Phylum: Apicomplexa

( because the apical point of the parasite complex)

(Blood and tissue Sporozoa)
 They are obligatory intracellular protozoan protozoa.
They are unicellular, spor-forming.
 apical complex stracture involved in penetrating a host’s cells.
apical complex stractures is present at some stage and consist of
elements visible with electron microscope.
Has no organ of locomotion.
Previously classified as sporozoa or Sporozoans.
 Typically producing sporozoites during the life cycle.
 Has asexual life cycle human (As intermediate host)
Disease: (MALARIA).
 Has sexual life cycle in final host (female of anopheles).
They include 2 pathogenic human genera:
1-Genus: Plasmodium
2-Genus: Toxoplasma
Four Plasmodium spps are responsible for human malaria:

1- P. falciparum→ causes (malignant tertian malaria)

the periodicity of attack becom tertian (36-48) shortest
incubation period 7-10.
2- P. malariae → causes (quartan malaria) are the most
common species, the periodicity if attack becomes quartan
(every 72 hours) incubation period 18-40.
3- P. vivax → causes (benign tertian malaria) the periodicity of
attack becomes tertian (every 48 hours) incubation period 10-
17 days
4- P. ovale → causes (ovale tertian malaria) the periodicity of
attack becomes tertian (every 48-50 hours) incubation period
10-17 days
 Life cycle of Plasmodium (Malaria)
Malaria parasite passes its life cycle in 2 hosts.
Definitive host: Female Anopheles mosquito.
Intermediate host: Man.
The life cycle of malarial parasite comprises of 2 stages
• an asexual phase occurring in humans (intermediate host)
• a sexual phase occurring in mosquito (definitive host).

I-Asexual cycle (in human):

Sporozoites (infective stage) enter into the blood stream of a host when the female
anopheles mosquito feeds on blood.
In humans, schizogony occurs in 2 locations:
1. Liver (tissue, exo-erythrocytic or pre-erythrocytic ) phase:
2. 2-Erythrocytic (RBC) phase:
1. Liver (tissue, exo-erythrocytic or pre-erythrocytic ) phase:
Following the inoculation, the sporozoites leave the blood within 40 minutes
and enter the parenchymal cells of the liver (hepatocytes), process known as
pre-erythrocytic schizogony, to produce thousands of tiny merozoites which
are released into the circulation after about 16 days.
Some sporozoites differentiate into hypnozoites which remain dormant in
hepatocytes, when they are “reactivated” they undergo asexual division and
produce a clinical (relapse).

The malaria parasite multiplies by division or splitting a process designated

to as Schizogony (from schizo: to split, and gone: generation).

Because schizogony in the liver is an essential step before the parasites can
invade erythrocytes, it is called pre-erythrocytic schizogony.

The products of schizogony, whether erythrocytic or exoerythrocytic, are

called merozoites (meros: apart, zoon: animal).
2-Erythrocytic (RBC) phase:
The released merozoites from liver cells
invade the red cells and develop into
trophozoites.
They attach to the erythrocytes by their
apex enter red cell membrane by a
process of invagination.
In RBC the merozoite loses its internal
organelles and appears as a rounded
body having a vacuole in the center with
the cytoplasm pushed to the periphery
and the nucleus at one pole. These
young parasites are, therefore called the
ring
After feeding on RBC, this ring stage
becomes irregular in shape to form
amoeboid stage .
After a period of growth, the trophozoite
undergoes an asexual division
When the mature trophozoite starts to divide
in the red blood cell, separate merozoites are
formed resulting in a schizont.
When fully developed, the schizont ruptures
the red blood cell containing it, liberating the
merozoites into the circulation.
These merozoites will infect new red cells
and cycle is repeated in the new RBC.

Some of the merozoites entering red

blood cells do not form trophozoite then
schizont, but develop into male
(microgametocytes) and female
(macrogametocytes) gametocytes and
this process takes place in deep tissue
capillaries.
A mature schizont contains 8–32 merozoites and hemozoin (a crystalline,
brown pigment that is formed and sequestered in the digestive vacuole of
Plasmodium as a product of hemoglobin (Hb) catabolism.

This cycle is called erythrocytic Schizogony, it is repeated sequentially,

leading to progressive increase in the parasitemia, till it is arrested by the
development of host immune response.
The rupture of the mature schizont releases large quantities of pyrogens.
This is responsible for the febrile paroxysms characterizing malaria.

The interval between the entry of sporozoite into the host and the earliest
manifestation of clinical illness is the incubation period.

While prepatent period, which is the time taken from entry of the
sporozoites to the first appearance of malaria parasite in peripheral blood.
II-Sexual cycle (in mosquito)
When a female Anopheles mosquito bites an infected
person, it ingests blood which may contain the mature
sexual cells (male and female gametocytes) which
undergo a series of developmental stages in the
stomach of the mosquito.

Exflagellation, the extrusion of rapidly waving

flagellum-like male gametes (microgametes) from
male gametocytes, resulting in the production of male
gametes (microgametes).

Female gametes (macrogametocytes), also develops

into macrogametes by reduction division of the
nuclear matter.
Fertilization occurs between male & female
gametes producing a zygote in the stomach of
the mosquito which matures to an ookinete.

The ookinete penetrates the stomach wall of the

mosquito where it grows into an oocyst and it
further matures to become a motile sporozoite.

The length of the developmental stage in the

mosquito may range from eight days in
Plasmodium vivax to as long as 30 days in
Plasmodium malariae.

The sporozoites migrate from the body cavity

of the mosquito to the salivary glands and the
mosquito now becomes infective.
Plasmodium (Malaria) in general.

• Infective stage: Sporozoite

• Distribution: depend on the spp of Plasmodium.
• Life cycle: Indirect with vector.
• Vector: female anopheles mosquito(final host with sexual L.C).
• Human is the intermediate host ( carries the asexual life cycle)
in liver and RBCS.
• Pathogenic stage: all liver and RBCS stages.
• Habitat: 1-intra-Liver cells 2- Intra-RBCS
• Diagnostic stage: All intracellular RBCS STAGES.
• Prevention: Measurements to keep vector away from human
life and contact.
• Diagnosis: Detection of parasite in intracellular of RBC.
Pathogeicity and symptoms
Patients who suffering from malaria infection may developed
1- Febrile Attack (Malaria Paroxysm): periodic episodes of fever alternating
with symptom-free periods or a sudden recurrence of symptoms. Paroxysms
associated with synchrony of merozoite release from RBC rupture
2-Relapse: 2 kinds of sporozoites are seen, some of which multiply inside
hepatocytes promptly to form schizonts and others which remain dormant.
These latter forms are called hypnozoites (from hypnos: sleep), Reactivation of
hypnozoites leads to initiation of fresh erythrocytic cycles and new attacks of
malarial fever.
3- Recrudescence: the recurrence of clinical symptoms in a malaria patient
because plasmodium is not eliminated either by immue system or treatment
failure.
4- Clinical incubation period: the time elapsed between exposure to a
pathogenic organism and when symptoms and signs are first apparent.
5- Biological incubation period: the time elapsed between exposure to a
pathogenic organism and when organism are first appear.
Pathogenesis and symptoms
Pathogenesis of malaria is due to multiplication of the parasites inside RBCs and
liver cells.

Antibody can neutralize a parasite directly by blocking attachment of merozoite to

the RBCs to prevent enter red blood cells through a special receptor

RBCs invasion requires receptor or specific determinants on the surface of the RBC.

The growing parasite converted hemoglobin into haemozoin pigment.

Rupture of infected RBCs with the consequent release of merozoites, pigment and
cell debris.

The pigment is engulfed by phagocytes and deposited in the organs rich in reticulo-
endothelial cells e.g. liver, spleen leading to their enlargement due to hyperplasia
(splenomegaly & hepatomegaly).

The initial symptoms of malaria are flu-like symptoms and include a high (fever).
After infection liver and RBC, typical picture of malaria is
1- Febrile paroxysm. Has three stages
a) Cold stage: it lasts for 15–60 minutes, the patient has intense cold and
uncontrolled shivering
b) Hot stage: it lasts for 2-6 hrs. & the patient feels intensely hot, the temperature is
41°C or higher
c) Sweating: when the patient goes in profuse sweat. The temperature drops rapidly
and the patient usually falls into deep sleep, to wake up refreshed.

This starts when the mature schizont rupture releasing (red cell fragments,
merozoites, malaria pigments and other parasite debris) which phagocytes by
PMNS &MØ and then release pyrogenic factors (IL-1 & TNF) which cause
elevation of temperature
2-Anemia: due to
a) Suppression of erythropoiesis,
b) Destruction of infected RBC,
c) Phagocytosis of uninfected RBC.
3-Splenomegally:
Massive proliferation of MΦ which phagocytized both infected and non-
infected RBC.
All clinical manifestation in malaria due to products of erythrocytes schizogony
and host reaction to them.
Clinical manifestations of P.falciparum:
Severe or complicated malaria caused by P. falciparum infections.

P.Falciparum virulence is attributed to its ability to evade the human immune system
by modifying infected host red blood cells to adhere to the vascular endothelium.

The brain (cerebral malaria) is most often seen in P.falciparum infection.

Capillary plugging from an adhesion of infected red blood cells with each other and
endothelial linings of capillaries causes hypoxic injury to the brain that can result in
coma and death, which is sever in malignant malaria than others.

 Red blood cells burst in the bloodstream (hemolysis), releasing hemoglobin directly

into the blood vessels and into the urine, frequently leading to kidney failure ,called
“black water fever”.

Produce autoantibodies against infected RBCs (autoimmune response). This leads to

more complications and maybe death.
Mode of infection
1- Insect bite 2-Blood transfusion from infected donors.
3-Organ transplantation. 4-Congenitally trasplacentally.
5-Needle stick injury: In case of drugs addiction.

Laboratory diagnosis
• Clinically from febrile paroxysm
•Microscopic examination of thick and thin blood films of blood is the method
of choice for confirming the clinical diagnosis of malaria and identifying the
specific species responsible for disease.
•Serologic procedures are available but they are used primarily for
epidemiological study.
•Surveys or for screening blood donors.
TREATMENT
1-Bed rest with fluid supply.
2-Drugs
The drug of choice for treating acute malaria is Chloroquine. In 2013 a trial was
completed, that studied a single dose alternative drug named Tafenoquine. Primaquine
used for EEC
Global Malaria Prevention and Control
• Most death occur among children living in Africa
where a child dies every minute from malaria.
• Malaria mortality rates among children in Africa
have reduced by an estimated 54% since 2000's.
• Diagnosis and prompt treatment to prevent
complication.
• Avoidance of exposure to mosquitoes at there peak
feeding time (usually dusk to dawn.
• Insect repellents, insecticide - impregnated bed or
other materials.
• suitable clothing.
• Widespread use of bed nets.
• Chemoprophylaxis refer to the administration of a
medication for the purpose of preventing disease
or infection.
 2-GENUS TOXOPLASMA
Toxoplasma gondii

• Disease: Toxoplasmosis.
• It will probably infect almost any mammal.
• Like most of the apicomplexa, toxoplasma is an obligate
intracellular parasite.
• Life cycle includes two phases called the intestinal (or
enteroepithelial) and extraintestinal phases.
• The intastinal phases occurs in cats only (wild as will as
domesticated cats) and produces oocyst.
• Extraintestinal phases occurs in all infected animals
(including cats) and produced “tachyzoites” and eventually,
“bradyzoites”
• Intermediate host: human (Accidental host ), cattle ,
rodents.
• Final host: cats (sexual cycle) gives mature oocyst in
faeces.

• Infective stage: fecal oocyst from cats , or tissue cyst

from cattle or Tachyzoite → from pregnant women
by bloodstream.
Mode of infection mostly:
Mode of infection →mostly:
Eating uncooked infected meat, particularly
lamb and pork containing tissue cyst.
Ingestion of mature Oocyst through food,
water, or fingers contaminated with cat feces.
Intrauterine infection from mother to fetus
(congenital toxoplasmosis).
Blood transfusion or transplantation from
infected donors.
Habitat: obligatory intracellular in different
RES and all nucleated cell in different organ.
Oocyst: excreted in cat feces contains 2
sporocysts, each one contain 4 Sporozoites .
Toxoplasa gondii morphology
•The name Toxoplasma is derived from the shape of the organism, which is crescent-like
(toxon is Greek for “arc”). Plasma mean “form”
•Has anterior apical end with conoid and posterior rounded end.
•The conoid end is believed to be central in breaching the host’s cell membrane.
•It has three main secretary organelles used for adhesion and attachment, also facilitated
the motility, penetration of the organism.
•Central nucleus.
•Single mitochondrion, golgi body and rough endoplasmic reticulum (ER)
•Tachyzoite has no organ of locomotion, but it moves by gliding, flexing, undulating &
rotating.

Tachyzoite MØ with ↑Tachyzoite ↑Tissue cyst ↑Oocyst

In human:
Tachyzoite: trophozoite multiply rapidly.
Bradyzoite: trophozoite multiply slowly.
Life cycle of Toxoplasma
1-The asexual stage in the intermediate hosts (Man &mammals)
Exoenteric cycle occurs in humans, rodents, cattle, pigs and birds , which are
the intermediate hosts.

Humans acquire infection after:

•Eating uncooked infected meat, particularly lamb and pork containing tissue
cysts, ingestion of mature oocysts through food, water, or fingers contaminated
with cat feces directly or indirectly.
•Intrauterine infection from mother to fetus (congenital toxoplasmosis).
•Blood transfusion or transplantation from infected donors.

Sporozoites from the oocysts and bradyzoites from the tissue cysts enter into the
intestinal mucosa and multiply asexually and tachyzoites are formed
(endodyogeny).
• Multiplication is a process called “ endodyogeny “ which is asexual
multiplication in which two daughter cyst are formed with in parent cells

Tachyzoites continue to multiply and spread by lymphatic system and blood.

Some tachyzoites also spread to distant extraintestinal organs like brain, eye,
liver, spleen, lung, and skeletal muscles and form tissue cysts.
Tachyzoite (The slowly multiplying form inside the tissue cysts) remain
viable for years and may be reactived in immune suppression causing
renewed infection in the host.
The sexual stage in the definitive host cat, (Intestinal or Enteric cycle).
Both sexual reproduction (gametogony) and asexual reproduction (schizogony) occur
within the mucoscalepithelial cells of the small intestine of the cat.

Cat acquires infection by ingestion of tissue cysts in the meat of rats and other animals
or by ingestion of oocysts passed in its feces.

The bradyzoites are released in the small intestine and they undergo asexual
multiplication (schizogony) leading to formation of merozoites.

Some merozoites enter extraintestinal tissues resulting in the formation of tissue cysts in
other organs.

Other merozoites transform into male and female gametocytes and sexual cycle
(gametogony) begins with the formation of microgamete and macrogamete zygote
oocyst maturation stages (sporulation) in the soil with feces.

Mature oocyst containing 8 sporozoites is the infective form ingested by either

Intermediate host to form tissue cyst or taken by Final host to complete the sexual life
cycle.
Zygot↓ ↓Mature Sporulated Oocyst
Pathogenicity:-
As an obligatory parasite, it gets nutrients and escapes from the host’s
immune response. T. gondii invades and multiplies asexually as tachyziotes
within the cytoplasm of any nucleated cell.

The parasite affects especially the tissues of lung, heart, brain, RES, and
lymphoid tissues leading to necrosis and inflammation.

In immunocompetent persons, multiplication of tachyziotes stops and tissue

cysts form which persist for years, especially in brain and muscle.

In immunocompromised patients, cyst rupture or primary exposure to the

infection leads to dissemination to other tissues via blood and lymphatics.
Clinical manifestations:
After infection of the intestinal epithelium, the organisms spread to other organs,
especially the brain, lungs, liver, and eyes.

Toxoplasmosis rarely produces symptoms in normal individuals. So, most primary

infections in immunocompetent adults are asymptomatic.

Most common recognized finding is cervical lymphadenopathy, usually painless and

fever, Single or multiple enlarged nodes may persist at one site or there may be
involvement of many scattered nodes.

Its serious consequences are limited to:

1-Pregnant women 2- Immuno-deficient hosts.
The Toxoplasma may infect the placenta in the course of acute primary disease, and
if the parasite penetrates to the fetal side, the fetus may become infected.

The ability of the parasite to cross the placenta depends on the anatomic
characteristics of the placenta, which change with the stage of gestation.
Total maternal-fetal transmission is about 30% throughout all of gestation, but
varies from 6% at 13 weeks to 72% at 36 weeks.

VS, the severity of fetal damage is highest when the infection is transmitted in early
pregnancy.

Infections in the first trimester and early second trimester may lead to spontaneous
abortion, stillbirth or severe neonatal disease with encephalitis, chorioretinitis and
hepatosplenomegaly. Intracranial calcifications are also seen.

Positive IgG results indicate that the woman is immunized and is not at risk of
transmitting the infection to the fetus.

Negative IgG results with confirmed positive IgM results indicate a recent infection.

In conclusive results should be confirmed on a new specimen 3 weeks after the first
test.
 The great majority of infants born with toxoplasmosis are asymptomatic or have
disease that is not detected by routine neonatal examination.

Most babies infected during pregnancy show no sign of toxoplasmosis when they are
born.

But many of them develop learning, visual, and hearing disabilities later in life.

Congenital Toxoplasmosis characterized by classical Sabin tetrad which they are:

1-Hydrocephalus (Microcephaly 2-Chorioretinitis 3-Cerebral calcification

4-Convulsion (Seizure)
Diagnosis:
The demonstration of the Toxoplasma gondii organism in blood, body fluids, or tissue.
Detection of Toxoplasma gondii antigen in blood or body fluids (ELISA) technique.
Serologically: IgM and IgG.
Polymerase Chain Reaction on body fluids, including CSF, amniotic fluid, and blood.
Animal inoculation: inoculation of suspected infected tissues into experimental
animals.
Culture: inoculation of suspected infected tissues into tissue culture.
Treatment:
1- Acute infections benefit from pyrimethamine or sulphadiazine.

2- For pregnant woman spiramycin is a successful alternative drug for toxoplasmosis

Control:
Pregnant women are advised to avoid cat litter.

Management to control and handle uncooked and undercooked meat carefully.

Wear gloves when handling soil.

Wash hands with soap and water after outdoor activities

When preparing raw meat, wash any cutting boards, sinks, knives that touched the
raw meat thoroughly with soap and hot water to avoid contaminating other foods.