Entamoeba histolytica Sharmin Begum,1 Hayley Gorman,1 Attinder Chadha,1 and Kris Chadee1, * 1 Departments of Microbiology, Immunology, and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada TrendsTrendsininParasitologyParasitology Mature cyst (ii) (iii) (iv) (ii) (iv) (iii) (i) (i) Ingestion through contaminated food or water(ii) Mature cysts excyst in the small intestine (iii) Trophozoites migrate to the large intestine Trophozoites colonize the colon (asymptomatic infection) or can invade the mucosa and disseminate to extraintestinal sites (liver, lung, brain) (iv) Newly generated cysts are excreted in stool Entamoeba histolytica Life Cycle Entamoeba histolytica is a human enteric protozoan parasite responsible for the disease amebiasis. Infection starts through the ingestion of E. histolytica cysts contaminating food or water. The vast majority (90%) of infected individuals are asymptomatic carriers in which the parasite resides firmly within the lumen of the colon and excrete cysts in stool to complete the direct life cycle. In 10% of infected cases (symptomatic), E. histolytica breaches the intestinal mucosa and invades the underlying lamina propria where it interacts with host immune cells, triggering a raging proinflammatory cytokine response resulting in tissue damage and the hallmark amebic 'flask-shaped ulcer' formation. It is not known why a large proportion of E. histolytica-colonized individuals do not progress to invasive disease. Several parasite virulence factors along with host genetics, microbiota, and immune responses, are likely to drive the complex pathogenesis. KEY FACTS: Friedrick Lösch discovered E. histolytica in 1873 and was the first to describe the relationship between the parasite and disease, although reports of bloody diarrhea, consistent with amebiasis, date back to 1000 BC. E. histolytica is morphologically identical to the noninfectious Entamoeba dispar which lacks key cysteine proteinases that are important for pathogenesis. E. histolytica exists as an infectious cyst with four nuclei. Upon ingestion, it excysts in the terminal ileum to give rise to disease-causing motile trophozoites through its pseudopodium. Virulence factors allow the parasite to colonize colonic mucus and to overcome innate epithelial barrier function. DISEASE FACTS: E. histolytica is prevalent in developing countries due to poor sanitation and hygiene but it has also emerged globally from returning travelers and is spread by sexual transmission through oral–anal contact. ~100 million cases occur annually. In 2013, 11 300 deaths from amebiasis ranked it the fourth leading cause of parasitic death. Infection can lead to mild to bloody diarrhea, cramping and fever, abdominal pain, and weight loss. If left untreated, it may contribute to extraintestinal amebiasis, mostly liver abscess. Stool sample analysis for cysts or trophozoites, PCR, ELISA, and serological evaluation for diagnosis. Nitroimidazoles: metronidazole, are the mainstay drug therapy for invasive amebiasis. TAXONOMY AND CLASSIFICATION: PHYLUM: Amoebozoa CLASS: Lobosea ORDER: Amoebida FAMILY: Entamoebidae GENUS: Entamoeba SPECIES: E. histolytica TrendsTrendsininParasitologyParasitology Inner mucus layer NF-κB IL-1β NO Tumor necrosis factor (TNF)-α IL-1β TNF-α NO NO IL-8 IL-8 Interleukin (IL)-8 Intestinal epithelial cell (IEC) Lamina propria Macrophage Dendritic cell Cell death Goblet cell Outer mucus layer E. histolytica and microbiota in contact with host cell (iii) Invasion Neutrophil recruitment Inflammatory responses Amebicidal macrophage (iv) In contact with macrophage (ii) Binding to epithelial cells (i) Dissolution of the mucus layer Am ebic *Correspondence: kchadee@ucalgary.ca (K. Chadee). 676 Trends in Parasitology, July 2021, Vol. 37, No. 7 © 2021 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.pt.2021.01.001 Trends in Parasitology | Parasite of the Month Acknowledgments K.C. is grateful for funding from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-04136) and the Canadian Institutes of Health Research (PJT-407276) for original research summarized here. Declaration of Interests The authors declare no competing interests. Resources https://amoebadb.org/ www.who.int/ith/diseases/amoebiasis/en/ www.cdc.gov/parasites/amebiasis/index.html Literature 1. Abubakar, I. et al. (2015) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385, 117–171 2. Mortimer, L. and Chadee, K. (2010) The immunopathogenesis of Entamoeba histolytica. Exp. Parasitol. 126, 366–380 3. Ralston, K.S. and Petri, W.A. (2011) Tissue destruction and invasion by Entamoeba histolytica. Trends Parasitol. 27, 254–263 4. Cornick, S. and Chadee, K. (2017) Entamoeba histolytica: Host parasite interactions at the colonic epithelium. Tissue Barriers 5, e1283386 5. Begum, S. et al. (2020) Role of inflammasomes in innate host defense against Entamoeba histolytica. J. Leukoc. Biol. 108, 801–812 6. Gorman, H. and Chadee, K. (2019) Entamoeba histolytica: Biology and host immunity. In Encyclopedia of Microbiology (4th edn) (Schmidt, T.M., ed.), pp. 147–155, Elsevier 7. Stanley, S.L., Jr (2003) Amoebiasis. Lancet 361, 1025–1034 8. Riddle, M.S. et al. (2017) Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. J. Travel. Med. 24, S63–S80 9. Haque, R. et al. (2003) Amebiasis. NEJM 348, 1565–1573 10. Shirley, D.A.T. et al. (2018) A review of the global burden, new diagnostics, and current therapeutics for amebiasis. Open Forum Infect. Dis. 5, ofy161 Trends in Parasitology | Parasite of the Month Trends in Parasitology, July 2021, Vol. 37, No. 7 © 2021 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.pt.2021.01.001 677