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PLoS Neglected Tropical Diseases Jul 2016Amebic colitis, caused by intestinal infection with the parasite, Entamoeba histolytica, is a common cause of diarrhea worldwide. Fulminant amebic colitis is the most... (Review)
Review
BACKGROUND
Amebic colitis, caused by intestinal infection with the parasite, Entamoeba histolytica, is a common cause of diarrhea worldwide. Fulminant amebic colitis is the most devastating complication of this infection, associated with both high mortality and morbidity. We conducted a review of the English literature to describe cases of fulminant amebic colitis associated with exposure to corticosteroid medications in order to identify the risk factors for poor outcome and determine difficulties in diagnosis and treatment.
METHODOLOGY AND PRINCIPAL FINDINGS
Articles reporting severe and fulminant forms of amebic colitis between 1991 and 2016 were collected. 525 records were screened to identify 24 cases for qualitative analysis associated with corticosteroid use. Cases arose from areas of high endemicity or travel to such areas. Most cases (14 of 24, 58%) were given corticosteroids for initially misdiagnosed colitis, mainly inflammatory bowel, resulting in rapid progression of disease. Nearly half of all cases underwent surgical intervention, and 25% of cases died, despite all patients eventually receiving treatment with metronidazole. The odds of death did not differ significantly by prior misdiagnosis, co-morbidities, bowel perforation or need for surgery.
CONCLUSIONS AND SIGNIFICANCE
Infection with E. histolytica should be considered prior to the administration of corticosteroids, in particular for patients residing in endemic areas or those with appropriate travel history, especially prior to the diagnosis of inflammatory bowel disease. The development of preventative and treatment interventions are needed to improve outcomes of fulminant disease.
Topics: Adrenal Cortex Hormones; Dysentery, Amebic; Humans; Immunosuppression Therapy
PubMed: 27467600
DOI: 10.1371/journal.pntd.0004879 -
Human Vaccines & Immunotherapeutics 2014Entamoeba histolytica is the causative agent of amebiasis, one of the top three parasitic causes of mortality worldwide. In the majority of infected individuals, E.... (Review)
Review
Entamoeba histolytica is the causative agent of amebiasis, one of the top three parasitic causes of mortality worldwide. In the majority of infected individuals, E. histolytica asymptomatically colonizes the large intestine, while in others, the parasite breaches the mucosal epithelial barrier to cause amebic colitis and can disseminate to soft organs to cause abscesses. Vaccinations using native and recombinant forms of the parasite Gal-lectin have been successful in protecting animals against intestinal amebiasis and amebic liver abscess. Protection against amebic liver abscesses has also been reported by targeting other E. histolytica components including the serine-rich protein and the 29-kDa-reductase antigen. To date, vaccines against the Gal-lectin hold the most promise but clinical trials will be required to validate its efficacy in humans. Here, we review the current strategies and future perspectives involved in the development of a vaccine against E. histolytica.
Topics: Animals; Disease Models, Animal; Drug Discovery; Entamoeba histolytica; Entamoebiasis; Humans; Protozoan Vaccines
PubMed: 24504133
DOI: 10.4161/hv.27796 -
Frontiers in Cellular and Infection... 2019
Topics: Amebicides; Anisomycin; Asymptomatic Diseases; Drug Discovery; Dysentery, Amebic; Entamoeba histolytica; Flavonoids; Gene Expression Regulation; Humans; Life Cycle Stages; Metabolic Networks and Pathways; Metronidazole; Piperidines; Prodigiosin; Protozoan Proteins; Pyridines; Severity of Illness Index
PubMed: 31338336
DOI: 10.3389/fcimb.2019.00247 -
BMJ Clinical Evidence Jan 2007Amoebic dysentery is caused by the protozoan parasite Entamoeba histolytica. It is transmitted in areas where poor sanitation allows contamination of drinking water and... (Review)
Review
INTRODUCTION
Amoebic dysentery is caused by the protozoan parasite Entamoeba histolytica. It is transmitted in areas where poor sanitation allows contamination of drinking water and food with faeces. In these areas, up to 40% of people with diarrhoea may have amoebic dysentery.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of drug treatments for amoebic dysentery in endemic areas? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 11 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: emetine, metronidazole, ornidazole, paromomycin, secnidazole, and tinidazole.
Topics: Administration, Oral; Antibodies, Protozoan; Diarrhea; Dysentery, Amebic; Entamoeba histolytica; Feces; Gene Library; Humans; Metronidazole; Tinidazole
PubMed: 19454043
DOI: No ID Found -
Gastrointestinal Endoscopy Oct 1998
Topics: Adult; Carrier State; Colitis, Ulcerative; Colonoscopy; Diagnosis, Differential; Dysentery, Amebic; Female; Humans
PubMed: 9786131
DOI: 10.1016/s0016-5107(98)70028-8 -
Mucosal Immunology Jan 2022Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we...
Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage. Treatment with recombinant IL-33 protected mice from amebic infection and intestinal tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to amebiasis. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the cecum. Type 2 immune responses were upregulated by IL-33 treatment during amebic infection. Interestingly, administration of IL-33 protected RAG2 mice but not RAG2γc mice, demonstrating that IL-33-mediated protection required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2 mice. At baseline and after amebic infection, there was a significantly higher IL13+ILC2s in C57BL/J mice, which are naturally resistant to amebiasis, than CBA/J mice. Adoptive transfer of ILC2s to RAG2γc mice restored IL-33-mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.
Topics: Animals; Cell Movement; Colon; DNA-Binding Proteins; Disease Resistance; Dysentery, Amebic; Entamoeba histolytica; Entamoebiasis; Gene Expression Profiling; Genetic Background; Humans; Immunity, Innate; Interleukin-33; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; RNA, Messenger; Signal Transduction; Th1 Cells; Th2 Cells
PubMed: 34400793
DOI: 10.1038/s41385-021-00442-2 -
Microorganisms May 2023The innate immune response is highly dependent on the action of macrophages. They are abundant in the intestine subepithelial lamina propria of the mucosa, where they...
The innate immune response is highly dependent on the action of macrophages. They are abundant in the intestine subepithelial lamina propria of the mucosa, where they deploy multiple tasks and play a critical role. The balance between the gut microbiota and M2 macrophages is critical for gut health and homeostasis. Gut microbiota has the power to change macrophage phenotype and replenish the resident macrophage niche during and post infection. As far as the extracellular enteric parasitic infections invasive amebic colitis and giardiasis are concerned, a change of macrophages phenotype to a pro-inflammatory state is dependent on direct contact of the protozoan parasites with host cells. Macrophages induce strong pro-inflammatory response by inflammasome activation and secretion of interleukin IL-1β. Inflammasomes play a key role in the response to cellular stress and microbe attacks. The balance between gut mucosal homeostasis and infection is dependent on the crosstalk between microbiota and resident macrophages. Parasitic infections involve NLRP1 and NLRP3 inflammasome activation. For and infections, inflammasome NLRP3 activation is crucial to promote the host defenses. More studies are needed to further elucidate possible therapeutic and protective strategies against these protozoan enteric parasites' invasive infections in humans.
PubMed: 37317178
DOI: 10.3390/microorganisms11051203 -
PLoS Pathogens Aug 2017The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a...
The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a modifier of E. histolytica virulence. Here we have explored the association of the microbiome with susceptibility to amebiasis in infants and in the mouse model of amebic colitis. Dysbiosis occurred symptomatic E. histolytica infection in children, as evidenced by a lower Shannon diversity index of the gut microbiota. To test if dysbiosis was a cause of susceptibility, wild type C57BL/6 mice (which are innately resistant to E. histiolytica infection) were treated with antibiotics prior to cecal challenge with E. histolytica. Compared with untreated mice, antibiotic pre-treated mice had more severe colitis and delayed clearance of E. histolytica. Gut IL-25 and mucus protein Muc2, both shown to provide innate immunity in the mouse model of amebic colitis, were lower in antibiotic pre-treated mice. Moreover, dysbiotic mice had fewer cecal neutrophils and myeloperoxidase activity. Paradoxically, the neutrophil chemoattractant chemokines CXCL1 and CXCL2, as well as IL-1β, were higher in the colon of mice with antibiotic-induced dysbiosis. Neutrophils from antibiotic pre-treated mice had diminished surface expression of the chemokine receptor CXCR2, potentially explaining their inability to migrate to the site of infection. Blockade of CXCR2 increased susceptibility of control non-antibiotic treated mice to amebiasis. In conclusion, dysbiosis increased the severity of amebic colitis due to decreased neutrophil recruitment to the gut, which was due in part to decreased surface expression on neutrophils of CXCR2.
Topics: Animals; Child, Preschool; Disease Models, Animal; Dysentery, Amebic; Entamoeba histolytica; Feces; Flow Cytometry; Humans; Infant; Mice; Mice, Inbred C57BL; Microbiota; Neutrophil Infiltration; Real-Time Polymerase Chain Reaction; Receptors, Interleukin-8B
PubMed: 28817707
DOI: 10.1371/journal.ppat.1006513 -
Experimental & Molecular Medicine Mar 2013The parasite Entamoeba histolytica causes amebic colitis and systemic amebiasis. Among the known amebic factors contributing to pathogenesis are signaling pathways... (Review)
Review
The parasite Entamoeba histolytica causes amebic colitis and systemic amebiasis. Among the known amebic factors contributing to pathogenesis are signaling pathways involving heterotrimeric and Ras superfamily G proteins. Here, we review the current knowledge of the roles of heterotrimeric G protein subunits, Ras, Rho and Rab GTPase families in E. histolytica pathogenesis, as well as of their downstream signaling effectors and nucleotide cycle regulators. Heterotrimeric G protein signaling likely modulates amebic motility and attachment to and killing of host cells, in part through activation of an RGS-RhoGEF (regulator of G protein signaling-Rho guanine nucleotide exchange factor) effector. Rho family GTPases, as well as RhoGEFs and Rho effectors (formins and p21-activated kinases) regulate the dynamic actin cytoskeleton of E. histolytica and associated pathogenesis-related cellular processes, such as migration, invasion, phagocytosis and evasion of the host immune response by surface receptor capping. A remarkably large family of 91 Rab GTPases has multiple roles in a complex amebic vesicular trafficking system required for phagocytosis and pinocytosis and secretion of known virulence factors, such as amebapores and cysteine proteases. Although much remains to be discovered, recent studies of G protein signaling in E. histolytica have enhanced our understanding of parasitic pathogenesis and have also highlighted possible targets for pharmacological manipulation.
Topics: Animals; Entamoeba histolytica; Entamoebiasis; GTP-Binding Proteins; Heterotrimeric GTP-Binding Proteins; Humans; Signal Transduction; ras Proteins
PubMed: 23519208
DOI: 10.1038/emm.2013.30 -
MBio Aug 2017ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue...
ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue invasion, which is a hallmark of invasive amebic colitis. Work done prior to the discovery of amebic trogocytosis showed that acid vesicles are required for amebic cytotoxicity. In the present study, we show that acidified lysosomes are required for amebic trogocytosis and cell killing. Interference with lysosome acidification using ammonium chloride, a weak base, or concanamycin A, a vacuolar H ATPase inhibitor, decreased amebic trogocytosis and amebic cytotoxicity. Our data suggest that the inhibitors do not impair the ingestion of an initial fragment but rather block continued trogocytosis and the ingestion of multiple fragments. The acidification inhibitors also decreased phagocytosis, but not fluid-phase endocytosis. These data suggest that amebic lysosomes play a crucial role in amebic trogocytosis, phagocytosis, and cell killing. is a protozoan parasite that is prevalent in low-income countries, where it causes potentially fatal diarrhea, dysentery, and liver abscesses. Tissue destruction is a hallmark of invasive infection. The parasite is highly cytotoxic to a wide range of human cells, and parasite cytotoxic activity is likely to drive tissue destruction. is able to kill human cells through amebic trogocytosis. This process also contributes to tissue invasion. Trogocytosis has been observed in other organisms; however, little is known about the mechanism in any system. We show that interference with lysosomal acidification impairs amebic trogocytosis, phagocytosis, and cell killing, indicating that amebic lysosomes are critically important for these processes.
Topics: Ammonium Chloride; Cell Survival; Endocytosis; Entamoeba histolytica; Host-Pathogen Interactions; Humans; Hydrogen-Ion Concentration; Jurkat Cells; Lysosomes; Macrolides; Phagocytosis; Pinocytosis
PubMed: 28851845
DOI: 10.1128/mBio.01187-17