Amoebiasis

6 Interesting Facts of Amoebiasis 

1. Amoebiasis is an intestinal parasitic infection acquired through ingestion of contaminated food or water
2. Many people are asymptomatic; a symptomatic presentation may include fever, diarrhea, abdominal pain, or weight loss 
3. Diagnosis is based on patient history, clinical presentation, microscopic identification of parasite or antigen in fecal or other specimens, or by serology 
4. Treatment with paromomycin or iodoquinol is indicated for asymptomatic or mild intestinal infections; treatment with metronidazole or tinidazole followed by paromomycin or iodoquinol is indicated for invasive intestinal or extraintestinal infection 
5. Complications include peritonitis, colonic perforation, and abscess rupture 
6. With appropriate treatment, uncomplicated infection usually resolves within 2 weeks with low morbidity and mortality rates 

Pitfalls

• Failure to detect organism in fecal specimen does not rule out diagnosis
• Patients with amoebiasis are at risk for other parasitic infections; coinfection may occur
• Failure to treat asymptomatic infection could allow for ongoing transmission in a household or institution

• Amoebiasis is an infection caused by an amoeba, usually the intestinal protozoan parasite Entamoeba histolytica 
  • 2 species that are morphologically indistinguishable from Entamoeba histolytica are recognized as human commensals (Entamoeba dispar, Entamoeba moshkovskii) 
    • Entamoeba moshkovskii is not well understood
  • For clinical purposes, WHO defines amoebiasis as infection due to Entamoeba histolytica 
• Clinical manifestations can range from asymptomatic colonization to invasive disease, which may manifest as dysentery, colitis, or liver abscess 
• Rarely, progression may result in hematogenous spread to other organs 

Classification

• Asymptomatic amoebiasis
  • Presence of Entamoeba histolytica in stool in the absence of diarrhea, colitis, or extraintestinal infection
• Symptomatic amoebiasis resulting from invasive disease
  • Intestinal amoebiasis
    • A spectrum of gastrointestinal symptoms ranging from loose stools to dysentery (eg, bloody diarrhea, mucus, cramping, tenesmus)
      • Amoebic colitis
        • Results from destruction of colonic submucosa, with fever, bloody diarrhea, and abdominal pain
      • Less common intestinal manifestations include the following:
        • Amoeboma, a granulomatous mass in the lumen of the colon
        • Chronic diarrhea
        • Perirectal cutaneous amoebiasis
  • Extraintestinal amoebiasis
    • Liver abscess
      • Occurs in 1% or less of cases 
    • Very rarely
      • Brain abscess
      • Splenic abscess
      • Empyema
      • Pericarditis

Clinical Presentation

History

• 80% to 90% of affected people are asymptomatic; in those who are symptomatic, typically develop between 7 and 28 days after exposure to Entamoeba histolytica 
• Invasive intestinal infection (a spectrum including dysentery and colitis)
  • Diarrhea is present in 94% to 100% of patients
    • Passage of 3 to 8 semiformed stools per day (mild) 
    • Passage of 10 to 20 watery stools (severe) 
    • Stools may be soft with mucus 
    • Blood is present in approximately 70% of cases, either gross or microscopic 
    • Tenesmus may be noted
  • Abdominal pain or cramps (12% to 80% of patients) 
  • Weight loss (44%) 
  • Excessive flatulence
  • Vomiting
  • Fatigue
• Liver abscess can occur months to years after exposure
  • May present acutely with fever and upper right abdominal pain
  • May present subacutely with weight loss (may be prominent)
  • Often asymptomatic, with liver abscess found incidentally on imaging obtained for another reason
  • May have a history of dysentery within the last year, but concurrent diarrhea or colitis is unusual 
  • History of alcohol abuse is common with amoebic liver abscess

Physical examination

• Fever (38.5°C to 39.5°C) is present in 8% to 38% of people with colitis
  • More common in patients with amoebic liver abscess 
• Abdominal tenderness upon palpation
  • May be localized to the right side; the ascending colon is most commonly involved in invasive intestinal disease 
• Patients with colitis may have peritoneal signs including diminished bowel sounds, guarding, rigidity, and rebound tenderness
• In cases of amoebic abscess, tender hepatomegaly may be palpable
  • Rarely, extension across the diaphragm results in pleural or pericardial effusion
    • Dullness to percussion
    • Decreased breath sounds
    • A pleural friction rub may be heard
    • Pericardial friction rub or decreased heart tones may be noted

Causes

• Entamoeba histolytica is spread through fecal-oral route; infectious cysts are ingested in food or water contaminated with feces 
• Also spread through person-to-person transmission and sexual transmission

Risk factors and/or associations

Age

• People younger than 50 years are at increased risk (odds ratio, 4.73) 

Sex

• Male sex is an independent risk factor (odds ratio, 8.39) 
• Liver abscess is 10 times more common in young adult men
  • Male to female ratio is equal in children and infants

Other risk factors/associations

• Most common in tropical areas
  • Travel to, residence in, or emigration from endemic areas increases risk 
    • Africa
    • Asia and Pacific Islands
    • Central and South America
• Crowded living conditions and poor sanitation increase risk
  • In the United States, amoebiasis is associated with people living in institutions because of poor personal hygiene 
• Risk factors that increase the likelihood of developing severe amoebiasis are the following: 
  • Alcoholism
  • Malnutrition
  • Cancer-associated immunodeficiency or immunosuppression
  • Corticosteroid use
• A history of syphilis or HIV is an independent risk factor for the development of amoebic colitis (odds ratios, 2.90 and 15.85, respectively) 

Diagnostic Procedures

Primary diagnostic tools

• Diagnosis is suggested by patient history, clinical presentation, and physical examination 
  • Bloody and/or watery diarrhea accompanied by abdominal pain is the classic presentation 
  • Tender hepatomegaly in the presence of fever and weight loss 
  • Living in, travel to, or immigration from endemic countries
• Laboratory analysis is essential for making the diagnosis
  • Stool microscopy is usually the first step in evaluating for intestinal amoebiasis 
    • Because excretion of the organism may be intermittent, submit 3 stool specimens from different days over a 10-day period to improve yield 
    • A positive result on fecal analysis provides evidence of Entamoeba species, but stool microscopy cannot distinguish Entamoeba histolytica from Entamoeba dispar or Entamoeba moshkovskii unless RBC inclusions are observed, suggesting Entamoeba histolytica 
    • Failure to detect organism in fecal specimen does not rule out diagnosis
  • Further testing is needed for definitive identification of Entamoeba histolytica when microscopy is positive, and is an additional diagnostic approach to cases in which microscopy result is negative
    • Fecal antigen detection tests
      • Distinguish Entamoeba histolytica from morphologically similar commensals
      • May provide diagnosis in patients with negative fecal microscopy results
      • Aid in interpreting clinical relevance of positive serology test results in patients from endemic areas whose antibody levels may reflect past infection
    • Serologic analysis to detect species-specific antibodies
      • Useful in patients with suspected invasive intestinal or extraintestinal disease
        • High antibody titers support the diagnosis of amoebic abscess in symptomatic patients with suggestive imaging results 
      • Most appropriate for patients from nonendemic countries
    • Nucleic acid amplification tests are highly sensitive and specific but are not widely available 
    • Culture techniques for amoeba are not generally available in clinical laboratories; further, failure to isolate the organism from stool does not rule out infection 
• Findings from colonoscopy with biopsy are helpful in diagnosing invasive intestinal amoebiasis or in excluding alternate diagnoses 
• Image the affected area for patients in whom extraintestinal amoebiasis is suspected
  • Chest and abdominal radiography may provide preliminary clues (eg, elevated right hemidiaphragm in liver abscess)
  • Ultrasonography, CT, and MRI can detect presence and determine size of abscess 
  • Entamoeba histolytica is confirmed by detection of high antibody titers in blood 
    • If the collection is aspirated (eg, for suspected pyogenic abscess), microscopy and antigen testing can be done but aspiration is not usually required for the diagnosis of amoebic abscess 

Laboratory

• Stool microscopy
  • Examine stool within 15 minutes of collection; if prompt examination is not possible, place the specimen immediately in a fixative to prevent deterioration of organisms 
  • Positive identification of cysts and trophozoites via trichrome stain
    • Cysts range from 10 μm to 16 μm in diameter 
    • May contain up to 4 nuclei each, with central irregular dots and chromatin on the peripheral rim 
    • Chromatoid bodies are typically present 
    • Trophozoites with ingested RBCs are strongly indicative of invasive amoebiasis (ie, infection caused by Entamoeba histolytica) 
  • Nonspecific, lacks sensitivity, fails to identify one-half to two-thirds of Entamoeba histolytica infections 
  • Failure to detect organism in fecal specimen does not rule out diagnosis
• Antigen detection tests
  • ELISA test for detection of Entamoeba histolytica species
    • Widely available in clinical laboratories
    • Very sensitive but may have low specificity in nonendemic areas 
    • In a patient with positive serology results in an endemic setting, presence of a positive fecal antigen distinguishes current from past infection
  • Some tests are designed for use on blood and body fluids as well as on fecal specimens 
• Serologic analyses
  • Good sensitivity and specificity (approximately 95%) for detecting invasive intestinal or extraintestinal disease 
  • Cannot distinguish between past and current infection
    • IgM antibodies are short-lived and rarely detected
    • IgG antibodies are long-lived and prevalent in endemic areas
  • Antibodies are not detectable until 7 to 10 days after infection
• Besides serology, blood tests are neither required nor specific for diagnosis but are often done in the course of evaluating diarrhea, fever, and abdominal pain
  • Anemia can be seen in amoebic colitis 
  • Amoebic abscess can be associated with leukocytosis; liver function test results may or may not show elevated levels 

Imaging

• Chest radiograph
  • May identify pleural effusion and raised right hemidiaphragm overlying the involved lobe of the liver
• Ultrasonography of the liver or spleen
  • May show well-defined hypoechoic lesions with rounded edges
• CT and MRI of the liver
  • May show rounded, well-defined, and low-attenuated lesions
  • Abscess cavity may appear homogeneous or with observable fluid or debris
  • May be an unexpected or incidental finding in imaging of other organs (eg, lung, brain) in the course of a work-up for symptoms in those areas

Procedures

• Gastroenterologist passes a colonoscope into the colon to visually inspect the mucosa and to obtain biopsies of suspicious lesions or ulcerations for histopathologic analysis 
• Patients suspected of having amoebiasis in whom diagnosis has not been made by noninvasive testing 
• Peritonitis
• Severe dehydration
• Shock
• Uncontrolled coagulopathy
• Large-bowel ulcers may be seen in mild disease 
• The following are indicative of more severe disease: 
  • Granular, friable, and diffusely ulcerated mucosa
  • Hemorrhage
  • Colonic stricture
  • Amoeboma
• Histopathology
  • Flask-shaped mucosal ulcers are characteristic histopathologic features of amoebiasis
  • Periodic acid–Schiff staining identifies Entamoeba histolytica parasite

Differential Diagnosis

Most common

• For intestinal amoebiasis
  • Infectious causes
    • Note that coinfection may occur, particularly in residents of or travelers to developing countries
    • Campylobacter, Shigella, Salmonella, or toxigenic Escherichia coli 
      • All commonly present with fever, abdominal pain, and diarrhea that may contain occult or gross blood 
      • Differentiated from amoebiasis and from each other using culture to isolate and identify the infectious organism
    • Tuberculosis
      • Intestinal tuberculosis is common in developing countries and may present as fever, abdominal pain, dysentery, and weight loss
      • Other typical manifestations of tuberculosis (eg, pulmonary) may or may not be present
      • Differentiated by recovery of Mycobacterium tuberculosis or Mycobacterium bovis from stool; endoscopy and biopsy of gastrointestinal ulcerations show typical caseating granulomas containing acid-fast bacilli
    • Other parasitic infections
      • Schistosomiasis
        • Acute schistosomiasis (Katayama fever) may present with fever, abdominal pain, and diarrhea, sometimes with bloody stools
        • Patients with chronic schistosomiasis may have episodes of dysentery
        • Differentiated by presence of schistosome eggs in stool, tissue biopsy, or by polymerase chain reaction on stool
          • Antibody tests may be helpful in people from nonendemic areas who may have become infected through travel to an endemic area
      • Giardiasis
        • Presents with abdominal pain, bloating, diarrhea, and weight loss
        • Stools are characteristically greasy and foul-smelling; the presence of gross blood is uncommon
        • Differentiated by presence of Giardia on microscopy or Giardia antigen in stool or duodenal contents
      • Cryptosporidiosis
        • Presents with abdominal cramping and frequent watery stools
        • Visible blood in stool is uncommon
        • Differentiated by identification of oocysts in specially stained stool preparations (acid-fast or immunofluorescent) or by Cryptosporidium antigen test
      • Strongyloidiasis
        • In immunocompromised patients, may present with fever, abdominal pain, and bloody diarrhea
        • May include extraintestinal involvement (eg, lungs, central nervous system, skin)
        • Differentiated by the finding of rhabditiform larvae in stool, duodenal fluid, or biopsy; immunoassay or polymerase chain reaction techniques are available for stool testing
  • Noninfectious causes
    • Inflammatory bowel disease
      • Chronic inflammation of the colon and small intestine 
      • Signs and symptoms are similar to those of amoebiasis: diarrhea, abdominal pain
      • Visible blood in the stool is common in ulcerative colitis
      • Definitive diagnosis and distinction from amoebiasis is by intestinal biopsy showing the characteristic histopathologic lesions, as follows: 
        • Ulcerative colitis: crypt abscesses in the lamina propria
        • Crohn disease: transmural ulcerations with cryptitis, crypt abscesses, and noncaseating granulomas
    • Ischemic colitis
      • Acute reduction of blood flow to the colon 
      • Presents with abdominal pain, diarrhea (often bloody)
      • Onset of pain is sudden and degree of pain is severe
      • Peritoneal findings and signs of impending shock (eg, tachycardia, tachypnea, hypotension, pallor, diaphoresis) may be present on examination
      • Diagnostic examination includes clinical evaluation; analysis of risk factors; and abdominal CT angiography showing occluded vessel, distended bowel, bowel-wall thickening, mesenteric stranding, and gas in bowel wall or portal vein 
    • Diverticulitis
      • Inflammation of colonic diverticula 
      • May present with fever, abdominal pain, and bloating; stools may contain pus and blood
      • Distinguished by imaging or colonoscopy to identify inflamed diverticula 
• For extraintestinal amoebiasis
  • For amoebic liver abscess
    • Pyogenic abscess (due to bacteria)
      • Presents similarly to amoebic abscess, with fever, right upper quadrant pain, and similar appearance on imaging
      • Differentiated by laboratory findings (eg, absence of antibodies to Entamoeba histolytica, presence of bacteria on Gram stain, and culture of aspirate)
    • Echinococcal disease
      • Presents similarly to amoebic liver abscess, with fever and right upper quadrant pain
      • There is often history of exposure to sheep or goats
      • CT appearance differs from amoebic abscess, and is characterized by the presence of a multiloculated cystic mass; detection of antibodies to Echinococcus granulosus confirms the diagnosis 

Treatment Goals

• Eliminate parasite 
• Prevent progression to invasive disease in asymptomatic amoebiasis 
• Eliminate shedding of Entamoeba histolytica cysts, which is a public health concern 

Admission criteria

Hospital admission may be required for patients with severe colitis and hypovolemia, liver abscess not responding to treatment, or peritonitis 

Criteria for ICU admission

• Patients with acute fulminant or necrotizing amoebic colitis
  • Surgical intervention may be necessary

Recommendations for specialist referral

• Abdominal or colorectal surgeon for patients with acute fulminant or necrotizing amoebic colitis 
• Gastroenterologist or colorectal surgeon for patients requiring colonoscopic examination

Treatment Options

WHO recommends treating all patients in whom Entamoeba histolytica infection is confirmed, whether or not symptoms are present 

• Purpose of treating asymptomatic people is to prevent progression to invasive disease and to eliminate shedding of Entamoeba histolytica cysts, which is a public health concern
• However, when resources do not permit confirmation of tentative morphologic identification, WHO recommends against treating asymptomatic patients to avoid widespread treatment of nonpathogenic amoebae and to reduce the risk of generating antimicrobial resistance 

Failure to treat asymptomatic infection could allow for ongoing transmission in a household or institution

Treatment of asymptomatic disease involves use of a luminal amoebicide; tissue penetration by the amoebicidal agent is not necessary

• Luminal amoebicides include paromomycin, iodoquinol, and diloxanide furoate; the latter is not available in the United States

Treatment of symptomatic intestinal disease or extraintestinal infections requires use of a tissue amoebicide followed by a luminal agent to prevent relapse or recurrence and eliminate shedding of cysts 

• Metronidazole is the most commonly used tissue amoebicide and is the drug of choice for extraintestinal infection 
  • A 5- to 10-day regimen of metronidazole followed by a luminal agent is highly effective even for amoebic liver abscesses, which usually do not require drainage 
  • Percutaneous or surgical drainage may be necessary for patients who do not respond to antimicrobial therapy or who have abscesses exceeding 5 cm in diameter
• Tinidazole is an alternative tissue amoebicide 

In very severe invasive intestinal disease, surgical resection may be required, but it should be avoided unless absolutely indicated (in patients with perforation, obstruction, or toxic megacolon) because of poor tissue quality 

Drug therapy

• Antiprotozoal agents (luminal)
  • Paromomycin
    • Paromomycin Sulfate Oral capsule; Adults, Adolescents, and Children: 25 to 35 mg/kg/day PO in 3 divided doses for 7 days.
  • Iodoquinol
    • Iodoquinol Oral tablet; Children and Adolescents: 10 to 13.3 mg/kg/dose (Max: 650 mg/dose) PO every 8 hours for 20 days.
    • Iodoquinol Oral tablet; Adults: 650 mg PO every 8 hours for 20 days.
• Nitroimidazole antimicrobial
  • Metronidazole
    • Metronidazole benzoate Oral powder; Infants, Children, and Adolescents: 35 to 50 mg/kg/day PO divided every 8 hours (Max: 2,250 mg/day) for 7 to 10 days.
    • Metronidazole Oral capsule; Adults: 500 or 750 mg PO every 8 hours for 5 to 10 days.
  • Tinidazole
    • Tinidazole Oral tablet; Children and Adolescents 4 to 17 years: 50 mg/kg/dose (Max: 2 g/dose) PO once daily for 3 days followed by either iodoquinol or paromomycin.
    • Tinidazole Oral tablet; Adults: 2 g PO once daily for 3 days followed by either iodoquinol or paromomycin.
    • Treatment of amoebic liver abscess may be extended to 5 days 

Nondrug and supportive care

Procedures

Partial or total colectomy with exteriorization of the ends 

General explanation

• Surgical removal of nonviable, nonfunctional, or diseased bowel with creation of a stoma

Indication

• Patients with acute fulminant or necrotizing colitis complicated by perforation, obstruction (amoeboma), or toxic megacolon 

Contraindications

• Uncorrected bleeding dyscrasia

Drainage of abscess

General explanation

• Usually done using ultrasonography or CT guidance by percutaneous needle aspiration, with or without placement of a drainage catheter

Indication

• Presence of a large collection (over 5 cm) of pus or failure of medical therapy

Contraindications

• Uncontrolled bleeding disorder
• Possibility of echinococcosis

Comorbidities

• Patients with amoebiasis are at risk for other parasitic infections; coinfection may occur

Monitoring

• Routine follow-up imaging studies are not necessary for patients with amoebic liver abscess who have responded clinically to treatment 

Complications

• Patients with severe invasive disease (eg, colitis, liver abscess) require immediate treatment to prevent further complications, including bowel perforation 
• Intestinal amoebiasis
  • Rectovaginal fistula 
  • Acute necrotizing colitis
    • Occurs in less than 0.5% of cases 
    • May be complicated by peritonitis or frank perforation of the colon 
    • Surgical intervention is indicated if there is bowel perforation or if the patient does not respond to antiamoebic therapy 
• Amoebic liver abscess
  • Rupture of abscess may spread infection to peritoneum, pleural space, or pericardium 

Prognosis

• With appropriate treatment, uncomplicated infection usually resolves within 2 weeks; outcome is usually good with treatment, with low morbidity and mortality rates 
• Acute fulminant/necrotizing amoebic colitis is associated with mortality rates of over 40% 

Screening

At-risk populations

• Close (household, sexual, institutional) contacts of a person diagnosed with amoebiasis
  • Fellow travelers in cases of travel-related infection

Screening tests

• Stool microscopy with confirmation by antigen detection or serology

Prevention

• Wash or disinfect hands frequently (especially after using the toilet, changing diapers, or contact with animals or their environments), before preparing or eating food, and before and after caring for someone who is ill 
• When traveling to endemic areas or areas with poor sanitation
  • Drink bottled water or water that has been brought to a rolling boil for 1 minute
  • If purified or boiled water is not available, pass water through filter with pore size of 1 μm or less
  • Do not eat uncooked vegetables or unpeeled fruit
  • Do not drink beverages containing ice cubes
  • Do not eat or drink unpasteurized dairy products or fruit juices
  • Avoid foods sold from street vendors
  • Avoid swimming in water that may be contaminated

References

Petri WA Jr et al: Diagnosis and management of amebiasis. Clin Infect Dis. 29(5):1117-25, 1999