Orientation notes for study. After this note you should be able to draw the life cycle, explain how the trophozoite invades, name the intestinal and extra-intestinal forms, choose the right drug for each stage, and separate the free-living amoebae that cause brain disease.
Definition
Amoebiasis is infection with Entamoeba histolytica, a protozoan of the intestine that can invade the colon and spread to the liver. About 90% of infected people are asymptomatic cyst passers. Most of those carry the harmless look-alike E. dispar; true invasive disease is caused by E. histolytica. Worldwide it is a leading parasitic cause of death after malaria and schistosomiasis, mostly in places with poor sanitation.
Life cycle
- Infective stage = the cyst (quadrinucleate, 10-15 micrometres), swallowed in faecally contaminated food or water (also sexual and oral-anal contact).
- The cyst survives gastric acid; in the small intestine it excysts into eight small trophozoites.
- Trophozoites live and multiply in the large intestine lumen (commensal, feeding on bacteria).
- As the stool dries they round up into cysts (the diagnostic and transmitting stage in formed stool).
- In some patients trophozoites invade the colonic wall, cause ulcers and may enter the portal blood to reach the liver.
Key point: cysts are the infective stage and are passed in formed stool; trophozoites are the invasive stage and are found in dysenteric (liquid) stool. Trophozoites die quickly outside the body and are not infective.
Pathogenesis
- Gal/GalNAc lectin on the trophozoite attaches to colonic mucin and epithelium.
- Amoebapores (pore-forming proteins) and cysteine proteases kill host cells, degrade extracellular matrix and kill neutrophils, so there is little inflammation.
- The ulcer undermines the mucosa as it penetrates the submucosa: the classic flask-shaped ulcer (narrow neck, wide base), found in the caecum, ascending colon, rectosigmoid.
- Haematophagous trophozoites contain ingested red cells, a hallmark of E. histolytica.
- Risk factors: poor sanitation, travel to endemic areas, immunosuppression (malnutrition, steroids, pregnancy), alcoholism, men who have sex with men.
Clinical syndromes
| Syndrome | Features |
|---|---|
| Asymptomatic carriage | Cysts in stool; no symptoms; a reservoir of infection |
| Amoebic colitis (dysentery) | Gradual onset over 1-3 weeks of bloody, mucoid diarrhoea, cramps, tenesmus; fever is mild or absent |
| Fulminant colitis | Toxic megacolon, perforation, peritonitis; more in children, pregnancy and steroid users |
| Amoeboma | A localised granulomatous mass in the caecum or rectosigmoid that mimics carcinoma |
| Amoebic liver abscess (the commonest extra-intestinal form) | Right upper quadrant pain, fever, tender hepatomegaly, often without preceding diarrhoea; usually a single abscess in the right lobe (portal drainage from the caecum); pus is sterile "anchovy paste" (liquefied necrotic liver, brown-red) |
| Other | Rupture into the pleura, lung (empyema, hepatobronchial fistula), pericardium (rare, dangerous) or peritoneum; amoebic brain abscess (rare); skin (perianal) |
Differential diagnosis
| Condition | What points to it | What separates it |
|---|---|---|
| Bacillary dysentery (Shigella, Campylobacter, EHEC) | High fever, acute onset, many small stools with pus cells | Stool culture; neutrophils in the stool |
| Ulcerative colitis | Relapsing bloody diarrhoea, young adult | Biopsy and colonoscopy; stool negative for amoebae; may be triggered by steroids given for presumed IBD, which can make amoebiasis fulminant |
| Pyogenic liver abscess | Biliary disease, older, often multiple | Culture of pus; antibiotics and drainage |
| Hydatid cyst | Calcified cyst, eosinophilia | Serology, characteristic ultrasound |
| Hepatocellular carcinoma | Cirrhosis, AFP | Imaging, no response to metronidazole |
| Schistosomiasis | Freshwater exposure, eosinophilia | Eggs in stool or urine |
| Colonic carcinoma (versus amoeboma) | Older patient, change in bowel habit | Biopsy; amoeboma regresses on treatment |
Diagnosis
- Stool microscopy (saline and iodine wet preparations): trophozoites with ingested red cells in fresh dysenteric stool, or cysts in formed stool. A negative single sample does not exclude disease: repeat 3 samples. Microscopy **cannot separate E. histolytica from *E. dispar*** by morphology, so use:
- Stool antigen tests and PCR to identify E. histolytica specifically.
- Serology (indirect haemagglutination or ELISA): positive in most patients with invasive disease and liver abscess; negative in asymptomatic carriers and may take about a week to turn positive. In endemic areas a positive result may reflect past infection.
- Liver abscess: ultrasound or CT shows a round, hypoechoic cavity in the right lobe; aspirate only if the diagnosis is uncertain or no response, or for impending rupture. Leucocytosis without eosinophilia, raised ALP and a raised right hemidiaphragm on chest X-ray support the diagnosis.
- Colonoscopy and biopsy when the cause of colitis is unclear (flask-shaped ulcers, trophozoites in the biopsy).
Treatment
- Tissue (invasive) disease, dysentery or liver abscess: a nitroimidazole, either metronidazole or tinidazole, which kills trophozoites in tissue.
- Then a luminal amoebicide, paromomycin or diloxanide furoate, to clear cysts in the bowel (metronidazole does not reach the lumen well); otherwise relapse and transmission continue.
- Asymptomatic cyst passers with E. histolytica: luminal agent alone.
- Liver abscess: metronidazole is usually enough; aspiration is added for large abscesses (over about 5 cm), left-lobe abscesses (rupture into the pericardium), impending rupture or no response in 3 to 5 days.
- Fulminant colitis or perforation: surgery and broad-spectrum antibiotics, together with the nitroimidazole.
- Do not give corticosteroids or antimotility drugs (they worsen amoebic colitis).
Safety: no alcohol during and after metronidazole (a disulfiram-like reaction); common adverse effects are a metallic taste, nausea and peripheral neuropathy with prolonged use.
Prevention
Safe water, boiling or filtering, hand-washing, food hygiene, proper sewage disposal, not using human faeces as fertiliser, and treatment of carriers. There is no vaccine.
Free-living amoebae
These are environmental amoebae that cause rare but lethal brain infections. They are not spread person to person.
| Organism | Disease | How it is acquired | Key features |
|---|---|---|---|
| Naegleria fowleri ("brain-eating amoeba") | Primary amoebic meningoencephalitis (PAM) | Warm fresh water forced up the nose (swimming, diving) | Enters via the cribriform plate and olfactory nerve; fulminant, death in 5 to 10 days; CSF is purulent with motile trophozoites; treatment with amphotericin B and other agents, usually too late |
| Acanthamoeba spp. | Granulomatous amoebic encephalitis (GAE); amoebic keratitis | Skin or lung entry, contact lenses rinsed with tap water | GAE in immunocompromised (HIV) patients, subacute; keratitis with severe pain and a ring infiltrate |
| Balamuthia mandrillaris | GAE | Skin lesions or inhalation | Subacute, can affect immunocompetent people; skin lesion first |
High-yield exam points
- Cyst = infective; trophozoite = invasive (with ingested RBCs).
- Flask-shaped ulcers in the caecum and rectosigmoid, with little inflammation because the amoeba kills neutrophils.
- Amoebic liver abscess: right lobe, single, "anchovy paste" sterile pus, no diarrhoea in most patients.
- Treatment is two steps: a nitroimidazole for tissue, then paromomycin or diloxanide for the lumen.
- Avoid steroids in suspected amoebiasis; amoeboma mimics carcinoma.
- ***E. dispar* is non-pathogenic** and looks identical on microscopy.
- ***Naegleria* via the cribriform plate after swimming; Acanthamoeba keratitis in contact-lens wearers.**
Clinical case
A 32-year-old man presents with 10 days of fever, right-sided chest and upper abdominal pain and weight loss. There is no diarrhoea. He is tender over the lower right ribs and the liver is enlarged. The chest X-ray shows a raised right hemidiaphragm. Ultrasound shows a 6 cm hypoechoic cavity in the right lobe. Serology for E. histolytica is positive; stool shows no cysts.
- Diagnosis? Amoebic liver abscess.
- Why no diarrhoea? Trophozoites invade the colon silently, then reach the liver through the portal vein; only a minority have colitis at the time.
- Management? Metronidazole (or tinidazole) for the tissue disease, followed by paromomycin or diloxanide furoate to clear the bowel; aspirate if there is no response in 3 to 5 days or the abscess is large or near the pericardium; avoid alcohol.
Practice questions
Question 1
A man has a 5-day history of bloody, mucoid diarrhoea with mild fever. Stool microscopy shows trophozoites that have ingested red blood cells. What is the best treatment plan?
A. Metronidazole alone B. Metronidazole followed by paromomycin or diloxanide furoate C. Ciprofloxacin alone D. Oral steroids and loperamide
Answer: B. Metronidazole followed by paromomycin or diloxanide furoate Explanation: A nitroimidazole kills tissue trophozoites; a luminal agent is needed to clear the cysts from the gut lumen and prevent relapse.
Question 2
Which finding best identifies pathogenic Entamoeba histolytica in a stool sample?
A. Quadrinucleate cysts B. Trophozoites containing ingested red blood cells C. Eosinophils in stool D. Motile flagellates
Answer: B. Trophozoites containing ingested red blood cells Explanation: Haematophagous trophozoites distinguish E. histolytica from non-pathogenic E. dispar, although antigen testing or PCR is more specific.
Question 3
Which is the commonest extra-intestinal site of amoebiasis?
A. Brain B. Lung C. Liver D. Spleen
Answer: C. Liver Explanation: Trophozoites travel in the portal vein from the caecum, forming an abscess, usually single and in the right lobe.
Question 4
A man with amoebic liver abscess is being treated with metronidazole. What advice about alcohol is correct?
A. Moderate alcohol is safe B. Avoid alcohol because of a disulfiram-like reaction C. Alcohol increases drug efficacy D. Only spirits need to be avoided
Answer: B. Avoid alcohol because of a disulfiram-like reaction Explanation: Metronidazole inhibits acetaldehyde dehydrogenase, causing flushing, vomiting and tachycardia with alcohol.
Question 5
A 14-year-old boy swims in a warm freshwater lake and 5 days later has severe headache, fever, vomiting and confusion. CSF is purulent with motile amoebae. What is the most likely organism?
A. Entamoeba histolytica B. Acanthamoeba castellanii C. Naegleria fowleri D. Giardia lamblia
Answer: C. Naegleria fowleri Explanation: Naegleria enters through the cribriform plate after exposure to warm fresh water and causes rapidly fatal primary amoebic meningoencephalitis.
Question 6
A patient with ulcerative colitis diagnosed elsewhere worsens dramatically after starting steroids. A repeat stool shows trophozoites. Which statement is correct?
A. Steroids are the treatment of choice for amoebic colitis B. Steroids can cause fulminant amoebic colitis, so amoebiasis should be excluded before steroids C. Amoebiasis never mimics ulcerative colitis D. Serology is always negative in colitis
Answer: B. Steroids can cause fulminant amoebic colitis, so amoebiasis should be excluded before steroids Explanation: Immunosuppression allows invasive amoebiasis to progress to fulminant colitis; stool examination, antigen testing and serology should come first.
Written for study from standard parasitology and tropical medicine references. Check details against your lecture notes and the current guideline.