Amebiasis Is Most Commonly Seen in Immigrants from and Travelers to Developing Countries

AMOEBIASIS

Introduction

Amebiasis is most commonly seen in immigrants from and travelers to developing countries.

Most infections will be asymptomatic, however some can be severe and life threatening.

Symptoms may occur acutely or years follwing initial infection.

Pathology

Organism

Entamoeba histolytica, a eukaryotic protozoan parasite that exists in two forms:

● An infective cyst

● A potentially pathogenic trophozoite.

It should not be confused with the morphologically identical but non-pathogenic Entamoeba dispar.

Molecular studies show entamoeba to belong to one of the most ancient branches of the eukaryotic tree.

Life cycle

See appendix 1 below.

Epidemiology

● Although uncommon in Australia on a global scale, Entamoeba histolytica is one of the most common parasitic infections, being the third leading parasitic cause of death in humans after malaria and schistosomiasis. Globally it is responsible for 40,000-100,000 deaths per year.

● It is endemic world wide, but particularly in India and South East Asia

● In Australia it is most commonly seen in the Northern regions in indigenous populations. Male homosexuals are also at increased risk.

Transmission

Amoebiasis can be transmitted by:

● Ingestion of water contaminated with faeces containing amoebic cysts

● Ingestion after faecal contamination of hands

● Contaminated raw vegetables

● Unprotected oral-anal sexual contact.

Incubation Period

● The average incubation period is two to four weeks.

● Note however that patients may present months to years after the initial infection.

Reservoir

● Humans are often asymptomatic carriers.

Period of Communicability

● Cases are infectious as long as cysts are present in the faeces. In some instances cyst excretion may persist for years.

Susceptibility and Resistance

● All non-immune people are susceptible to infection.

● People with E. dispar do not develop symptoms.

● Reinfection is possible but rare.

Clinical Features

1. Most infections are in fact asymptomatic. Occasionally however clinically important intestinal or extra-intestinal disease may result.

2. Intestinal disease:

This can vary from mild to severe and life threatening disease. Onset is usually insidious.

● Fever, (but only in less than half of cases).

● GIT upset with nausea, abdominal discomfort and diarrhea, alternating with periods of constipation or remission.

● Diarrhea may be bloody (amoebic dysentery).

Intestinal amoebiasis may be complicated by:

● Fulminant colitis, including toxic megacolon.

● Colonic perforation and haemorrhage

● Perianal ulceration or fistula formation.

● Granuloma of the large intestine

3. Extra-intestinal amoebiasis:

● Dissemination via the bloodstream may lead to extra-intestinal amoebiasis.

● This is most commonly manifested as abscess formation in:

The liver, (most common)

Brain or lungs, (less commonly).

Differential Diagnosis

The differential diagnosis of an infectious diarrheal illness with occult or grossly bloody stools (dysentery) includes infection with:

● Shigella

● Salmonella

● Campylobacter

● Enteroinvasive and enterohemorrhagic Escherichia coli.

● Non-infectious causes may include inflammatory bowel disease, ischemic colitis and diverticulitis.

Investigations

Microscopy

Diagnosis is confirmed by microscopic examination for trophozoites or cysts in:

● Fresh or suitably preserved faecal specimens

● Smears of aspirates or scrapings obtained by proctoscopy

● Aspirates of abscesses or other tissue specimens.

Repeated stool specimens may be needed to establish a diagnosis as cysts are shed intermittently in asymptomatic and mild infections.

The presence of trophozoites containing red blood cells is suggestive of invasive amoebiasis.

Note that E. histolytica is morphologically identical to the nonpathogenic species E. dispar and E. moshkovskii, microscopy can not distinguish between the three species, and further testing will be required for speciation.

Culture

Culture techniques have been used to detect E. histolytica for a century.

However, culture methods are time-consuming, difficult and have low sensitivity of only about 50%.

Culture methods are thus largely restricted to specialized parasitology research laboratories.

Antigen Testing

● May be done on stool samples.

● These use monoclonal antibodies directed against various proteins of E. histolytica.

● These tests are rapid and less subjective than microscopy, but unfortunately can have some cross reactivity with non pathogenic species.

PCR

● Entamoeba histolytica can be detected with PCR testing, looking for E. histolytica genes, and this is the most sensitive and specific test. It requires a high level of expertise however and is expensive.

Serology

● Serology using indirect haemagglutination (IHA) and enzyme immunoassays (EIA) is useful in the diagnosis of extra-intestinal disease such as liver abscesses, when stool examination is often negative.

● Serology is also important in the differentiation between strains of the pathogenic E. histolytica and strains of the non-pathogenic E. dispar.

Imaging

● X-ray, ultrasound and CT scans are also useful in the identification of amoebic abscesses and can be considered diagnostic in the presence of a specific antibody response to E. histolytica.

Colonoscopy and flexible sigmoidoscopy

● These are useful in patients with acute colitis when E. histolytica infection is suspected on clinical grounds but not detected in stool samples.

● Examinations of scrapings and biopsies for trophozoites have a higher sensitivity than examinations of faecal specimens.

Management

1. Treat immediate fluid and electrolyte disturbances, as clinically indicted.

2. Antibiotics

● Specialist Infectious Disease Advice should be sought.

In general terms:

Asymptomatic carriers of E. histolytica should be treated with a luminal agent to minimise the risk of transmission of disease to minimise the risk of developing invasive disease.

In patients with invasive disease, metronidazole should be used in conjunction with a luminal agent to eradicate the organism

Asymptomatic carriage:

Treat with luminal amoebicide only:

● Oral paromomycin 500mg three times daily for 7 days

Invasive disease, (Acute amoebic dysentery):

Treat with tissue amoebicide and luminal amoebicide:

● Oral metronidazole 750–800mg three times daily for 6–10 days

Or

● Oral tinidazole 2 g once daily for 2–3 days (up to 10 days) and oral paromomycin 500mg three times daily for 7 days

Liver abscess:

Treat with tissue amoebicide and luminal amoebicide:

● Oral or intravenous metronidazole 750–800mg three times daily for 14 days

Or

● Oral tinidazole 2 g once daily for 5 days and oral paromomycin 500mg three times daily for 7 days

To eradicate cysts and prevent relapse after acute treatment, follow with paromomycin

Control of Contacts

● Consider faecal screening for household members and institutional contacts.

● Faecal screening is advised for fellow travellers of a confirmed case.

● Confirmed carriers should also be treated.

Patient Education

● A patient education handout is available via the Blue Book Website

Notification:

● Notification is not required.

School exclusion:

● Exclude until diarrhoea has ceased.

Appendix 1 Life Cycle 2

Trophozoites Trophozoites Cysts

Left and middle: Trophozoites of Entamoeba histolytica with ingested erythrocytes (trichrome stain). The ingested erythrocytes appear as dark inclusions. Erythrophagocytosis is the only characteristic that can be used to differentiate morphologically E. histolytica from the nonpathogenic E. dispar. Right: Cysts of Entamoeba histolytica, wet mounts stained with iodine

(From CDC Website, 2007)

● Cysts and trophozoites are passed in feces (1).

● Cysts are typically found in formed stool, whereas trophozoites are typically found in diarrheal stool.

● Infection by Entamoeba histolytica occurs by ingestion of mature cysts (2) in fecally contaminated food, water, or hands.

● Excystation (3) occurs in the small intestine and trophozoites (4) are released, which migrate to the large intestine.

● The trophozoites multiply by binary fission and produce cysts (5), and both stages are passed in the feces (1).

● Because of the protection conferred by their walls, the cysts can survive days to weeks in the external environment and are responsible for transmission.

● Trophozoites passed in the stool are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric environment.

● In many cases, the trophozoites remain confined to the intestinal lumen (A): (noninvasive infection) of individuals who are asymptomatic carriers, passing cysts in their stool. In some patients the trophozoites invade the intestinal mucosa (B): (intestinal disease), or, through the bloodstream, extraintestinal sites such as the liver, brain, and lungs (C): (extraintestinal disease), with resultant pathologic manifestations.

● It has been established that the invasive and noninvasive forms represent two separate species, respectively E. histolytica and E. dispar. These two species are morphologically indistinguishable unless E. histolytica is observed with ingested red blood cells (erythrophagocystosis).

● Transmission can also occur through exposure to fecal matter during sexual contact (in which case not only cysts, but also trophozoites could prove infective).