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.

Intestinal amoebiasis in a patient with acute graft-versus-host disease after allogeneic bone marrow transplantation successfully treated by metronidazole.

Amoebiasis has rarely been reported in patients undergoing hematopoietic stem cell transplantation, although it is a world-wide infection and extremely common. We present a case of intestinal amoebiasis unexpectedly revealed by colonoscopy after allogeneic bone marrow transplantation from a human leukocyte antigen-mismatched unrelated donor for acute myeloid leukemia arising from chronic myelomonocytic leukemia and successfully treated by metronidazole.

The antiretroviral lectin cyanovirin-N targets well-known and novel targets on the surface of Entamoeba histolytica trophozoites.

Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, has a truncated Asn-linked glycan (N-glycan) precursor composed of seven sugars (Man(5)GlcNAc(2)). Here, we show that glycoproteins with unmodified N-glycans are aggregated and capped on the surface of E. histolytica trophozoites by the antiretroviral lectin cyanovirin-N and then replenished from large intracellular pools. Cyanovirin-N cocaps the Gal/GalNAc adherence lectin, as well as glycoproteins containing O-phosphodiester-linked glycans recognized by an anti-proteophosphoglycan monoclonal antibody. Cyanovirin-N inhibits phagocytosis by E. histolytica trophozoites of mucin-coated beads, a surrogate assay for amebic virulence. For technical reasons, we used the plant lectin concanavalin A rather than cyanovirin-N to enrich secreted and membrane proteins for mass spectrometric identification. E. histolytica glycoproteins with occupied N-glycan sites include Gal/GalNAc lectins, proteases, and 17 previously hypothetical proteins. The latter glycoproteins, as well as 50 previously hypothetical proteins enriched by concanavalin A, may be vaccine targets as they are abundant and unique. In summary, the antiretroviral lectin cyanovirin-N binds to well-known and novel targets on the surface of E. histolytica that are rapidly replenished from large intracellular pools.

Fulminant amoebic colitis during chemotherapy for advanced gastric cancer.

A 52-year-old man had bloody stools during chemotherapy for gastric cancer. A colonoscopy revealed necrotizing ulcer-like changes. A biopsy confirmed the presence of amoebic trophozoites. Subsequently, peritonitis with intestinal perforation developed, and emergency peritoneal lavage and colostomy were performed. After surgery, endotoxin adsorption therapy was performed and metronidazole was given. Symptoms of peritonitis and colonitis resolved. However, the patient's general condition worsened with the progression of gastric cancer. The patient died 50 d after surgery. Fulminant amoebic colitis is very rarely associated with chemotherapy. Amoebic colitis should be considered in the differential diagnosis of patients who have bloody stools during chemotherapy.

Mecanismos fisiopatogênicos e diagnóstico laboratorial da infecção causada pela Entamoeba histolytica / Physiopathogenic mechanisms and laboratorial diagnosis of Entamoeba histolytica infection

A amebíase é a segunda causa de morte entre as doenças parasitárias no mundo. Seu agente etiológico é o protozoário Entamoeba histolytica, que através da secreção de proteinases é capazes de destruir o tecido hospedeiro, matando as células-alvo por contato e fagocitando eritrócitos. Dessa forma, os trofozoítos invadem a mucosa intestinal, provocando a colite amebiana. Em alguns casos atravessam a mucosa e, através da circulação porta, chegam ao fígado, onde causam necrose constituída por poucos trofozoítos rodeados de hepatócitos mortos e debris celulares liquefeitos. Essa invasão está diretamente relacionada com a capacidade de síntese e a secreção de moléculas responsáveis pela virulência dos trofozoítos, como os amebaporos, as lectinas e as cisteína proteinases. O diagnóstico da infecção causada pelo patógeno é rotineiramente realizado através da microscopia óptica de amostras frescas ou espécimes fixados. Entretanto essa metodologia apresenta limitações, sendo incapaz de distinguir as espécies pertencentes ao complexo E. histolytica/E. dispar. A pesquisa de coproantígenos e a reação em cadeia da polimerase (PCR) têm sido utilizadas para diferenciação desses protozoários em amostras fecais. No entanto, estudos mais aprofundados são necessários para maior compreensão sobre a relação parasita/hospedeiro, a proteômica e a genômica do protozoário, o desenvolvimento de vacinas e a real prevalência dessa infecção no Brasil e no mundo.

Amebiasis is the second cause of death among parasitary diseases in the world. Its etiologic agent is the protozoan Entamoeba histolytica, which destroys the host tissue by means of the secretion of proteinases, kills the target-cells by contact and phagocytizes erythrocytes. Accordingly, the trophozoites invade the intestinal mucosa, what causes amoebaean colitis. In some cases, they pass through the mucosa and reach the liver through the portal system, where they cause necrosis, which is composed of a few trophozoites surrounded by dead hepatocytes and liquefied cellular debris. This invasion is directly related to the synthesis capacity and secretion of molecules responsible for the virulence of trophozoites such as amoebapores, lectins and cysteine proteinases. The diagnosis of infection caused by this pathogen is routinely performed through optical microscopy of fresh samples or fixed specimens. However this methodology presents limitations insofar as it is unable to distinguish the specimens belonging to the complex E. histolytica /E. dispar. The research on coproantigens and the polymerase chain reaction (PCR) method have been used to differentiate these protozoa in fecal samples. However further studies are required for a better understanding of the host-parasite relationship, the proteomics and genomics of the protozoa, the development of vaccines and the real prevalence of this infection in Brazil and worldwide.

Anterior necrotizing scleritis after strabismus surgery in a child.

Anterior necrotizing scleritis is a rare but potentially devastating complication of ocular surgery that most often occurs after cataract surgery in elderly patients who may have an underlying systemic autoimmune condition(1) or, less likely, an infectious cause.(2) We describe the management and outcome of a case of bilateral anterior necrotizing scleritis after postoperative infection in a 19-month-old girl who had recently undergone strabismus surgery.

Massive Trichuris trichiura infection as a cause of chronic bloody diarrhea in a child.

The differential diagnosis of chronic diarrhea is extensive and requires the investigation of several diseases, such as celiac disease, inflammatory bowel disease and irritable bowel syndrome. A few patients infected by Trichuris trichiura may present a chronic dysentery-like syndrome in the context of a massive infestation of the colon leading to anemia and growth retardation, but the rarity of that finding demands a high level of suspicion. Herein we report the case of an 8-year-old boy from the rural zone who had suffered diarrhea without blood or mucus for 4 years and was taken to our Service because his mother had noticed the presence of blood on the feces on the 3 previous months. The diagnosis of a massive Trichuris trichiura infestation as the cause of the process was only reached by colonoscopy. We stress that Trichuris trichiura infection can mimic other forms of inflammatory bowel disease and lead to physical growth retardation and that prolonged regimens of albendazole may be required to the effective treatment of massive infestations.

Expression of amoebapores is required for full expression of Entamoeba histolytica virulence in amebic liver abscess but is not necessary for the induction of inflammation or tissue damage in amebic colitis.

Entamoeba histolytica trophozoites produce amoebapores, a family of small amphipathic peptides capable of insertion into bacterial or eukaryotic membranes and causing cellular lysis. Recently, E. histolytica trophozoites that are totally deficient in the production of amoebapore-A were created through a gene silencing mechanism (R. Bracha, Y. Nuchamowitz, and D. Mirelman, Eukaryot. Cell 2:295-305, 2003). Here we tested the virulence of amoebapore A(-) trophozoites in models of the two major forms of amebic disease: amebic liver abscess and amebic colitis. We demonstrate that amoebapore expression is required for full virulence in the SCID mouse model of amebic liver abscess, but E. histolytica trophozoites that do not express amoebapore-A can still cause inflammation and tissue damage in infected human colonic xenografts. These data are consistent with the concept that tissue damage may proceed by different mechanisms in amebic liver abscess compared to amebic colitis.

Epidemiologic and clinical characteristics of acute diarrhea with emphasis on Entamoeba histolytica infections in preschool children in an urban slum of Dhaka, Bangladesh.

The epidemiology, clinical features, nutritional status, and causative agents of diarrhea were studied in 289 Bangladeshi children (147 boys and 142 girls) 2-5 years old. The use of improved diagnostic tests for amebiasis enabled for the first time analysis of the contribution of Entamoeba histolytica to total diarrheal illness in this community setting. The average incidence rate of diarrhea was 1.8/child-year, and the average number of diarrheal days was 3.7 days/child-year over an average observation period of 2.8 years/child. Seventy-five percent of the diarrheal episodes were < or = 2 days in duration. Persistent diarrhea was relatively uncommon (0.2% of the children) and chronic diarrhea was observed in only one episode. Compared with malnourished and/or stunted children, better-nourished children experienced significantly fewer diarrheal episodes. The diarrheal incidence rate for children with blood group A was significantly less that that of the children with blood groups O and AB. The most frequent bacterial enteropathogens isolated from diarrheal stool specimens were enterotoxigenic Escherichia coli (9%) and Aeromonas species (9%), followed by Plesimonas shigelloides (4%) and Shigella flexneri (3.8%). Rotavirus was the most common viral agent isolated from diarrheal stool samples (5%). Giardia lamblia, Cryptosporidium parvum, and E. histolytica were identified in 11%, 8.4%, and 8%, respectively, of the diarrheal stool specimens. Dysentery was observed in 7.7% of all diarrheal episodes. The most common pathogens isolated from dysenteric stool were S. flexneri (11.6%), Aeromonas sp. (10%), E. histolytica (8.7%), Campylobacter jejunii (5.8%), P. shigelloides (4.3%), and A. caviae (4.3%). The overall incidence rate of E. histolytica-associated diarrhea was 0.08/child-year. Visible blood and hemoccult test-detected blood loss was found in 7% and 25%, respectively, of cases of E. histolytica-associated diarrhea. Children who had recovered from a diarrheal episode with E. histolytica, but not E. dispar, had half the chance of developing subsequent E. histolytica-associated diarrhea, consistent with the development of species-specific acquired immunity. In conclusion, the use of modern diagnostic tests demonstrated that E. histolytica contributed to overall morbidity from diarrheal illness. Understanding the etiology, frequency, and consequences of acute diarrhea in children from a developing country should aid in the design of interventions to improve child health.

Tumor necrosis factor alpha is a key mediator of gut inflammation seen in amebic colitis in human intestine in the SCID mouse-human intestinal xenograft model of disease.

We used Entamoeba histolytica infection in human intestinal xenografts to study the roles interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in the pathogenesis of amebic colitis. We found that blockade of TNF-alpha reduced inflammation and intestinal damage in amebic infection, while inhibition of IL-1 reduced cytokine production but had less marked effects on inflammation and disease.

Treatment of infectious diarrhea in children.

Diarrheal diseases remain an important cause of childhood morbidity and death in developing countries, although diarrheal deaths have significantly declined in recent years, mostly due to successes in the implementation of oral rehydration therapy (ORT), which is the principal treatment modality. Diarrhea may occur for varied reasons; however, most episodes of diarrhea in developing countries are infectious in origin. Three clinical forms of diarrhea (acute watery diarrhea, invasive diarrhea, and persistent diarrhea) have been identified to formulate a management plan. Acute diarrhea may be watery (where features of dehydration are prominent) or dysenteric (where stools contain blood and mucus). Rehydration therapy is the key to management of acute watery diarrhea, whereas antimicrobial agents play a vital role in the management of acute invasive diarrhea, particularly shigellosis and amebiasis. In persistent diarrhea, nutritional therapy, including dietary manipulations, is a very important aspect in its management, in addition to rehydration therapy. Rehydration may be carried out either by the oral or intravenous route, depending upon the degree of dehydration. Oral rehydration salts (ORS) solution (World Health Organization formula) is recommended for ORT. Intravenous fluid is recommended for initial management of severe dehydration due to diarrhea, followed by ORT with ORS solution for correction of ongoing fluid losses. Antimicrobial therapy is beneficial for cholera and shigellosis. Antiparasitic agents are indicated only if amebiasis and giardiasis are present. Appropriate feeding during diarrhea is recommended for nutritional recovery and to prevent bodyweight loss. Antidiarrheal agents do not provide additional benefit in the management of infectious diarrhea. Although some probiotics have been shown to be beneficial in the treatment of acute diarrhea due to rotavirus, their use in the treatment of diarrhea is yet to be recommended, even in developed countries. The children of developing countries might benefit from zinc supplementation during the diarrheal illness, but its mode of delivery and cost effectiveness are yet to be decided.