AmebiasisAmebiasis

Mitra Ranjbar M.D.Mitra Ranjbar M.D.

Associate Professor of Associate Professor of MedicineMedicine

Intestinal amebiasis is caused by Intestinal amebiasis is caused by the protozoan Entamoeba the protozoan Entamoeba histolytica. Worldwide, histolytica. Worldwide, approximately 40 to 50 million approximately 40 to 50 million people develop colitis or people develop colitis or extraintestinal disease annually extraintestinal disease annually with 40,000 deaths.with 40,000 deaths.

Most infection is asymptomatic, Most infection is asymptomatic, but amebic dysentery, amebic but amebic dysentery, amebic liver abscess, and rarely other liver abscess, and rarely other manifestations such as manifestations such as pulmonary, cardiac or brain pulmonary, cardiac or brain involvement can occur.involvement can occur.

The parasite exists in two forms, The parasite exists in two forms, a cyst stage which is the infective a cyst stage which is the infective form, and a trophozoite stage form, and a trophozoite stage which is the form that causes which is the form that causes invasive disease. invasive disease.

Infection occurs following Infection occurs following ingestion of amebic cysts; this is ingestion of amebic cysts; this is usually via contaminated food or usually via contaminated food or water but can be associated with water but can be associated with venereal transmission through venereal transmission through fecal-oral contact, particularly in fecal-oral contact, particularly in sexually active homosexuals. sexually active homosexuals.

Cysts can remain viable in the Cysts can remain viable in the environment for weeks to environment for weeks to months, and ingestion of a single months, and ingestion of a single cyst is sufficient to cause disease. cyst is sufficient to cause disease.

The cysts pass through the stomach The cysts pass through the stomach to the small intestine where they to the small intestine where they excyst to form trophozoites. The excyst to form trophozoites. The trophozoites can invade and trophozoites can invade and penetrate the mucous barrier of the penetrate the mucous barrier of the colon causing tissue destruction and colon causing tissue destruction and increased intestinal secretion, and increased intestinal secretion, and can thereby ultimately lead to bloody can thereby ultimately lead to bloody diarrhea. diarrhea.

It has become progressively It has become progressively apparent over the last 15 to 20 apparent over the last 15 to 20 years that intestinal amebae with years that intestinal amebae with identical morphologic identical morphologic appearances can in fact be one of appearances can in fact be one of three species, E. histolytica or E. three species, E. histolytica or E. dispar or E. moshkovskii.dispar or E. moshkovskii.

The clinical importance is that E. The clinical importance is that E. dispar and E. moshkovskii are dispar and E. moshkovskii are non-pathogenic and do not cause non-pathogenic and do not cause clinical disease; thus all clinical disease; thus all symptomatic disease is caused by symptomatic disease is caused by E. histolytica. E. histolytica.

PATHOGENESISPATHOGENESIS

Investigators have shown that Investigators have shown that the pathogenicity of amebic the pathogenicity of amebic trophozoites is associated with trophozoites is associated with their adherence to colonic their adherence to colonic epithelial cells via a specific lectin epithelial cells via a specific lectin (the galactose/N-(the galactose/N-acetylgalactosamine lectin).acetylgalactosamine lectin).

Mammalian cells without N-Mammalian cells without N-terminal galactose or N-terminal galactose or N-acetylgalactosamine residues are acetylgalactosamine residues are resistant to adherence by amebic resistant to adherence by amebic trophozoites, which is consistent trophozoites, which is consistent with an important role for the with an important role for the lectin in adhesion. lectin in adhesion.

This lectin also plays a role in This lectin also plays a role in immunity, since mucosal immunity, since mucosal immunity against the lectin immunity against the lectin seems to mediate some degree of seems to mediate some degree of protection from invasive disease protection from invasive disease following colonization. following colonization.

One study from Bangladesh One study from Bangladesh showed that children with a showed that children with a mucosal IgA response against the mucosal IgA response against the lectin had 86 percent fewer new lectin had 86 percent fewer new infections during a one-year period infections during a one-year period than children without this response than children without this response and while reinfected had a lower and while reinfected had a lower incidence of infection and disease incidence of infection and disease over a four year follow-up period.over a four year follow-up period.

Colitis results after penetration of Colitis results after penetration of the trophozoite through the the trophozoite through the intestinal mucous layer, which intestinal mucous layer, which would otherwise act as a barrier would otherwise act as a barrier to invasion.to invasion.

the trophozoite is able to kill both the trophozoite is able to kill both epithelial cells and inflammatory epithelial cells and inflammatory cells. This is thought to occur cells. This is thought to occur through a number of different through a number of different mechanisms including: mechanisms including:

Secretion of proteinases by the trophozoitesSecretion of proteinases by the trophozoites Lysis of target cells via a contact-dependent Lysis of target cells via a contact-dependent

mechanism mechanism Killing of mammalian cells by apoptosis Killing of mammalian cells by apoptosis

(programmed cell death) (programmed cell death) Formation of amebepores, a family of small Formation of amebepores, a family of small

peptides that can form pores in lipid bilayers, peptides that can form pores in lipid bilayers, resulting in cytolysis of infected cells resulting in cytolysis of infected cells

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

EPIDEMIOLOGYEPIDEMIOLOGY

Amebiasis is a worldwide disease, Amebiasis is a worldwide disease, however developing countries however developing countries have significantly higher have significantly higher prevalence rates because of prevalence rates because of poorer socioeconomic conditions poorer socioeconomic conditions and sanitation levels. and sanitation levels.

Areas that have high rates of amebic Areas that have high rates of amebic infection include India, Africa, Mexico infection include India, Africa, Mexico and parts of Central and South America. and parts of Central and South America. E. dispar and E. moshkovskii infections E. dispar and E. moshkovskii infections occurs approximately ten times more occurs approximately ten times more commonly than infection with E. commonly than infection with E. histolytica, and the overall prevalence histolytica, and the overall prevalence of amebic infection may be as high as of amebic infection may be as high as 50 percent in certain developing areas.50 percent in certain developing areas.

Although many epidemiologic Although many epidemiologic studies of amebiasis were studies of amebiasis were performed prior to the recognition performed prior to the recognition of the three distinct species, more of the three distinct species, more recent antigen detection methods recent antigen detection methods and serology have been used to and serology have been used to estimate the prevalence of E. estimate the prevalence of E. histolytica infection.histolytica infection.

As an example, the As an example, the seroprevalence of E. histolytica in seroprevalence of E. histolytica in one Mexican study was 8.4 one Mexican study was 8.4 percent. In another series from percent. In another series from urban Bangladesh, children had a urban Bangladesh, children had a 4.2 percent prevalence rate of E. 4.2 percent prevalence rate of E. histolytica infection.histolytica infection.

Infection with pathogenic E. Infection with pathogenic E. histolytica is not a common cause of histolytica is not a common cause of travelers' diarrhea, and travelers' diarrhea, and gastrointestinal infection is gastrointestinal infection is uncommon in travelers who have uncommon in travelers who have spent less than one month in spent less than one month in endemic areas. In one prospective endemic areas. In one prospective study of German travelers to the study of German travelers to the tropics, only 0.3 percent had tropics, only 0.3 percent had pathogenic E. histolytica infection.pathogenic E. histolytica infection.

In Japan and Taiwan, however, E. In Japan and Taiwan, however, E. histolytica is much more prevalent histolytica is much more prevalent amongst male homosexuals. amongst male homosexuals. Invasive, extraintestinal amebiasis Invasive, extraintestinal amebiasis (eg, hepatic abscesses) are more (eg, hepatic abscesses) are more frequent in HIV-infected patients in frequent in HIV-infected patients in these countries, whereas the same these countries, whereas the same is not true elsewhere, including is not true elsewhere, including Mexico.Mexico.

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONS E. dispar infection and E. E. dispar infection and E.

moshkovskii infections and 90 moshkovskii infections and 90 percent of E. histolytica infections percent of E. histolytica infections are asymptomatic.are asymptomatic.

The strain of E. histolytica as well The strain of E. histolytica as well as host factors such as genetic as host factors such as genetic susceptibility, age and susceptibility, age and immunocompetence ultimately immunocompetence ultimately determine whether infection leads determine whether infection leads to asymptomatic or invasive to asymptomatic or invasive disease.disease.

Young age, pregnancy, Young age, pregnancy, corticosteroid treatment, corticosteroid treatment, malignancy, malnutrition, and malignancy, malnutrition, and alcoholism are risk factors for alcoholism are risk factors for severe disease and increased severe disease and increased mortality following E. histolytica mortality following E. histolytica infection. infection.

Clinical amebiasis generally has a Clinical amebiasis generally has a subacute onset, usually over one subacute onset, usually over one to three weeks. Symptoms range to three weeks. Symptoms range from mild diarrhea to severe from mild diarrhea to severe dysentery producing abdominal dysentery producing abdominal pain (12 to 80 percent), diarrhea pain (12 to 80 percent), diarrhea (94 to 100 percent), and bloody (94 to 100 percent), and bloody stools (94 to 100 percent). stools (94 to 100 percent).

Weight loss is present in just Weight loss is present in just under 50 percent of patients. under 50 percent of patients. Fever occurs in 8 to 38 percent.Fever occurs in 8 to 38 percent.

Fulminant colitis with bowel Fulminant colitis with bowel necrosis leading to perforation necrosis leading to perforation and peritonitis occurs in and peritonitis occurs in approximately 0.5 percent of approximately 0.5 percent of cases but is associated with a cases but is associated with a mortality rate of more than 40 mortality rate of more than 40 percent. Toxic megacolon can percent. Toxic megacolon can also develop. also develop.

Intestinal amebiasis can probably Intestinal amebiasis can probably also present as a chronic, also present as a chronic, nondysenteric syndrome of nondysenteric syndrome of diarrhea, weight loss, and diarrhea, weight loss, and abdominal pain which can last for abdominal pain which can last for years and can mimic inflammatory years and can mimic inflammatory bowel disease, although one study bowel disease, although one study has called into question whether has called into question whether nondysenteric intestinal amebiasis nondysenteric intestinal amebiasis truly exists.truly exists.

No differences were noted in the No differences were noted in the occurrence of E. histolytica occurrence of E. histolytica infection, assessed by stool infection, assessed by stool examination and serology, among examination and serology, among 144 Indian patients with intestinal 144 Indian patients with intestinal symptoms and 100 controls symptoms and 100 controls without symptoms.without symptoms.

Amebic colitis has been recognized Amebic colitis has been recognized even in asymptomatic patients. In even in asymptomatic patients. In Japan, for example, amongst 5193 Japan, for example, amongst 5193 asymptomatic subjects undergoing asymptomatic subjects undergoing colonoscopy solely for positive fecal colonoscopy solely for positive fecal occult blood tests, four were found occult blood tests, four were found to have amebic ulcerative lesions in to have amebic ulcerative lesions in the cecum or ascending colon.the cecum or ascending colon.

Localized colonic infection resulting in a Localized colonic infection resulting in a mass of granulation tissue forming an mass of granulation tissue forming an ameboma is another uncommon ameboma is another uncommon presentation, which can mimic colon presentation, which can mimic colon cancer Patients with amebomas usually cancer Patients with amebomas usually are found to have a tender palpable are found to have a tender palpable mass. Perianal cutaneous amebiasis and mass. Perianal cutaneous amebiasis and rectovaginal fistulae are other rare rectovaginal fistulae are other rare complications of amebic intestinal complications of amebic intestinal disease. disease.

DIAGNOSIS DIAGNOSIS

The demonstration of cysts or The demonstration of cysts or trophozoites in the stool suggests trophozoites in the stool suggests an intestinal amebic infection, but an intestinal amebic infection, but microscopy cannot differentiate microscopy cannot differentiate between E. histolytica and E. between E. histolytica and E. dispar or E. moshkovskii strains. dispar or E. moshkovskii strains.

Antigen testing Antigen testing

Fecal and serum antigen detection Fecal and serum antigen detection assays that use monoclonal assays that use monoclonal antibodies to bind to epitopes antibodies to bind to epitopes present on pathogenic E. histolytica present on pathogenic E. histolytica strains but not on nonpathogenic E. strains but not on nonpathogenic E. dispar or E. moshkovskii strains are dispar or E. moshkovskii strains are now being used commercially to now being used commercially to detect E. histolytica infection.detect E. histolytica infection.

Antigen detection kits using Antigen detection kits using either enzyme linked either enzyme linked immunosorbent assay (ELISA), immunosorbent assay (ELISA), radioimmunoassay or radioimmunoassay or immunofluorescence have been immunofluorescence have been developed.developed.

Antigen detection has many Antigen detection has many advantages including: advantages including:

Ease and rapidity of the tests Ease and rapidity of the tests Ability to differentiate between Ability to differentiate between Greater sensitivity than microscopyGreater sensitivity than microscopy Potential for diagnosis in early Potential for diagnosis in early

infection and in endemic areas infection and in endemic areas where serology is less useful where serology is less useful

Serology Serology

Serology is also useful for Serology is also useful for diagnosing amebiasis. Infection diagnosing amebiasis. Infection with E. histolytica results in the with E. histolytica results in the development of antibodies, while E. development of antibodies, while E. dispar infection does not. dispar infection does not. Antibodies will usually be Antibodies will usually be detectable within five to seven days detectable within five to seven days of acute infection and may persist of acute infection and may persist for years.for years.

Between 10 to 35 percent of Between 10 to 35 percent of uninfected individuals in endemic uninfected individuals in endemic areas have anti-amebic areas have anti-amebic antibodies due to previous, often antibodies due to previous, often undiagnosed infection with E. undiagnosed infection with E. histolytica.histolytica.

Consequently, negative serology Consequently, negative serology in these populations helps to in these populations helps to exclude disease, but a positive exclude disease, but a positive serology is not particularly helpful serology is not particularly helpful since it does not distinguish since it does not distinguish between acute infection and past between acute infection and past exposure to the parasite. exposure to the parasite.

Indirect hemagglutination (IHA) is Indirect hemagglutination (IHA) is the most sensitive assay and is the most sensitive assay and is positive in approximately 90 positive in approximately 90 percent of patients with percent of patients with symptomatic intestinal infection.symptomatic intestinal infection.

Agar gel diffusion and Agar gel diffusion and counterimmunophoresis are less counterimmunophoresis are less sensitive than IHA but usually only sensitive than IHA but usually only remain positive for 6 to 12 months remain positive for 6 to 12 months which may make them more useful which may make them more useful in endemic areas. A commercially in endemic areas. A commercially available ELISA that has a available ELISA that has a sensitivity of 93 percent compared sensitivity of 93 percent compared to IHA has also been developed.to IHA has also been developed.

Stool examinationStool examination

Stool microscopy is a relatively poor Stool microscopy is a relatively poor method for making the diagnosis of method for making the diagnosis of intestinal amebiasis since it is less intestinal amebiasis since it is less sensitive than antigen testing sensitive than antigen testing (misses one-half to two-thirds of E. (misses one-half to two-thirds of E. histolytica colonic infections histolytica colonic infections detected by culture ) and because it detected by culture ) and because it cannot differentiate between cannot differentiate between species. species.

Moreover, fecal leukocytes and Moreover, fecal leukocytes and nonpathogenic intestinal nonpathogenic intestinal protozoans may be misidentified protozoans may be misidentified by inexpert diagnosticians.by inexpert diagnosticians.

Stool specimens will invariably be Stool specimens will invariably be positive for microscopic (and often positive for microscopic (and often macroscopic) blood when invasive macroscopic) blood when invasive intestinal amebic disease is present. intestinal amebic disease is present. However, ingested erythrocytes have However, ingested erythrocytes have been observed with E. dispar organisms been observed with E. dispar organisms as well, so the presence of ingested as well, so the presence of ingested erythrocytes is not pathognomonic for E. erythrocytes is not pathognomonic for E. histolytica infection. Fecal leukocytes are histolytica infection. Fecal leukocytes are not always present since white cells may not always present since white cells may be destroyed by the organisms. be destroyed by the organisms.

A saline wet mount of stool A saline wet mount of stool should be performed and also a should be performed and also a fresh smear stained with iron fresh smear stained with iron hematoxylin and/or Wheatley's hematoxylin and/or Wheatley's trichrome to look for trophozoites; trichrome to look for trophozoites; fixation with polyvinyl alcohol for fixation with polyvinyl alcohol for delayed staining is often useful. delayed staining is often useful.

Specimens can also be Specimens can also be concentrated and stained with concentrated and stained with iodine to detect cysts. Organism iodine to detect cysts. Organism excretion can vary; thus, a excretion can vary; thus, a minimum of three specimens on minimum of three specimens on separate days should be sent to separate days should be sent to detect 85 to 95 percent of detect 85 to 95 percent of infections. infections.

Other methods Other methods

Detection of parasitic DNA or RNA Detection of parasitic DNA or RNA in feces via probes can also be in feces via probes can also be used to diagnose amebic infection used to diagnose amebic infection and to differentiate between the and to differentiate between the three different strains, but these three different strains, but these methods currently are primarily methods currently are primarily reserved as research tools. Fecal reserved as research tools. Fecal culture is available but only in the culture is available but only in the research setting. research setting.

PCR techniques can detect E. PCR techniques can detect E. histolytica in stool specimens but histolytica in stool specimens but are not currently widely available. are not currently widely available. One study showed that PCR was One study showed that PCR was significantly more sensitive than significantly more sensitive than either microscopy or cultures, and either microscopy or cultures, and that it was 100 percent specific that it was 100 percent specific for E. histolytica.for E. histolytica.

Visual inspection of Visual inspection of the colonthe colon Sigmoidoscopy and/or Sigmoidoscopy and/or

colonoscopy can be performed colonoscopy can be performed either to make the diagnosis of either to make the diagnosis of amebiasis or to exclude other amebiasis or to exclude other causes of the patients' symptoms. causes of the patients' symptoms.

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

Colonic lesions in amebic dysentery Colonic lesions in amebic dysentery range from nonspecific mucosal range from nonspecific mucosal thickening and inflammation to thickening and inflammation to classic flask-shaped amebic ulcers. classic flask-shaped amebic ulcers. However, colonoscopy is not However, colonoscopy is not recommended as a routine recommended as a routine diagnostic approach since intestinal diagnostic approach since intestinal amebic ulcerations increase the amebic ulcerations increase the likelihood of perforation during likelihood of perforation during instillation of air to expand the colon. instillation of air to expand the colon.

Recommendations Recommendations

Antigen detection assays are the Antigen detection assays are the best current means for best current means for diagnosing intestinal amebiasis diagnosing intestinal amebiasis since they are sensitive, specific, since they are sensitive, specific, rapid, easy to perform and rapid, easy to perform and distinguish E. histolytica from E. distinguish E. histolytica from E. dispar infections. dispar infections.

Antibody measurements are also Antibody measurements are also available but remain positive for available but remain positive for years. Stool specimens for years. Stool specimens for microscopy are far less sensitive microscopy are far less sensitive than antigen detection and than antigen detection and cannot differentiate between the cannot differentiate between the species. species.

TREATMENTTREATMENT

E. dispar and E. moshkovskii E. dispar and E. moshkovskii infections does not require infections does not require treatment, whereas even treatment, whereas even asymptomatic E. histolytica asymptomatic E. histolytica infection should be treated because infection should be treated because of the potential risk of developing of the potential risk of developing invasive disease and the risk of invasive disease and the risk of spread to family members.spread to family members.

In countries where amebic In countries where amebic infections are endemic, infections are endemic, asymptomatic patients asymptomatic patients incidentally found to have stools incidentally found to have stools positive for amebae are often positive for amebae are often presumed to have infection with presumed to have infection with E. dispar/E. moshkovskii and are E. dispar/E. moshkovskii and are not further evaluated or treated. not further evaluated or treated.

When antigen tests that can When antigen tests that can differentiate between E. dispar/E. differentiate between E. dispar/E. moshkovskii and E. histolytica are moshkovskii and E. histolytica are more widely available in these more widely available in these countries, this practice may countries, this practice may change. change.

MetronidazoleMetronidazole

The goals of antibiotic therapy of The goals of antibiotic therapy of intestinal amebiasis are both to intestinal amebiasis are both to eliminate the invading eliminate the invading trophozoites and to eradicate trophozoites and to eradicate intestinal carriage of the intestinal carriage of the organism.organism.

Metronidazole (500 to 750 mg PO Metronidazole (500 to 750 mg PO three times daily for 7 to 10 days three times daily for 7 to 10 days in adults and 35 to 50 mg/kg per in adults and 35 to 50 mg/kg per day in three divided doses for 7 to day in three divided doses for 7 to 10 days in children) is the usual 10 days in children) is the usual treatment for invasive colitis. The treatment for invasive colitis. The cure rate is approximately 90 cure rate is approximately 90 percent.percent.

Metronidazole is so well absorbed Metronidazole is so well absorbed from the gastrointestinal tract from the gastrointestinal tract that intravenous therapy offers no that intravenous therapy offers no significant advantage as long as significant advantage as long as the patient can take oral the patient can take oral medications and has no major medications and has no major defect in small bowel absorption. defect in small bowel absorption.

A small number of patients have A small number of patients have been treated with 2 g/day for been treated with 2 g/day for three days, but cure rates were three days, but cure rates were only 55 to 59 percent [39,40]. only 55 to 59 percent [39,40]. Metronidazole resistance in E. Metronidazole resistance in E. histolytica trophozoites has not histolytica trophozoites has not been reported.been reported.

Alternative drugs Alternative drugs

In countries where they are In countries where they are available, tinidazole and ornidazole available, tinidazole and ornidazole are alternative therapies. Tinidazole are alternative therapies. Tinidazole (2 g PO daily for three days) has a (2 g PO daily for three days) has a cure rate of 90 to 93 percent [39,40]. cure rate of 90 to 93 percent [39,40]. It has been approved for the It has been approved for the treatment of amebiasis by the United treatment of amebiasis by the United States Food and Drug Administration States Food and Drug Administration (FDA).(FDA).

Agents for eliminating Agents for eliminating luminal cysts luminal cysts Following therapy for invasive Following therapy for invasive

amebiasis with a nitroimidazole, amebiasis with a nitroimidazole, treatment with a luminal agent treatment with a luminal agent may be required to eliminate may be required to eliminate intraluminal encysted organisms. intraluminal encysted organisms.

A ten day course of metronidazole A ten day course of metronidazole will eliminate intraluminal will eliminate intraluminal infection in many cases, but a infection in many cases, but a second agent is still second agent is still recommended. recommended.

Intraluminal infection can be Intraluminal infection can be treated with one of the following treated with one of the following regimens: regimens:

Paromomycin — 25-30 mg/kg per Paromomycin — 25-30 mg/kg per day orally in three divided doses day orally in three divided doses for 7 daysfor 7 days

Diiodohydroxyquin (iodoquinol) — 650 Diiodohydroxyquin (iodoquinol) — 650 mg orally three times daily for 20 days mg orally three times daily for 20 days for adults and 30-40 mg/kg per day in 3 for adults and 30-40 mg/kg per day in 3 divided doses for 20 days for childrendivided doses for 20 days for children

Diloxanide furoate — 500 mg orally Diloxanide furoate — 500 mg orally three times daily for 10 days for adults three times daily for 10 days for adults and 20 mg/kg per day in 3 divided doses and 20 mg/kg per day in 3 divided doses for 10 days for children; this drug is not for 10 days for children; this drug is not currently available in the United States. currently available in the United States.

Parasitologic cure rates are Parasitologic cure rates are approximately 86 to 90 percent. approximately 86 to 90 percent. Follow-up stool examinations are Follow-up stool examinations are required after completion of the required after completion of the therapy since no regimen is therapy since no regimen is completely effective. completely effective.

Treatment of Treatment of associated peritonitis associated peritonitis In patients who have suspected In patients who have suspected

or proven peritonitis, broad or proven peritonitis, broad spectrum antibacterial therapy spectrum antibacterial therapy should also be given.should also be given.

Intestinal amebiasis can usually be Intestinal amebiasis can usually be treated medically with antibiotics, treated medically with antibiotics, but surgical intervention is required but surgical intervention is required if a significant bowel perforation if a significant bowel perforation occurs or if patients with abscesses occurs or if patients with abscesses following perforation fail to respond following perforation fail to respond to antibiotic therapy. to antibiotic therapy.

It is unclear how beneficial surgical It is unclear how beneficial surgical intervention is, even in cases of intervention is, even in cases of fulminant colitis with perforation, fulminant colitis with perforation, because it is often impossible to because it is often impossible to successfully suture the necrotic successfully suture the necrotic bowel. The one definitive indication bowel. The one definitive indication for surgery is toxic megacolon for surgery is toxic megacolon which requires colectomy. which requires colectomy.

RecommendationsRecommendations

Metronidazole (500 to 750 mg PO Metronidazole (500 to 750 mg PO three times daily for 7 to 10 days three times daily for 7 to 10 days in adults and 35 to 50 mg/kg per in adults and 35 to 50 mg/kg per day in three divided doses for 7 to day in three divided doses for 7 to 10 days in children) is the usual 10 days in children) is the usual treatment for invasive colitis. treatment for invasive colitis.

Patients with invasive colitis should Patients with invasive colitis should generally be treated with a luminal generally be treated with a luminal agent following a nitroimidazole. agent following a nitroimidazole. Paromomycin and diiodohydroxyquin Paromomycin and diiodohydroxyquin (iodoquinol) are available in the United (iodoquinol) are available in the United States. States.

Asymptomatic patients with E. Asymptomatic patients with E. histolytica (and not E. dispar/E. histolytica (and not E. dispar/E. moshkovskii) should be treated with an moshkovskii) should be treated with an intraluminal agent alone. intraluminal agent alone.

PREVENTIONPREVENTION

Prevention of amebic infection in Prevention of amebic infection in travelers involves avoidance of travelers involves avoidance of drinking unboiled or unbottled drinking unboiled or unbottled water in endemic areas. water in endemic areas. Uncooked food such as fruit and Uncooked food such as fruit and vegetables that may have been vegetables that may have been washed in local water should also washed in local water should also not be consumed. not be consumed.

Amebic cysts are resistant to Amebic cysts are resistant to chlorine at the levels used in chlorine at the levels used in water supplies, but disinfection water supplies, but disinfection with iodine may be effective. with iodine may be effective. Avoiding sexual practices that Avoiding sexual practices that may lead to fecal-oral contact is may lead to fecal-oral contact is also advisable. also advisable.

Vaccine developmentVaccine development

There is some epidemiologic There is some epidemiologic evidence in humans of partial evidence in humans of partial acquired immunity to the acquired immunity to the organism. Protection from organism. Protection from invasive disease has been invasive disease has been associated with mucosal IgA associated with mucosal IgA antibodies to the amebic antibodies to the amebic adherence lectin.adherence lectin.

However, recurrent intestinal However, recurrent intestinal infection and persistent infection and persistent colonization does occur despite colonization does occur despite detectable antiamebic antibodies; detectable antiamebic antibodies; even in the study in children from even in the study in children from Bangladesh, the immunity that Bangladesh, the immunity that developed was short-lived.developed was short-lived.

Thus, it seems probable that Thus, it seems probable that acquired, but incomplete, acquired, but incomplete, immunity against infection immunity against infection occurs, and a vaccine that can occurs, and a vaccine that can reduce infection and/or invasive reduce infection and/or invasive disease may therefore be disease may therefore be feasible. feasible.

The relative importance of systemic The relative importance of systemic and mucosal, cellular and humoral and mucosal, cellular and humoral immunity is unclear. Several immunity is unclear. Several amebic proteins associated with amebic proteins associated with virulence have been identified and virulence have been identified and are being studied as potential are being studied as potential vaccine components. Development vaccine components. Development of both parenteral and oral of both parenteral and oral vaccines for humans is in progress.vaccines for humans is in progress.

Extraintestinal Extraintestinal Entamoeba histolytica Entamoeba histolytica amebiasisamebiasis AMEBIC LIVER ABSCESS — AMEBIC LIVER ABSCESS —

Amebic liver abscess is the most Amebic liver abscess is the most common extraintestinal common extraintestinal manifestation of amebiasis. manifestation of amebiasis. Amebae establish hepatic Amebae establish hepatic infection by ascending the portal infection by ascending the portal venous system.venous system.

Epidemiology — There are some Epidemiology — There are some epidemiologic features of amebic epidemiologic features of amebic liver abscess that are strikingly liver abscess that are strikingly different from intestinal different from intestinal amebiasis.amebiasis.

Amebic liver abscess (and other Amebic liver abscess (and other extraintestinal disease) is 7 to 10 extraintestinal disease) is 7 to 10 times more common in adult men times more common in adult men despite an equal gender despite an equal gender distribution in children and distribution in children and despite an approximately equal despite an approximately equal sex distribution of colonic amebic sex distribution of colonic amebic disease.disease.

Although the reasons for the Although the reasons for the differences in gender distribution differences in gender distribution have not been fully explained, some have not been fully explained, some possible mechanisms that have possible mechanisms that have been suggested include: hormonal been suggested include: hormonal effects (postmenopausal women effects (postmenopausal women have increased rates) and a have increased rates) and a potential role of alcoholic potential role of alcoholic hepatocellular damage in creating a hepatocellular damage in creating a nidus for portal seeding.nidus for portal seeding.

Intestinal amebiasis is not common Intestinal amebiasis is not common in short term travelers, but amebic in short term travelers, but amebic liver abscesses can occur after liver abscesses can occur after travel exposures as short as four travel exposures as short as four days. In one study, 35 percent of days. In one study, 35 percent of travelers with amebic liver abscess travelers with amebic liver abscess had spent less than six weeks in an had spent less than six weeks in an endemic area.endemic area.

Most patients diagnosed with Most patients diagnosed with amebic liver abscess in the United amebic liver abscess in the United States will either be from a States will either be from a country where amebiasis is country where amebiasis is endemic or will have a relevant endemic or will have a relevant travel history. travel history.

Conditions that affect cell Conditions that affect cell mediated immunity such as mediated immunity such as extremes of age, pregnancy, extremes of age, pregnancy, corticosteroid therapy, malignancy, corticosteroid therapy, malignancy, and malnutrition may also increase and malnutrition may also increase the chances that E. histolytica the chances that E. histolytica infection results in invasive disease infection results in invasive disease with liver involvement. with liver involvement.

Clinical manifestations Clinical manifestations

Patients with amebic liver Patients with amebic liver abscess usually present acutely abscess usually present acutely with one to two weeks of fever with one to two weeks of fever (38.5 to 39.5ºC) and right upper (38.5 to 39.5ºC) and right upper quadrant pain. quadrant pain.

Concurrent diarrhea is present in Concurrent diarrhea is present in less than one-third of patients, less than one-third of patients, although some patients will give a although some patients will give a history of having had dysentery history of having had dysentery within the previous few months. within the previous few months.

Jaundice is uncommon. For Jaundice is uncommon. For travelers returning from an endemic travelers returning from an endemic area, presentation usually occurs area, presentation usually occurs within 8 to 20 weeks (median 12 within 8 to 20 weeks (median 12 weeks) and will be within five weeks) and will be within five months of their return in 95 percent months of their return in 95 percent of patients, although a longer lag of patients, although a longer lag (sometimes years) has been (sometimes years) has been reported.reported.

Occasionally, patients have a Occasionally, patients have a more chronic presentation with more chronic presentation with months of fever, weight loss and months of fever, weight loss and abdominal pain. In these patients, abdominal pain. In these patients, hepatomegaly and anemia are hepatomegaly and anemia are often associated findings. often associated findings.

Patients with secondary cardiac or Patients with secondary cardiac or pulmonary involvement may present pulmonary involvement may present with symptoms primarily due to these with symptoms primarily due to these complications. Examination of patients complications. Examination of patients with uncomplicated liver abscess will with uncomplicated liver abscess will reveal hepatomegaly and point reveal hepatomegaly and point tenderness over the liver in tenderness over the liver in approximately 50 percent of cases. approximately 50 percent of cases. Clinical jaundice occurs in less than 10 Clinical jaundice occurs in less than 10 percent of patients.percent of patients.

Occasionally, the abscess Occasionally, the abscess ruptures into the peritoneum ruptures into the peritoneum causing clinical peritonitis (2 to 7 causing clinical peritonitis (2 to 7 percent) . percent) .

Patients with amebic hepatic Patients with amebic hepatic abscesses may also have abscesses may also have ileocecal mass lesions, that are ileocecal mass lesions, that are frequently amebomas frequently amebomas

Diagnosis Diagnosis

Patients with amebic liver abscess Patients with amebic liver abscess will often have a leukocytosis will often have a leukocytosis (>10,000/mm3) without (>10,000/mm3) without eosinophilia. Liver function testing eosinophilia. Liver function testing will reveal an elevated alkaline will reveal an elevated alkaline phosphatase in 80 percent, and phosphatase in 80 percent, and hepatic transaminases may also be hepatic transaminases may also be raised.raised.

Fecal microscopy will be positive for Fecal microscopy will be positive for amebae in only 18 percent of cases, amebae in only 18 percent of cases, although culture, which is only although culture, which is only available as a research tool, is available as a research tool, is positive in approximately 75 positive in approximately 75 percent . Other common percent . Other common nonspecific findings include an nonspecific findings include an abnormal chest radiograph and abnormal chest radiograph and proteinuria. proteinuria.

Imaging Imaging

Radiologic imaging of the liver is Radiologic imaging of the liver is the major method for diagnosing the major method for diagnosing amebic liver abscess. This can be amebic liver abscess. This can be accomplished with ultrasound, accomplished with ultrasound, computed tomography (CT) or computed tomography (CT) or magnetic resonance imaging magnetic resonance imaging (MRI). (MRI).

At least one of these studies At least one of these studies should be performed in all should be performed in all suspected cases. A single abscess suspected cases. A single abscess in the right lobe of the liver will in the right lobe of the liver will often be found (70 to 80 percent), often be found (70 to 80 percent), although multiple lesions can be although multiple lesions can be present.present.

Although none of these tests can Although none of these tests can definitively differentiate among a definitively differentiate among a pyogenic abscess, an amebic pyogenic abscess, an amebic abscess, or malignant disease, a abscess, or malignant disease, a patient with appropriate patient with appropriate epidemiologic risk factors and a epidemiologic risk factors and a suspicious lesion on scanning can suspicious lesion on scanning can usually be presumed to have usually be presumed to have amebic infection, at least while amebic infection, at least while awaiting other test results. awaiting other test results.

Even with appropriate therapy, the Even with appropriate therapy, the abscess may appear to increase in abscess may appear to increase in size initially and complete radiologic size initially and complete radiologic resolution may take up to two years; resolution may take up to two years; thus, repeated imaging is usually not thus, repeated imaging is usually not helpful. Sometimes a gallium scan helpful. Sometimes a gallium scan may be useful since amebic may be useful since amebic abscesses are "cold", possibly with a abscesses are "cold", possibly with a bright rim, whereas pyogenic bright rim, whereas pyogenic abscesses are "hot". abscesses are "hot".

    Serologic testingSerologic testing

Serum antibodies will be Serum antibodies will be detectable in 92 to 97 percent of detectable in 92 to 97 percent of patients at the time of presentation patients at the time of presentation with amebic liver abscess. with amebic liver abscess. Eventually 99 percent of patients Eventually 99 percent of patients will have positive antibody tests, will have positive antibody tests, but serologic testing may be but serologic testing may be negative in the first seven days.negative in the first seven days.

Up to 25 percent of uninfected Up to 25 percent of uninfected individuals in endemic areas have individuals in endemic areas have anti-amebic antibodies due to anti-amebic antibodies due to previous, often undiagnosed previous, often undiagnosed infection with E. histolytica. infection with E. histolytica.

Consequently, positive serology Consequently, positive serology in these populations is not nearly in these populations is not nearly as helpful although negative as helpful although negative serology still assists in excluding serology still assists in excluding this infection.this infection.

ndirect hemagglutination (IHA) is ndirect hemagglutination (IHA) is the most sensitive agar gel the most sensitive agar gel diffusion and diffusion and counterimmunophoresis are less counterimmunophoresis are less sensitive than IHA but usually sensitive than IHA but usually only remain positive for 6 to 12 only remain positive for 6 to 12 months, which may make them months, which may make them more useful in endemic areas.more useful in endemic areas.

Other new serologic tests based Other new serologic tests based upon recombinant E. histolytica upon recombinant E. histolytica antigens have also been developed. antigens have also been developed. In one study performing serial tests In one study performing serial tests with two different antigens in 20 with two different antigens in 20 patients with known amebic liver patients with known amebic liver abscesses, more than 50 percent abscesses, more than 50 percent became negative in one or both became negative in one or both tests within 180 days.tests within 180 days.

Other newer techniques for Other newer techniques for diagnosis include a rapid enzyme diagnosis include a rapid enzyme immunoassay with a sensitivity of immunoassay with a sensitivity of 93 percent compared to IHA and a 93 percent compared to IHA and a serum antigen detection test that is serum antigen detection test that is positive in 75 percent of patients positive in 75 percent of patients with amebic liver abscess . These with amebic liver abscess . These newer techniques may prove to be newer techniques may prove to be particularly useful in endemic particularly useful in endemic areas. areas.

Aspiration Aspiration

Needle aspiration has not conventionally Needle aspiration has not conventionally been recommended and is not usually been recommended and is not usually required. However, if there has been no required. However, if there has been no response to antibiotic therapy after three response to antibiotic therapy after three to five days, if a cyst appears to be at to five days, if a cyst appears to be at imminent risk of rupture, or if rapid imminent risk of rupture, or if rapid exclusion of other diagnoses is necessary, exclusion of other diagnoses is necessary, aspiration under ultrasound or CT aspiration under ultrasound or CT guidance should be strongly considered. guidance should be strongly considered.

In cases refractory to medical In cases refractory to medical therapy, percutaneous aspiration therapy, percutaneous aspiration has enhanced clinical has enhanced clinical recovery .Amebic liver abscesses recovery .Amebic liver abscesses contain acellular, proteinaceous contain acellular, proteinaceous debris and an "anchovy paste", debris and an "anchovy paste", chocolate colored fluid, consisting chocolate colored fluid, consisting predominantly of necrotic predominantly of necrotic hepatocytes. hepatocytes.

Trophozoites are seen on Trophozoites are seen on microscopy of the aspirate in microscopy of the aspirate in fewer than 20 percent of cases fewer than 20 percent of cases and are often present only in the and are often present only in the peripheral parts of the abscess, peripheral parts of the abscess, invading and destroying adjacent invading and destroying adjacent tissue.tissue.

This is in contrast to aspirates from This is in contrast to aspirates from pyogenic liver abscesses in which pyogenic liver abscesses in which organisms (usually mixed organisms (usually mixed morphologies) are usually readily morphologies) are usually readily apparent by Gram stain. Antigen apparent by Gram stain. Antigen tests and polymerase chain reaction tests and polymerase chain reaction (PCR) on aspirated material may (PCR) on aspirated material may also be helpful in establishing the also be helpful in establishing the diagnosis diagnosis

Although highly uncommon, Although highly uncommon, amebic hepatic abscesses may amebic hepatic abscesses may become secondarily infected with become secondarily infected with enteric bacteria, so aspirated fluid enteric bacteria, so aspirated fluid should be cultured for bacteria. should be cultured for bacteria.

Suggested clinical Suggested clinical approach approach In cases where the clinician suspects In cases where the clinician suspects

the diagnosis of amoebic liver abscess the diagnosis of amoebic liver abscess because of a consistent clinical history because of a consistent clinical history (usually acute presentation with 1 to 2 (usually acute presentation with 1 to 2 weeks of fever and right upper weeks of fever and right upper quadrant pain), relevant epidemiology quadrant pain), relevant epidemiology (resident in, migration from or travel to (resident in, migration from or travel to an endemic area), and suspicious an endemic area), and suspicious imaging (most common in the right imaging (most common in the right lobe and 70 to 80 percent are solitary lobe and 70 to 80 percent are solitary lesions), it is reasonable to send off lesions), it is reasonable to send off serology and begin empiric therapy. serology and begin empiric therapy.

Compared to patients with Compared to patients with pyogenic liver abscesses, those pyogenic liver abscesses, those with amebic abscesses are more with amebic abscesses are more also more likely to be <50 years also more likely to be <50 years old and male . In addition, those old and male . In addition, those with pyogenic abscesses are more with pyogenic abscesses are more likely to be jaundiced and septic likely to be jaundiced and septic and have a history of abdominal and have a history of abdominal surgery or biliary disease.surgery or biliary disease.

If the results of serology are If the results of serology are already known to be positive, already known to be positive, then a trial of empiric therapy is then a trial of empiric therapy is almost always justified, even in almost always justified, even in endemic countries. endemic countries.

In situations where the epidemiologic In situations where the epidemiologic history, clinical profile and serologic history, clinical profile and serologic studies (taken >7 days from symptom studies (taken >7 days from symptom onset) are non-characteristic or non-onset) are non-characteristic or non-diagnostic, or if the patient deteriorates diagnostic, or if the patient deteriorates on therapy, then aspiration may need on therapy, then aspiration may need to be performed to exclude alternative to be performed to exclude alternative diagnoses, in particular a pyogenic diagnoses, in particular a pyogenic abscess. In addition, therapeutic abscess. In addition, therapeutic aspiration may need to be considered if aspiration may need to be considered if there is a high risk of rupture there is a high risk of rupture (particularly lesions in the left lobe). (particularly lesions in the left lobe).

OTHER OTHER EXTRAINTESTINAL EXTRAINTESTINAL SITESSITES Although rare, amebic disease Although rare, amebic disease

occasionally involves other sites. occasionally involves other sites. Brain abscess, lung disease, Brain abscess, lung disease, cardiac involvement, perinephric cardiac involvement, perinephric or splenic abscess, vaginal or or splenic abscess, vaginal or uterine involvement, rectovaginal uterine involvement, rectovaginal fistulae and cutaneous disease fistulae and cutaneous disease can all occur. can all occur.

Pleuropulmonary Pleuropulmonary infectioninfection Pleuropulmonary involvement following Pleuropulmonary involvement following

E. histolytica infection often occurs E. histolytica infection often occurs secondary to a liver abscess. secondary to a liver abscess. Mechanisms of lung and/or pleural Mechanisms of lung and/or pleural infection include: development of a infection include: development of a sympathetic serous effusion, rupture of sympathetic serous effusion, rupture of a liver abscess into the chest cavity a liver abscess into the chest cavity leading to empyema, or hematogenous leading to empyema, or hematogenous spread resulting in parenchymal spread resulting in parenchymal infection. infection.

Factors that have been shown to Factors that have been shown to contribute to the development of contribute to the development of pulmonary amebiasis include: pulmonary amebiasis include: malnutrition, chronic alcoholism, malnutrition, chronic alcoholism, and atrial septal defect with left and atrial septal defect with left to right shunt.to right shunt.

Pulmonary symptoms including Pulmonary symptoms including cough, dyspnea and pleuritic cough, dyspnea and pleuritic chest pain may be present, and chest pain may be present, and patients are often quite ill. If a patients are often quite ill. If a bronchopleural fistula develops, bronchopleural fistula develops, patients may expectorate necrotic patients may expectorate necrotic material which can include material which can include contents of the liver abscess. contents of the liver abscess.

An abnormality on chest An abnormality on chest radiograph will be seen an radiograph will be seen an approximately 50 percent of approximately 50 percent of patients with an amebic liver patients with an amebic liver abscess, most commonly elevation abscess, most commonly elevation of the right hemidiaphragm . This of the right hemidiaphragm . This latter finding does not necessarily latter finding does not necessarily signal pulmonary involvement in signal pulmonary involvement in the infection. the infection.

Cardiac infectionCardiac infection

Cardiac involvement in amebic Cardiac involvement in amebic disease is much rarer than disease is much rarer than pleuropulmonary disease. When it pleuropulmonary disease. When it occurs, it usually results from occurs, it usually results from rupture of a liver abscess, rupture of a liver abscess, particularly abscesses involving particularly abscesses involving the left lobe of the liver, into the the left lobe of the liver, into the pericardium.pericardium.

This can result in severe chest This can result in severe chest pain, congestive cardiac failure pain, congestive cardiac failure and pericardial tamponade. The and pericardial tamponade. The associated mortality is high. associated mortality is high.

Brain abscess Brain abscess

Cerebral amebiasis is a rare Cerebral amebiasis is a rare cause of brain abscess which cause of brain abscess which results from hematogenous results from hematogenous dissemination. This form of dissemination. This form of amebiasis is characterized by an amebiasis is characterized by an abrupt onset of symptoms and abrupt onset of symptoms and rapid progression to death if rapid progression to death if untreated. untreated.

Lesions may be seen on CT scan as Lesions may be seen on CT scan as irregular foci without a capsule or irregular foci without a capsule or surrounding enhancement . CNS surrounding enhancement . CNS abscesses due to E. histolytica are abscesses due to E. histolytica are distinct from CNS lesions caused by distinct from CNS lesions caused by free-living amebae. Treatment with free-living amebae. Treatment with metronidazole should be started metronidazole should be started immediately, and surgical intervention immediately, and surgical intervention for decompression and/or tissue biopsy for decompression and/or tissue biopsy may be required.may be required.