
Splenomegaly After a few paroxysms, spleen gets enlarged and becomes
palpable. Splenomegaly is due to massive proliferation of macrophages which
phagocytose both parasitized and non-parasitized red blood cells
Pernicious malaria
is a complex of life-threatening complications that sometimes appear in acute
falciparum malaria, due to heavy parasitization, and is of three types:
1. Cerebral malaria 2. Algid malaria 3. Septicaemic malaria.
Diagnosis:
-Microscopy: Thin and thick blood films taken just before or at the height of
malarial paroxysm will detect number of parasites.
1. Thick blood film for rapid examination of a large volume of blood in small
area on the slide (concentration of parasite).
6
2. Thin blood film for specific diagnosis of species.
-immunochromatographic methods: to detect the antigens in blood.
-other methods: as serology (detect antibodies) and PCR.
Challenges in diagnosis:
There are some issues with the various stages of the P. vivax lifecycle that
complicate diagnosis.
1- Low parasite density
Ex. P. vivax merozoites only invade immature red blood cells (reticulocytes).
As these occur most often in the bone marrow, rather than in the blood
circulation, parasite densities in blood are often low, making the parasite
detection more challenging.
2- Complex life cycle
Gametocytes appear at approximately the same time as asexual parasites,
usually
before the onset of symptoms. Thus, individuals may be infectious before
diagnosis. P. vivax hypnozoites, which lie dormant in the liver, are undetectable
with any currently available diagnostic methods.
Treatment:
Treatment of malarial attacks: chloroquine and amodiaquine. Resistant malaria
P. falciparum showing drug resistant, and treated with quinine alone or with
combination with other drugs.
Control: requires community rather than individual reports.
1. Antimosquito chemicals: like DDT (Dichloro Diphenyl Trichloroethane)
and Malathion are found to be effective to control by preventing the
breeding of Anopheles mosquito.
2. Avoiding exposure to mosquito bites.
7
3. Taking chemoprophylaxis: Chloroquine and the antifolate drugs.
