Amebiasis

Chloroquine (Aralen)
o High liver concentrations (concentrates in liver)
o Very effective in combination with dehydroemetine (Mebadin) (or emetine
(generic)) for:
Prevention/treatment of amebic liver abscess
o Ineffective for intestinal amebiasis-drug inactive against luminal amebas
Emetine & Dehydroemetine (Mebadin)
o Overview:
Parenteral administration due to erratic oral administration
Oral administration may cause vomiting (emetine (generic) can be
derived from ipecac)
Parenteral administration results and emetine (generic) stored mainly in
the:
Liver
Lungs
Spleen
Kidneys
Slow elimination (renal)
o Pharmacological effects
Blocks eukaryotic protein synthesis
Animal-toxic doses:
Renal common hepatic, skeletal, cardiac muscle cellular damage
Cardiac induction/contraction depression -- arrhythmias
Adrenergic/cholinergic-receptor locking activity
o Anti-amebic Effects:-act only against trophozoites
o Clinical Uses:
 Inappropriate management for mild/asymptomatic intestinal infection
Severe intestinal disease (amebic dysentery)
Parenteral emetine (generic)/dehydroemetine (Mebadin)
o Rapid improvement
o Usually not curative
o Reduced likelihood of toxicity of drugs used < seven days
Action against other parasites:
Secondary choices for management of infections due to:
o Balantidium coli
o Fasciola hepatica
o Paragonimus westermani
o Adverse/Side effects
Short duration (3-5 days) --few/mild adverse effects
Intermediate duration (up to 10 days) -- mild/severe side effects
Extended duration > 10 days -- serious toxicity (contraindicated for
prolonged administration)
Muscle weakness/tenderness/pain: injection region), common effect)
Occasional:
Nausea/vomiting
Sterile abscess
Diarrhea: more common, several days after treatment initiation
Minor ECG changes-frequent
Serious cardiac conduction defects-infrequent
Most serious symptoms/findings:
Tachycardia (other arrhythmias)
Precordial pain
Congestive heart failure (+dyspnea & hypotension)
Frequent reported effects:
 Muscle weakness/tenderness/stiffness/aching & tremor
Mild paresthesias
o Contraindications
Patients with cardiac/renal disease
Patients with recent history of polyneuritis
In young children unless alternative drugs have been ineffective in
managing liver abscess or severe dysentery
Pregnancy
Diloxanide furoate (Furamide)
o Overview:
Directly amebicidal
Few drug effects in animals
o Pharmacokinetics:
Diloxanide furoate (Furamide) is split into diloxanide and furoic acid
(depth bacteria)
Most of the diloxanide is absorbed (and conjugated to the glucuronide-
which is rapidly excreted in the urine)
Unabsorbed diloxanide is amebicidal
o Clinical Uses:
Drug of choice for asymptomatic intestinal amebiasis
Used in combination with another drug for mild intestinal amebiasis
Diloxanide furoate (Furamide) can be used to eliminate luminal amebas in
combination with a nitroimidazole which can eliminate luminal & tissue
amebas
Diloxanide-not effective as the primary drug in severe/moderate
intestinal amebiasis since it is not effective against tissue
trophozoites.
o Contraindications/Adverse Effects:
Common: flatulence; uncommon/rare-- nausea,abdominal cramps, rash
 Diloxanide furoate (Furamide) should not be used in pregnancy or given
the children < 2 years old.
Iodoquinol (Yodoxin, Moebequin)
o Overview:
Effectiveness limited to bowel luminal organisms (i.e. not effective
against intestinal wall/extraintestinal tissue trophozoites)
Poor absorption (90% unabsorbed)
Renal excretion-following glucuronidation
May interfere with some thyroid function tests (for up to six months
buying increasing proteins-bound serum iodine, which decreases 131I
uptake.
o Clinical Uses: iodoquinol (Yodoxin, Moebequin)
Intestinal Amebiasis
Alternative drug in treating asymptomatic/model/moderate
disease
Ineffective an initial management of severe intestinal amebiasis
(may be used later)
May be used concurrent with other anti-amebiasis drugs (a target
extraintestinal sites) to manage concurrent intestinal infection
Management of other Intestinal Parasites
Effective as monotherapy or with a tetracycline for Dientamoeba
fragilis treatment
Effective as monotherapy for treating Balantidium coli.
o Adverse Effects:iodoquinol (Yodoxin, Moebequin)
Adverse effects associated with halogenated hydroxyquinolines
(iodoquinol (Yodoxin, Moebequin) is an example of this group))
Neurotoxicity (potentially severe)
o More likely to occur with long dosing periods and at higher
than recommended doses
 o Neurotoxicity not likely to occur at normal dosage and
normal dosing duration
o At high doses/long periods:
o Optic atrophy
o Peripheral neuropathy
o Visual loss
o Neurotoxic effects tend to be reversible; however complete
reversal may not occur
Other-typically mild/infrequent:
o Diarrhea (several days)
o Gastrointestinal symptoms
o Headache
o Slight thyroid enlargement
o Contraindications/Cautions:iodoquinol (Yodoxin, Moebequin)
Should not be used for treatment/prophylaxis of travelers' diarrhea or
nonspecific diarrhea
Use only recommended dosage
Cautious use in patients with preexisting:
Optic neuropathy
Renal disease
Thyroid disease
Hepatic disease (other than secondary to amebiasis)
Cause for discontinuation:
Persistent diarrhea
Symptoms of iodine reaction (urticaria, pruritus, fever, skin
eruptions)
Hepatic disease unrelated to amebiasis
Renal disease
Thyroid disease
 Cautious use in young children/infants-iodoquinol (Yodoxin, Moebequin)
may be more toxic in the young
Recommendation: careful opthalmological examination before &
during iodoquinol administration.
Metronidazole (Flagyl) in amebiasis & other protozoal infections
o Overview-metronidazole (Flagyl)
Readily absorbed
Urinary excretion of drug & drug metabolites
o Mechanism of action: metronidazole (Flagyl)
Metronidazole (Flagyl) undergoes chemical reduction by ferredoxin or
ferredoxin-related processes
Reduced-products are responsible for bacteriocidal effects against
anaerobic bacteria
Amebiasis: metronidazole (Flagyl) kills Entamoeba histolytica
trophozoites (but not cysts)
In dracunculiasis: metronidazole (Flagyl) Effexor anti-
inflammatory
Clinical Uses:
Treatment of extraluminal amebiasis:
o Eliminates tissue infections (hepatic abscess; intestinal
wall/extraintestinal infections)
o Note: luminal amebicides should be used concurrently to
insure cure of luminal infections
o Metronidazole (Flagyl): kills trophozoites --does not kill E
histolytica systems
Other Clinical uses:
o Urogenital trichomoniasis
o "Trichomonas vaginalis, a flagellate, is the most
common pathogenic protozoan of humans in
industrialized countries."-CDC
 http://www.dpd.cdc.gov/DPDx/HTML/Trichomoni
asis.htm
o Life Cycle:Trichomonas vaginalis
o "Trichomonas vaginalis resides in the
female lower genital tract and the male
urethra and prostate, where it replicates by
binary fission.
o The parasite does not appear to have a cyst
form, and does not survive well in the
external environment.
o Trichomonas vaginalis is transmitted among
humans, its only known host, primarily by
sexual intercourse."-CDC
o Geographic Distribution: Trichomonas vaginalis
o "Worldwide. Higher prevalence among
persons with multiple sexual partners or
other venereal diseases."-CDC
o Clinical Features/Laboratory Diagnosis
o "Trichomonas vaginalis infection in women
is frequently symptomatic.
o Vaginitis with a purulent discharge is the
prominent symptom, and can be
accompanied by vulvar and cervical lesions,
abdominal pain, dysuria and dyspareunia.
o The incubation period is 5 to 28 days.
o In men, the infection is frequently
asymptomatic; occasionally, urethritis,
epididymitis, and prostatitis can occur."
o "Microscopic examination of wet mounts
may establish the diagnosis by detecting
 actively motile organisms.
o This is the most practical and rapid method
of diagnosis (allowing immediate
treatment), but it is relatively insensitive.
o Direct immunofluorescent antibody staining
is more sensitive than wet mounts, but
technically more complex. Culture of the
parasite is the most sensitive method, but
results are not available for 3 to 7 days.
o In women, examination should be
performed on vaginal and urethral
secretions.
o In men, anterior urethral or prostatic
secretions should be examined."
http://www.dpd.cdc.gov/DPDx/HT
ML/Trichomoniasis.htm
o Treatment:"The Medical Letter recommends
metronidazole or tinidazole as drugs of
choice. To prevent reinfection, all sexual
partners should be treated.
o Metronidazole-resistant strains have been
reported."-CDC
Metronidazole (Flagyl):Alternative drug in:
o Giardia lamblia (Giardia lamblia, a protozoan flagellate
(Diplomonadida).
o Life Cycle
o Giardia Clinical Features/Laboratory Diagnosis
o Microscopy
o Trophozoites
o Giardia in culture
 o Giardia cysts
o Balantidium coli, a large ciliated protozoal parasite.
o Life Cycle
o "The trophozoites reside in the lumen of the
large intestine of humans and animals,
where they replicate by binary fission with
occasional conjugation.
o Cysts are formed and passed with feces.
o The cyst is the infectious stage and is
acquired by the host through ingestion of
contaminated food or water.
o Following ingestion, excystation occurs in
the small intestine, and the trophozoites
colonize the large intestine"
o courtesy of the Division of Parasitic
Diseases at the National Center for
Infectious Diseases, Centers for Disease
Control & Prevention
http://www.dpd.cdc.gov/DPDx/HT
ML/Balantidiasis.htm
o Clinical Features/Laboratory Diagnosis
o Clinical Features:
"Most cases are asymptomatic.
Clinical manifestations, when
present, include persistent diarrhea,
occasionally dysentery, abdominal
pain, and weight loss.
Symptoms can be severe in
debilitated individuals."
o Laboratory Diagnosis:
 "Diagnosis is based on detection of
trophozoites in stool specimens or in
tissue collected during endoscopy.
Cysts are less frequently
encountered.
Balantidium coli is passed
intermittently and once outside the
colon is rapidly destroyed.
Thus stool specimens should be
collected repeatedly, and
immediately examined or preserved
to enhance detection of the parasite."
o Treatment:
The Medical Letter recommends
tetracycline (Achromycin) as the
drug of choice, with iodoquinol
(Yodoxin, Moebequin) and
metronidazole (Flagyl) as
alternatives.
Tetracyclines is
contraindicated in pregnancy
and in children less than 8
years old."
o courtesy of the Division of Parasitic
Diseases at the National Center for
Infectious Diseases, Centers for Disease
Control & Prevention
http://www.dpd.cdc.gov/DPDx/HT
ML/Giardiasis.htm
o Microscopy
o Blastocystis hominis-"Whether or not Blastocystis hominis
can cause symptomatic infection in humans is a point of
active debate. This is due to the common occurrence of the
organism in both asymptomatic and symptomatic
individuals, parasitized or not."-CDC
http://www.dpd.cdc.gov/DPDx/HTML/Blastocystis.htm
o Dracunculus mediensis-Dracunculiasis (guinea worm
disease) is caused by the nematode (roundworm)
Dracunculus medinensis
o http://www.dpd.cdc.gov/DPDx/HTML/Dracunculia
sis.htm
o "An ongoing eradication campaign has dramatically
reduced the incidence of dracunculiasis, which is
now restricted to rural, isolated areas in a narrow
belt of African countries and Yemen."-CDC
o Life Cycle/Geographic Distribution
o Life Cycle:
"Humans become infected by
drinking unfiltered water containing
copepods (small crustaceans) which
are infected with larvae of D.
medinensis.
Following ingestion, the
copepods are killed and
release the larvae, which
penetrate the host stomach
and intestinal wall and enter
the abdominal cavity and
retroperitoneal space.
After maturation into adults
and copulation, the male
 worms die and the females
(length: 70 cm to 120 cm)
migrate in the subcutaneous
tissues towards the skin
surface.
Approximately one year after
infection, the female worm
induces a blister on the skin
(generally on the distal lower
extremity), which ruptures.
When this lesion comes into
contact with water (a contact
that the patient seeks to
relieve the local discomfort),
the female worm emerges
and releases larvae into the
water.
The larvae are ingested by a
copepod and after two weeks
(and two molts) have
developed into infective
larvae. Ingestion of the
copepods closes the cycle."
o Geographic Distribution:
"An ongoing eradication campaign
has dramatically reduced the
incidence of dracunculiasis, which is
now restricted to rural, isolated areas
in a narrow belt of African countries
and Yemen."
o courtesy of the Division of Parasitic
 Diseases at the National Center for
Infectious Diseases, Centers for Disease
Control & Prevention
http://www.dpd.cdc.gov/DPDx/HT
ML/Dracunculiasis.htm
o Clinical Features
o Treatment:
o "Local cleansing of the lesion and local
application of antibiotics.
o Mechanical, progressive extraction of the
worm over a period of several days.
o No active antihelminthic treatment is
available.
o The Medical Letter recommends
metronidazole (Flagyl) , not as a curative
drug, but as a drug that decreases
inflammation and facilitates removing the
worm."-CDC-
http://www.dpd.cdc.gov/DPDx/HTML/Drac
unculiasis.htm
o Not effective (significantly) against:
o facultative anaerobes
o obligate aerobes
o Candida albicans
Adverse Effects:metronidazole (Flagyl)
Common:
o headache, dry mouth, nausea, metallic-taste
o Urine:-dark/reddish-brown
Uncommon:
o Vomiting, diarrhea, dizziness, weakness, stomatitis,
 urethral burning, vertigo paresthesias, insomnia (reduced
gastrointestinal irritation if taken with food)
Rare:
o Pancreatitis
o Severe CNS effects, i.e. mental changes, ataxia, peripheral
neuropathy, seizures
Unusual effect:disulfram (Antabuse)-like, causes vomiting/nausea
if alcohol is consumed during metronidazole
Cautions/Contraindications:
long-term used in patients with a history of:
o Blood dyscrasias
o Severe liver dysfunction
o Organic brain disease
Cautious use in pregnancy-particularly first trimester