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Amebiasis

  • Chloroquine (Aralen)

    • High liver concentrations (concentrates in liver)

    • Very effective in combination with dehydroemetine (Mebadin) (or emetine (generic)) for:

      • Prevention/treatment of amebic liver abscess

    • Ineffective for intestinal amebiasis-drug inactive against luminal amebas

  • Emetine & Dehydroemetine (Mebadin)

    •  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)

    • 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

    • Anti-amebic Effects:-act only against trophozoites

    • Clinical Uses:

      • Inappropriate management for mild/asymptomatic intestinal infection

      • Severe intestinal disease (amebic dysentery)

        •  Parenteral emetine (generic)/dehydroemetine (Mebadin)

          • Rapid improvement

          • Usually not curative

          • Reduced likelihood of toxicity of drugs used < seven days

      • Action against other parasites:

        •  Secondary choices for management of infections due to:

          • Balantidium coli

          • Fasciola hepatica

          • Paragonimus westermani

    •  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

    •  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)

    • Overview:

      • Directly amebicidal

      • Few drug effects in animals

    • 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

    • 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.

    • 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)

    • 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.

    • 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.

    •  Adverse Effects:iodoquinol (Yodoxin, Moebequin)

      • Adverse effects associated with halogenated hydroxyquinolines (iodoquinol (Yodoxin, Moebequin) is an example of this group))

        •  Neurotoxicity (potentially severe)

          • More likely to occur with long dosing periods and at higher than recommended doses

          • Neurotoxicity not likely to occur at normal dosage and normal dosing duration

          • At high doses/long periods:

            •  Optic atrophy

            •  Peripheral neuropathy

            •  Visual loss

          • Neurotoxic effects tend to be reversible; however complete reversal may not occur

        • Other-typically mild/infrequent:

          •  Diarrhea (several days)

          •  Gastrointestinal symptoms

          •  Headache

          •  Slight thyroid enlargement

    • 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

    • Overview-metronidazole (Flagyl)

      • Readily absorbed

      • Urinary excretion of drug & drug metabolites

    • 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:

          •  Eliminates tissue infections (hepatic abscess; intestinal wall/extraintestinal infections)

          •  Note: luminal amebicides should be used concurrently to insure cure of luminal infections

          •  Metronidazole (Flagyl): kills trophozoites --does not kill E histolytica systems

        • Other Clinical uses:

          • Urogenital trichomoniasis

            • "Trichomonas vaginalis, a flagellate, is the most common pathogenic protozoan of humans in industrialized countries."-CDC http://www.dpd.cdc.gov/DPDx/HTML/Trichomoniasis.htm

            • Life Cycle:Trichomonas vaginalis

              • "Trichomonas vaginalis resides in the female lower genital tract and the male urethra and prostate, where it replicates by binary fission. 

              • The parasite does not appear to have a cyst form, and does not survive well in the external environment. 

              • Trichomonas vaginalis is transmitted among humans, its only known host, primarily by sexual intercourse."-CDC

            • Geographic Distribution: Trichomonas vaginalis

              • "Worldwide.  Higher prevalence among persons with multiple sexual partners or other venereal diseases."-CDC

            • Clinical Features/Laboratory Diagnosis

              • "Trichomonas vaginalis infection in women is frequently symptomatic. 

              • Vaginitis with a purulent discharge is the prominent symptom, and can be accompanied by vulvar and cervical lesions, abdominal pain, dysuria and dyspareunia. 

              • The incubation period is 5 to 28 days.

              • In men, the infection is frequently asymptomatic; occasionally, urethritis, epididymitis, and prostatitis can occur."

              • "Microscopic examination of wet mounts may establish the diagnosis by detecting actively motile organisms. 

              • This is the most practical and rapid method of diagnosis (allowing immediate treatment), but it is relatively insensitive. 

              • 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. 

              • In women, examination should be performed on vaginal and urethral secretions. 

              • In men, anterior urethral or prostatic secretions should be examined."

              • Treatment:"The Medical Letter recommends metronidazole or tinidazole as drugs of choice.  To prevent reinfection, all sexual partners should be treated. 

              •  Metronidazole-resistant strains have been reported."-CDC

        • Metronidazole (Flagyl):Alternative drug in:

          • Giardia lamblia (Giardia lamblia, a protozoan flagellate (Diplomonadida).

          • Balantidium coli, a large ciliated protozoal parasite.

            • Life Cycle

              •  "The trophozoites reside in the lumen of the large intestine of humans and animals, where they replicate by binary fission with occasional conjugation.  

              • Cysts are formed and passed with feces. 

              • The cyst is the infectious stage and is acquired by the host through ingestion of contaminated food or water. 

              • Following ingestion, excystation occurs in the small intestine, and the trophozoites colonize the large intestine"

              • courtesy of the Division of Parasitic Diseases at the National Center for Infectious Diseases, Centers for Disease Control & Prevention

            • Clinical Features/Laboratory Diagnosis

              • 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."

              • 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."

              • 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."

              • courtesy of the Division of Parasitic Diseases at the National Center for Infectious Diseases, Centers for Disease Control & Prevention

            • Microscopy

          • 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 

          • Dracunculus mediensis-Dracunculiasis (guinea worm disease) is caused by the nematode (roundworm) Dracunculus medinensis

            • http://www.dpd.cdc.gov/DPDx/HTML/Dracunculiasis.htm

            • "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

            • Life Cycle/Geographic Distribution

              • 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."

              • 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."

              • courtesy of the Division of Parasitic Diseases at the National Center for Infectious Diseases, Centers for Disease Control & Prevention

            • Clinical Features

            • Treatment:

              • "Local cleansing of the lesion and local application of antibiotics. 

              • Mechanical, progressive extraction of the worm over a period of several days. 

              • No active antihelminthic treatment is available. 

              • 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/Dracunculiasis.htm

          •  Not effective (significantly) against:

            • facultative anaerobes

            • obligate aerobes

            • Candida albicans

      • Adverse Effects:metronidazole (Flagyl)

        •  Common:

          •  headache, dry mouth, nausea, metallic-taste

          •  Urine:-dark/reddish-brown

        •  Uncommon:

          •  Vomiting, diarrhea, dizziness, weakness, stomatitis, urethral burning, vertigo paresthesias, insomnia (reduced gastrointestinal irritation if taken with food)

        •  Rare:

          • Pancreatitis

          • 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:

          • Blood dyscrasias

          • Severe liver dysfunction

          • Organic brain disease

        •  Cautious use in pregnancy-particularly first trimester

Primary Reference: Goldsmith, R. S., Antiprotozoal Drugs in Basic and Clinical Pharmacology (Katzung, B. G., ed) Appleton-Lange, 1998, p. 838-861.

Primary Reference: Morgan, Juliette and del Rio, Carlos, Amebiasis in Medicine for the Practicing Physician (Hurst, J. W., ed) Appleton-Lange, 1996, pp. 457-459.