Subphylum Sarcodina. Entamoeba histolytica. Entamoeba dispar. Entamoeba gingivalis

At a glance

1. Entamoeba are amoebas: they move and feed with pseudopodia. Entamoeba histolytica, in the large intestine, causes amoebiasis; E. dispar looks exactly like it and is harmless; E. gingivalis lives in the mouth.
2. E. histolytica has a trophozoite, which lives and multiplies in the colon, and a cyst, with four nuclei when mature, which is swallowed in water or food or from hands.
3. Most infections cause no symptoms. When the trophozoites invade, they make flask-shaped ulcers in the colon, amoebic colitis, and can reach the liver in the blood and make an abscess.
4. A trophozoite that has swallowed red cells is the classic sign of invasion. Microscopy cannot tell E. histolytica from E. dispar: PCR can.
5. Invasive amoebiasis is treated with metronidazole or tinidazole, then a luminal agent to clear the gut. Boiling kills the cysts; there is no vaccine.

01Entamoeba, amoebas of the gut and the mouth

The Sarcodina, as the older classification and the syllabus call them, are the protozoa that move and feed with pseudopodia, flowing extensions of the cell. In the gut and the mouth the genus that matters is Entamoeba, with three species in this topic. Free-living amoebae, Naegleria and Acanthamoeba, can also infect people, in the brain and the eye, but are not covered here.

E. histolytica and E. dispar look exactly the same under the microscope, and are told apart only by their DNA or antigens. A third look-alike, E. moshkovskii, may cause diarrhoea. A fourth gut amoeba, Entamoeba coli, is harmless, and is worth knowing only so as not to mistake it.

02The trophozoite and the cyst

E. histolytica has two forms:

The parts to know:

• Ectoplasm and endoplasm: the trophozoite's cytoplasm has a clear outer layer, the ectoplasm, and a granular inner one, the endoplasm, like ground glass. The ectoplasm flows out as a broad, blunt pseudopodium and the endoplasm streams in after it, so the cell crawls in one direction.
• Nucleus: round, with a small karyosome in its centre and its chromatin in fine, even beads under the membrane, a ring with a dot. The harmless E. coli has a coarser, uneven pattern and, in its mature cyst, usually eight nuclei, at times more.
• Swallowed red cells: a trophozoite with red blood cells inside it is the classic sign of invasive E. histolytica, though E. dispar can occasionally swallow them too.
• Chromatoid bodies and the glycogen vacuole: stores in the young cyst, bars of ribosomes with blunt, rounded ends and a pool of glycogen. As the cyst matures and its nucleus divides twice, to four, the glycogen is used up and the chromatoid bodies become fewer, though one or two are often still seen.

03The life cycle

The mature cyst is swallowed in food or water contaminated with faeces, or from hand to mouth; it can also pass in sexual contact that involves the faeces. It passes the stomach, opens in the small intestine and releases trophozoites, which move on to the large intestine. There they multiply by binary fission and form cysts, and both forms are passed in the faeces. The cysts survive for days to weeks outside the body; trophozoites passed in diarrhoea soon die outside the body, and if swallowed do not survive the stomach.

From here the infection goes one of three ways. In most people the trophozoites stay in the lumen of the colon, causing no symptoms, and these carriers pass cysts and keep the parasite going. In some, the trophozoites invade the colon's wall; and from the wall they can be carried in the portal vein to the liver. More rarely they reach the lungs, most often when a liver abscess bursts through the diaphragm, or travel on in the blood to the brain.

04Amoebiasis

Amoebiasis is found worldwide, most of all in the tropics and subtropics where water and sanitation are poor, and kills more than 55,000 people a year. Most infections, 80 to 90 per cent, cause no symptoms.

Amoebic colitis

The trophozoites invade the lining of the colon, killing the cells they touch and swallowing red cells, and dig flask-shaped ulcers: narrow at the surface and wide underneath, most often in the caecum.

• The incubation is anything from a few days to months.
• Usually it runs a slow course, with mild diarrhoea that comes and goes and abdominal discomfort, which can turn to diarrhoea with blood and mucus. Less often it starts as an acute dysentery.
• It can be mistaken for ulcerative colitis, and corticosteroids can turn it into a fulminant colitis that may dilate and perforate the colon.
• Other complications are a stricture, heavy bleeding, and an amoeboma, a mass of inflamed tissue in the colon's wall that can look like a cancer.

Amoebic liver abscess

Trophozoites carried to the liver in the portal vein make an amoebic liver abscess, the commonest form of amoebiasis outside the gut. It is ten times more common in men than in women, and is usually a single abscess in the right lobe.

• The patient has fever, sweats, weight loss and pain under the right ribs, with a tender, enlarged liver, and at times an effusion at the base of the right lung. Jaundice is unusual.
• Often there has been no dysentery, so it must be thought of in anyone who has lived in or travelled to a place where amoebiasis is common, even years before.
• Aspirated, the abscess holds a thick, brown fluid likened to anchovy paste, of dead liver cells rather than pus.
• It can burst into the chest, the pericardium or the abdomen, or become infected.

Diagnosis

• Microscopy of a fresh stool finds cysts and trophozoites, but cannot tell E. histolytica from E. dispar. Cysts alone do not mean disease; trophozoites with red cells inside them point to invasion.
• PCR on stool identifies the species and is now the reference test. Stool antigen tests specific to E. histolytica are an alternative.
• Antibodies are found in at least 90 per cent of people with a liver abscess and in 60 to 70 per cent with active colitis. They stay for years after a cure, so they cannot tell a past infection from a present one where amoebiasis is common.
• Ultrasound or CT finds a liver abscess.

Treatment and prevention

• Invasive disease, colitis or abscess: metronidazole or tinidazole kills the trophozoites in the tissue, but not those in the lumen, so it is followed by a luminal agent, paromomycin or diloxanide furoate.
• Carriers of E. histolytica with no symptoms: a luminal agent alone, since they can still fall ill and spread the infection. E. dispar needs no treatment.
• A liver abscess usually heals on the drugs alone. It is drained with a needle if it does not respond, if it is very large or in the left lobe, or if it is about to burst.

The cysts are killed by boiling, but chlorine and iodine tablets do not reliably kill them. Prevention rests on clean water, sanitation and washing hands, and on peeling or cooking food where water is unsafe. There is no vaccine.

05Entamoeba gingivalis

Entamoeba gingivalis lives in the mouth, in the pockets between the gums and the teeth and on plaque. It has no cyst, so it is thought to pass directly from mouth to mouth, by kissing or on shared cutlery and cups. Its trophozoites are about the size of E. histolytica's, usually 10 to 20 µm, and swallow bacteria and white blood cells, and only very rarely red cells. It is found in most sites of periodontitis, and far less often in healthy gums. Whether it helps cause gum disease or simply thrives in it is not settled.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1How many nuclei does a mature Entamoeba histolytica cyst have?

OneTwoFourEight

2Which finding in a fresh stool sample points most to invasive amoebiasis?

Cysts with four nucleiTrophozoites with red blood cells inside themCysts with chromatoid bodiesMany white blood cells and no parasites

3A healthy man's stool shows four-nucleus Entamoeba cysts. What tells E. histolytica from E. dispar?

The size of the cystsThe number of nucleiA test for its DNA or antigen, since the two look exactly alikeWhether the cysts contain chromatoid bodies

4A man back from a year working in Mexico has two weeks of fever, sweats and pain under the right ribs. His liver is tender, and he has had no diarrhoea. Ultrasound shows one round abscess in the right lobe. What is most likely?

Hydatid cystAmoebic liver abscessHepatitis ALiver metastasis

5Why is metronidazole for amoebic colitis followed by paromomycin?

To treat the liver abscessBecause metronidazole does not clear the cysts in the lumen of the colonTo prevent the side effects of metronidazoleParomomycin is a vaccine

6Why must amoebiasis be ruled out before treating a new bloody colitis with corticosteroids?

Steroids make the cysts infectiveAmoebic colitis can look like ulcerative colitis, and steroids can turn it into a fulminant colitisSteroids cause liver abscessesSteroids stop metronidazole working