Entamoeba histolytica: Life Cycle, Diseases, Lab Diagnosis

Entamoeba histolytica is an enteric protozoan parasite with worldwide distribution. It is responsible for amoebic dysentery (bloody diarrhea) and invasive extraintestinal amebiasis (such as liver abscess, peritonitis, and pleuropulmonary abscess). Other species of Entamoeba; Entamoeba hartmanii, Entamoeba coli, and Entamoeba dispar do not cause diseases but their trophozoite is difficult to distinguish from those of E.histolytica by light microscopy.

Mode of transmission

Feco-oral route, via the ingestion of contaminated food or water containing mature quadrinucleate cyst of Entamoeba histolytica. Trophozoites if ingested would not survive exposure to the gastric environment.

Mneomonic: EntAmoeba HistoLytica  

Ent: enterocytes (a cell of the intestinal lining);

Amoeba: protozoa;

Histo: tissue;

Lytica: lysis.

As this protozoan parasite lyse the cells of the intestinal tract; there will be bleeding; so the stool contains blood and mucus (amoebic dysentry). 

Infective form: Mature quadrinucleate cyst; it is spherical in shape with a refractile wall

Note: Giardia lamblia cyst also has four nuclei, but the cyst is oval in shape.

Geographical distribution: Worldwide, more common in the tropics and subtropics,  especially in areas with poor sanitation (developing and under-developed countries).

Habitat: Trophozoites of E. histolytica live in the mucosal and submucosal layers of the large intestine of man. Life cycle of Entamoeba histolytica has two-stage: motile trophozoite and non-motile cyst. Trophozoites are found in intestinal lesions, extra-intestinal lesions, and diarrheal stools whereas cyst predominates in non-diarrheal stools.

Life cycle of Entamoeba histolytica

Infection by Entamoeba histolytica occurs by the ingestion of mature quadrinucleate cysts in fecally contaminated food, water, or hands. The quadrinucleate cyst is resistant to the gastric environment and passes unaltered through the stomach

• When the cyst of E.histolytica reaches caecum or lower part of ileum excystation occurs and an amoeba with four nuclei emerges and that divides by binary fission to form eight trophozoites.
• Trophozoites migrate to the large intestine and lodge into the submucosal tissue.
• Trophozoites grow and multiply by binary fission in the large intestine (Trophozoite phase of the life cycle is responsible for producing characteristics lesion of amoebiasis). 
• Certain numbers of trophozoites are discharged into the lumen of the bowel and are transformed into cystic forms.
• The cysts thus formed are unable to develop in the same host and therefore necessitate a transference to another susceptible host. The cysts are passed in the feces.

Note: Because of the protection conferred by their walls, the cysts can survive days to weeks in the external environment. Cysts are not highly resistant and are readily killed by boiling. But they are resistant to chlorination or can be removed by filtration. Trophozoites can also be passed in diarrheal stools, but are rapidly destroyed once outside the body.

Trophozoites are responsible for disease conditions;

• The trophozoites invade the colonic epithelium and secrete enzymes that cause localized necrosis. Little inflammation occurs at the site.
• As the lesion reaches the muscularis layer, a typical “flask-shaped” ulcer forms, which can undermine and destroy large areas of the intestinal epithelium.
• Progression into submucosa leads to invasion of the portal circulation by the trophozoites.

Diseases

1. Non-invasive infection: In many cases, the trophozoites remain confined to the intestinal lumen of individuals who are thus asymptomatic carriers and cysts passers.
2. Intestinal disease: In some patients, the trophozoites invade the intestinal mucosa,
3. Extra-intestinal disease: through the bloodstream, trophozoites invade extraintestinal sites such as the liver, brain, and lungs, with resultant pathologic manifestations.

Amoebic liver abscess

• About 2-10% of individuals infected with E. histolytica suffer from hepatic complications.
• In 50% of cases, history of amoebic dysentery may not be seen.
• The trophozoites of E.histolytica are carried as emboli by the radicles of the portal vein from the base of amoebic ulcer in the large intestine.
• Capillary system of the liver acts as an efficient filter and holds the trophozoites that multiply inside liver cells and carries on cytolytic actions.
• This leads to obstruction to the circulation and produces thrombosis of the portal venules (sinusoids) resulting in anemic necrosis of the liver cells
• Progressive destruction of concentric layers of liver cells occurs. A large-sized abscess is formed by the coalescence of miliary abscesses.
• Amebic abscess of the liver is characterized by right upper quadrant pain, weight loss, fever, and a tender enlarged liver.
• Right-lobe abscesses can penetrate the diaphragm and cause lung disease (pulmonary amoebiasis)
• Other metastatic lesions:
  • Cerebral amoebiasis
  • Amoebic pericarditis
  • Cutaneous amoebiasis
  • Splenic abscess etc.
• Most cases of amebic liver abscess occur in patients who have not had overt intestinal amebiasis.
• Aspiration of the liver abscess yields brownish-yellow pus with the consistency of anchovy-paste.

Clinical Findings

• Acute intestinal amebiasis
  • dysentery (i.e. bloody, mucus containing diarrhea)
  • lower abdominal discomfort,
  • flatulence.
• Chronic amebiasis: low-grade symptoms such as occasional diarrhea, weight loss, and fatigue also occurs.
• Roughly 90% of infected individuals have an asymptomatic infection but they may be carriers.
• Ameboma, a granulomatous lesion may form in the cecal or rectosigmoid areas of the colon in some patients. These lesions resemble an adenocarcinoma of the colon and must be distinguished from them.

Laboratory diagnosis

Diagnosis of intestinal amebiasis rests on finding either trophozoites in diarrheal stools or cysts in formed stools. Diarrheal stools should be examined within one hour of collection to see the ameboid motility of the trophozoite. The trophozoite characteristically contains ingested red blood cells. 

Characteristics of Stool

• Macroscopic appearance of stool: Offensive dark brown semisolid stool, acid in reaction, admixed with blood, mucus, and much fecal matter.
• General microscopic examination:
  • Presence of Charcot-Leyden crystals. Scanty cellular exudates, and consists of only the nuclear masses (pyknotic bodies).
  • E. histolytica infection is distinguished from bacillary dysentery by the lack of high fever and absence PMN leukocytosis.

You may like to check: Difference between Amoebic dysentery and Bacillary dysentery

A. Microscopy: 

E. histolytica can be distinguished from other amoebas by two major criteria

1. Nature of the nucleus of the trophozoite.
   The E. histolytica nucleus has a small central nucleolus and fine chromatin granules along the border of the nuclear membrane. The nuclei of other amebas are quite different.  

   Note: The trophozoites of Entamobea dispar, a nonpathogenic species of Entamoeba, are morphologically  indistinguishable from those of E. histolytica 
2. Cyst size and the number of its nuclei.
   Mature cysts of E. histolytica are smaller than those of Entamoeba coli and contain four nuclei, whereas E. coli cysts have eight nuclei.

B. Antigen detection: detection of E.histolytica antigen in the stool

C. Serologic testing is useful for the diagnosis of invasive amebiasis.

C. Detection of the nucleic acid of this protozoan parasite by PCR-based assay.

References and further readings

• Sastry A.S. & Bhat S. (2014) Essentials of Medical Parasitology. Jaypee Brothers Medical Publishers (P) Ltd
• Gracia, L.S. (2016). Diagnostic Medical Parasitology. ASM Press.