AMEBIASIS Lecture-6- Hazem Al-Khafaji 2016

The causitive organism is parasitic protozoan, called Entamoeba histolytica. What was once thought to be a single entity, is now recognised as two morphologically identical but genetically distinct forms; E. histolytica (pathogen) and E. dispar (commensal),this has affected our understanding of amoeba distribution. Many suspected cases of E. histolytica carrier, may simply have been E. dispar colonisation The WHO recommendes that E. histolytica colonisation should be treated, however, treatment is unnecessary for E. dispar colonisation

Epidemiology Amoebiasis is found primarily in developing tropical and subtropical countries where sanitation is poor, leading to a direct link between faeces and ingestion (see Box-1). Occasionally cases are reported in non-endemic areas e.g. UK and USA. Usually due to travel and immigration from endemic areas. There are an estimated 40,000-100,000 deaths due to amoebiasis worldwide each year.

Life cycle and transmission Entammoeba histolytica has a biphasic life cycle, existing in two forms; as an infectious cyst and an amoeboid trophozoite Mouth - Cyst ingested Invades gut mucosa – cyst formation Cyst Passed in stool Excyst to trophozoite Trophozoite Amoebic disease

Life cycle Cysts (10-15μm) are ingested via contaminated food or water. The cyst wall is hard & can overcome gastric acidity. In the terminal ileum or colon, the parasite excysts and begins the trophozoite stage. Trophozoites (10-50μm) are highly motile and pleomorphic. They are unable to survive outside the human gut. Energy is derived from the ingestion of bacteria and food particles. No mitochondria are present in trophozoites. Trophozoites reproduce by binary fission and encyst in the colonic wall. Cysts are passed in the stool where they become infectious. The signal for encystation is thought to be via epithelial galactose/N-acetylgalactosamine specific lectin (gal-lectin) binding protein.

Pathogenesis Amoebic trophozoites invade the colon causing colitis. They may also invade the portal circulation and travel to the liver via portal circulation, causing liver abscess (Extension of an amebic liver abscess into the peritoneum or pericardium) is a very acute clinical presentation that is more likely with a left lobe abscess. Disease can extend to the pleura, causing empyema, or less likely, disseminate hematogenously to the lung and brain. Gastrointestinal Pathology The spectrum of colitis in amoebiasis ranges from mucosal thickening, to multiple cyst formation, to diffuse Inflammation / oedema, to necrosis and perforation of colonic wall. Binding of E. histolytica to epithelial cells via gal-lectin. This molecule shows homologous to human CD59, conferring resistance to complement . A change in the epithelial permeability is induced, probably via the inter-cellular tight junctions. Cell lysis and apoptosis of mucosa are thought to be mediated by amoebapores, peptides capable of forming pores in lipid bi-layers. Trophozoites invade through to the submucosa causing flask shaped cysts . Cysteine proteases released by trophozoites digest extracellular matrix in liver and colon,. Neutrophils and macrophages are drawn to invasion sites. E. histolytica can lyse neutrophils leading to further tissue damage, and contributing towards the induction of diarrhoea. Inflammation is a significant cause of tissue damage, however, innate immunity may be the main combatant against the disease.

Pathogenesis Amoebic liver abscess Histological cross section of classical flask shaped amoebic ulcer in colonic mucosa Amoebic liver abscess

Clinical features Gastro-intestinal Abdominal pain and tenderness. Some individuals carry E. histolytica asymptomatically. 4 -10% will go on to develop the disease within a year. Gastro-intestinal Gradual onset (weeks) of bloody diarrhoea, occasionally with small volumes of mucoid & blood stool. If blood is not visible, stool is usually ‘haem’ positive due to the breach of the mucosa. Abdominal pain and tenderness. Leucocytes and pus may be present in stool. Fever present in <40% of patients. Weight loss and anorexia can be present. In more severe cases fulminant amoebic colitis develops. Liver involvement(amoebic hepatitis) is more common in these cases, along with paralytic ileus, toxic megacolon and mucosal sloughing. Over 75% of patients with fulminant colitis develop intestinal perforation. Local inflammatory masses, amoebomas, may cause obstructive symptoms.

Hepatic More common in men Liver abscess can present in conjunction with bowel symptoms (10% of cases), or in isolation. Sudden onset of upper abdominal pain with fever. Pain may radiate to right shoulder or be exacerbated by repiratory movements. Hepatic tenderness may be present. Jaundice is unusual. Complicated liver abscess may develop if abscess ruptures into the peritoneal, pericardial or pleural cavity. Morbidity and mortality is high.

CLINICAL MANIFESTATIONS Incubation peroid from 2 weeks up to years Clinical syndromes caused by E.histolytica infection: A- Intestinal: 1- Asymtomatic infection. 2- Acute rectocolitis(dysentery). 3- Fulminant colitis with perforation. 4- Toxic megacolon. 5- Chronic non dysenteric colitis 6- Amoeboma. 7- Appendicitis B- Extra-intestinal: 1- Amoebic hepatitis. 2- Hepatic abscess( Amoebic liver abscess): complicated by : Peritonotis,empyema,pericarditis,lung abscess,splenic abscess & brain abscess. 3- Cuteneous amoebiasis( genitourinary disease)

Differential diagnosis Acute amebic colitis should be differentiated from: 1- infection due to Shigella(bacillary dysentry). 2- Infection with Campylobacter, Salmonella or Yersinia. 3- Invasive Escherichia coli species. 4- Clostridium difficile toxin-mediated disease(antibiotic associated diarrhoea) 5- chronic disease differentiated from ulcerative colitis. 6-Amoeboma differentiated from colonic carcinoma.

Diagnosis Clinical history is important. Demonstration of E. histolytica in stool (active ,motile trophozoites & the vacuoles cotain RBCs) by microscopy . or ELISA assay for antigen detection or PCR . Trophozoites only survive for short periods of time, therefore, fresh stool samples should be used Colonoscopy to confirm colitis and tissue biopsy to dirrerentiate it from ulcerative colitis 7 differentiates amoeboma fronm carcinoma Liver abscess; space occupying lesion on CT/US with ) positive amoebic serology

Management Amoebiasis, in particular with liver involvement, can be fatal if not treated. Chemotherapy can effectively cure ameobiasis. Nitroimidazole (e.g.metronidazole) is used to treat the invasive pathogens – 800mg t.d.s for 10 days. This is followed by a luminal agent (e.g.diloxanide furoate) to eliminate colonisation) – 500mg t.d.s for 10 days. This is also suitable for asymptomatic individuals. Complicated liver abscesses should be drained surgically.

Prevention E. histolytica infection can be prevented by the availability of clean water, adequate sanitation, and avoidance of eating undercooked foods especially from un clean source(food handlers are the main source of infection),that facilitate direct fecal-oral contamination. Boiling is the only reliable way of killing cysts(Boiling water for at least ten minutes kills amoebic cysts effectively. Chlorine and iodine tablets are not thought to be 100% effective). In endemic areas, uncooked foods such as salads and vegetables should be avoided.

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