for PG TRAINEES

1. • 20yr old female along with her grand parents went out to a
restaurant for dinner, two weeks later she developed abdominal
cramps and loose stools. Next day her sypmtoms became severe
and she developed fever, bloody stools and abdominal pain. Her
mother took her to get examined by a local physician who ran
several tests including a complete blood count which showed she
was anemic and microscopic stool studies that revealed this
trophozoite.
• Identify the organism?
• Life cycle of organism?
• How will you treat and prevent?

2. INTRODUCTION
• Entamoeba histolytica is a parasite of global distribution
but most of the morbidity and mortality from amebiasis
occurs in developing countries.
• The total burden of disease caused by E. histolytica is
unknown, however roughly 2% of life-threatening
diarrhea in children ages 12 to 23 months of age.

3. • There are three species of intestinal amebae with
identical morphologic characteristics: E. histolytica, E.
dispar, and E. moshkovskii
• E. dispar and E. moshkovskii are non-pathogenic and do
not cause clinical disease.

4. • E. histolytica has a simple, 2-stage life cycle that
consists of an infectious cyst and a motile trophozoite.
• The cyst form measures 5 to 20 μm in diameter and
contains 4 or fewer nuclei.
• The ameboid trophozoite, which is responsible for tissue
invasion, measures 10 to 60 μm and contains a single
nucleus with a central karyosome

5. • The cysts are relatively resistant to chlorination and
desiccation, and they can survive in a moist environment
for several weeks.

7. • Infection occurs following ingestion of cysts in fecally
contaminated food or water.
• Within the lumen of the small intestine, the
quadrinucleate cyst undergoes nuclear then cytoplasmic
division, giving rise to eight trophozoites.

8. • Only about 10% of infected persons develop invasive
disease characterized by invasion of the colonic
epithelium by trophozoites.
• Trophozoites that gain access to the bloodstream can
spread hematogenously to establish infection at distant
sites .

9. • Why some persons develop invasive disease and others
remain asymptomatic remains a mystery; parasite and
host differences are likely to be important in this regard.

10. PATHOGENESIS
• After excystation within the lumen of the small intestine,
trophozoites adhere to colonic mucins and epithelial
cells, largely via an amebic galactose/N-acetyl-d-
galactosamine inhibitable surface lectin.

11. • Secreted cysteine proteinases then facilitate tissue
invasion by degrading human colonic mucus and
extracellular matrix proteins.

12. • Further disruption of the colonic epithelium results
directly from contact-dependent cytolysis of epithelial
and immune cells
• and from an acute epithelial cell inflammatory response
with recruitment of neutrophils and immune-mediated
tissue damage.

13. Fig. 113.2 Model for stepwise
invasion of the colonic mucosa by
Ent amoeba histolytica. Following
excystation, trophozoites (blue)
adhere to colonic mucins, and
degradation of mucus by amebic
proteinases enables contact with
the epithelium. Contact-dependent
killing of epithelial cells and
activation of an epithelial cell
response marked by pro-
inflammatory cytokine release
follow. Amebapore is a protein that
forms ion channels or pores in lipid
membranes and depolarizes target
cells, thus contributing to the
virulence of the trophozoite.
Activation of pro-interleukin (IL)-1β
by amebic cysteine proteinases,
with resulting recruitment of
neutrophils, further contributes to
tissue damage. NFκβ, nuclear
factor kappa beta. (From Huston
CD. Parasite and host
con tributions to the pathogenesis
of amebic colitis. Trends Parasitol
2004; 20:23-6.

14. • The cecum and ascending colon are affected most
commonly, although in severe disease the entire colon
may be involved.
• On gross examination, pathology can range from
mucosal thickening to multiple punctate ulcers with
normal intervening tissue to frank necrosis.

15. • For unknown reasons, the downward invasion of amebic
trophozoites often is halted at the level of the muscularis
mucosa.

20. • Subsequent lateral spread of amebae undermines the
overlying epithelium, resulting in the clean-based, flask-
shaped ulcers that characterize amebic colitis.
• Early in infection, an influx of neutrophils is typical, but
in well-established ulcers, few inflammatory cells are
seen.

21. • Organisms may be seen ingesting red blood cells
(erythrophagocytosis).
• At distant sites of infection (e.g., liver abscess), similar
pathologic characteristics include central liquefaction of
tissue surrounded by a minimal mononuclear cell
infiltrate

22. • Because more than 90% of persons colonized with E.
histolytica spontaneously clear the infection within a
year, an effective immune response to amebiasis seems
to develop.
• Children with fecal anti-amebic lectin immunoglobulin
(Ig)A have short-lived protection from subsequent
intestinal infection.

23. • The protective role of secretory IgA is not certain,
however, and the contributions of humoral and cellular
immunity to protection from amebiasis remain unknown.

24. • Nearly everyone with invasive amebiasis develops a
systemic and a mucosal humoral immune response.
• Antibodies alone are unable to clear established
infection, however, because asymptomatic cyst passers
remain infected for months after anti-amebic antibodies
develop.

25. CLINICAL FEATURES
• Infection with E. histolytica results in one of three
outcomes.
• Approximately 90% of infected persons remain
asymptomatic.

26. • The other 10% of infections result in invasive amebiasis
characterized by dysentery (amebic colitis) or, in a
minority of cases, extraintestinal disease (most
commonly amebic liver abscess.

28. • The major diagnostic challenge for the clinician seeing a
patient with amebic colitis is to distinguish the illness
from other causes of bloody diarrhea.

29. • The differential diagnosis includes the causes of
bacterial dysentery, such as Shigella, Salmonella, and
Campylobacter species and enteroinvasive or
enterohemorrhagic Escherichia coli, and noninfectious
diseases, including inflammatory bowel disease, and
ischemic colitis.

30. • In contrast to bacterial dysentery, which typically begins
abruptly, amebic colitis begins gradually over one to
several weeks
• Although more than 90% of patients with amebic colitis
present with diarrhea, abdominal pain can occur without
diarrhea; abdominal pain, tenesmus, and fever are highly
variable.

31. • Weight loss is common because of the chronicity of the
illness. Microscopic blood is present in the stool of most
patients with amebic dysentery.

33. • The most feared complication of amebic dysentery,
acute necrotizing colitis with toxic megacolon, occurs in
0.5% of cases.
• This complication manifests as an acute dilatation of the
colon, and 40% of patients die from sepsis unless it is
promptly recognized and treated surgically.

34. • Unusual complications include the formation of
enterocutaneous, rectovaginal, and enterovesicular
fistulas and ameboma.
• Ameboma, due to intraluminal granulation tissue, can
cause bowel obstruction and mimic carcinoma of the
colon.

35. • Although a history of dysentery early in the illness is
common, dysentery has resolved in most patients by the
time of presentation
• Extraintestinal sites of infection are involved and typically
result either from direct extension of liver abscesses
(e.g., amebic pericarditis or lung abscess) or from
hematogenous spread of disease (e.g., brain abscess)

36. DIAGNOSIS
• The gold standard for diagnosis of amebic colitis remains
colonoscopy with biopsy,
• colonoscopy should be performed whenever infectious
causes of bloody diarrhea are strong considerations in
the differential diagnosis of ulcerative colitis.

37. • Because the cecum and ascending colon are affected
most often, colonoscopy is preferred to sigmoidoscopy.
• Identification of amebae can be aided by periodic acid–
Schiff staining of biopsy tissue, which stains trophozoites
magenta.

38. • Stool examination for ova and parasites, the traditional
method for diagnosing amebiasis, should not be relied
upon.
• Although the presence of amebic trophozoites with
ingested erythrocytes strongly correlates with E.
histolytica infection, these rarely are present.

39. • and in the absence of hematophagous trophozoites,
microscopy cannot distinguish E. histolytica from E.
dispar.
• Noninvasive methods to accurately differentiate E.
histolytica from E. dispar include stool culture with
isoenzyme analysis

40. • serum amebic-antibody titers, PCR, and an enzyme-
linked immunosorbent assay (ELISA) that detects the
amebic lectin antigen in stool samples
• Of these, only serum amebic-antibody titers and the
stool ELISA are widely available for clinical use.

41. • Because serum anti-amebic antibodies do not develop in
patients infected with E. dispar, serologic tests for
amebiasis accurately distinguish E. histolytica and E.
dispar infection.
• From 75% to 85% of patients with acute amebic colitis
have detectable anti-amebic antibodies on presentation,
and convalescent titers develop in more than 90% of
patients.

42. • For amebic liver abscess, 70% to 80% of patients have
detectable antibody titers on presentation, and
convalescent titers develop in more than 90% of
patients.
• Antiamebic antibodies can persist for years, however, a
positive result must be interpreted with caution.

44. • Because approximately 10% of asymptomatic cyst
passers develop invasive amebiasis, E. histolytica
carriers should be treated.
• For non-invasive disease, treatment with a luminal agent
alone is adequate (e.g., paromomycin 25 to 35 mg/kg/
day in 3 divided doses for 7 days).

45. • Patients with amebic colitis should first be treated with
an oral nitroimidazole (either metronidazole [500-750 mg
3 times daily for 10 days] or tinidazole [2 g once daily for
3 to 5 days]) to eliminate invasive trophozoites.

46. • Metronidazole and tinidazole are believed to be less
effective against organisms in the colonic lumen, and
subsequent treatment with a luminal agent such as
paromomycin is recommended to prevent recurrent
disease

47. Prevention
• Water can be made safe for drinking and food
preparation by boiling it for 1 minute, by halogenation
(with chlorine or iodine), or by filtration.
• Naturally acquired immunity to intestinal amebiasis
provides short-lived protection against reinfection, giving
hope that a vaccine may be feasible.

48. Other Amebae
• Nine other amebae species commonly infect the human
GI tract. These include
1. E. dispar,
2. Entamoeba moshkovskii,
3. Entamoeba bangladeshi,
4. Entamoeba coli,
5. Entamoeba hartmanni,
6. Entamoeba gingivalis,
7. Entamoeba polecki,
8. Endolimax nana, and 9. Iodamoeba butschlii.

49. • With the exception of E. gingivalis, which has no known
cyst stage, all of these true amebae have simple 2-stage
life cycles, consisting of an infectious cyst form and a
motile trophozoite form.
• E. dispar is a nonpathogenic protozoan parasite that is
morphologically indistinguishable from Entamoeba
histolytica by light microscopy.

50. • infection with E. dispar is approximately 10 times more
prevalent than E. histolytica infection.
• Although E. dispar has been demonstrated to cause
mucosal ulcerations in animal models, it has not been
demonstrated to cause human disease and does not
require treatment.

51. • Entamoeba moshkovskii, indistinguishable from E.
dispar and E. histolytica except that trophozoites of E.
histolytica might show erythrophagocytosis.
• its causation of human disease is still controversial,
infection by E. moshkovskii is associated with diarrhea in
infants.

52. • Entamoeba coli trophozoites contain a single nucleus
with a prominent karyosome that usually is eccentric in
location, distinguishing them from E. histolytica and E.
dispar trophozoites, which have a centrally located
karyosome.
• Entamoeba coli is nonpathogenic and requires no
specific treatment

53. • E. gingivalis is the only ameba found in the oral cavity,
where it lives in the anaerobic environment of the
gingival crease.
• The trophozoite is identical in size to that of E. histolytica
and contains a single nucleus with a prominent central
karyosome.

54. • oral-oral contact is believed to be its mode of
transmission.
• E. gingivalis is associated with poor dental hygiene and
periodontal disease
• The increased frequency of colonization in this setting
might simply reflect a hospitable host environment.

55. • E. gingivalis often is associated with periodontal disease
in AIDS patients, however, and treatment with
metronidazole has been reported to be effective.

56. • E. polecki, characterized by a uninucleated cyst, is
primarily a parasite of pigs and monkeys that sometimes
infects humans.
• It has been suggested that several distinct uninucleated
cystproducing Entamoeba species can infect humans,
and it has been proposed that these organisms
collectively be termed “E. polecki-like”.

57. • At present, specific treatment of E. polecki-like infections
is not routinely recommended, but persons with heavy
burdens of this parasite can develop nonspecific GI
symptoms and might benefit from treatment.
• Good clinical responses to metronidazole and diloxanide
furoate have been reported.

58. • Endolimax nana is a nonpathogenic intestinal ameba
that often infects humans.
• Distribution is most common in the tropics, where 5% to
33% of persons are infected.
• Infection requires no specific treatment, but it serves as
a useful marker for fecal-oral exposure.