Amebiasis

Paul R. Earl
Facultad de Ciencias Biológicas
Universidad Autónoma de Nuevo León
San Nicolas, NL, Mexico
pearl@dsi.uanl.mx
Amebiasis or amebic dysentary is
caused by the protozoan Entamoeba
histolytica. Improved sanitation and
clean water supply decrease the
incidence of amebiasis. The amount of
chlorine normally used to control
pathogens is inadequate in killing the
cysts. Drinking water can be rendered
safe by boiling or iodination with
tetraglycine hydroperiodide.
Nevertheless, drinking water is usually
not much of the problem.
 Generalities.
Amebiasis is an intestinal infection in which
cysts are passed in the feces. Symptoms can
include fever, chills and diarrhea, sometimes
bloody or with mucus and often with
cramps. Some people may have only mild
abdominal discomfort or no symptoms at all.
Symptoms can start 2 or more weeks after
infection. Rarely, trophozoites (the mobile
amebas) may invade the liver, lung or brain,
or perforate the colon causing septicemia.
E. dispar is a nonpathogenic protozoon
morphologically identical to E histolytica.
Previously reported asymptomatic infections
due to the so-called nonpathogenic strains of
E histolytica now are recognized to be due to
E. dispar. These 2 species of Entameba can
be distinguished by monoclonal antibodies.
Other morphologically distinct organisms,
such as Entamoeba coli ( E. coli ! ! ) and
Entamoeba hartmanni are also
nonpathogenic.
Amebiasis is the third leading
parasitic cause of death worldwide,
surpassed only by malaria and
schistosomiasis. On a global basis,
amebiasis affects approximately 50
million persons each year,
resulting in nearly 100,000 deaths.
Laboratory diagnosis.
An iodine-stained cyst of the pathogen Entamoeba
hystolytica with 4 nuclei is illustrated. The
harmless commensal Entamoeba coli has larger
cyts with 8 nuclei. Furthermore, recall that E.
histolytica has a lookalike E. dispars that is
harmless.
The cyst of E histolytica averages 12
m, ranging from 5-20 m. It has 1-4
nuclei that are morphologically similar
to the nuclei of the trophozoite. The
cyst may have iodine-stainable
glycogen clumps and chromatoid
bodies with smooth rounded edges. The
ending –oid means LIKE so chromatoid
bodies are like chromatin in that they
stain with hematoxylin.
 Trophozoites
Entamoeba coli Entamoeba histolytica
15 m - 40 m in size 10 m - 35 m size
Nondirectional motility Unidirectional motility
Multiple pseudopodia Single pseudopodia
No ingested erythrocytes Ingested erythrocytes
Cytoplasm rough looking Finely granular cytoplasm
Large, eccentric karyosome Small, central karyosome
Clumped nuclear chromatin Finely beaded chromatin
 Cysts
Entamoeba coli
10 m - 35 m in size
May have 8 nuclei
Karyosomes eccentric
Nuclear chromatin clumped
Splintered chromatoidal bars
Entamoeba histolytica
10 m - 20 m in size
Never more than 4 nuclei
Karyosomes small, central
Chromatin finely beaded
Rounded chromatoidal bars
Leukocytosis and mild anemia can occur.
Erythrocyte sedimentation rate generally
is elevated. Liver function tests reveal
elevated alkaline phosphatase in 80% of
patients, elevated transaminases and
reduced albumin. Urinalysis may reveal
proteinuria.
Rectosigmoidoscopy and colonoscopy
may show small mucosal ulcers covered
with yellowish exudates. The intervening
mucosa appears normal. Biopsy results
and scrapings of ulcer edge may locate
trophozoites.
Symptoms and pathology.
Primary intestinal flask-shaped
(button hole) necrotic ulcers occur in
the submucosa of the large intestine,
most commonly the cecal and
sigmoidorectal regions.Ulcers contain
necrotic debris, actively feeding
trophozoites with ingested
erythrocytes, cytolyzed cells and
mucous; polymorphonuclear
leukocytes and round inflammatory
cells.
Extraintestinal features.
Hematogenous spread may result in
abscesses of the liver, spleen, lung or
brain. Hepatic amebiasis (abscess,
hepatitis) is the most common and
grave complication: Enlarged, tender
liver and upper abdominal pain that
may radiate to the right shoulder.
Mild jaundice may be evident,
transaminases and alkaline
phosphatase elevations may be seen.
 Drugs for treatment.
Five pharmaceuticals are briefly noted.
Asymptomatic intestinal infection may be
treated with iodoquinol, paromomycin or
diloxanide furoate. Recommended drugs
for treatment of symptomatic intestinal
disease and for hepatic abscess are
metronidazole and tinidazole. Since these
drugs may not eliminate the cysts of the
intestine, immediately follow
metronidazole and tinidazole with
iodoquinol, paromomycin or diloxanide
furoate.
1/ Metronidazole (Flagyl,
Protostat). Kills trophozoites of E.
histolytica in intestine and tissue.
Does not eradicate cysts from
intestines. Adult oral dose: 500-
750 mg 3 times per day for 10
day. Elimination is accelerated by
simultaneous use of phenytoin
and phenobarbital; clearance is
decreased by cimetidine.
2/Tinidazole (Fasigyn). 5-
nitroimidazole derivative with
selective antimicrobial activity
against anaerobic bacteria and
protozoa. Not available in United
States. Adult oral dose: 600 mg
bid or 800 mg 2 times a day for 5
days. Pediatric dose 50-60 mg/kg
for 5 days, not to exceed 2 g/day.
3/Paromomycin (Humatin).
Amebicidal aminoglycoside antibiotic
that is poorly absorbed. Active only
against intestinal form of amebiasis.
Used to eradicate cysts of E.
histolytica following treatment with
metronidazole or tinidazole for an
invasive disease. Adult oral dose:
25-35 mg/kg/day divided 3 times
for 7 days. Pediatric dose:
Administer as in adults.
4/Diloxanide furoate (Furamid,
Entamizole, Furamide). Luminal
amebicide; acts primarily in bowel
lumen since it is poorly absorbed.
Used to eradicate cysts of E. histolytica
after treatment of invasive disease.
Available through US CDC Drug
Service (404-639-3670). Adult oral
dose 500 mg 2 times a day for 10
days. Pediatric dose 20 mg/kg/
divided twice a day for 10 days, not to
exceed 1500 mg/day.
5/Iodoquinol (Yodoxin). Halogenated
hydroxyquinoline. Luminal amebicide;
acts primarily in bowel lumen since it is
poorly absorbed. Best tolerated when
given with meals. Since active only
against intraluminal form of amebiasis,
used to eradicate cysts of E. histolytica
after treatment of invasive disease. Adult
oral dose 650 mg 2 times a day for 20
days. Pediatric dose: 30-40 mg/kg/day
divided 2 times for 20 days; not to
exceed 2 g/day.
The control of infection.
The epidemiology of amebiasis is
folkloric, beginning with infected
foodhandlers. While elements of
truth are scattered through this
neglected syndrome, much more
can be done. Frankly, the ecology
is unknown. Are there reservoir
animals?
What civic water treatments kill and
which ones tolerate E. histolytica? What
part does chronic malnutrition play in
susceptibility to infection? What part
does exposure then the rise of natural
antibodies play in defense? What are the
water-borne pathogens intimately
associated with E. histolytica? Has
radioactivity been used to trace
ecological dispersion of an element like
phosphorus in a parasite? If ever, how is
E. histolytica considered in civic water
management?
The main point of this lecture
is to sketch E. histolytica as a
distinct pathogen differing from
E. coli and E. dispar. More,
decades pass without fruitful
reseach results. Perhaps you
find this a challenge.