Intestinal Protozoan Infections

Giardia Lamblia
Causes giardiasis

Only common pathogenic protozoan found in duodenum and jejunum of humans

Exists in 2 forms

trophozoite

heart-shaped organism, has 4 pairs of flagella

a large concave sucking disk on the ventral surface helps the organism to
adhere the intestinal villi.

cyst

as the organism passes into the colon, they typically encyst, the cysts are
passed in the stool

cysts are ellipsoid, thick-walled, highly resistant,

cysts contain two nuclei as - immature forms and four as - mature cysts

Intestinal Protozoan Infections 1

 only pathogenic for humans (weakly)

cysts may be found in large numbers in stools of ENTIRELY ASYMPTOMATIC

persons

In some persons, however, large numbers of parasites attached to the bowel wall
may cause irritation and low-grade inflammation of the duodenal or jejunal
mucosa, with consequent acute or chronic diarrhea associated with crypt
hypertrophy, villous atrophy or flattening,
and
epithelial cell damage.

Stools - watery, semisolid, greasy, bulky, foul-smelling

Additional Symptoms: malaise, weakness, weight loss, abdominal cramps,

distention and flatulence may continue for long periods.

collecting multiple samples over several days - recommended to increase the

likelihood of microscopically detecting cysts in smears.

Humans are infected:

by ingestion of fecally contaminated water or food containing giardia cysts

by direct fecal contamination, (may occur in day care centers, refugee camps,
and institutions, or during oral–anal sex).

Intestinal Protozoan Infections 2

 Cysts can survive in water for up to 3 months.

Humans may be infected with various animal giardia harbored by rodents, deer,
cattle, sheep, horses, or household pets.

Associated with campers

Entamoeba Histolytica
cysts are present only in the lumen of the colon and in mushy/formed feces

the cyst may contain a glycogen vacuole and chromatoid (masses of

ribonucleoprotein) bodies with characteristic rounded ends (in contrast to splinter
chromatoidals in developing cysts of Entamoeba coli).

Nuclear division occurs within the cyst, resulting in a quadrinucleated cyst, and the
chromatoid bodies and glycogen vacuoles disappear.

Diagnosis in most cases rests on the characteristics of the cyst, as trophozoites

usually appear only in diarrheic feces in active cases and survive for only a few
hours.

The ameboid trophozoite is the only form present in tissues.

The cytoplasm has two zones, a hyaline outer margin and a granular inner
region that may contain red blood cells (pathognomonic) but ordinarily contains no
bacteria.

The nuclear membrane is lined by fine, regular granules of chromatin with a small
central body (endosome or karyosome).

Intestinal Protozoan Infections 3

 Disease results when the trophozoies invade the intestinal epithelium and form
discrete ulcers with a pinhead-sized center and raised edges, from which mucus,
necrotic cells, and amebae pass.

Intestinal Protozoan Infections 4

 The trophozoites multiply and accumulate above the muscularis mucosae (The
muscularis mucosa is the outermost layer of the mucosa), often spreading laterally.

Rapid lateral spread of the multiplying amebae follows, undermining the mucosa
and producing the characteristic “flask-shaped” ulcer of primary amebiasis:

a small point of entry, leading via a narrow neck through the mucosa into an
expanded necrotic area in the submucosa.

Bacterial invasion usually does not occur at this time, cellular reaction is limited, and
damage is by lytic necrosis.

Subsequent spread may coalesce colonies of amebae, undermining large areas of

the mucosal surface.

Trophozoites may penetrate the muscle layers and occasionally the serosa,
leading to perforation into the peritoneal cavity.

Subsequent enlargement of the necrotic area produces gross changes in the ulcer,
which may develop shaggy overhanging edges, secondary bacterial invasion,
and accumulation of neutrophilic leukocytes.

Secondary intestinal lesions may develop as extensions from the primary lesion
(usually in the cecum, appendix, or nearby portion of the ascending colon).

The organisms may travel to the ileocecal valve and terminal ileum,
producing a

Intestinal Protozoan Infections 5

 chronic infection.

The sigmoid colon and rectum are favored sites for later lesions.

An amebic inflammatory or granulomatous tumorlike mass (ameboma) may form on

the intestinal wall, sometimes growing sufficiently large to block the lumen.

Factors that determine invasion of amebae include the following:

the number of amebae ingested,

the pathogenic capacity of the parasite strain,

host factors such as gut motility and immune competence,

the presence of suitable enteric bacteria that enhance amebic growth.

Trophozoites, especially with red blood cells in the cytoplasm, found in liquid or
semiformed stools are pathognomonic (specific).

Symptoms vary greatly depending on the site and intensity of lesions. in serious
disease symptoms may be:

Extreme abdominal tenderness,

fulminating dysentery,

dehydration,

incapacitation

In less acute disease,

onset of symptoms - usually gradual and often includes:

episodes of diarrhea,

Intestinal Protozoan Infections 6

 abdominal cramps,

nausea

vomiting,

urgent desire to defecate.

More frequently, there will be weeks of cramps and general discomfort, loss of
appetite, and weight loss, with general malaise.

Symptoms may develop within 4 days of exposure, may occur up to a year later, or
may never occur.

Extraintestinal infection is metastatic and rarely occurs by direct extension from

the bowel.

By far the most common form is amebic hepatitis or liver abscess, which is
assumed to be due to microemboli, including trophozoites carried through the portal
circulation.

It is assumed that hepatic microembolism with trophozoites is a common

accompaniment of bowel lesions but that these diffuse focal lesions rarely
progress.

A true amebic abscess is progressive, nonsuppurative (unless secondarily

infected), and destructive without compression and formation of a wall.

The contents are necrotic and bacteriologically sterile, active amebae being
confined to the walls. A characteristic “anchovy paste” is produced in the abscess
and seen on surgical drainage.

More than half of patients with amebic liver abscess give no history of intestinal
infection, and rarely, amebic abscesses occur elsewhere (eg, lung, brain, spleen).

Any organ or tissue in contact with active trophozoites may become a site of
invasion and abscess.

Hepatic abscess, usually showing as an elevation of the right dome of the

diaphragm,
can be observed by ultrasonography, computerized tomography, magnetic
resonance imaging, or radioisotope scanning.

Serologic tests in these cases are usually strongly positive.

Intestinal Protozoan Infections 7

Intestinal Protozoan Infections 8
 Cryptosporidium
Cryptosporidium species, typically Cryptosporidium hominis, can infect the
intestine in immunocompromised persons and cause severe, intractable diarrhea

they have long been known as parasites of rodents, fowl, rhesus monkeys, cattle,
and other herbivores and have probably been an unrecognized cause of self-
limited, mild gastroenteritis and diarrhea in humans.

Oocysts measuring 4–5 μm are passed in feces in enormous numbers and are
immediately infectious.

When oocysts in contaminated foods and water are ingested, sporozoites excyst
and invade intestinal cells; the parasites multiply asexually within the apical portion

Intestinal Protozoan Infections 9

 of the intestinal cells, are released, and infect other intestinal cells to begin a new
cycle. (https://youtu.be/ee159M3wxA8?si=etUTcubCjwdL9sM-)

They also reproduce sexually, forming male microgamonts and female

macrogamonts that
fuse and develop into the oocysts.

Cryptosporidium inhabits the brush border of mucosal epithelial cells of the GI

tract, especially the surface of villi of the lower small bowel.

Intestinal Protozoan Infections 10

 The prominent clinical feature of cryptosporidiosis is watery diarrhea, which is mild
and self-limited (1–2 weeks) in normal persons but may be severe ,prolonged
immunocompromised or
very young or old individuals.

The small intestine is the most commonly infected site, but Cryptosporidium
infections have
also been found in other organs, including other digestive tract organs and the
lungs.

Diagnosis depends on detection of oocysts in fresh stool samples.

Stool concentration techniques using a modified acid-fast stain are usually

necessary, and
monoclonal antibody–based tests are available that can detect low levels of
fecal antigen.

The incubation period for cryptosporidiosis is from 1 to 12 days, and the disease is
acquired from infected animal or human feces or from fecally contaminated food or
water.

Intestinal Protozoan Infections 11

 The organisms are widespread and probably infect asymptomatically a significant
proportion of
the human population.

Occasional outbreaks, can result from inadequate protection, treatment, or filtration

of water supplies for large urban centers.

As few as 30 organisms can initiate an infection—and the ability of the parasite to

complete its life cycle, including the sexual phase, within the same individual makes
possible the fulminating infections frequently observed in immunosuppressed
individuals.

Intestinal Protozoan Infections 12

Intestinal Protozoan Infections 13
 Cyclospora

The life cycle of Cyclospora is similar to that of Cryptosporidium and appears to

involve only a single host.

Cyclospora, however, differs from Cryptosporidium in that Cyclospora oocysts are

not immediately infectious when passed in stools.

Unlike Cryptosporidium oocysts, which are infectious in the feces, Cyclospora

oocysts take days or weeks to become infectious, and because of this, direct
person-to-person transmission
through fecal exposure is
unlikely to occur.

Cyclosporiasis has been linked to waterborne and foodborne infections from

various types of fresh produce, including raspberries, mesclun, and basil, since the
1990s.

Altered mucosal architecture with shortening of intestinal villi due to diffuse edema
and infiltration of inflammatory cells leads to diarrhea, anorexia, fatigue, and
weight loss.

The duration of symptoms among untreated, nonimmune persons is often

prolonged but ultimately self-limited, with remitting-relapsing symptoms lasting up to
several weeks or months.

The incubation period for Cyclospora infections is about 1 week, similar to infections
with Cryptosporidium.

Specific requests for laboratory testing of Cyclospora are necessary (same for
Cryptosporidium) when examining stools for oocysts (8–10 μm), which are acid-fast
positive (reddish).

Unlike infections with Cryptosporidium, Cyclospora infections are treatable with

trimethoprim–sulfamethoxazole (TMP-SMZ).

Intestinal Protozoan Infections 14

 Trichomonas vaginalis
exists only as a trophozoite (no cyst stage);

has four free flagella that arise from a single stalk and a fifth flagellum, which forms
an undulating membrane.

Intestinal Protozoan Infections 15

 It is pyriform and approximately 20 μm in length and 10 μm wide.

T vaginalis is sexually transmitted, and most infections are asymptomatic or mild

for both women and men.

In women:

The infection is normally limited to the vulva, vagina, and cervix; it does not
usually extend to the uterus.

The mucosal surfaces may be tender, inflamed, eroded, and covered with a
frothy yellow or cream-colored discharge.

In men:

The prostate, seminal vesicles, and urethra may be infected.

Signs and symptoms in females:

profuse vaginal discharge, local tenderness, vulval pruritus, and burning.

About 10% of infected males have a thin, white urethral discharge.

The incubation period is from around 5 to 28 days.

Infants may be infected during birth.

Intestinal Protozoan Infections 16

 Control of T vaginalis infections always requires simultaneous treatment of both
sexual
partners.

Mechanical protection (condoms) should be used during intercourse until the

infection is eradicated in both partners

Intestinal Protozoan Infections 17

Intestinal Protozoan Infections 18
 Blood And Tissue Protozoan Infections
Trypanosoma
The genus Trypanosoma appears in the blood as trypomastigotes, with elongated
bodies supporting a longitudinal lateral undulating membrane and a flagellum
that borders the free
edge of the membrane and emerges at the anterior end as a whiplike extension.

The kinetoplast (circular DNA inside the single mitochondrion) is a darkly staining
body lying immediately adjacent to the basal body from which the flagellum arises.

Intestinal Protozoan Infections 19

 T brucei rhodesiense, T brucei gambiense, and Trypanosoma brucei brucei (which
causes a
sleeping sickness called nagana in livestock and game animals) are
indistinguishable morphologically but differ biochemically, ecologically, and
epidemiologically.

Infective trypanosomes of T brucei gambiense and T brucei rhodesiense are

introduced through the bite of the tsetse fly and multiply at the site of inoculation to
cause variable induration and swelling (the primary lesion), which may progress to
form a trypanosomal chancre.

The African forms multiply extracellularly as trypomastigotes in the blood as well as

in
lymphoid tissues. They spread to lymph nodes, to the bloodstream, and, in terminal
stages, to the central nervous system (CNS), where they produce the typical
sleeping sickness
syndrome: lassitude, inability to eat, tissue wasting, unconsciousness, and death.
CNS involvement is most characteristic of African trypanosomiasis. T brucei
rhodesiense appears in the cerebrospinal fluid in about 1 month and T brucei
gambiense in several
months, but both are present in small numbers. T brucei
gambiense infection is chronic and leads to progressive diffuse
meningoencephalitis, with death from the sleeping syndrome usually following in 1–
2 years. The more rapidly fatal
T brucei rhodesiense produces somnolence and coma only
during the final weeks of a terminal infection. The trypanosomes are transmissible
through the placenta, and congenital
infections occur in hyperendemic areas.
The African trypanosomes of the T brucei complex are
remarkable in that they undergo antigenic variation through a
series of genetically controlled surface glycoproteins that coat
the surface of the organism (variant surface glycoproteins, or
VSGs). Successive waves of parasites in the host bloodstream
are each covered with a distinct coat. This process is due to
genetically induced changes of the surface glycoprotein.
By producing different antigenic surface membranes, the

Intestinal Protozoan Infections 20

 parasite is able to evade the host’s antibody response. Each
population is reduced but is promptly replaced with another
antigenic type before the preceding one is eliminated. Each

trypanosome is thought to possess about 1000 VSG genes, an

example of mosaic gene formation.
Epidemiology
African trypanosomiasis is restricted to recognized tsetse
fly belts. T brucei gambiense, transmitted by the streamside
tsetse Glossina palpalis and several other humid forest tsetse
vectors, extends from West to Central Africa and produces
a relatively chronic infection with progressive CNS involvement. T brueci rhodesiense,
transmitted by the woodlandsavanna Glossina morsitans, Glossina pallidipes, and
Glossina
fuscipes, occurs in the eastern and southeastern savannas of
Africa, with foci west of Lake Victoria. It causes a smaller
number of cases but is more virulent. Bushbuck and other
antelopes may serve as reservoirs of T brucei rhodesiense,
whereas humans are the principal reservoir of T brucei gambiense. Control depends on
searching for and then isolating
and treating patients with the disease; controlling movement of people in and out of fly
belts; using insecticides in
vehicles; and instituting fly control, principally with aerial
insecticides and by altering habitats. Contact with reservoir
animals is difficult to control, and insect repellent is of little
value against tsetse bites.

TRYPANOSOMA CRUZI (BLOOD

FLAGELLATE)
The Organism
T cruzi has three developmental stages: epimastigotes in the
vector, trypomastigotes (in the bloodstream), and a rounded
intracellular stage, the amastigote. The blood forms of T cruzi
are present during the early acute stage and at intervals thereafter in smaller numbers.
They are typical trypomastigotes with

Intestinal Protozoan Infections 21

 a large, rounded terminal kinetoplast in stained preparations,
but they are difficult to morphologically distinguish from African trypanosomes. The
tissue forms, which are most common
in heart muscle, liver, and brain, develop as amastigotes that
multiply to form an intracellular colony after invasion of the
host cell or phagocytosis of the parasite (Figure 46-5).
Pathology and Pathogenesis
Infective forms of T cruzi do not pass to humans by triatomine bug bites (which is the
mode of entry of the nonpathogenic Trypanosoma rangeli); rather, they are introduced
when
infected bug feces are rubbed into the conjunctiva, the bite
site, or a break in the skin. At the site of T cruzi entry, there
may be a subcutaneous inflammatory nodule or chagoma.
Unilateral swelling of the eyelids (Romaña’s sign) is characteristic at onset, especially in
children. The primary lesion is
accompanied by fever, acute regional lymphadenitis, and dissemination to blood and
tissues.
Interstitial myocarditis is the most common serious condition in Chagas disease. Other
organs affected are the liver,
spleen, and bone marrow, especially with chronic T cruzi infection. Invasion or toxic
destruction of nerve plexuses in the alimentary tract walls leads to megaesophagus and
megacolon,
especially in Brazilian Chagas disease. Megaesophagus and
megacolon are absent in Colombian, Venezuelan, and Central
American Chagas disease. T rangeli of South and Central America
infects humans without causing disease and must therefore be
carefully distinguished from the pathogenic species.
Epidemiology
American trypanosomiasis (Chagas disease) is especially
important in Central and South America, although infection
of animals extends much more widely—for example, to Maryland and southern
California. A few autochthonous human
cases have been reported in Texas and southern California.
Since no effective treatment is known, it is particularly important to control the vectors
with residual insecticides and habitat modification, such as replacement of mud-brick

Intestinal Protozoan Infections 22

 (adobe)
houses with thatched roofs where the insects live, and to avoid
contact with animal reservoirs. Chagas disease occurs largely
among people in poor economic circumstances. An estimated
7–8 million people harbor the parasite, and many of these
individuals sustain heart damage, with the result that their
ability to work and their life expectancy are sharply reduced.

LEISHMANIA SPECIES (BLOOD

FLAGELLATES)
The Organisms
The sandfly transmits the infective promastigotes during a bite. The promastigotes
rapidly change to amastigotes
after phagocytosis by macrophages or monocytes, and then
multiply, filling the cytoplasm of the cell. The infected cells
burst, and the released parasites are again phagocytosed.
This process is repeated, producing a cutaneous lesion or visceral infection depending
on the species of parasite and the host
response. The amastigotes are ovoid and approximately 2–3 μm
in size. The nucleus and a dark-staining, rodlike kinetoplast
can be seen as a “dot” and a “dash.”
The genus Leishmania, widely distributed in nature, has
a number of species that are nearly identical morphologically.
Clinical characteristics of the disease are traditional differentiating characteristics, but
many exceptions are now recognized. The different leishmanias present a range of
clinical
and epidemiologic characteristics that, for convenience only,
are combined under three clinical groupings: (1) cutaneous
leishmaniasis (Oriental sore, Baghdad boil, wet cutaneous sore, dry cutaneous sore,
chiclero ulcer, uta, and other
names), (2) mucocutaneous leishmaniasis (espundia), and
(3) visceral leishmaniasis (kala-azar—Hindi for black fever).

Intestinal Protozoan Infections 23

 There are strain differences in virulence, tissue tropism,
and biologic and epidemiologic characteristics, as well as
in the serologic and biochemical criteria. Some species can
induce several disease syndromes (eg, visceral leishmaniasis from organisms of
cutaneous leishmaniasis or cutaneous leishmaniasis from organisms of visceral
leishmaniasis).
Similarly, the same clinical condition can be caused by different agents.
Pathology and Pathogenesis
Leishmania tropica, Leishmania major, Leishmania mexicana, Leishmania braziliensis,
and other cutaneous forms
induce a dermal lesion at the site of inoculation by the sandfly (cutaneous
leishmaniasis, Oriental sore, Delhi boil, etc).
The dermal layers are first affected, with cellular infiltration
and proliferation of amastigotes intracellularly and spreading
extracellularly, until the infection penetrates the epidermis
and causes ulceration. Satellite lesions may be found (hypersensitivity or recidivans
type of cutaneous leishmaniasis) that
contain few or no parasites, do not readily respond to treatment, and induce a strong
granulomatous scarring reaction.
In Venezuela, a cutaneous disseminating form, caused by L
mexicana pifanoi, is known. In Ethiopia, a form known as
Leishmania aethiopica causes a similar nonulcerating, blistering, spreading cutaneous
leishmaniasis. Both forms are
typically anergic and nonreactive to skin test antigen and
contain large numbers of parasites in the dermal blisters.
Leishmania braziliensis braziliensis causes mucocutaneous or nasopharyngeal
leishmaniasis in Amazonian
South America. It is known by many local names. The lesions
are slow growing but extensive (sometimes 5–10 cm). From
these sites, migration appears to occur rapidly to the nasopharyngeal or palatine
mucosal surfaces, where no further
growth may take place for years. After months to more than
20 years, relentless erosion may develop, destroying the nasal
septum and surrounding regions. In some instances, death
occurs from asphyxiation due to blockage of the trachea,
FIGURE 46-6 A patient with espundia caused by Leishmania

Intestinal Protozoan Infections 24

 braziliensis. (Reproduced with permission from WHO/TDR image
library.)
starvation, or respiratory infection. This is the classic clinical
picture of espundia (Figure 46-6), most commonly found in
the Amazon basin. At high altitudes in Peru, the clinical features (uta) resemble those of
Oriental sore. L braziliensis guyanensis infection frequently spreads along lymphatic
routes,
where it appears as a linear chain of nonulcerating lesions.
L mexicana infection is more typically confined to a single,
indolent, ulcerative lesion that heals in about 1 year, leaving a
characteristic depressed circular scar. In Mexico and Guatemala, the ears are frequently
involved (chiclero ulcer), usually
with a cartilage-attacking infection without ulceration and
with few parasites.
Leishmania donovani, which causes visceral leishmaniasis or kala-azar, spreads from
the site of inoculation to multiply in reticuloendothelial cells, especially macrophages in
spleen, liver, lymph nodes, and bone marrow (Figure 46-7).
This is accompanied by marked hyperplasia of the spleen.
Progressive emaciation is accompanied by growing weakness. There is irregular fever,
sometimes hectic. Untreated
cases with symptoms of kala-azar usually are fatal. Some
forms, especially in India, develop a postcure florid cutaneous resurgence, with
abundant parasites in cutaneous vesicles, 1–2 years later (post-kala-azar dermal
leishmanoid).

Epidemiology
According to the World Health Organization (WHO), there
are an estimated 1.3 million new cases of leishmaniasis
occurring annually with 20,000–30,000 deaths (WHO 2014).
Oriental sore occurs mostly in the Mediterranean region,
North Africa, and the Middle and Near East. The “wet” type,
caused by L major, is rural, and burrowing rodents are the
main reservoir; the “dry” type, caused by L tropica, is urban,
and humans are presumably the only reservoir. For L braziliensis, there are a number of
wild animal hosts, but apparently there are no domestic animal reservoirs. Sandfly

Intestinal Protozoan Infections 25

 vectors
are involved in all forms.
L donovani is found focally in most tropical and subtropical countries. Its local
distribution is related to the prevalence
of specific sandfly vectors. In the Mediterranean littoral and
in middle Asia and South America, domestic and wild canids
are reservoirs, and in the Sudan, various wild carnivores and
rodents are reservoirs of endemic kala-azar. No animal reservoirs have been found for
the forms from India and Kenya.
Control is aimed at destroying breeding places and dogs,
where appropriate, and protecting people from sandfly bites.

Intestinal Protozoan Infections 26