Amoebiasis

Introduction

Intestinal amoebae are protozoa of which there are three main species; Entamoeba histolytica, E. dispar and E. moshkovskii, which are morphologically identical. Intestinal disease (amoebiasis) is primarily caused by E. histolytica. E. dispar is generally considered non-pathogenic and the pathogenicity of E. moshkovskii is uncertain.

Most infections are asymptomatic but clinical manifestations include dysentery and extra-intestinal disease. Worldwide E. histolytica and E. dispar infect approximately 500 million people, although the majority of people previously thought to be infected with E. histolytica actually carry the non-pathogenic E. dispar. There are around 100,000 deaths per year due to E. histolytica.

Pathogenesis

Amoebic cysts are ingested from faecally contaminated food or water or hands. Transmission can also occur via exposure to feces during sexual practices. Once mature cysts are ingested, excystation occurs in the small intestine of the individual and results in the release of amoebic trophozoites which travel to the large intestine. Once in the large intestine trophozoites multiply and produce cysts that are passed in feces. Cysts can survive in the external environment for many weeks due to the protection provided by their cell wall. The ingestion of only one cyst can cause disease. The trophozoites can also invade the intestinal wall or can travel to extra-intestinal sites (especially the liver, lungs, and brain) via hematogenous spread.

Differential Diagnoses

The differential diagnoses of amoebic dysentery are predominantly other infective causes of diarrhea including E.coli, shigella, campylobacter, salmonella, Clostridium difficile, cholera, giardia, and cryptosporidia. Non-infective causes of diarrhea (e.g. inflammatory bowel disease) should also be considered, especially in individuals with chronic or atypical symptoms.

Clinical Features

Most (>90%) infections are asymptomatic, including many of those with E. histolytica. Individuals who become symptomatic usually develop progressive diarrhea over seven to 21 days. Symptoms range from mild diarrhea to severe dysentery with colitis and/or extraintestinal features. Symptoms of intestinal amoebiasis include:

• Diarrhoea with blood and mucous

• Foul-smelling flatus

• Weight loss and malnutrition

• Abdominal pain

• Fever

• Rectal bleeding without diarrhoea (mainly children)

In some cases, individuals can have relatively mild symptoms for several months or even years. This can be mistaken for inflammatory bowel disease (ulcerative colitis, Crohn’s disease, especially in children) or other non-infective gastrointestinal pathologies.

Amoebic colitis can result in intestinal perforation, intestinal necrosis, peritonitis and toxic megacolon.

Amoeboma is rare and represents granulomatous tissue due to an amoebic abscess in the intestinal wall. They present with a palpable abdominal mass but individuals also frequently have amoebic dysentery.

Extra-intestinal features:
The most common extra-intestinal sites of amoebic infection are the liver, lungs and brain with liver abscesses the most frequently reported, although all are very rare. Only 5% of amoebic liver abscesses occur in children.

Epidemiology

Amoebiasis is a worldwide problem but is most common in developing nations due to poor sanitation, malnutrition, and poor socioeconomic conditions. Studies show up to 50% seroprevalence in children less than five years old in some endemic areas. Males and females are equally affected. In developed nations high-risk groups include those with immunodeficiency, including HIV, institutionalized individuals, men who have sex with men and immigrants from, and travelers to, endemic areas. Humans are the only known reservoir of E. histolytica.

There are up to 500 million infections per year, although only 40-50 million of these are symptomatic as E. dispar is 10 times more common than E. histolytica. There are approximately 100,000 deaths per year, almost exclusively in developing nations.

Investigations

Stool Microscopy

Stool microscopy can demonstrate cysts or trophozoites but usually cannot differentiate different species of amoeba (i.e. E. histolytica versus E. dispar versus E. moshkovskii). Noting ingested erythrocytes within amoeba is suggestive of E. histolytica, but can also be found in the usually non-pathogenic E. dispar. At least three stool samples on separate days should be examined and this can detect up to 95% of infections.

Antigen Tests

Antigen tests can reliably (>95%) distinguish between E. histolytica and E. dispar and are commercially available. They can be used on both stool and serum samples and are more sensitive than stool microscopy. In endemic areas, they are especially useful as serological tests may be difficult to interpret.

Serological Tests

Serological tests are useful in non-endemic settings but much less so in endemic areas as up to 35% of asymptomatic individuals in endemic areas will have antibodies from a previous infection. Thus a negative test can exclude the disease but a positive test could infer acute or previous infection. Over 90% of individuals develop antibodies to E. histolytica whereas antibodies are not generally formed against E. dispar. Antibodies are present from five to seven days after acute infection and can persist for many years.

Molecular Techniques

Molecular techniques, including polymerase chain reaction (PCR), are more sensitive and specific than either microscopy or antigen tests but are expensive and not yet widely available.

Histology and Imaging

In ambiguous cases, histological samples from either colonoscopy biopsies or surgical samples can be examined for amoebic trophozoites or cysts. Histology may show non-specific mucosal inflammation or amoebic ulcers. Samples are best obtained from ulcer margins. Microscopy, antigen tests, or molecular techniques can be used to examine histological samples for the amoeba.

Imaging of the gastrointestinal tract using ultrasound, CT, or MRI may be useful in some cases.

Investigations

There are several techniques for diagnosing amoebic dysentery including direct microscopy, antigen detection, serology, molecular techniques, and histology from intestinal biopsies.

Stool microscopy can demonstrate cysts or trophozoites but usually cannot differentiate different species of amoeba (i.e. E. histolytica versus E. dispar versus E. moshkovskii). Noting ingested erythrocytes within amoeba is suggestive of E. histolytica, but can also be found in the usually non-pathogenic E. dispar. At least three stool samples on separate days should be examined and this can detect up to 95% of infections.

Treatment

All E. histolytica infections (including asymptomatic infections) should be treated. Treatment aims to eliminate mucosa-invading trophozoites and amoeba in the intestinal lumen. E. dispar infections do not usually require treatment and E. moshkovskii infections may be treated although the benefit of this is uncertain.

Asymptomatic (intraluminal) infections with E. histolytica should be treated with a luminal agent only.

Luminal agents include:

• Paromomycin (25-35 mg/kg/d in 3 divided doses orally for 7 days)

• Diloxanide furoate (20 mg/kg/d in 3 divided doses orally for 10 days)

• Iodoquinol (30-40 mg/kg/d [max 2 g/day] in 3 divided doses orally for 20 days)

Individuals with gastrointestinal symptoms or extra-intestinal manifestations should be treated with metronidazole (35-50 mg/kg/d in 3 divided doses orally for 7-10 days) or tinidazole (if =3 y, 50 mg/kg/d [max 2 g] once daily orally for 3-5 days) followed by a luminal agent.

Corticosteroids and antimotility agents should be avoided as they worsen the disease.

Surgical treatment may be required for severe disease or amoebic abscesses.

Prevention

Prevention is focused on avoiding contaminated food and water and excellent hand hygiene. Although amoebic cysts are resistant to chlorine, disinfection of water with iodine or boiling the water is usually effective. There is currently no vaccine available.