Infectious Diseases

Entamoeba

OVERVIEW: What every clinician needs to know

Parasite name and classification

Entamoeba histolytica – protozoan parasite

E. histolytica is one of three morphologically identical species of Entamoeba commonly found in humans; the others are E. dispar and E. moshkovskii. Only E. histolytica causes invasive disease in humans; the others are non-pathogenic.

What is the best treatment?

  • Asymptomatic infection

    • Asymptomatic infection should be treated because of the potential risk of progression to invasive disease, the risk of spread to family members, and the potential impact on Public Health.

    • Current U.S. treatment guidelines recommend for asymptomatic infection: Iodoquinol 650 mg PO three times a day for 20 days in adults and 30-40 mg/kg/d PO in three divided doses for 20 days in children OR paromomycin 25-35 mg/kg/d PO in three divided doses for 7 days in adults and children OR diloxanide furoate 500 mg PO three times a day for 10 days in adults and 20 mg/kg/d PO in three divided doses for 10 days in children.

  • Intestinal amoebiasis

    • The goals of treatment for intestinal amoebiasis are two-fold: to treat the invasive disease (using tissue agents) and to eradicate intestinal carriage of the organism (using luminal agents).

    • Metronidazole is often used for treating the invasive component of intestinal amoebiasis, with a reported cure rate of approximately 90%.

    • Tinidazole has a similar efficacy and has been shown in a Cochrane review to reduce clinical failure with fewer adverse events as compared to metronidazole in the treatment of amoebic colitis.

    • Current U.S. treatment guidelines recommend as first line treatment either metronidazole 500-750 mg PO three times daily for 7-10 days in adults and 35-50 mg/kg/d PO in three divided doses for 7-10 days in children OR tinidazole 2g PO once daily for 3 days in adults and 50 mg/kg/d PO in a single dose for 3 days in children.

    • It is recommended that patients with invasive amoebiasis should be given a luminal agent after treatment with a tissue agent to eliminate any surviving organisms in the colon.

    • Luminal agents used to eradicate intestinal carriage of the organism include Paromomycin, Diiodohydroxyquin (iodoquinol) and diloxanide furoate.

    • Metronidazole (or tinidazole) and paromomycin should be given sequentially, not concurrently, since the diarrhea that is a common side effect of paromomycin can make it difficult to assess the patient’s response to therapy.

    • Current U.S. treatment guidelines recommend as first line treatment either iodoquinol 650 mg PO three times a day for 20 days in adults and 30-40 mg/kg/d PO in three divided doses for 20 days in children OR paromomycin 25-35 mg/kg/d PO in three divided doses for 7 days in both children and adults.

  • Amoebic liver abscess

    • Both tissue and luminal agents are also used in the treatment of amoebic liver abscess.

    • Metronidazole has been reported to be very effective, with cure rates of 95% and reports of resolution of fever, pain, and anorexia within 72-96 hours.

    • Tinidazole is also very effective, with several studies reporting a single dose of 2 g daily for 2-5 days was as effective as, or more effective than, metronidazole. Fewer side effects were reported with tinidazole.

    • Current U.S. treatment guidelines recommend as first line either metronidazole 750 mg PO tid for 7-10 days (35-50 mg/kg/d in children) OR tinidazole 2 g once PO daily for 5 days (50 mg/kg/day in children 3 years of age or older).

    • Luminal agents used are paromomycin, iodoquinol, and diloxanide furoate. Doses are identical to those mentioned in the section on intestinal amoebiasis.

  • Treatment failures have been reported with metronidazole with most failures attributed to incorrect diagnosis, unsuitable choice of drug, or poor compliance rather than drug resistance. However, laboratory studies have shown that the indiscriminate use of antiamoebic drugs can result in the development of metronidazole-resistant E. histolytica strains in the laboratory.

  • Intestinal amoebiasis

    • Other nitroimidazoles

      • Other nitroimidazole drugs, such as ornidazole and secnidazole, have been used successfully in the treatment of E. histolytica and have been recommended as alternative antiamoebic drugs to metronidazole. These drugs are less readily available than metronidazole or tinidazole

      • Secnidazole has been successfully used in the treatment of uncomplicated amoebic colitis in Brazil as a single dose of 2 g for 5 days.

    • Nitazoxanide

      • A promising new drug to treat E. histolytica is nitazoxanide, which has been shown to have an efficacy between 69 and 96%.

      • A study in Egypt showed treatment with a 3-day course of nitazoxanide was effective (94% efficacy) compared to placebo in the treatment of intestinal amoebiasis. A total of 94% of patients treated with nitazoxanide were free of Entamoeba histolytica in two post-treatment stool specimens compared with only 43% of patients receiving placebo.

      • According to the latest U.S. treatment guidelines, nitazoxanide is not FDA-approved for the treatment of amoebiasis.

  • Amoebic liver abscess

    • Utrasound-guided needle aspiration

      • Use of image-guided needle aspiration in the treatment of amoebic liver abscess is controversial.

      • A 2009 Cochrane review comparing metronidazole alone with metronidazole plus aspiration was inconclusive.

      • Several authors have suggested that aspiration may be used in patients who are slow to respond to metronidazole therapy, patients with large left-lobe abscesses (due to risk of rupture into the pericardium), and severely ill patients in whom an accelerated clinical course and large abscesses make rupture seem imminent.

    • Nitaxozanide

      • A small study of seventeen adults with hepatic amoebiasis demonstrated encouraging results, with all seventeen patients responding to nitaxozanide therapy. Further studies are warranted.

What are the clinical manifestations of infection with E. histolytica?

  • Asymptomatic infection

    • Between 80 and 90% of infected individuals are asymptomatic; however, it is important to note that 4-10% of asymptomatic individuals infected with E. histolytica develop disease in the subsequent year.

  • Intestinal amoebiasis (amoebic colitis)

    • Patients with amoebic colitis can present with symptoms ranging from mild diarrhea to fulminant colitis. The onset is often gradual, and patients frequently report several weeks of symptoms.

    • Presenting features of amoebic colitis include:

      • Diarrhea (94-100%)

      • Bloody stools (70%)

      • Abdominal pain (12-80%)

      • Weight loss (44%)

      • Fever greater than 38°C (10%)

    • Intestinal amoebiasis can also present with:

      • Asymptomatic colitis

      • Fulminant colitis–reported in about 0.5% of cases

      • Amoeboma–reported in approximately 1.5% of all cases

      • Toxic megacolon–reported in about 0.5% of cases

  • Amoebic liver abscess

    • Amoebic liver abscess is the most common extra-intestinal manifestation of amoebiasis and is a result of spread via the portal venous system.

    • Amoebic liver abscesses are ten times more common in men than women and are rare in children. Other risk factors include travel to endemic areas and a history of alcohol abuse.

    • Presenting features of amoebic liver abscess include:

      • Fever (85-98%)

      • Right upper quadrant pain (84-100%)

      • Hepatomegaly (30-80%)

      • Diarrhea (20-35%)

      • Cough (10-30%)

    • Other reported symptoms include malaise, nausea, vomiting, weight loss, and anorexia.

    • Jaundice is uncommon, reported in approximately 5% of cases. The presence of jaundice suggests the existence of large or multiple abscesses, bacterial superinfection, and hepatic derangement and may indicate a poorer prognosis.

    • Patients with amoebic liver abscess may have concurrent intestinal amoebiasis, but more often they have no bowel symptoms and stool microscopy is usually negative for E. histolytica trophozoites and cysts.

  • Other extra-intestinal sites

    • Pleuropulmonary involvement

      • Pulmonary symptoms include cough (87-100%), pleuritic chest pain (50-100%), hemoptysis (44-50%), and dyspnea (20-25%). In the case of a hepatobronchial fistula, patients may have a cough productive of copious amounts of brown sputum.

    • Cardiac involvement

      • Cardiac symptoms include chest pain and dyspnea.

    • Brain involvement

      • Clinical features have been reported to include headache, vomiting, seizures, mental state changes, neck stiffness, and motor deficits.

    • Urinary tract problems; genital disease, including rectovaginal fistulae; perianal disease; and cutaneous lesions have been described as case reports.

  • Amoebic colitis

    • Fever

    • Abdominal tenderness

    • Weight loss

    • Per-rectal bleeding or bloody stools

  • Amoebic liver abscess

    • Hepatomegaly is the most important physical sign and varies depending on the size and site of the lesion. There may be a palpable hepatic mass.

    • Hepatic tenderness may be diffuse or localized.

Do other diseases mimic its manifestations?

  • Amoebic colitis

    • Salmonellosis (infection with Salmonella spp)

    • Shigellosis (infection with Shigella spp)

    • Campylobacter infections

    • Giardiasis (Giardia lamblia infection)

    • Cytomegalovirus colitis

    • Escherichia coli infections

    • Cryptosporidiosis (Cryptosporidium parvum infection)

    • Cyclosporiasis (Cyclospora cayetanensis infection)

    • Irritable bowel syndrome

    • Inflammatory bowel disease

    • Ischemic colitis

    • Diverticulitis

    • Balantidium coli

  • Ameboma

    • Ileo-caecal tuberculosis

    • Carcinoma of bowel

  • Amoebic Liver Abscess

    • Pyogenic liver abscess

    • Hepatoma

    • Acute cholecystitis

    • Parasitic cysts (such as hydatid disease)

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis:

  • Leukocytosis without eosinophilia, mild anemia, and raised alkaline phosphatase are the most common findings in amoebic liver abscess. Other abnormalities include elevated levels of bilirubin.

  • Positive fecal occult blood test is seen in at least 70% of patients with amoebic colitis.

Results that confirm the diagnosis

  • There is no worldwide gold standard test for the diagnosis of amoebiasis because of the lack of availability of certain tests in developing world settings and the diversity of presentations of intestinal and extra-intestinal amoebiasis in which different testing methods have variable sensitivity and specificity.

  • Stool microscopy may be difficult to interpret because of the inability to differentiate between different species of Entamoeba. However, in the presence of symptoms of acute colitis, it can be presumed there is infection with E. histolytica.

  • Stool antigen tests are increasingly used for diagnosis, although there are conflicting reports of the sensitivity and specificity of stool antigen testing in developing versus developed world settings.

  • Serology has limitations in differentiating between acute and past infection with E. histolytica.

  • Polymerase chain reaction (PCR)-based approaches are generally considered the method of choice in developed countries and have been strongly endorsed by the World Health Organization (WHO). However, these methods may not be available in all clinical settings.

  • The non-invasive diagnosis of amoebic liver abscess is challenging, as most patients at the time of diagnosis do not have concurrent intestinal infection with E. histolytica and fecal testing is negative in the majority of patients.

  • Stool samples, tissue samples

    • Stool microscopy

      • Examination of a minimum of three stool samples is recommended, with a detection rate of 85-95% reported.

      • Microscopy is confounded with false positives, because E. histolytica is microscopically indistinguishable from the nonpathogenic entamoeba species E. dispar and E. moshkovskii.

      • Finding trophozoites containing ingested red blood cells (RBC) has previously been considered diagnostic for amoebic colitis. However, these are not seen in the majority of patients and have also been found in vitro and in vivo when E. dispar was found.

      • Most patients with amoebic liver abscess do not have concurrent intestinal infection at the time of diagnosis, and fecal testing is negative in the majority of patients.

      • Treatment based on stool microscopy is reasonable if there are consistent clinical symptoms, but, in asymptomatic infections, stool microscopy results may be difficult to interpret.

    • Culture

      • Culture has a significant false-negative rate and is technically difficult, so it not routinely performed.

    • Stool antigen detection

      • Stool antigen detection is generally performed using antigen-based enzyme-linked immunosorbent assay (ELISA) kits.

      • Antigen detection has a number of advantages over microscopy, including the ability to differentiate between species of Entamoeba, rapidity of testing, and greater sensitivity.

      • Several studies in regions of the world in which E. histolytica is endemic have reported high sensitivities between 95 and 100% with stool antigen detection kits. However, these results have not been reproduced in non-endemic areas in which sensitivities as low as 0-38% have been reported when compared with PCR.

      • Stool antigen detection kits are relatively cheap and simple to perform and are a viable option for resource limited settings without access to PCR and where serology is less useful.

    • Colonic biopsy

      • Colonic biopsy may be helpful in the diagnosis of amoebic colitis if other diagnostic tests are negative. The detection rate of trophozoites on histopathologic examination of biopsy specimens from patients with amoebic colitis varies in different reports from all to only some patients.

    • Aspiration and culture of fluid from amoebic abscesses

      • Amoebic pus is often described as having a classic “anchovy paste” or “chocolate sauce” appearance; however, the color can vary from pink to dark brown.

      • Aspirated pus is usually sterile, although bacterial superinfection can occur.

      • The microscopy detection rate of active trophozoites varies from 0 to 100% in different series.

  • Other tests

    • PCR

      • PCR, particularly real-time PCR, is a costly procedure compared with fecal microscopy and antigen-based detection tests and is not available in most clinical settings.

      • PCR, including real-time PCR, is able to identify Entamoeba histolytica in a variety of clinical specimens, including feces, tissues, and liver abscess aspirates.

      • PCR has been shown to be 100% specific compared to isoenzyme analysis from culture and significantly more sensitive than microscopy or culture in the diagnosis of Entamoeba histolytica and Entamoeba dispar.

      • PCR has also been reported approximately 100 times more sensitive than the best ELISA stool antigen detection kit currently available.

      • The detection of E. histolytica DNA by PCR in aspirates from liver abscesses has been reported to show high sensitivity.

      • A recent study has also reported that detection of E. histolytica DNA in blood, urine, and saliva by PCR may assist in the diagnosis of liver abscess.

    • Serology

      • Serology is also useful for diagnosing amoebiasis. Many different assays have been developed for the detection of antibodies, including indirect haemagglutination (IHA), agar gel diffusion, counterimmunophoresis indirect immunofluorescence assay (IFA), and ELISA.

      • Serum antibodies to E. histolytica are usually detectable within 5-10 days of acute infection.

      • Serum IgG antibodies persist for years, whereas serum IgM levels generally become negative within 6-12 months of treatment.

      • Between 10-35% of uninfected individuals in endemic areas have anti-amoebic antibodies due to previous, often undiagnosed infection with E. histolytica. Consequently, negative serology in these populations helps exclude disease, but positive serology is difficult to interpret as it does not distinguish between acute infection and past exposure to the parasite.

      • Techniques reported to have excellent sensitivity and specificity include ELISA, indirect hemagglutination (IHA), and immunofluorescence. Agar gel diffusion and counterimmunophoresis are less sensitive than IHA but are inexpensive and, in most patients, only remain positive for 6-12 months, which may make them more useful in endemic areas.

      • Amoebic serology is highly sensitive (94%) and specific (95%) for the diagnosis of liver abscess; however, a false-negative serological test can be obtained early during infection (within the first 7-10 days).

    • Immunochromatographic assays

      • The Triage parasite panel (TPP; Biosite Diagnostic Inc., San Diego, CA) is an immunochromatographic assay for the simultaneous detection of antigens specific for Giardia lamblia, E. histolytica/E. dispar, and Cryptosporidium parvum.

      • Several studies have reported high sensitivity compared to microscopy; however, a lower sensitivity has been reported when compared to PCR or ELISA.

      • The TPP is unable to differentiate between E. histolytica, E. dispar, and E. moshkovskii and, therefore, has limited clinical application.

  • Histopathology

    • Pathological findings in amoebic colitis include mucosal thickening, multiple discrete ulcers separated by normal colonic mucosa, diffusely inflamed and edematous mucosa, and necrosis and perforation of the intestinal wall.

    • Typically, trophozoites of E. histolytica are seen within the inflammatory debris or localized to the advancing edges of ulcers.

    • The classically described “flask-shaped” amoebic ulcer is caused by lateral spread of trophozoites after invasion of the submucosa.

    • Histopathology in amoebic liver abscesses demonstrates well circumscribed regions of dead hepatocytes, liquefied cells, and cellular debris. A ring of connective tissue, with few inflammatory cells and amoebic trophozoites, which usually surrounds the lesion. Amoeba can be found at the edge of the lesion but are rarely detected in the pus or within the abscess cavity itself.

    • Hepatocyte death is thought to be mediated by lysis of neutrophils by E. histolytica, which causes release of cellular mediators. The lysis of neutrophils may also explain the paucity of inflammatory cells in typical histopathology of amoebic liver abscess.

What imaging studies will be helpful in making or excluding the diagnosis of amoebiasis?

  • Imaging techniques, such as ultrasound, CT, and MRI, have excellent sensitivities for the detection of liver abscess and can help to support the diagnosis; however, there are no findings specific for amoebic liver abscess on imaging.

  • Ultrasound ($)

    • Ultrasound is cheap, accessible, and noninvasive. It is very sensitive in the diagnosis of liver abscess (approximately 95%) but lacks specificity.

    • Abscesses are seen as well-defined hypoechoic areas in the liver parenchyma, which are homogenous in appearance with rounded edge.

    • The majority of patients have single abscesses of variable size located in the right liver lobe, predominantly within segments six to eight.

    • Multiple abscesses or abscesses located in the left liver lobe are found less frequently but are more likely to result in severe and complicated clinical courses.

    • The vast majority of successfully treated abscesses completely resolve to a sonographically normal parenchymal pattern; however, 7-10% of patients may still have typical residual lesions 1-13 years after resolution of clinical symptoms.

  • Plain films (x-ray) ($)

    • Abdominal x-rays may be useful in toxic megacolon, where there is total or segmental non-obstructive dilatation of the colon to an external diameter greater than or equal to 6 cm.

    • In patients with perforation, free gas may be seen under the diaphragm.

    • In amoebic liver abscess, patients may have an elevated right hemidiaphragm on x-ray or a right-sided pleural effusion.

  • Barium enema ($)

    • Generally, the radiographic findings in the colon are nonspecific and may be observed in diseases other than amoebiasis. However, a barium enema can pick up perforation, luminal narrowing in amoeboma, and dilatation of the colon in toxic megacolon.

    • Patients with amoebic colitis may have focal short segmental colitis with skip areas or diffuse colitis. The right side of the colon tends to be more severely involved, invariably sparing the terminal ileum.

  • Computed Tomography (CT) ($$)

    • CT is slightly more sensitive in the diagnosis of liver abscess than ultrasound but is more expensive and may not be as readily available in endemic areas

    • Contrast-enhanced CT shows a low-density mass that may have a peripheral solid component and central liquefied component of different densities.

    • Chest CT imaging is useful in the investigation and diagnosis of pleuropulmonary amoebiasis.

  • Magnetic Resonance Imaging (MRI) ($$$$)

    • MRI in sensitive in identifying amoebic liver abscesses.

    • Amoebic liver abscess appears as a low signal intensity lesion on T1-weighted and high signal intensity on T2-weighted images. It may be unilocular or multiloculated.

  • Gallium Scan ($$)

    • A Gallium scan may be helpful in differentiating an amoebic liver abscess from a pyogenic abscess. Amoebic liver abscesses do not contain neutrophils, therefore, gallium scanning reveals a cold lesion, sometimes with a bright rim. Conversely, a pyogenic abscess would have increased gallium uptake in the center.

  • Sigmoidoscopy and/or Colonoscopy ($$)

    • The appearance of the colon in amoebic colitis ranges from non-specific mucosal thickening and inflammation to classic flask-shaped amoebic ulcers.

    • Colonoscopy must be performed with care because of the risk of perforation.

    • Scrapings or biopsy specimens taken from the edge of ulcers may be positive for cysts or trophozoites on microscopy, and antigen testing for E. histolytica may be positive.

  • $ = 60-125; $$ 125-500; $$$ 500-1,000; $$$$ > 1,000

What complications can be associated with this infection, and are there additional treatments that can help to alleviate these complications?

Complications can be grouped into those that occur in intestinal amoebiasis (amoebic colitis, amoeboma, toxic megacolon, peritonitis, and cutaneous amoebiasis) and those that occur in extra-intestinal amoebiasis (amoebic liver abscess, splenic abscess, brain abscess, empyema, and pericarditis).

Complications of Intestinal Amoebiasis:

  • Fulminant amoebic colitis

    • Fulminant colitis occurs in approximately 0.5% of cases.

    • Clinical presentation is characterized by profuse bloody diarrhea, fever, pronounced leukocytosis, and widespread abdominal pain, and it is often complicated by bowel necrosis leading to perforation.

    • Signs of peritonitis (e.g., guarding, rebound tenderness) may be present.

    • A case series of 50 adult patients in Colombia with fulminant colitis, reported an intestinal perforation rate of approximately 75% and a mortality rate greater than 40%.

    • Treatment is with nitroimidazoles, and early surgical management is frequently required, along with broad spectrum antibiotics in patients with intestinal perforation.

    • Pregnant women, immunocompromised individuals, and patients receiving corticosteroids are especially at risk of fulminant disease.

  • Amoeboma

    • Localized colonic infection can result in the formation of a mass of granulation tissue called an amoeboma.

    • Amoeboma is an uncommon complication of intestinal amoebiasis, occurring in approximately 1.5% of all cases.

    • Symptoms and signs include localized tenderness and pain and concurrent amoebic colitis, and/or amoebic liver abscess may be seen.

    • Amoeboma is important to be aware of, as it can mimic colon cancer.

  • Toxic megacolon, seen in approximately 0.5% of cases

    • Toxic megacolon is a potential complication of any form of colitis, and the differential diagnosis includes both inflammatory and infectious causes. It is defined as total or segmental non-obstructive dilatation of the colon to an external diameter greater than or equal to 6 cm associated with systemic toxicity.

    • Joint surgical and medical management are critical. Mortality is increased following perforation. Colectomy is indicated if the dilatation persists beyond the first 24 hours of admission in association with pyrexia and tachycardia.

    • Amoebic colitis has also been reported in asymptomatic patients. In a cohort of 5193 Japanese patients undergoing colonoscopy for investigation of positive fecal occult blood tests, 4 were found to have amoebic ulcerative lesions in the caecum and ascending colon, none of whom had abdominal symptoms.

Complications of Extra-intestinal Amoebiasis and Hematogenous Spread

  • Pleuropulmonary involvement

    • Pleuropulmonary involvement can result from atelectasis and development of a sympathetic transudative pleural effusion, rupture of a liver abscess into the chest cavity leading to empyema, or hematogenous spread resulting in parenchymal infection.

    • It is the second most common extra-intestinal manifestation of amoebiasis after hepatic involvement

    • Symptoms include cough (87-100%), pleuritic chest pain (50-100%), hemoptysis (44-50%) and dyspnea (20-25%).

    • If a hepatobronchial fistula develops, patients may have a cough productive of copious amounts of brown sputum containing necrotic material and occasionally amoebic trophozoites.

    • Physical examination may reveal hepatic enlargement and tenderness, dullness to percussion (particularly in the right lung base), and diminished or absent breath sounds. Fever may be present in 82-100% of patients. In chronic cases, patients may be severely emaciated and digital clubbing may be prominent.

    • It is common to hear a pleural friction rub in patients with an amoebic liver abscess extending to the pleura.

  • Cardiac involvement

    • Cardiac involvement is rare but has a mortality of approximately 30%. It results from liver abscess rupture into the pericardium and can present with signs and symptoms of pericarditis (chest pain, pericardial rub, dyspnea, tachycardia) or cardiac tamponade.

  • Brain involvement

    • Cerebral amoebiasis is a rare cause of brain abscess thought to result from hematogenous dissemination from the colon via hepatic, pulmonary, or vertebral veins.

    • Infection of the central nervous system (CNS) without hepatic involvement is rare, and the incidence of brain abscesses in patients with confirmed amoebic liver abscesses has been reported to vary from 0.6 to 8.1%.

    • Clinical features have been reported to include headache, vomiting, seizures, mental state changes, neck stiffness, and motor deficits.

  • Urinary tract problems; genital disease, including rectovaginal fistulae; perianal disease; and cutaneous lesions have been described as case reports.

Other complications

  • Lactose malabsorption is significantly more common in individuals infected with E. histolytica and passing cysts compared with control subjects.

  • Amoebiasis has also been linked with malnutrition in children.

What is the life cycle of the parasite, and how does the life cycle explain infection in humans?

  • Entamoeba histolytica has two morphological forms: the infectious cyst and the invasive trophozoite, both of which may be found in the feces of infected patients (cysts are typically found in formed stool, whereas trophozoites are typically found in diarrheal stool) (see Figure 1).

  • Infection occurs when the cysts are ingested in fecal-contaminated food, water, or by hands. Transmission can also occur through exposure to fecal matter during sexual contact. Entamoeba cysts are relatively environmentally resistant and can survive for days to weeks in the external environment.

  • Excystation occurs in the small intestine, and trophozoites are released; they migrate to the large intestine where they multiply by binary fission

  • In asymptomatic carriers, the trophozoites remain confined to the intestinal lumen, and cysts are passed in stools.

  • When the trophozoites invade the intestinal mucosa, patients typically present with intestinal disease.

  • Spread of trophozoites through the bloodstream to extra-intestinal sites, such as the liver, brain, and lungs, results in pathologic manifestations involving these organs (extra-intestinal disease).

Figure 1.

Life cycle of Entamoeba histolytica from the CDC DPDx Website (http://www.dpd.cdc.gov/dpdx/)

Transmission, risk factors and prevalence

  • Entamoeba histolytica can be transmitted by ingestion of contaminated water or food; via the fecal-oral route (via fomites or person-to-person spread); or via oral, anal, and oral-genital sexual practices.

  • Limited data are available on seasonal variation in incidence of E. histolytica infection

  • Deficiencies in hygiene and sanitary practices and overcrowding are predisposing factors for infection

  • Entamoeba histolytica is found worldwide and remains an important health problem in developing countries in which sanitation, infrastructure, and health education are not adequate. However, E. histolytica is also seen in developed countries, predominantly due to immigration and increases in international travel.

  • Endemic countries include Mexico, India, Bangladesh, South Africa, some Central and South American countries, and Asian Pacific countries.

  • Hepatic amoebiasis is endemic in Thailand, India, Egypt, and South Africa. In a single hospital in Vietnam, more than 1200 cases of hepatic amoebiasis were identified during an 8-year period. The incidence is also high in Central and South America, particularly in Mexico and in the Amazon regions of Brazil.

  • Recent studies using techniques able to isolate E. histolytica from the other species, such as ELISA, PCR, and isoenzyme analysis, have demonstrated prevalence of intestinal amoebiasis ranging from 1 to 76% in a diverse range of patient populations.

  • In developed countries, high-risk groups include travelers, immigrants from endemic areas, and men who have sex with men (MSM).

  • Amoebic liver abscesses are ten times more common in men than women and are rare in children. Other risk factors include travel to endemic areas and a history of alcohol abuse. They are most common in adults in their fourth and fifth decades of life

    • Travelers to endemic areas

      • Travelers to any endemic area may contract Entamoeba, but travelers to Asia seem at most risk.

      • Patients can present with amoebic liver abscess months to years after travel or residency in an endemic area, so a careful travel history is extremely important.

    • Men who have sex with men (MSM)

      • Oral, anal, and oral-genital sexual practices are reported to predispose MSM to infection with E. histolytica.

      • Pregnant women, immunocompromised individuals, and patients receiving corticosteroids are especially at risk of fulminant disease.

  • Infection control and prevention issues

    • Anti-infective prophylaxis is not recommended.

    • No vaccination is currently available.

  • Travelers to endemic areas should avoid drinking local water and should eat only cooked food or peeled fruit.

  • Cysts are resistant to low doses of chlorine or iodine, so, if safe bottled water is unavailable, water should be boiled.

  • Prevention of amoebic infection could be accomplished by improvements in sanitation, a clean water supply, health education, and public health measures to identify and treat carriers. There are no epidemiologically significant animal carriers.

How does this organism cause disease?

  • Trophozoites of E. histolytica adhere to colonic epithelial cells via a specific lectin, the galactose/N-acetylgalactosamine lectin. This lectin also seems to play a role in immunity, with one study from Bangladesh indicating that children with a mucosal IgA response against the lectin had 86% fewer new infections during a 1-year period than children without this response.

  • Colitis results after penetration of the trophozoite through the intestinal mucous layer. E. histolytica trophozoites are cytolytic and are able to kill both epithelial cells and inflammatory cells. This is thought to be medicated by a number of mechanisms, including:

    • Secretion of proteinases by the trophozoites

    • Lysis of target cells via a contact-dependent mechanism

    • Induction of programmed cell death (apoptosis)

    • Formation of amoebapores, small peptides capable of forming pores in lipid bilayers

    • Changes in intestinal permeability, probably via disruption of tight-junction proteins

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

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