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Dose- and time-dependent functional and structural damage to the colon mucosa by Entamoeba histolytica trophozoite lysates.

Analysis of the initial interaction between Entamoeba histolytica trophozoites and the large intestine is impossible in humans and very difficult in experimental animals. To circumvent this obstacle we treated the luminal side of full-thickness rabbit colon segments mounted in Ussing-type chambers with trophozoite lysates of the E. histolytica HM1 virulent strain. Exposure to lysates for up to 90 min produced dose- and time-dependent effects on the colon, consisting of (a) increased decay rates for potential difference, short-circuit current, and transmural resistance and (b) mucosal damage ranging from vacuolation at the bases and shortening of epithelial cells to the loss of intercellular junctions, destruction of microvilli, and necrosis of interglandular epithelial zones. This acute model of intestinal amebiasis is sensitive, fast, and reliable.

Animals↗

Amebiasis. The ancient scourge is still with us.

Amebiasis is usually contracted in geographic areas where sanitation is poor, but outbreaks can still occur anywhere that drinking water becomes contaminated with sewage. In the majority of persons infected with the parasite, colonization of the intestine is asymptomatic. In others, symptoms of gastrointestinal distress can appear within a week. In rare cases, extra-intestinal amebiasis can cause abscesses in the liver or elsewhere. Many questions about the disease course in different patients remain to be answered. Diagnosis can be made through symptom identification; findings of right-upper-quadrant tenderness, leukocytosis, and an elevated level of alkaline phosphatase; and testing the feces for trophozoites or cysts. Clinicians disagree on whether asymptomatic persons need to be treated, but anyone who is capable of transmitting the disease should be advised of how to avoid exposing others to it.

Amebiasis↗

[Amebiasis--retrospective analysis of 453 cases in the Zürich region].

In a retrospective study 453 cases of amebiasis were analyzed with regard to duration, purpose, and location of the patients' stay abroad. Diarrhea and abdominal complaints were the predominating features of the history, but occasionally constipation was the only symptom. The patients usually had chronic intestinal amebiasis which was intermittently slightly dysenteric, rather than non-dysenteric as defined by the WHO. There were two cases each of ameboma and colonic stricture and three liver abscesses, one of which proved fatal after complicating peritonitis. Therapy with a tissue and a lumenal amebicide proved to be the most efficient combination, with a success rate exceeding 94% in the controlled cases.

Adolescent↗

The pathology of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus). Liver changes and amebic liver abscess formation.

The pathogenesis of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus) was studied from 5 to 60 days after inoculation. Ulcerative lesions were noted 10 to 60 days after inoculation. The sequential development of lesions was asynchronous and progressed from destruction of the interglandular epithelium and of glandular crypt elements to loss of mucosa and formation of granulomatous lesions in the submucosa involving the muscularis mucosae. Pathologic changes in the liver correlated with the formation of ulcerative cecal lesions. Subacute hepatic changes showed lymphocytic portal infiltrate, Kupffer cell hyperplasia, multinucleated giant cells, granuloma formation, and sinusoidal mononuclear and granulocytic infiltrates. Metastatic amebic liver abscesses occurred as early as 10 days after inoculation, and small abscesses were found in the portal areas of the right liver lobe. The sequential development and pathologic manifestation of the infection and the usefulness of the gerbil for the study of human intestinal amebiasis are discussed.

Amebiasis↗

Resistance to intestinal Entamoeba histolytica infection is conferred by innate immunity and Gr-1+ cells.

Establishment of intestinal infection with Entamoeba histolytica depends on the mouse strain; C57BL/6 mice are highly resistant, and C3H/HeJ mice are relatively susceptible. We found that resistance to intestinal infection was independent of lymphocyte activity or H-2 haplotype and occurred in the first hours to days postchallenge according to in vivo imaging. At 18 h postchallenge, the ceca of resistant C57BL/6 mice were histologically unremarkable, in contrast to the severe inflammation observed in susceptible C3H/HeJ mice. Comparison of cecal gene expression in C3H/HeJ and C57BL/6 mice demonstrated that there was parasite-induced upregulation of proinflammatory and neutrophil chemotaxis transcripts and there was downregulation of transforming growth factor beta signaling molecules. Pretreatment with dexamethasone abrogated the partial resistance of C3H/HeJ or CBA mice through an innate, lymphocyte-independent mechanism, but it had no effect on the high-level resistance of C57BL/6 mice. Similarly, administration of a neutrophil-depleting anti-Gr-1 monoclonal antibody (RB6-8C5) decreased the partial resistance of CBA mice and led to severe pathology compared to control antibody-treated mice, but it had no effect on C57BL/6 resistance. These data indicate that there are discrete mechanisms of innate resistance to E. histolytica depending on the host background and, in contrast to other reports, imply that neutrophils are protective and not damaging in intestinal amebiasis.

Animals↗

Downregulation of selected cytokines in amebiasis.

A 220-kDa E. histolytica lectin is capable of downregulating some inflammatory cytokines (IL-5, IL-6, INF-gamma and TNF-alpha) and thus of inducing an overall anti-inflammatory Th-phenotype in leucocytes of selected, perhaps constitutionally predisposed, individuals irrespective of their HLA-DR3 profile (i.e., in this study patients long recovered from amebic abscess of the liver). This probably inhibited cytokine response pattern could increase the risk for developing amebic abscess of the liver in the course of invasive intestinal amebiasis.

Amebiasis↗

Diagnosis of amebic liver abscess and intestinal infection with the TechLab Entamoeba histolytica II antigen detection and antibody tests.

A noninvasive diagnostic test for amebic liver abscess is needed, because amebic and bacterial abscesses appear identical on ultrasound or computer tomography and because it is rarely possible to identify Entamoeba histolytica in stool specimens from patients with amebic liver abscess. Here we report a method of detection in serum of circulating E. histolytica Gal/GalNAc lectin to diagnose amebic liver abscess, which was used in patients from Dhaka, Bangladesh. The TechLab E. histolytica II test (which differentiates the true pathogen E. histolytica from Entamoeba dispar) detected Gal/GalNAc lectin in the sera of 22 of 23 (96%) amebic liver abscess patients tested prior to treatment with the antiamebic drug metronidazole and 0 of 70 (0%) controls. After 1 week of treatment with metronidazole, 9 of 11 (82%) patients became serum lectin antigen negative. The sensitivity of the E. histolytica II antigen detection test for intestinal infection was also evaluated. Antigen detection identified E. histolytica infection in 50 samples from 1, 164 asymptomatic preschool children aged 2 to 5 years, including 16 of 16 (100%) culture-positive specimens. PCR analysis of stool specimens was used to confirm that most antigen-positive but culture-negative specimens were true-positive: PCR identified parasite DNA in 27 of 34 (79%) of the antigen-positive, culture-negative stool specimens. Antigen detection was a more sensitive test for infection than antilectin antibodies, which were detected in only 76 of 98 (78%) amebic liver abscess patients and in 26 of 50 (52%) patients with intestinal infection. We conclude that the TechLab E. histolytica II kit is a sensitive means to diagnose hepatic and intestinal amebiasis prior to the institution of metronidazole treatment.

Adult↗

[Urinary amebiasis: a parasitosis of exceptional presentation].

We report a case of urinary tract amebiasis localized to the bladder. We reviewed the different ways secondary infection can spread to the urinary tract (rupture of hepatic amebic abscess, perforation in amebic dysentery, or hematogenous spread of amebas) and the primary form of presentation and spread that have been recently focussed upon, i.e. via the "ascending route" in deviant sexual habits of bisexuals and homosexuals, parasites in the anorectal area can colonize the urethra. We discuss the different diagnostic methods and treatment of urinary and intestinal amebiasis, as well as their possible relationship.

Amebiasis↗

[Determination of Entamoeba histolytica infection in patients from Greater Metropolitan Belém, Para, Brazil, by enzyme-linked immunosorbent assay (ELISA) for antigen detection].

The epidemiological status of amebiasis has been reevaluated since Entamoeba histolytica (pathogenic) was considered a distinct species from Entamoeba dispar (non-pathogenic). We investigated E. histolytica antigens in stool samples from residents of Belém, Para State, Brazil, with commercially available enzyme-linked immunosorbent assay (E. histolytica Test, TechLab Inc., Blacksburg, USA). A total of 845 samples were analyzed, of which 248 were positive (29.35%). E. histolytica infection was more frequent in the over-14-year age group (30.36%) than in the 0-14-year group (28.28%), but the difference was not statistically significant (p < 0.05). Of all the samples, 334 were also submitted to parasitological methods (direct, Hoffman, and Faust et al.). There were discordant results between ELISA and parasitological methods in 83 samples (24.85%), with more positive results using ELISA. Our results thus suggest that intestinal amebiasis is an important public health problem in Greater Metropolitan Belém.

Adolescent↗

Amebic liver abscess: a study of 11 cases compared with a series of 38 patients with pyogenic liver abscess.

Amebic liver abscess is an uncommon disease in the northern states of North America with 11 cases seen among approximately 500,000 Mount Sinai Hospital admissions over a 16-year period. Five of 11 cases originated in, or had recently visited South America. In three of these, and two patients with concomitant intestinal amebiasis, the diagnosis was suspected on admission. Diagnosis after admission was rapid, mean 5 days, compared with a mean of 13 days in pyogenic liver abscess. There was a higher incidence of male patients, nine males versus two females which was greater than the excess found in our pyogenic abscesses, 22 versus 16. Multiplicity was less common than in pyogenic abscess, 27 versus 50%, respectively. All three patients with multiple abscesses survived with surgical drainage and antibiotic therapy despite numerous complicating factors, including secondary bacterial infection. One patient resolved with drug treatment only; all others were treated with drugs and concomitant drainage; surgical drainage in earlier cases, and percutaneous drainage more recently. There was a single postoperative death. Drug treatment is the first therapeutic modality, and if recovery is delayed more than 2 days percutaneous aspiration should be carried out. This was successful in four cases. Surgery should seldom be required with present methods of accurately localizing amebic liver abscess, but is essential for ruptured abscess with peritonitis, and liver abscess with associated intestinal problems such as toxic megacolon, colonic perforation, or fulminating colitis. There has been a significant reduction in mortality of amebic liver abscess over the past 50 years and particularly within the past decade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Ultramicroscopic study of the invasion of the mucosa of the colon by Entamoeba histolytica in axenic cultures].

Animal models have been utilized to study experimentally produced intestinal amebiasis. The guinea pig has been the animal of choice to study the mechanisms by which trophozoites of E. histolytica produce colonic lesions. The purpose of this study was to produce lesions in the colon of newborn guinea pigs by the injection of E. histolytica, HM-1 IMSS, strain grown axenically, and to characterize the early changes with the light and electron microscopes. A total of 35 guinea pigs, one to two days old, were inoculated into the cecum with one and a half million of trophozoites of E. histolytica. Thirteen surviving animals were sacrificed. In four there were clear cut amebic lesions. Sections were taken from neighbouring transitional zones. The most important changes were the migrations of trophozoites to the bottom of colonic glands with many parasites located within the crypts. There was passage of ameabae to the lamina propia with practically no inflammatory reaction. It is thought that the parasite, in contact with epithelial crypt cell, produce direct lysis of these elements leading to migration of amebae into the lamina propia.

Animals↗

Fulminant amebic colitis. A morphologic study of four cases.

PURPOSE: The morphologic features of fulminant amebic colitis are poorly documented. In this report, we describe the clinical and pathologic findings in four of these cases. METHODS: The surgical pathology reports and accompanying histologic slides were examined from four patients who underwent surgical resections for fulminant amebic colitis. Clinical information was obtained from the patients' medical records. RESULTS: Large, geographic mucosal ulcers were typically present and were accompanied by yellow-green pseudomembranes. The muscularis externa was usually attenuated and necrotic, imparting a "wet blotting paper" consistency. Large numbers of amebic trophozoites were present within the inflammatory exudates. The mucosa adjacent to and undermined by the ulcers was often hemorrhagic or inflamed, resembling ischemic colitis or idiopathic inflammatory bowel disease, respectively. Two patients died within four weeks of their surgery. A third patient died one year later as a result of AIDS-related complications. The remaining patient has been lost to follow-up. CONCLUSION: An uncommon but life-threatening manifestation of intestinal amebiasis is a fulminant colitis. Early surgical intervention and intensive antiamebic chemotherapy are essential for efficacious management.

AIDS-Related Opportunistic Infections↗

Necrotizing amebic colitis in a child.

Necrotizing amebic colitis (NAC) is a rare complication of intestinal amebiasis, and only a few cases have been reported in the literature. The outcome of NAC is dismal, particularly in children. We encountered a 3-year-old child who presented with bloody diarrhea, fever, toxemia, and peritonitis. At laparotomy the whole colon was found to be necrotic with several perforations. Histopathology of the resected colon showed features of NAC. This is a rare case of survival of a child with NAC involving the whole colon.

Child, Preschool↗

An experimental model of ameboma in guinea pig.

Among the wide variety of clinicopathological manifestations of intestinal amebiasis, amebomas occur rarely and their pathogenesis is not well understood. When cholesterol-fed, 2- to 4-week-old guinea pigs were infected intracecally with a virulent, monoaxenic strain of Entamoeba histolytica, gross and histologically characteristic amebomas developed in 85% of the animals by the 3rd day, in 94% by the 9th day, and in 96% by the 12th day postinfection, by which time most of them had died. Amebomas were confirmed by histopathology. Thus, a model of consistent production of amebomas was documented.

Animals↗

Humoral immune response against proteophosphoglycan surface antigens of Entamoeba histolytica elicited by immunization with synthetic mimotope peptides.

The protozoan parasite Entamoeba histolytica, which is responsible for intestinal amebiasis and amebic liver abscess, is causing significant morbidity and mortality worldwide. Proteophosphoglycans (PPGs, also known as lipophosphoglycans, LPGs, or lipopeptidophosphoglycans, LPPGs) are major surface components of E. histolytica. Passive immunization with a monoclonal antibody (EH5) directed against the PPGs protected severe combined immune-deficient mice from amebic liver abscess. The structure of the PPGs is very complex and only known in part. To find peptide mimics of E. histolytica PPG antigens, we had screened phage-displayed random peptide libraries with the antibody EH5. We identified various peptide mimics of E. histolytica PPGs, all sharing a consensus sequence Gly-Thr-His-Pro-X-Leu. Several of the phage clones induced a significant, specific IgG response against membrane antigens of E. histolytica after immunization of mice with whole phage particles. In the present work, in order to avoid the use of phage particles for immunization, we coupled two selected chemically synthesized peptides to keyhole limpet hemocyanin (KLH). The two KLH-conjugated peptides were immunogenic in mice and induced the production of high titers of anti-peptide antibodies, and one of the two peptides was also able to induce significant titers of antibodies against E. histolytica PPGs. Our results demonstrate that the KLH-conjugated peptides are able to mimic the EH5 epitope without the M13 phage sequences flanking the peptide inserts and independent of the structural framework of the phage.

Adjuvants, Immunologic↗

Human secretory immunoglobulin A anti-Entamoeba histolytica antibodies inhibit adherence of amebae to MDCK cells.

The presence of secretory immunoglobulin A (IgA) anti-Entamoeba histolytica antibodies in the saliva of patients with intestinal amebiasis was demonstrated by immunoblot assay, and the capacity of these antibodies to inhibit amebic adherence to a monolayer of MDCK cells was analyzed. Inhibition was due to IgA antiamebic antibodies and in part to anti-Gal-binding-lectin antibodies, as demonstrated by absorption experiments with total amebic extract and with the fraction of Gal-binding lectin. These results emphasize the relevance of secretory IgA antibodies in the phenomenon of E. histolytica adherence to epithelial cells.

Animals↗