A rare case of an intestinal ulcer: AIDS and amebic colitis in a homosexual man with ulcerative colitis.

A 56-year-old man with half of year history of UC was admitted to our hospital due to abdominal pain, diarrhea, and hematochezia (more than ten times per day) for two weeks. He had had homosexual intercourse with many men. Subsequent laboratory findings revealed that there was a significant increase in elevated white blood cells (WBC, 11.77x109/L), C-Reactive Protein (CRP, 83.7 mg/L), tumor necrosis factor-alpha (TNF-ɑ, 6.83 pg/ml), interleukin-2 (IL-2, 75.78 pg/ml), IL-6 (124.68 pg/ml), IL-10 (58.24 pg/ml) and IL-17 (128.76 pg/ml), and fecal calprotectin (FC >1800 µg/g). Albumin (ALB, 22.5 g/L) and Hemoglobin (Hb, 98 g/L) were significantly decreased. Amoeba was identified in the stool. The abdominal contrast-enhanced Computed Tomography (CT) showed that there was thickened intestinal wall in the sigmoid colon and rectum. Colonoscopy and intestinal histopathology suggested active severe UC (E2) and Entamoeba Histolytica (trophozoites) in the necrotic tissue (Figure 1). The result of enzyme immunoassay (EIA) screening for HIV was positive. The HIV viral load was 7.85x109 copies/mL, and the CD4+ cell count was 43/µL.

A case of amoebic colitis with Crohn-like endoscopic and histopathological features.

Amoebic colitis represents a common parasitic infection in developing countries. In western world, it is encountered only sporadically. The clinical presentation is usually non-specific, non-invasive laboratory tests are often false negative and endoscopic and histopathological appearance may mimic other illnesses, especially Crohns disease. The disease therefore harbours a huge risk of misdiagnosing and a proper diagnosis is usually challenging. We present a case of an amoebic colitis with Crohn-like features and negative parasitological testing in a 53-years-old woman, in which the final diagnosis was established on the basis of its histopathological examination.

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis.

The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with the intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity. Introduction of C. scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte progenitors (GMPs) and resulted in increased intestinal neutrophils with subsequent challenge with E. histolytica. Introduction of C. scindens alone was sufficient to expand GMPs in gnotobiotic mice. Adoptive transfer of bone marrow from C. scindens-colonized mice into naive mice protected against amebic colitis and increased intestinal neutrophils. Children without E. histolytica diarrhea also had a higher abundance of Lachnoclostridia. Lachnoclostridia C. scindens can metabolize the bile salt cholate, so we measured deoxycholate and discovered that it was increased in the sera of C. scindens-colonized specific pathogen-free and gnotobiotic mice, as well as in children protected from amebiasis. Administration of deoxycholate alone increased GMPs and provided protection from amebiasis. We elucidated a mechanism by which C. scindens and the microbially metabolized bile salt deoxycholic acid alter hematopoietic precursors and provide innate protection from later infection with E. histolytica.

Weissella paramesenteroides WpK4 ameliorate the experimental amoebic colitis by increasing the expression of MUC-2 and the intestinal epithelial regeneration.

AIMS: This study evaluates the action of Weissella paramesenteroides WpK4 on amoebic colitis. METHODS AND RESULTS: Weissella paramesenteroides WpK4 was administered in Entamoeba dispar infected and noninfected mice and clinical parameters were evaluated. Following 7 days, the caeca were collected for histopathology, morphometry and immunohistochemical staining of MUC-2, CDC-47 and IgA. The treatment reduced diarrhoea and the presence of blood in the faeces and diminished the area of necrosis, also causing weight gain. Also, the addition of this bacterium enhanced the expression of the mucin (MUC-2). The reduction in necrosis and increased CDC-47 expression indicates significant epithelial regeneration. The negative correlation between CDC-47 and the necrosis area reveals that the bacterium favoured the recovery of the necrotic regions and the positive correlation found between the expression of MUC-2 and CDC-47 indicates that the epithelial regeneration also supports the synthesis of MUC-2. CONCLUSIONS: Weissella paramesenteroides WpK4 was able to increase the protection of the intestinal mucosa against experimental amoebic colitis through the increase of MUC-2 and epithelial regeneration. SIGNIFICANCE AND IMPACT OF THE STUDY: Weissella paramesenteroides WpK4 presents the potential to become a complementary tool in the treatment of amoebic colitis.

Insights into amebiasis using a human 3D-intestinal model.

Entamoeba histolytica is the causative agent of amebiasis, an infectious disease targeting the intestine and the liver in humans. Two types of intestinal infection are caused by this parasite: silent infection, which occurs in the majority of cases, and invasive disease, which affects 10% of infected persons. To understand the intestinal pathogenic process, several in vitro models, such as cell cultures, human tissue explants or human intestine xenografts in mice, have been employed. Nevertheless, our knowledge on the early steps of amebic intestinal infection and the molecules involved during human-parasite interaction is scarce, in part due to limitations in the experimental settings. In the present work, we took advantage of tissue engineering approaches to build a three-dimensional (3D)-intestinal model that is able to replicate the general characteristics of the human colon. This system consists of an epithelial layer that develops tight and adherens junctions, a mucus layer and a lamina propria-like compartment made up of collagen containing macrophages and fibroblast. By means of microscopy imaging, omics assays and the evaluation of immune responses, we show a very dynamic interaction between E. histolytica and the 3D-intestinal model. Our data highlight the importance of several virulence markers occurring in patients or in experimental models, but they also demonstrate the involvement of under described molecules and regulatory factors in the amoebic invasive process.

The delicate balance between Entamoeba histolytica, mucus and microbiota.

Entamoeba histolytica (Eh) is a protozoan parasite of humans that colonizes the outer colonic mucus layer. Under conditions not fully understood, Eh breaches innate host defenses and invades the intestinal mucosa-causing amebic colitis and liver abscess. In asymptomatic infection, Eh interacts with and feeds on resident microbiota that forms biofilms on the outer colonic mucus layer. Despite the close association between Eh and commensal microbiota, we still lack basic knowledge on whether microbiota and/or their metabolites influence Eh virulence traits critical in disease pathogenesis. In the pathogenesis of intestinal amebiasis, Eh overcomes the protective mucus layer using a combination of mucinase/glycosidase and potent mucus secretagogue activity. In this addendum, we discuss the interconnected role of a healthy mucus barrier and the role commensal microbiota play in shaping innate host defense against Eh-induced pro-inflammatory and secretory responses critical in disease pathogenesis.

Amoebic colitis presenting with hypo-albuminaemia in an eight-month-old breastfed girl.

Entamoeba histolytica is a protozoan parasite that affects a large proportion of the world's population and causes amoebic dysentery and extra-intestinal disease. Many individuals remain asymptomatic during colonisation; in 10% of individuals, the parasite breaks through the mucosal barrier and leads to invasive disease. An eight-month-old girl who was evaluated for hypo-albuminaemia and was diagnosed with amoebic colitis is reported. To the best of our knowledge, this is the first report of hypo-albuminaemia owing to amoebic colitis in any age group.

Learning points from a case of severe amoebic colitis.

A case of amoebic colitis and liver abscess is described in a previously fit 59-year old man who had been given the incorrect diagnosis of ulcerative colitis. His symptoms were so severe that a colectomy was being considered. The patient had a significant travel history including trips to Morocco, the Gambia and Cape Verde, putting him at risk of acquiring amoebic disease. However, this history was not ascertained until much later on in the disease process. The case highlighted crucial learning points including the importance of taking a lifelong travel history, the difficulties in telling ulcerative colitis and amoebic colitis apart both clinically and histopathologically, and the importance of sending multiple stool samples for parasitological microscopy analysis in patients being investigated for inflammatory bowel disease.

Entamoeba histolytica-Encoded Homolog of Macrophage Migration Inhibitory Factor Contributes to Mucosal Inflammation during Amebic Colitis.

Understanding the mechanisms by which Entamoeba histolytica drives gut inflammation is critical for the development of improved preventive and therapeutic strategies. E. histolytica encodes a homolog of the human cytokine macrophage migration inhibitory factor (MIF). Here, we investigated the role of E. histolytica MIF (EhMIF) during infection. We found that the concentration of fecal EhMIF correlated with the level of intestinal inflammation in persons with intestinal amebiasis. Mice treated with antibodies that specifically block EhMIF had reduced chemokine expression and neutrophil infiltration in the mucosa. In addition to antibody-mediated neutralization, we used a genetic approach to test the effect of EhMIF on mucosal inflammation. Mice infected with parasites overexpressing EhMIF had increased chemokine expression, neutrophil influx, and mucosal damage. Together, these results uncover a specific parasite protein that increases mucosal inflammation, expands our knowledge of host-parasite interaction during amebic colitis, and highlights a potential immunomodulatory target.

Diagnosis of colonic amebiasis and coexisting signet-ring cell carcinoma in intestinal biopsy.

Amebiasis is uncommon in developed countries. Several case reports in the literature emphasize that both the presenting symptoms and the radiological findings of colonic amebiasis closely resemble more common conditions, such as idiopathic inflammatory bowel disease and gastro-intestinal malignancy. We describe a unique case of colonic amebiasis (amebomas) coexisting with signet-ring cell carcinoma of the ileocecal valve, the cecum and the appendix. Endoscopically, the ulcerated tumor was indistinguishable from the ulcerations and pseudotumors (amebomas) detected in the ascending colon. Histological examination of biopsy specimens revealed the pathognomonic features of protozoa with ingested erythrocytes in combination with signet-ring cell infiltration. The author concludes that amebiasis may not only mimic carcinoma but, rarely, may coexist with carcinoma in the same patient. Clinicians and pathologists should be aware of this possibility in order not to delay diagnosis and treatment of malignant disease.

Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic 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.

Entamoeba histolytica Cysteine Proteinase 5 Evokes Mucin Exocytosis from Colonic Goblet Cells via αvß3 Integrin.

Critical to the pathogenesis of intestinal amebiasis, Entamoeba histolytica (Eh) induces mucus hypersecretion and degrades the colonic mucus layer at the site of invasion. The parasite component(s) responsible for hypersecretion are poorly defined, as are regulators of mucin secretion within the host. In this study, we have identified the key virulence factor in live Eh that elicits the fast release of mucin by goblets cells as cysteine protease 5 (EhCP5) whereas, modest mucus secretion occurred with secreted soluble EhCP5 and recombinant CP5. Coupling of EhCP5-αvß3 integrin on goblet cells facilitated outside-in signaling by activating SRC family kinases (SFK) and focal adhesion kinase that resulted in the activation/phosphorlyation of PI3K at the site of Eh contact and production of PIP3. PKCδ was activated at the EhCP5-αvß3 integrin contact site that specifically regulated mucin secretion though the trafficking vesicle marker myristoylated alanine-rich C-kinase substrate (MARCKS). This study has identified that EhCP5 coupling with goblet cell αvß3 receptors can initiate a signal cascade involving PI3K, PKCδ and MARCKS to drive mucin secretion from goblet cells critical in disease pathogenesis.

The differentiation of amebic colitis from inflammatory bowel disease on endoscopic mucosal biopsies.

BACKGROUND: Intestinal amebiasis is one of the important differential diagnoses of Inflammatory Bowel Disorders in areas where it is highly prevalent. AIM: Studies comparing the clinical, endoscopic and histological features of these disorders have never been done, so we undertook this study. MATERIALS AND METHODS: A retrospective study comparing mucosal biopsies of 14 consecutive cases of intestinal amebiasis with 14 cases of Ulcerative colitis and 12 cases of Crohn's disease. A total of 65 biopsies from patients with amebiasis, 56 biopsies from patients with Crohn's disease and 65 biopsies of patients with Ulcerative colitis were reviewed. RESULTS AND CONCLUSIONS: Discrete small ulcers less than 2 cm in diameter in the cecum or rectosigmoid, with intervening normal mucosa, were the most common finding on endoscopy in patients with amebiasis. On histology, necrotic material admixed with mucin, proteinaceous exudate and blood clot lining ulcers, significant surface epithelial changes such as shortening and tufting adjacent to sites of ulceration, mild chronic inflammation extending into the deep mucosa and mild architectural alteration were features of amebiasis. Trophozoite forms of ameba were seen in the necrotic material lining sites of ulceration or lying separately, as well as over intact mucosa. Necrotic material lining ulcers was less common in IBD, but chronic inflammation, crypt abscess formation and architectural alteration were more severe.

Fulminant amoebic enteritis that developed in the perinatal period.

We present a case of a 30-year-old postpartum woman who delivered by caesarean section at 34 weeks. On postoperative day 9, she was admitted to our hospital in shock. Emergency abdominal surgery was performed. Massive purulent ascites collected in the abdominal cavity and was associated with intestinal necrosis, which extended from the ascending colon to one-third of the descending colon. The necrotic lesion was excised, and an artificial anus was constructed at the ileum end. A histological finding on the 15th day indicated the possibility of amoebic enteritis, and the patient was started on metronidazole therapy. The diarrhoea improved dramatically after metronidazole treatment was started. The patient was able to walk unassisted on the 45th day and was subsequently discharged. Amoebic enteritis has been thought to be epidemic in developing countries, but today, the incidence of amoebic enteritis as a sexually transmitted disease is increasing in developed countries.

[A clinical study of fulminant amebic colitis].

The administration of metronidazole is generally effective to treat amebic colitis. Fulminant amebic colitis is relatively rare, and it is associated with a high mortality rate. Three cases of fulminant amebic colitis were diagnosed in our hospital between 1993 and 2014. One of these patients died despite our efforts. Amebic colitis often presents with no obvious risk factors and with atypical clinical symptoms. Therefore, the diagnosis of amebic colitis can be difficult. Early diagnosis is the most important factor in successful treatment of fulminant amebic colitis. The present cases demonstrate that it is important to consider the possibility of amebic colitis during evaluation of the acute abdomen.