Amoebiasis is an infection of the mucous membrane of the large intestine where Entamoeba histolytica is the causative organism. This organism occurs in the intestine in the form of trophozoites and cysts. In most infections, trophozoites (vegetative form) appear to feed on intestinal bacterial flora and multiply in the colonic lumen without causing any symptoms. But under certain circumstances, trophozoites may get activated and invade the intestinal mucosa, causing tissue lysis and producing dysentery or diarrhea. Under an unfavorable atmosphere, however, trophozoites are encysted and the cyst form is excreted in the feces.
In the majority of cases, the infected persons do not show any symptoms and excrete both cysts and trophozoites in their feces. The cyst form of the organism is infective and the infection is acquired by ingestion of amoebic cysts in food or water contaminated due to handling by a such asymptomatic infected person. Ingested cysts liberate trophozoites in the intestine and continue the process in the new host. The infection usually prevails in areas of poor hygienic conditions and inadequate sanitation.
Amoebic dysentery: Amoeba can cause attacks of acute dysentery which is characterized by the presence of blood and mucous in the stools and severe abdominal pain. This occurs when the amoebae invade the wall of the intestine, multiply, and causes tissue damage, often forming ulcers. Later amoebae may invade the blood vessels and be carried to the liver and even to the brain. Death can occur from a liver abscess which can perforate into the lung and elsewhere. Of the several species of amoebae that occur in the human intestinal tract, only Entamoeba histolytica is pathogenic.
Invasive intestinal amoebiasis may vary in its symptoms from mild illness to severe amoebic dysentery with blood and mucous in the stool. Trophozoites may spread to the liver through the portal vein and produce either an acute amoebic hepatitis or may encyst and produce an amoebic liver abscess. The latter may be complicated by rupture or extension of infection to adjacent organs. It may be associated with chronic colonic dysfunction, acute colonic perforation, insidious peritonitis, and amoebic granuloma.
Amoebic abscess of the liver is the most common extra-intestinal manifestation of invasive amoebiasis. It may be characterized by abdominal pain, anorexia, fever, weight loss, and hepatomegaly. In mild amoebiasis, the symptoms are mainly of intestinal origin which appears due to the invasion of the intestinal wall by the multiplying trophozoites. In more severe form, other vital organs like the liver, lungs, brain, and genitourinary tract may get affected. This constitutes the cause of extra-intestinal symptoms.
Anti-Amoebic Agents: Entamoeba histolytica has two stages of development.
(i) Cyst: It is a source of infection, present in the colon. It can survive outside the body. It leads to asymptomatic intestinal infection (luminal amoebiosis) and
(ii) Trophozoites: Cysts develop further into trophozoites that spread into the intestine (leading to intestinal amoebiasis) and into tissues (leading to extra-intestinal infection) mainly into the liver (hepatic amoebiasis). Trophozoites are labile and do not survive outside the body.
Drugs used to treat luminal amoebiasis:
According to the site of action, the amoebicidal drugs are classified as:
(a) Luminal amoebicides: They act on parasites in the lumen of the bowel. These include diloxanide furoate (amide), iodoquinol, quinidochlor (8-hydroxy quinolones) and tetracyclin, paromomycin (antibiotics).
(i) Iodoquinol: It is a luminal amoebicide. Side effects include diarrhea, rashes, and dose-related neuropathy. Due to chronic iodine overload, iodism (furunculosis, inflammation of mucous membranes) is also reported.
(ii) Diloxanide furoate: It is a dichloroacetamide derivative. It is a highly effective luminal amoebicide. It directly kills trophozoites responsible for the production of cysts. It is effective against asymptomatic luminal infections and cyst passers. Side effects include nausea, flatulence, abdominal cramps, and rashes.
(iii) Niclosamide: It is used as a luminal amoebicide. It is a prodrug that gets converted to nitazoxanide. Side effects include vomiting, headache, and abdominal pain.
(iv) Tetracyclines: Due to poor systemic absorption, they reach the colon in high amounts and thus reduce the proliferation of amoebae in the colon. They are hence used as luminal amoebicides.
(b) Tissue amoebicides (both intestinal and extra-intestinal): These include metronidazole, tinidazole, ornidazole (belong to nitroimidazole class) and emetine, hydroemetine (alkaloids).
(i) Metronidazole: It is a highly effective amebicide. It is also extensively used in the treatment of infections caused by Giardia lamblia, Trichomonas vaginalis, Anaerobic cocci, and anaerobic gram-negative bacilli. It is a drug of choice for the treatment of pseudo membranous colitis caused by Clostridium difficile. All these susceptible microorganisms contain electron transport components such as ferredoxin and Fe-S proteins which donate electrons to metronidazole. The single electron transfer forms a highly reactive nitro radical anion that targets DNA leading to cell death. The most common adverse effects include nausea, vomiting, anorexia, epigastric distress, and abdominal cramps. Metronidazole has an unpleasant metallic taste.
(ii) Tinidazole: It has a longer duration of action. It is approved in 2004 for the treatment of amoebiasis, giardiasis, trichomoniasis, and amoebic liver abscess. It has a similar activity profile to that of metronidazole.
(iii) Ornidazole: It has a longer duration of action having an activity profile similar to tinidazole.
(iv) Paromomycin: It is an aminoglycoside antibiotic. It acts on cell membranes causing leakage and reducing the population of intestinal flora. Its adverse effects include diarrhea, epigastric distress, and abdominal pain. As it is completely absorbed from the upper intestine, it is not effective as luminal amoebicide.
(v) Chloroquine: It reaches high liver concentration. Hence, it is used in combination with nitroimidazole and diloxanide furoate to treat and prevent amoebic liver abscesses. It is not effective in the treatment of intestinal or another extrahepatic amoebiasis.
(vi) Emetine and Hydroemetine: These antiamoebic alkaloids are effective when given by subcutaneous or intramuscular route. They affect protein synthesis by inhibiting the elongation of the peptide chain, thus interfering breeding of trophozoites. They do not have any action on cysts. The drugs exhibit neuromuscular weakness and cardiotoxicity. Because of their toxicities, they are used only under close clinical observations.
(c) Mixed amoebicides: They are effective against both luminal and tissue amoebiasis. e.g., metronidazole.
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