Describe Entamoeba histolytica with its life cycle, pathogenesis, clinical features, laboratory diagnosis and treatment.

The Parasite and its Forms

• Man is the only significant host; transmission is faecal-oral through contaminated water, food and hands, and by flies and food handlers. Sexual transmission occurs
• Two morphologically identical but non-pathogenic species exist — Entamoeba dispar (much commoner than E. Histolytica) and E. Moshkovskii. They cannot be distinguished by microscopy, which is why a cyst seen in stool does not by itself justify treatment

Life Cycle and Pathogenesis

Mature quadrinucleate cysts are ingested in contaminated food or water → They resist gastric acid and excyst in the terminal ileum → Each cyst releases eight trophozoites (four nuclei divide once) → Trophozoites colonise the large intestine, chiefly the caecum, ascending colon and rectosigmoid → In most people they remain luminal commensals and encyst — the asymptomatic cyst passer, who excretes millions of cysts daily → In a minority they invade, using the GAL/GalNAc lectin to adhere, amoebapores to lyse cells and cysteine proteases to digest the matrix → Lysis of the mucosa produces the characteristic flask-shaped ulcer — a narrow neck through the mucosa opening into a broad base in the submucosa, where spread occurs laterally → Trophozoites entering portal venules travel to the liver — amoebic liver abscess

Clinical Features

• Asymptomatic infection is much the commonest outcome — about 90% of those infected, most of whom in fact carry E. Dispar
• Amoebic dysentery (intestinal amoebiasis) — gradual onset over days to weeks of abdominal cramps and loose stools containing blood and mucus, with tenesmus. Fever and systemic upset are mild or absent, unlike bacillary dysentery
• Amoeboma — a granulomatous mass in the caecum or ascending colon that mimics carcinoma radiologically and at operation; it responds to medical treatment, so recognising it prevents an unnecessary resection
• Complications — fulminant necrotising colitis with perforation, toxic megacolon, massive haemorrhage, stricture, and a chronic post-amoebic colitis
• Amoebic liver abscess — the commonest extra-intestinal form. Characteristically a single abscess in the right lobe (which receives most of the portal drainage from the right colon), presenting with fever, tender hepatomegaly, right upper quadrant pain and often referred right shoulder-tip pain. It affects adult men disproportionately, and alcohol is a recognised risk factor
• Only a minority give a history of dysentery, and stool examination is usually negative by the time the abscess presents — a point that repeatedly delays the diagnosis
• The pus is "anchovy sauce" — thick, reddish-brown, odourless and sterile on bacterial culture. It consists of necrotic liver, not pus cells. Trophozoites are found at the advancing edge of the abscess, not in the aspirated centre, so aspirate examination is usually negative
• Other sites — rupture into pleura, peritoneum or pericardium (the last being the most dangerous); lung; brain; and cutaneous amoebiasis around the perineum

Laboratory Diagnosis

• Stool microscopy — a fresh, warm specimen examined within 30 minutes in saline and iodine mounts. Motile trophozoites containing red cells indicate invasive disease; cysts indicate infection but not necessarily E. Histolytica
• Three specimens on different days improve the yield, since excretion is intermittent; concentration methods for cysts
• Antigen detection by ELISA for the GAL/GalNAc lectin, which distinguishes E. Histolytica from E. Dispar, and PCR, which is the reference method — this distinction is the central diagnostic problem
• Serology (indirect haemagglutination, ELISA) is positive in over 90% of liver abscess and in most invasive intestinal disease, but is negative in asymptomatic carriers. Its limitation in India is that antibody persists for years after past infection, so it cannot distinguish current from previous disease in an endemic population
• Imaging — ultrasound is the mainstay for liver abscess, showing a round hypoechoic lesion, usually single and in the right lobe
• Sigmoidoscopy with scraping from the ulcer edge (not from the stool), showing the flask-shaped ulcers
• Blood — neutrophil leucocytosis with a raised alkaline phosphatase and a normal or slightly raised bilirubin in liver abscess; eosinophilia is absent, which distinguishes it from helminth infection

Differentiating the Intestinal Amoebae

Treatment and Applied Aspects

• Invasive disease requires two drugs — a tissue amoebicide (metronidazole or tinidazole) to kill trophozoites in the bowel wall and liver, followed by a luminal amoebicide (diloxanide furoate or paromomycin) to clear cysts from the gut lumen. Metronidazole alone does not eradicate luminal cysts, and omitting the second drug is the commonest cause of relapse and of continued transmission
• Asymptomatic cyst passers are treated with a luminal amoebicide alone, chiefly to prevent transmission — and, in India, particularly in food handlers
• Liver abscess responds to metronidazole alone in most cases; aspiration is reserved for a large left-lobe abscess (which may rupture into the pericardium), failure to respond within 3 to 5 days, imminent rupture, or diagnostic uncertainty with pyogenic abscess
• Distinguish amoebic from pyogenic liver abscess — amoebic is usually single, right-lobed, in a younger man, with negative blood cultures, sterile pus and positive serology; pyogenic is often multiple, associated with biliary disease or diabetes, with positive blood cultures and frank pus. The treatments differ entirely
• Distinguish amoebic from bacillary dysentery — amoebic is insidious with little fever, few pus cells and motile trophozoites containing red cells; bacillary is acute and febrile with abundant pus cells. Both are common in India and the treatments differ
• Prevention — safe water and sanitation, handwashing, washing and peeling raw vegetables and fruit, and screening food handlers. Cysts resist ordinary chlorination, so filtration or boiling is needed where water quality is uncertain
• Eosinophilia is absent in amoebiasis, as in all protozoal infection; its presence in a patient with a liver lesion should raise hydatid disease or a tissue helminth instead
• Do not aspirate a liver abscess routinely; most respond to metronidazole alone, and aspiration carries a risk of rupture and of introducing bacterial infection
• A left-lobe abscess is the dangerous one, because rupture into the pericardium causes tamponade; it is an indication for aspiration even when the patient is stable
• Amoeboma responds to drugs, so a caecal mass in a patient from an endemic area with positive amoebic serology deserves a trial of metronidazole before resection is considered
• The stool is usually negative when a liver abscess presents, and this must not be taken as evidence against the diagnosis; serology and ultrasound are what establish it
• Treat food handlers who are cyst passers, since a single asymptomatic carrier in a kitchen can infect very large numbers of people
• Metronidazole alone leaves the gut lumen colonised, so the patient remains infectious to others even after the symptoms resolve; the luminal drug is a public health measure as much as an individual one
• Amoebic and bacillary dysentery both occur in India and may coexist; the presence of abundant pus cells favours a bacterial cause but does not exclude amoebiasis
• Sigmoidoscopic scrapings should be taken from the ulcer edge, not from the luminal exudate, where trophozoites are scanty
• Serology stays positive for years in an endemic population, so a positive result supports the diagnosis in a symptomatic patient but proves nothing in an asymptomatic one
• Consider amoebic liver abscess in any Indian adult with fever and right upper quadrant pain; ultrasound is quick, cheap and usually diagnostic
• Referred right shoulder-tip pain reflects diaphragmatic irritation and is a useful pointer that is easily overlooked when the history focuses on the abdomen