Amoebiasis

Definition, Etiology, PathogenesisTop

Amoebiasis refers to a protozoal infection caused by the parasite Entamoeba histolytica, with dysentery and blood-borne extraintestinal abscesses.

1. Etiologic agent: E histolytica, a protozoal parasite of the large intestine (most frequently colonizing the cecum and ascending colon). The parasite has a 2-stage life cycle: a cyst and a vegetative trophozoite. Cysts of E histolytica are infective. Once swallowed, they travel to the large intestine and release trophozoites, which produce proteolytic enzymes. Trophozoites penetrate the intestinal wall and cause crater-like ulcerations (often with bacterial superinfection). They may also enter the peritoneal cavity and disseminate via the hematogenous route to the liver, lungs, and brain (amoebic abscesses).

2. Reservoir and transmission: The reservoir is humans. The source of infection is a sick individual or a carrier shedding cysts. Infection occurs after the ingestion of cysts with contaminated water, food (typically raw vegetables), or via unwashed hands (after direct contact with a sick individual/carrier or with contaminated objects, such as banknotes). Cysts are destroyed by the boiling of water and foods.

3. Risk factors: Traveling to endemic areas, consumption of foods (raw vegetables) and unboiled water from dubious sources in endemic areas, oral-anal sexual contacts (particularly in men who have sex with men).

4. Incubation and contagious period: The incubation period is from 1 week to 4 months. The patient shedding the cysts is contagious for contacts. In a humid environment the cysts remain infective for up to several weeks.

EpidemiologyTop

Amoebiasis is endemic in developing countries of the tropical and subtropical zones. In developed countries it occurs as an imported infectious disease. Ninety percent of individuals with positive results of stool testing for the presence of Entamoeba cysts are actually infected with nonpathogenic E dispar (common in developed countries), which is morphologically identical to E histolytica.

Clinical Features and Natural HistoryTop

1. Asymptomatic infection: Resolves spontaneously in ~90% of cases; in the remaining 10%, invasive disease develops.

2. Amoebic colitis: Diarrhea with a high content of mucus, of varying intensity, from mild (with no blood content) to dysentery. Patients may have abdominal cramps, asthenia, low-grade fever, anorexia, weight loss, headache, and lumbar pain. The disease progresses slowly, often with remissions and exacerbations. Endoscopy reveals characteristic small ulcerations (2-10 mm) of the large intestinal mucosa, particularly in the cecum and ascending colon. In ~0.5% of patients the disease is fulminant, with necrosis of the intestinal wall, intestinal perforation, and peritonitis. Complications of amoebic colitis include toxic megacolon and amoeboma.

Types of amoebic colitis:

1) Amoebic dysentery: Acute diarrhea with mucus and blood; trophozoites with intracellular erythrocytes may be identified in stool and tissues (eg, mucosa).

2) Nondysenteric amoebic colitis: Recurrent episodes of diarrhea without blood in stool (mucus may be present), with abdominal pain and weight loss. Cysts and trophozoites without intracellular erythrocytes are identified in stool.

3) Amoeboma: Localized chronic amoebiasis of the cecum or the ascending colon; may lead to intestinal obstruction.

4) Appendicitis (rarely) may be the presenting symptom of amoebiasis in high-risk areas.

5) Perianal ulceration.

6) Rectovaginal fistula.

3. Extraintestinal amoebiasis

1) Amoebic abscess of the liver: The most frequent extraintestinal manifestation of the infection (develops as a result of the parasite getting into the liver from visceral vessels through the portal vein); always preceded by intestinal amoebiasis (not necessarily symptomatic). Signs and symptoms include right-sided epigastric pain and fever; frequently anorexia, nausea, asthenia, and weight loss. Hepatic enlargement and pain on palpation are present on physical examination. Jaundice is rare. Results of diagnostic tests reveal leukocytosis, elevated serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, and frequently also elevated serum C-reactive protein (CRP) levels. Imaging studies often show numerous small abscesses, most commonly in the right hepatic lobe, which later coalesce into one or a few larger abscesses. Amoebic liver abscesses are bacteriologically sterile, filled with thick chocolate-brown liquid (liquefaction necrosis), with the parasite present by the abscess wall.

2) Pulmonary amoebiasis.

3) Amoebic abscess of the brain.

4) Genitourinary amoebiasis.

5) Cutaneous amoebiasis.

DiagnosisTop

Diagnostic Criteria

1. Amoebic colitis:

1) Microscopic identification of trophozoites with intracellular erythrocytes (direct fecal smear) or cysts (the presence of cysts may be demonstrated in formalin-fixed stool samples): Low sensitivity of the test (~60%) does not allow for differentiation between E histolytica and morphologically identical nonpathogenic types of amoeba (eg, E dispar, E moshkovskii, E bangladeshi); a positive result must be confirmed with other tests.

2) Detection of specific parasitic antigens in stool (enzyme-linked immunosorbent assay [ELISA]) allows for differentiation between E histolytica and nonpathogenic types of amoeba.

3) Identification of the genetic material of E histolytica in stool through polymerase chain reaction (PCR).

4) Culturing of E histolytica from stool samples with isoenzyme analysis.

5) Identification of trophozoites in the biopsy specimens of the large intestinal mucosa; E histolytica may also be found in biopsy specimens collected from the edges of intestinal ulcerations found on endoscopy. Serologic tests may show specific antibodies in serum but do not distinguish between active and past amoebiasis.

2. Extraintestinal amoebiasis:

1) Positive serologic test result—detection of specific serum antibodies (ELISA, indirect immunofluorescence); direct hemagglutination test.

2) Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI) of involved organs.

3) Identification of the genetic material of E histolytica (PCR) in fine-needle aspiration biopsy specimens of the abscess.

4) Less commonly microscopic examination of fine-needle biopsy specimens of the abscess (this rarely allows for the identification of the amoeba, as it is typically present in the abscess wall).

Differential Diagnosis

1. Amoebic colitis: Dysentery of other etiologies, primarily infectious; ulcerative colitis; irritable bowel syndrome (IBS); colorectal cancer.

2. Amoebic abscess: Bacterial abscess, tumor of neoplastic or other etiology, cyst (including echinococcal cysts).

TreatmentTop

Symptomatic Treatment

As in diarrhea.

Antiprotozoal Treatment

1. Drugs used in tissue invasion:

1) Treatment of choice for all symptomatic patients with intestinal and extraintestinal amoebiasis: Oral tinidazole 2 g once daily for 3 days or oral metronidazole 500 to 750 mg tid for 7 to 10 days.

2) Second-line treatment: Oral nitazoxanide 500 mg bid for 3 to 10 days or oral chloroquine 500 mg bid for 2 days followed by 250 mg bid for 2 to 3 weeks, usually in combination with luminal amoebicides.

2. Luminal amoebicides: Eradication of the cysts (to be used in carriers and in all symptomatic patients who completed treatment): Oral diloxanide 500 mg tid for 10 days, oral iodoquinol 650 mg tid for 20 days, or oral paromomycin 8 to 12 mg/kg tid for 7 days (not absorbed, can be used in pregnant patients).

3. Amoebic liver abscesses: Small abscesses resolve after a 10-day treatment with 750 mg of oral or IV metronidazole tid or a 5-day treatment with 2 g of tinidazole once daily, followed by an agent acting in the intestinal lumen, eg, paromomycin; in patients with larger abscesses (>3 cm in diameter), an additional percutaneous needle aspiration is indicated or, rarely, drainage.

4. Symptomatic amoebiasis in pregnant women: Oral paromomycin 8 to 12 mg/kg tid for 7 days.

Follow-UpTop

Resolution of signs and symptoms after treatment is slow; features reminiscent of IBS may persist for years. Due to the possible recurrences perform follow-up parasitologic examinations of 2 to 3 stool samples collected on consecutive days 3 to 12 weeks after discontinuation of treatment. Use US to monitor resolution of liver abscesses (this may last several months).

ComplicationsTop

Abscess of the liver, lungs, or brain; amoeboma, obstruction of the large intestine; acute megacolon, perforation of the large intestine, peritonitis; rupture of a liver abscess into the pleural or pericardial cavity; intestinal bleeding. Pregnant and immunosuppressed individuals are at higher risk of complications and a severe course of the disease.

PreventionTop

Specific Prevention

None.

Nonspecific Prevention

Maintaining good hand hygiene and food safety precautions while visiting regions endemic for amoebiasis.