Amoebiasis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Amoebiasis is a parasitic infection caused by Entamoeba histolytica. It is usually contracted by ingesting water or food contaminated with amoebic cysts. Amoebiasis is an intestinal infection that may or may not be symptomatic. When symptoms are present it is generally known as invasive amoebiasis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

Amebiasis is thought to have been discovered by Hippocrates, who described a patient with fever and dysentery. In 1828, the association between dysentery and amebic liver abscess was reported by James Annesley, an Irish physician. In 1875, E. histolytica was first isolated from a patient with dysentery by Fedor Losch, a Russian physician.

• Amebiasis is thought to have been discovered by Hippocrates, who described a patient with fever and dysentery.^[1]
• 1828 – The association between dysentery and amebic liver abscess was reported by James Annesley, an Irish physician.^[2]
• 1875 – E. histolytica was first isolated from a patient with dysentery by Fedor Losch, a Russian physician.^[2][3]
• 1903 – The organism was named Entamoeba histolytica by Fritz Schaudinn, a German zoologist.
• 1912 – Leonard Rogers, an English pathologist and tropical medicine specialist, described the efficacy of emetine (first treatment) for the treatment of amebiasis.^[4]
• 1925 – The life cycle of E. histolytica was first described by Clifford Dobell, an English protozoologist.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

Amoebiasis may be classified based on the responsible organism (E. histolytica vs. E. dispar) or based on the extent of invasion of the infection (luminal [asymptomatic] vs. invasive intestinal or extraintestinal [symptomatic]). E. histolytica may cause either luminal or extraluminal infection, whereas E. dispar can only causes luminal infection.

• E. histolytica

Responsible for all symptomatic amoebiasis

May casuse either luminal (asymptomatic) or invasive infection (symptomatic)

• E. dispar

Responsible for the majority of colonization cases

Only causes luminal infection (asymptomatic)

• Luminal amoebiasis: parasite localized to the intestines, patients are asymptomatic
• Invasive amoebiasis: parasite was able to damage the integrity of the intestinal wall, patients symptomatic

• Invasive intestinal: parasite causes intestinal manifestations
• Invasive extraintestinal: parasite spreads to distant organs and causes extraintestinal manifestations

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

E. histolytica cyst is usually transmitted by the fecal-oral route (through contaminated drinking water or food) or by direct contact with infected individuals. Following transmission, E. histolytica trophozoites undergoes excystation in the small intestine, after which it migrates to the large intestine using pseudopods. The trophozoites invades the intestinal mucosa and migrates into the bloodstream. Simultaneously, they form resistant cysts in the large intestines that are then excreted in human stools. E. histolytica trophozoites secrete proteases and glycosidases to degrade the intestinal layers. Once cellular degradation occurs, upregulation of IL-8 and TNF-alpha results in the recruitment of neutrophils, macrophages, and eosinophils. The host immune system does not usually result in adequate destruction of the E. histolytica trophozoite, and the parasite continues to invade until it reaches the bloodstream, whereby it can then migrate to other organs and cause multisystem disease. On gross pathology, amebiasis may be characterized by wavy surface epithelium and formation of nodular and irregular ulcerations. On microscopic pathology, flask-shaped ulcers are characteristic, but interglandular ulcerations, hyperemia, mucosal thickening, reactive glandular hyperplasia, and neutrophilic infiltration are common findings. In late stages, amebiasis often results in tissue fibrinoid necrosis and formation of granulation tissue.

• E. histolytica cyst is usually transmitted by the fecal-oral route through contaminated drinking water or food
• E. histolytica cyst may also be transmitted through direct contact with infected individuals.

• Following transmission, E. histolytica trophozoites undergoes excystation in the small intestine, after which it migrates to the large intestine using pseudopods.
• In the large intestine, the trophozoites invades the intestinal mucosa into the bloodstream. Simultaneously, they form resistant cysts in the large intestines that are then excreted in human stools.
• Once in the bloodstream, the trophozoite migrates into the portal circulation and develops amebic liver abscess.^[1]

• E. histolytica trophozoites secrete proteases, which induce the release of mucin from goblet cells, resulting in glandular hyperplasia.^[1]
• E. histolytica is also thought to contain glycosidases that cleave glycsolyated mucin molecules, resulting in mucin degradation.^[2][3]
• Once the mucin layer is degraded, E. histolytica then adheres to the enterocyte plasma membrane and uses lectins, amebapores, and proteases to cause damage by a characteristic “hit and run” phenomenon.^[1]

• Lectin: responsible for adhesion of the parasite on Gal-GalNAc residues of the enterocyte
• Amebapore: Protein that forms channels that induce cytolysis in a process similar to perforin-mediated cytolysis of cytotoxic T-cells
• Protrease: Enzymes that metabolize cellular proteins

• As the trophozites creates interglandular lesions and degrades the extracellular matrix, it is propelled forward by locomotion.^[1][4][5]

• As the trophozoites invade, IL-8 and TNF-alpha secretion is upregulated, and the host immune cells are activated.^[6][7]
• Neutrophils migrate to the site of invasion and contribute to the inflammatory damage induced by E. histolytica, but are generally incapable of destroying the organism. The mechanism may which E. histolytica evades neutrophils is unknown.^[6][7][1]
• Once neutrophils are recruited, macrophages and eosinophils are also activated.^[1]
• The tropohozites can then invade into the bloodsteam, whereby they can ingest red blood cells (erythrophagocytosis) and migrate into distant organs (e.g. liver, brain, lungs).

On gross pathology, the following findings may be present in patients with amebiasis:^[1]

• Wavy surface epithelium (results from focal release of mucin and spasm of the muscular layer)
• Nodular and/or irregular ulcers in the cecum (most common), sigmoid colon, and rectum. Early ulcers are usually in the interglandular epithelium.

• Nodular: small (sub-centrimetric), rounded, elevated lesions with necrotic center and edematous rim
• Irregular: large (1-5 cm), shallow with broad elevated margins

Note: the mucosal folds may occasionally hide small colonic ulcers (false-negative results)

• On microscopic pathology, amebiasis is characterized by formation of multiple flask-shaped ulcers (deep, microhemorrhagic ulceration involving the submucosa), which are findings associated with advanced disease.^[1]
• Additional findings may be present in patients with amebiasis:^[1]

• Interglandular ulceration
• Hyperemia
• Thickened mucosa
• Reactive glandular hyperplasia
• Stromal edema
• Infiltration of neutrophils, eosinophils (rare), and macrophages
• Lymphoid aggregates
• Detection of amebas on surface exudate
• Tissue necrosis, usually fibrinoid (advanced lesion)
• Formation of granulation tissue (advanced lesion)

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  Invasive extraintestinal amebiasis. Adapted from Public Health Image Library (PHIL). ^[8]
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  Amebic abscess of liver. Adapted from Public Health Image Library (PHIL). ^[8]
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  Intestinal ulcers due to amebiasis. Adapted from Public Health Image Library (PHIL). ^[8]
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  Intestinal ulcers due to amebiasis. Adapted from Public Health Image Library (PHIL). ^[8]
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  Intestinal amebiasis. Adapted from Public Health Image Library (PHIL). ^[8]
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  Amebic abscess in liver. Adapted from Public Health Image Library (PHIL). ^[8]
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  Amebic abscess in liver. Adapted from Public Health Image Library (PHIL). ^[8]
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  Amebiasis in intestine. Adapted from Public Health Image Library (PHIL). ^[8]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[8]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]

Entamoeba histolytica is a an anaerobic parasitic protozoan that is responsible for the development of amoebiasis.

Cellular organisms; Eukaryota; Protista; Amoebozoa; Archamoebae; Entamoeba

• Usually humans (only)
• Reports of animals as natural reservoirs of E. histolytica have been described.

• The exact number of chromosomes in E. histolytica is still unknown.
• The cysts of E. histolytica contain 4 nuclei with even distribution of chromatin between the nuclei.
• The trophozoites are spherical/oval shaped with a thin cell membrane and a single nucleus.
• E. histolytica is able to move using pseudopods.

• Cysts and trophozoites are passed in human feces. Cysts are typically found in formed stool, whereas trophozoites are typically found in diarrheal stool.
• Infection by Entamoeba histolytica occurs by ingestion of mature cysts in fecally contaminated food, water, or hands.
• Excystation occurs in the small intestine and trophozoites are released, which migrate to the large intestine.
• The trophozoites multiply by binary fission and produce cysts, and both stages are passed in the feces.
• Because of the protection conferred by their walls, the cysts can survive days to weeks in the external environment and are responsible for transmission.
• Trophozoites passed in the stool are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric environment.
• In many cases, the trophozoites remain confined to the intestinal lumen (A: noninvasive infection) of individuals who are asymptomatic carriers, passing cysts in their stool.
• In some patients the trophozoites invade the intestinal mucosa (B: intestinal disease), or, through the bloodstream, extraintestinal sites such as the liver, brain, and lungs (C: extraintestinal disease), with resultant pathologic manifestations.
• It has been established that the invasive and noninvasive forms represent two separate species, respectively E. histolytica and E. dispar. These two species are morphologically indistinguishable unless E. histolytica is observed with ingested red blood cells (erythrophagocystosis).
• Transmission can also occur through exposure to fecal matter during sexual contact (in which case not only cysts, but also trophozoites could prove infective).

Entamoeba histolytica must be differentiated from other causes of viral, bacterial, and parasitic gastroentritis.

8Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient’s immunity system.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea^{[1][2][3][4][4]}

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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
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  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]
• 
  Entamoeba histolytica. From Public Health Image Library (PHIL). ^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

Amoebiasis must be differentiated from other causes of abdominal pain, bloating, acute or chronic diarrhea, and weight loss, such as other infectious causes of gastroenteritis, including bacterial, viral, fungal, and parasitic pathogens, in addition to non-infectious causes, including acute pancreatitis, appendicitis, bowel obstruction, diverticulitis, drug reaction, hyperthyroidism, inflammatory bowel disease, celiac disease, lactose intolerance, Whipple disease, tropical sprue, and lymphoma.

• Amoebiasis must be differentiated from other causes of acute or chronic diarrhea, bloating, abdominal pain, and fever (less common).
• Differential diagnosis of amoebiasis includes the following:

• Bacterial infections (e.g. E. coli infection, shigellosis, salmonellosis, C. jejuni infection)
• Viral infections (e.g. norovirus, rotavirus, astrovirus, HIV)
• Fungal infections (e.g. Candida spp.)
• Parasites (Giardia, Cryptosporidium spp., Cyclospora)

The following are the non-infectious differential diagnoses of E. coli enteritis:

• Acute pancreatitis
• Adrenal insufficiency and Waterhouse-Friedrichsen syndrome
• Allergy (e.g. insect bite allergy or anaphylaxis)
• Appendicitis
• Bowel obstruction
• Celiac disease
• Diverticulitis
• Drug reaction (e.g. antimicrobial agents, antihypertensive therapy, chemotherapy, anticonvulsants)
• Endometriosis
• Familial Mediterranean fever
• Gastrointestinal perforation
• Hyperthyroidism
• Ileus
• Inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
• Intussusception
• Ischemic colitis
• Ketoacidosis
• Lactose intolerance
• Lymphoma
• Mesenteric ischemia
• Necrotizing enterocolitis
• Ogilvie syndrome
• Peritonitis
• Pneumonia
• Poisoning and toxicity (e.g. carbon monoxide poisoning, organophosphate poisoning, digitoxin toxicity)
• Ruptured abdominal aortic aneurysm
• Spider bite
• Tropical sprue
• Volvulus
• Urinary tract infection
• Whipple disease

To view a comprehensive list of abdominal pain differential diagnoses, click here.
To view a comprehensive list of diarrhea differential diagnoses, click here.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea^{[1][2][3][4][4]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

Amoebiasis is a worldwide infection whose incidence is highly dependent on sanitation practices. Worldwide, the annual incidence of amoebiasis is approximately 50 million cases. Prevalence of amoebiasis ranges from approximately 4% in the USA to 50% in certain regions in developing countries. It is thought that the prevalence of E. dispar is much higher than that of E. histolytica, but E. dispar is frequently undiagnosed because colonized individuals are almost always asymptomatic. Worldwide, approximately 500 million individuals are thought to be colonized by E. dispar. Worldwide, amoabiasis is associated with 100,000 deaths each year and a case-fatality rate of approximately 200 per 100,000 cases. Elderly patients and young children are at higher risk of developing amoebiasis than adults, but adults are at higher risk of developing amebic liver abscess than children. Men are at higher risk of developing invasive amoebiasis and amebic liver abscess than women. In the USA, the prevalence of amoebiasis is much more common among Hispanic and Asian immigrants and immigrants from Pacific Islands. However, the higher prevalence is though to be due to the immigration status, not due to ethnic differences.

• Amoebiasis is a worldwide infection whose incidence is highly dependent on sanitation practices.
• Worldwide, the annual incidence of amoebiasis is approximately 50 million cases.^[1][2][3]
• Prevalence of amoebiasis ranges from approximately 4% in the USA to 50% in certain regions in developing countries.^[4]
• It is thought that the prevalence of E. dispar is much higher than that of E. histolytica, but E. dispar is frequently undiagnosed because colonized individuals are almost always asymptomatic. Worldwide, approximately 500 million individuals are thought to be colonized by E. dispar.^[5]
• In the USA, amoebiasis is more common among immigrants (Hispanic, Asian, or from Pacific Islands) than other groups.

• Worldwide, amoabiasis is associated with 100,000 deaths each year and a case-fatality rate of approximately 200 per 100,000 cases.^[1][2][3]
• Fewer than 10 amoebiasis-related deaths are reported annually in the USA.

• Elderly patients and young children are at higher risk of developing amoebiasis than adults.
• Adults are at higher risk of developing amebic liver abscess than children (the incidence of amebic liver abscess is up to 10x higher in adults than in children).

• There is no gender predilection for the development of amoebiasis.
• Men are at higher risk of developing invasive amoebiasis and amebic liver abscess than women (the incidence of amebic liver abscess is up to 3x-10x higher in men than in women).

• In the USA, the prevalence of amoebiasis is much more common among Hispanic and Asian immigrants and immigrants from Pacific Islands. However, the higher prevalence is though to be due to the immigration status, not due to ethnic differences.

• The incidence of amoebiasis is higher in developing countries than in developed countries, particulary in regioins with poor sanitation systems.
• The incidence of amoebiasis may reach up to 50% in certain regions.

• The incidence of amoebiasis is much lower in developed countries than in developing countries. The lower incidence is attributed to access to safe drinking water and food handling.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

Risk factors in the development of amoebiasis include exposure to infected individuals, drinking unsafe water, alcoholism, age extremes (elderly or young children), pregnancy, immunosuppression, recent sexual history with unprotected anal or oral-anal contact, and recent travel to developing countries.

Risk factors in the development of amoebiasis include the following:

• Exposure to infected individuals
• Drinking contaminated or untreated water (.e.g lakes, wells, streams, ponds)
• Alcoholism
• Age extremes (elderly or young children)
• Pregnancy
• Immunosuppression (e.g. use of corticosteroids or active malignancy)
• Individuals with recent sexual history of unprotected anal or oral-anal contact
• Recent travel to developing countries

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

• Following transmission, individuals typically remain asymptomatic for approximately 1 to 4 weeks (up to several years), during which the parasite starts to actively destroy to integrity of the intestinal wall.
• The majority of colonized patients do not develop any clinical manifestations.
• The infection rate of E. histolytica is approximately 10%-20%, whereas the infection rate of E. dispar is approximately 0% (since E. dispar is not associated with invasive disease).

• As the parasite continues to invade the intestinal wall, the integrity of the wall is compromised, and the host immune cells are activated. The activation of neutrophils, macrophages, lymphocytes, and eosinophils contribute to the inflammation and the development of clinical manifestations.
• The development of symptoms occurs gradually over 1-2 weeks. Early symptoms include profuse, watery diarrhea, abdominal pain, bloating, and nausea.
• If left untreated, the majority of patients report self-resolution of symptoms.
• In a minority of cases, however, the disease may progress and patients develop bloody diarrhea (dysentery), fulminant colitis, appendicitis, toxic megacolon, and ameboma (granulation tissue in the colon).

• As the infection advances, the parasite is able to migrate outside the intestinal lumen into the bloodstream, where it is able to migrate to distant organs.
• If left untreated, the most site of parasitic migration is the liver, whereby the parasite travels in the portal circulation and causes amoebic liver abscess.
• Other organs may also be affected, including the brain (cerebral amoebiasis), pulmonary system (pleuropulmonary abscess), skin, and genitals.

• Patients with untreated amoebiasis may develop chronic disease.
• The symptoms of chronic amoebiasis resemble inflammatory bowel disease (IBD).
• The distinction between chronic amoebiasis vs. IBD is important since corticosteroid therapy is effective for IBD but worsens amoebiasis.

Complications of amoebiasis may be either intestinal or extraintestinal:

• Dysentery
• Colitis
• Appendicitis^[1]
• Toxic megacolon
• Peritonitis
• Ameboma (granulation tissue in the colon)
• Intestinal perforation

• Amoebic liver abscess
• Cerebral amoebiasis
• Pleuropulmonary abscess
• Skin lesions
• Amoebic genital lesions
• Amoebic pericarditis

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