Amebiasis is caused by the protozoan Entamoeba histolytica. It commonly causes asymptomatic intestinal infection but can also cause intestinal disease ranging from dysentery to liver abscesses. The parasite exists in two forms - a motile trophozoite form and a cyst form. Infection occurs through ingestion of cysts in contaminated food or water. Most infections are asymptomatic, but 10% can cause intestinal or extraintestinal disease. Diagnosis involves stool examination and serology. Treatment involves luminal agents for intestinal infection and metronidazole or tinidazole for invasive disease. Surgery may be needed for complications like perforation or toxic megacolon.
2. ⢠Amebiasis is a common intestinal protozoal
infection that may also cause systemic
manifestations.
⢠About 90% of infections are asymptomatic,
and the remaining 10% produce a spectrum of
clinical syndromes ranging from dysentery to
abscesses of the liver or other organs.
3. Background
â Amebiasis is a parasitic infection caused by the
protozoon Entamoeba histolytica.
â Amebiasis is the third leading parasitic cause of
death worldwide.
4.
5.
6. Life cycle
Infection by Entamoeba histolytica
1 . Occurs by ingestion of mature cysts in fecally
contaminated food, water, or hands.
2 . Excystation occurs in the small intestine and
3 . Trophozoites are released, which migrate to the large
intestine.
4 . Trophozoites multiply by binary fission and produce cysts
, which are passed in the feces.
Because of the protection conferred by their walls, the cysts
can survive days to weeks in the external environment and
are responsible for transmission. (Trophozoites can also be
passed in diarrheal stools, but are rapidly destroyed once
outside the body, and if ingested would not survive exposure
to the gastric environment.)
7. .⢠In many cases, the trophozoites remain confined to the
intestinal lumen ( A: non-invasive infection) of
individuals who are asymptomatic carriers, passing cysts
in their stool.
⢠In some patients the trophozoites invade the intestinal
mucosa ( B : intestinal disease), or,
⢠Pass through the bloodstream, extraintestinal sites such
as the liver, brain, and lungs (C : extra-intestinal
disease), with resultant pathologic manifestations.
The invasive and noninvasive forms represent two
separate species, respectively E. histolytica and E.
dispar, however not all persons infected with E.
histolytica will have invasive disease. These two species
are morphologically indistinguishable.
8. .
The parasite has 2 forms:
- a motile form, called the trophozoite, and
- a cyst form
- The trophozoite of E histolytica inhabits
the large intestine to produce lesions of
amebic colitis.
âInvasion of the colonic mucosa leads to
dissemination of the organism to
extracolonic sites, predominantly the liver.
9. .
â Cysts passed in the feces can survive in moist
environmental conditions for weeks to months. Upon
ingestion of fecally contaminated food or water, the
cysts travel to the small intestine, where the
trophozoites are released.
â In 90% of patients, the trophozoites re-encyst and
produce asymptomatic infection, which usually
spontaneously resolves within 12 months.
â In the remaining 10% of patients who are infected,
the parasite causes symptomatic amebiasis.
â Under unfavorable conditions, the trophozoite
reverts to the cyst form, and the life cycle is
repeated.
10. .
âEntamoeba dispar is a nonpathogenic
protozoon morphologically identical to E
histolytica.
âThese 2 species of Entameba can be
distinguished by the monoclonal antibodies.
âSpecific and sensitive means to detect E
histolytica in stool are now available and
include antigen detection and polymerase
chain reaction (PCR).
11. Infections due to E histolytica
⢠Intestinal disease
â Asymptomatic infection
â Symptomatic noninvasive infection
â Acute proctocolitis( inflammation of the rectum and colon )
â Fulminant colitis (coming on suddenly with great severity ) with
perforation
â Toxic megacolon (dialated colon )
â Chronic nondysenteric colitis
â Ameboma (an inflamed, tumor like, spreading nodule )
â Perianal ulceration
⢠Extraintestinal disease
â Liver abscess
â Pleuropulmonary disease
â Peritonitis
â Pericarditis
â Brain abscess
â Genitourinary disease
12. Pathophysiology
⢠fecal-oral route
⢠excystation in the small bowel and invasion of the
colon by the trophozoites.
⢠Invasive disease begins with the adherence of E
histolytica to colonic mucins, epithelial cells, and
leukocytes.
⢠Adherence of the trophozoite is mediated by a
galactose-inhibitable adherence lectin.
13. Cont ..
⢠After adherence, trophozoites :-
â invade the colonic epithelium to produce the
ulcerative lesions typical of intestinal amebiasis .
â lyse the target cells by using lectin to bind to the
target cells' membranes and using the parasite's
ionophore like protein to induce a leak of ions (i.e,
Na+, K+, Ca+) from the target cell cytoplasm.
⢠An extracellular cysteine kinase causes
proteolytic destruction of the tissue, producing
flask-shaped ulcers
14. Cont ..
âSpread of amebiasis to the liver occurs via the
portal blood.
âTrophozoites ascend the portal veins to produce
liver abscesses filled with acellular
proteinaceous debris. This material has the
appearance of anchovy paste.
âThe trophozoites of E histolytica lyse the
hepatocytes and the neutrophils. This explains
the paucity (smallness of quantity ) of
inflammatory cells within the liver abscesses.
15. Cont ..
⢠Serum antibodies in patients with amebic liver
abscess develop in 7 days and persist for as
long as 10 years.
⢠E dispar infections do not elicit antibody
response
⢠Mucosal immunoglobulin A (IgA) response to
E histolytica occurs during invasive amebiasis.
⢠However, no evidence suggests that invasive
amebiasis is increased in incidence or severity
in patients with IgA deficiency.
16. Cont ..
⢠Cell-mediated immunity is important in limiting the
disease and preventing recurrences.
⢠production of lymphokines, including interferon-d
(IFN-d), which activates the killing of E histolytica
trophozoites by the macrophages. This killing
depends on contact, oxidative pathways,
nonoxidative pathways, and nitric oxide (NO).
⢠Lymphokines, such as tumor necrosis factor-alpha
(TNF-a), are capable of activating the amebicidal
activity of neutrophils.
⢠During acute invasive amebiasis, T-lymphocyte
response to E histolytica antigens is depressed by a
parasite-induced serum factor.
17. Mortality/Morbidity
⢠Mortality rate in patients with uncomplicated amebic
liver abscess is less than 1%.
⢠Fulminant amebic colitis has a mortality rate of more
than 50%.
⢠Pleuropulmonary amebiasis has a mortality rate of 15-
20%.
⢠Amebic pericarditis has a case fatality rate of 40%.
⢠Cerebral amebiasis is highly fatal, with a 90% death rate.
Increased severity of amebiasis is noted :
⢠in children (especially neonates),
⢠women who are pregnant or postpartum, individuals
who use corticosteroids,
⢠individuals with malignancy, and
⢠malnourished individuals.
18. Cont ..
Sex
⢠Invasive amebiasis, including amebic liver
abscess, is much more common in adult males
than in females. However, amebic liver
abscess is equally common in both sexes
among prepubertal children.
Age
⢠Symptomatic intestinal amebiasis occurs in all
age groups.
⢠Liver abscesses due to amebiasis are 10 times
more frequent in adults than in children.
19. ⢠Diagnosis
Clinical
History
⢠The incubation period is commonly 2-4 weeks but
ranges from a few days to years.
⢠Amebiasis is more severe in very young patients, in
elderly patients, and in patients receiving
corticosteroids.
⢠The clinical spectrum of amebiasis ranges from
asymptomatic infection to fulminant colitis and
peritonitis to extraintestinal amebiasis, most
commonly amebic liver abscess.
20. Cont ..
⢠Asymptomatic infections are common following
ingestion of the parasite. E dispar does not cause
invasive disease or antibody production.
⢠As many as 90% of E histolytica infections are also
asymptomatic. The infection is self-limited but may
be recurrent.
⢠Only antigen detection tests can distinguish between
E histolytica and E dispar.
21. Cont ..
Amebic colitis : -
â gradual in onset, with symptoms presenting over 1-2 weeks,
â Diarrhea is the most common symptom.
â cramping abdominal pain, watery or bloody diarrhea, and weight
loss.
â Fever is noted in 10% of patients.
⢠Fulminant (coming on suddenly with great severity )amebic
colitis : -
â is a rare complication of amebic dysentery (<0.5%).
â It presents with a rapid onset of severe bloody
diarrhea, severe abdominal pain, and high fever.
â Children younger than 2 years are at increased risk.
â Intestinal perforation is common.
22. Cont ..
⢠Patients may develop toxic megacolon, which is
typically associated with the use of corticosteroids.
⢠Chronic amebic colitis is clinically similar to
inflammatory bowel disease. Recurrent episodes of
bloody diarrhea and vague abdominal discomfort
develop in 90% of patients with chronic amebic
colitis who have antibodies to E histolytica.
⢠Amebic colitis should be ruled out prior to treatment
of suspected inflammatory bowel disease because
corticosteroid therapy worsens amebiasis.
23. Cont..
⢠A less common form of intestinal disease,
ameboma,
â results from formation of annular colonic
granulation in response to the infecting amebae,
resulting in a large local lesion of the bowel.
â It presents as a right lower quadrant abdominal
mass, which may be mistaken for
carcinoma,tuberculosis, Crohn`s disease, or
lymphoma.
â Biopsy findings assist in establishing the correct
diagnosis.
24. Cont..
⢠Amebic liver abscess is the most common
form of extraintestinal amebiasis.
âIt results from spread of the organisms from the
intestinal submucosa to the liver via the portal
system.
âApproximately 40% of patients who have
amebic liver abscess do not have a history of
prior bowel symptoms.
â5% of patients with symptomatic intestinal
amebiasis and is 10 times as frequent in men as
in women.
25. Cont ..
â presents with fever and a constant, dull, upper
right abdominal or epigastrium pain.
â Involvement of the diaphragmatic surface of the
liver may lead to right-sided pleuritic pain or
referred shoulder pain.
Associated GI symptoms : -
â occur in 10-35% of patients and include nausea,
vomiting, abdominal distention, diarrhea, and
constipation.
â May present with vague abdominal discomfort,
weight loss, and anemia.
26. Cont...
â Pleuropulmonary amebiasis is most commonly
the result of contiguous spread from a liver
abscess rupturing through the right
hemidiaphragm.
â cough, pleuritic pain, and dyspnea.
â Hepatobronchial fistula expectoration of sputum
resembling anchovy paste. The trophozoites of E
histolytica may be found in the sputum sample.
â Amebic peritonitis is generally secondary to a
ruptured liver abscess. Left lobe liver abscesses
are more likely to rupture. Patients present with
fever and rigid distended abdomen.
â Roughly 2-7% of liver abscesses rupture into the
peritoneum.
27. Cont..
Amebic pericarditis : -
â caused by a rupture of the left liver lobe abscess
and occurs in 3% of patients with hepatic
amebiasis. It presents with chest pain and the
features of congestive heart failure.
Cerebral amebiasis : -
â abrupt onset and rapid progression to death in 12-
72 hours.
â presents with altered consciousness and focal
neurologic signs.
â CT scanning reveals irregular lesions without a
surrounding capsule.
â Tissue biopsy :- trophozoites.
Genitourinary involvement : -
â may cause painful genital ulcers or fallopian tube
amebiasis.
28. Physical
Acute amebic colitis : -
â lower quadrant abdominal tenderness.
â Fever is noted in only a minority of patients.
â Dehydration is uncommon.
â Occult blood is nearly always present in stools.
Amebic liver abscess : -
- fever and tender hepatomegaly.
- Right lower intercostal tenderness, particularly
posteriorly.
- Breath sounds may be diminished at the right lung base,
and rales may be heard.
- hepatomegaly, weight loss, and anemia.
Pleuropulmonary amebiasis:-
â produce findings of right-sided pleural effusions,
empyema, pneumonia, and lung abscess.
29. Cont ..
Amebic peritonitis : -
⢠present with fever and a tender, rigid, and distended
abdomen.
Amebic pericarditis : -
⢠presents with features of congestive heart faliure.
⢠pericardial friction rub may be audible.
Cerebral amebiasis : -
presents with altered consciousness and focal neurologic
signs.
CT scanning reveals irregular lesions without a
surrounding capsule or enhancement.
Genital ulcers :-
punched-out appearance and profuse discharge.
30. Differential Diagnosis
⢠Intestinal amebiasis should be distinguished
from the following conditions:
⢠Infectious conditions
â Campylobacter
â Shigella
â Salmonella
â Yersinia
â Enteroinvasive Escherichia coli
â Enterohemorrhagic E coli
31. Cont..
⢠Noninfectious conditions
â Inflammatory bowel disease
â Diverticulitis
Amebic liver abscess should be distinguished
from the following conditions:
â Pyogenic liver abscess
â Necrotic hepatoma
â Echinococcal cyst
⢠The probability of a liver abscess to be amebic
rather than pyogenic is increased by the history
of residence in or recent travel to endemic
areas, male sex, increased age (>50 y), presence
of a single lesion in the right lobe of the liver,
and the absence of jaundice, biliary disease
32. Laboratory Studies
Stool
Light microscopy:
⢠Examination of a fresh stool smear for
trophozoites that contain ingested RBCs.
⢠Routine microscopy cannot distinguish the E
dispar (nonpathogenic amebae) from E
histolytica.
⢠PCR-based diagnostic tests
⢠Other stool tests
â The stool samples are always heme positive.
â Fecal leukocytes may be absent.
33. Serum tests
âAntibody tests:
âIndirect hemagglutination antibody (IHA)
test
â Detection of immunoglobulin M (IgM)
antibodies
âELISA for Ab detection (most sensitive test)
âSigmoidoscopy or biopsy of symptomatic
sick patients.
34. Imaging Studies
Chest radiography : -
âelevated right hemidiaphragm and a
right-sided pleural effusion in patients
with amebic liver abscess.
âUltrasonography (amebic liver abscess
)
âcerebral amebiasis, CT shows irregular
lesions without a surrounding capsule
âMRI
35. Other Tests
âLeukocytosis without eosinophilia is
observed in 80% of cases.
âMild anemia may be noted.
Liver function tests : -
âelevated alkaline phosphatase levels (in
80% of patients),
âelevated transaminase levels,
âmild elevation of serum bilirubin level,
âErythrocyte sedimentation rate is elevated.
36. Treatment
⢠Medical Care
â Luminal agents that are minimally absorbed by the GI tract
(eg, paromomycin, iodoquinol, diloxanide furoate) are best
suited for such therapy.
â Metronidazole is the mainstay of therapy for invasive
amebiasis.
â Tinidazole for intestinal or extraintestinal amebiasis.
â Other nitroimidazoles with longer half-lives (ie, secnidazole,
ornidazole)
â Nitroimidazole therapy leads to clinical response in
approximately 90% of patients with mild-to-moderate
amebic colitis.
â Chloroquine has also been used for patients with hepatic
amebiasis.
37. Cont..
⢠Intraluminal parasites are not affected by
nitroimidazole therapy. Therefore,
nitroimidazole therapy should be followed by
treatment with a luminal agent such as
paromomycin or diloxanide furoate to prevent
a relapse.
⢠Broad-spectrum antibiotics may be added to
treat bacterial superinfection in a case of
fulminant amebic colitis and suspected
perforation.
38. Surgical Care
Surgical intervention :-
â perforated amebic colitis, massive GI bleeding, or toxic
megacolon.
â Amebic liver abscess generally responds to medical
therapy alone and drainage is seldom necessary.
â When necessary, imaging-guided percutaneous
treatment (needle aspiration or catheter drainage) has
replaced surgical intervention as the procedure of choice
for reducing the size of an abscess.
Indications for drainage : -
â Presence of left-lobe abscess (>10 cm in diameter)
â Rupture and
â abscess that does not respond to medical therapy within
3-5 days
39. Antibiotics
- Metronidazole is considered the drug of choice for
symptomatic, invasive disease.
â Paromomycin is the drug of choice for noninvasive
disease. Because parasites persist in the intestine
of 40-60% of patients treated with metronidazole,
follow it with paromomycin to cure luminal
infection.
â Do not give the 2 medications at the same time
because the diarrhea that often results from
paromomycin might be confused with continuing
active intestinal disease from the parasite.
40. Metronidazole (Flagyl, Protostat )
â Kills trophozoites of E histolytica in intestine and
tissue. Does not eradicate cysts from intestines.
⢠Adult
â Intestinal amebiasis:
PO: 500-750 mg PO tid for 5-10 d; alternatively, 2
g PO qd for 3 d or a single dose of 50 mg/kg
IV: 500 mg IV q6h for 5-10 d
Amebic liver abscess: 500 mg IV q6h for 10 d
⢠Pediatric
â 35-50 mg/kg/d PO/IV divided q8h for 10 d
41. Tinidazole (Fasigyn, Tindamax)
â 5-nitroimidazole derivative with selective antimicrobial
activity against anaerobic bacteria and protozoa. The
mechanism by which tinidazole exhibits activity against
Giardia and Entamoeba species is not known.
⢠Adult
â Intestinal amebiasis: 600 mg bid or 800 mg tid PO for 5 d;
alternatively, 2 g PO qd for 3 d with food
Hepatic amebic abscess: 2 g PO qd for 3-5 d with food
⢠Pediatric
â <3 years: Not established
>3 years:
Intestinal amebiasis: 50 mg/kg/d PO for 3 d with food; not
to exceed 2 g/dose
Amebic liver abscess: 50 mg/kg/d PO for 3-5 d with food;
not to exceed 2 g/dose, limited data exist for
42. Paromomycin ( Humatin )
Amebicidal aminoglycoside antibiotic that is
poorly absorbed. Active only against
intraluminal form of amebiasis. Used to
eradicate cysts of E histolytica following
treatment with metronidazole or tinidazole
for an invasive disease.
⢠Adult
â25-35 mg/kg/d PO divided q8h for 7 d
⢠Pediatric
âAdminister as in adults
43. Anthelmintics
⢠Iodoquinol (Yodoxin)
â Halogenated hydroxyquinoline. Luminal
amebicide; acts primarily in bowel lumen because
it is poorly absorbed. Best tolerated when given
with meals. Because it is active only against
intraluminal form of amebiasis, it is used to
eradicate cysts of E histolytica after treatment of
invasive disease.
⢠Adult
â 650 mg PO tid for 20 d
⢠Pediatric
â 30-40 mg/kg/d PO divided tid for 20 d; not to
exceed 2 g/d
44. Chloroquine phosphate (Aralen)
â Inhibits growth by concentrating within acid vesicles of
parasite, which increases internal pH of organism. Also
inhibits hemoglobin utilization and metabolism of parasite. In
vitro studies with trophozoites of E histolytica demonstrate
that chloroquine possesses amebicidal activity.
â Highly effective in treatment of amebic liver abscess when
administered with emetine or dehydroemetine.
⢠Adult
â Hepatic amebiasis:
500 mg salt (300-mg base) PO bid for 2 d, followed by 250 mg
salt (150-mg base) bid for 2-3 wk
⢠Pediatric
â Hepatic amebiasis: 10 mg (as base)/kg/d PO divided bid for 2-3
wk
45. Diloxanide furoate (Furamid, Entamizole, Furamide)
â Luminal amebicide; acts primarily in bowel lumen
because it is poorly absorbed. Used to eradicate
cysts of E histolytica after treatment of invasive
disease.
⢠Adult
â 500 mg PO tid for 10 d
⢠Pediatric
â 20 mg/kg/d PO divided tid for 10 d; not to exceed
1500 mg/d
46. Follow-up
Prevention
â Improved sanitation is critical to preventing
orofecal transmission of organisms such as E
histolytica.
â Travelers to developing countries should be
advised to avoid consumption of unsafe food
and water.
â Eating only cooked food or self-peeled fruits
in endemic areas minimizes the risk.
â Travelers should avoid eating raw fruits and
salads, which are difficult to sterilize.
â The amount of chlorine normally used to
purify water is inadequate in killing the cysts.
Drinking water can be rendered safe by boiling
â Bottled water may be used for drinking when
traveling to endemic areas.
48. Prognosis
⢠Intestinal infections due to amebiasis generally respond
well to appropriate therapy. The severity of amebiasis is
increased in the following individuals:
â Children, especially neonates
â Pregnant and postpartum women
â Those using corticosteroids
â Those with malignancies
â Malnourished individuals
⢠uncomplicated amebic liver abscess is less than 1%.
⢠Fulminant amebic colitis has a mortality rate of more
than 50%.
⢠Pleuropulmonary amebiasis has a 15-20% mortality
rate.
⢠Amebic pericarditis has a case fatality rate of 40%.
⢠Cerebral amebiasis is highly fatal, with a 90% death rate.
49. Patient Education
- Educate patients about the
prevention : -
- avoiding drinking contaminated water
and avoiding eating raw fruits and
salads, which are difficult to sterilize.
- Bottled water may be used during such
travel.
- Eating only cooked food in endemic
areas minimizes risk.