Pathology of human amebiasis.
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The persistence of amebiasis as a global health problem, despite the availability of effective treatment, has led to the search for vaccines to prevent this deadly disease. Recent clinical studies suggest that mucosal immunity could provide some protection against recurrent intestinal infection with E. histolytica, but there is contradictory evidence about protective immunity after amebic liver abscess. Progress in vaccine development has been facilitated by new animal models that allow better testing of potential vaccine candidates and by the application of recombinant technology to vaccine design. Oral vaccines utilizing amebic antigens either co-administered with some form of cholera toxin or expressed in attenuated strains of Salmonella or Vibrio cholera have been developed and tested in animals for mucosal immunogenicity. Although there has been significant progress on a number of fronts, there are unanswered questions regarding the effectiveness of immune responses in preventing disease in man and, as yet, no testing of any of these vaccines in humans has been performed.
This article reviews current recommendations of therapy with antidiarrheal compounds and antimicrobial agents for acute infectious diarrhea in children. In most infants and children with acute infectious diarrhea, treatment with antidiarrheal compounds is not indicated. Many of these compounds interfere with identification of enteropathogens in stool specimens, and the antimotility class has an overdose potential. Antimicrobial therapy is given to reduce symptoms and to prevent the spread of infection by decreasing fecal shedding of organisms. Although effective therapy is not available for patients with enteric viruses, Cryptosporidium, and Microsporidium, therapy is useful for children with amebiasis, antimicrobial-associated colitis, cholera, giardiasis, various forms of Escherichia coli diarrhea and Salmonella disease, isosporiasis, shigellosis, and strongyloidiasis. For several other conditions, antimicrobial therapy is of questionable benefit (infection with Campylobacter jejuni or Yersinia enterocolitica, intestinal salmonellosis and enterohemorrhagic E. coli infection). Compounds such as the fluoroquinolones, which are effective in the treatment of acute infectious diarrhea in adults, are not approved for use in children because of potential side effects. Many bacterial, viral, and parasitic organisms cause acute infectious diarrhea; appropriate antimicrobial therapy requires the accurate, rapid identification of the offending enteropathogen. In children with an underlying illness such as acquired immunodeficiency syndrome, manifestations may be prolonged, severe, and recurrent despite appropriate therapy.
T-cell mediated immunity is an important defense mechanism against amebiasis. However, organ transplant recipients with severe T-cell immunosuppression are not at increased risk of having Entamoeba histolytica invasive disease. The reasons are unclear and probably multifactorial, but it is likely that the absence of intestinal colonization with pathogenic strains in countries where transplants occur and the judicious intake of possible contaminated food and water are important contributing factors. We describe the first report of a liver transplant recipient with severe E. histolytica colitis who was successfully treated with metronidazole without modifying his immunosuppression therapy.
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Depletion of colonic mucus occurs before invasion of the colonic mucosa by Entamoeba histolytica trophozoites. It is hypothesized that E. histolytica releases a mucus secretagogue; this was studied in a rat colonic loop model. In colonic loops exposed to live amebae, mucus secretion was quantitated by release of acid-precipitable [3H]glucosamine-labeled luminal glycoprotein and by specific immunoassay. Mucus secretion increased in dose-dependent fashion in response to greater than or equal to 1 X 10(5) trophozoites; cholera toxin (20 micrograms per loop), a known mucus secretagogue, elicited a similar response. Thin-section histological analysis of amebae and cholera toxin-exposed loops showed increased mucus release and streaming from mucosal goblet cells with cellular cavitation compared with control loops. Sepharose-4B chromatography of amebae and cholera toxin-stimulated glycoproteins demonstrated secretion of mucins and an 80%-90% increase in low-molecular-weight proteins. E. histolytica trophozoites and cholera toxin enhanced the secretion of preformed and newly synthesized mucin glycoproteins and stimulated colonic glycoprotein synthesis. The level of mucus secretion elicited by axenic E. histolytica strains correlated with their virulence in vivo and in vitro. The amebic secretagogue was released into the culture medium and was heat stable. Mucus secretagogue activity of E. histolytica may contribute to depletion or alteration of the protective mucus blanket, facilitating pathogenesis of invasive amebiasis.
A successfully treated case of acute fulminating necrotizing amebic colitis characterized by signs of toxemia, septicemia and peritonitis is reported. Early diagnosis and staged surgical procedures apparently lower the mortality. Intensive antiamebic therapy should be instituted as soon as amebiasis is confirmed, otherwise surgical therapy is likely to fail.
The history of the amebiasis investigation in Transcaucasia is presented. 16 cases of amebiasis are described. Data for 1982-1988 on the amebiasis in the moorland are given (41 fatal case).
Seven cases of amoebiasis have been seen at the Royal North Shore Hospital of Sydney, over a nine-year period from 1968 to 1976. Six of these patients had intestinal amoebiasis; these included four with amoebic colitis, one of whom died, one patient with a rectal amoeboma, which was surgically resected, and one case of amoebic dysentery. The patients with amoebic colitis were considered initially to have either ulcerative colitis or Crohn's disease. All patients with inflammatory bowel disease should have rectal swabs or scrapings examined by warm-stage microscopy, rectal biopsy and indirect haemagglutination (IHA) tests to exclude amoebiasis. Three patients had extraintestinal amoebiasis in the form of liver abscesses and one also had pulmonary involvement. In one patient with a hepatic abscess who presented with pyrexia and no evidence of intestinal amoebiasis, the abscess ruptured intraperitoneally. Surgery was performed on three patients, in two cases before diagnosis. Metronidazole appears to be the treatment of choice for intestinal amoebiasis and amoebic liver abscesses. Amoebiasis should be considered in patients resident in Australia who have not recently travelled abroad.
Lethal recognition between Entamoeba histolytica and the tissues and defence systems of the host results in a continuous interplay that determines the development of pathological lesions: (i) we have identified several of the steps and mediators utilized by the trophozoites to destroy host cells by contact-mediated cytolysis; (ii) we have established that the alternative complement system represents the main defence available to the host against the invading parasite. The amoebae recognize target cells by means of a lectin specific for N-acetylgalactosamine-containing surface glycoproteins. This recognition appears to activate the amoeba to release, in the area of contact, an attack complex that induces the host cells to undergo cytolysis. The main component of the attack complex is thought to be amoebapore, an ion-channel forming protein that incorporates spontaneously into target cells leading to their depolarization by creating a pathway for ions to flow down their concentration gradient. The known properties of amoebapore are described. The acquisition of complement resistance by the invading trophozoites is essential for their survival within the host and therefore underlies virulence. The resistance to complement killing is not a permanent property of the amoebae. It is lost during axenization and reappears on passage through the host or when the trophozoites are grown axenically in the presence of active complement.
To study the progression of HIV-1 infection and coreceptor usages in Central African Republic, clinical data, plasma viral load, and coreceptor usage of sequential HIV-1 isolates were analyzed in a seroincident prospective cohort (PRIMOCA). Twenty-three HIV-1 infected individuals from the Central African Armed Forces were followed from 1995 to 2000. Viruses were isolated from 17 patients at various time points after seroconversion and their coreceptor usage was examined using GHOST cells expressing CD4 and one of the HIV-1 chemokine coreceptors CCR5, CXCR4, BOB/GPR15, and Bonzo/STRL33/CXCR6. Eleven patients died from AIDS. Eight of them died between 2 and 5 years after seroconversion, after a brief symptomatic stage. Patients who rapidly progressed to AIDS and death displayed the highest viral loads after seroconversion. All isolates obtained soon after seroconversion used CCR5, albeit, in some cases, CXCR4, BOB, or Bonzo were also used. Most isolates remained R5 (59 out of 61 isolates), although viruses using CXCR4 appeared in some cases of progression to AIDS. In several cases, a broad tropism was observed during the course of infection, with a frequent usage of BOB and Bonzo in addition to CCR5. Rapid progression to disease and short survival time among Central African HIV-1 patients appear more frequent than those reported in industrialized countries. Viral coreceptor used was mainly CCR5, but, interestingly, a large part of isolates also used BOB and Bonzo. However, there was no strict correlation between the clinical outcome and extended viral tropism.
The cellular and antibody dependent cellular cytotoxic (ADCC) responses of splenic lymphocytes and peritoneal macrophages obtained from animals at variable intervals after inoculation were studied against trophozoites of axenic E histolytica (NIH:200). Cytotoxic responses of effector cells from infected animals were compared with those of effector cells from vaccine stimulated and unstimulated uninfected control animals. Cellular and antibody-dependent cellular cytotoxic responses of the effector cells from animals during the establishment and acute phase of infection were significantly suppressed, compared with unstimulated uninfected and vaccinated (FI amoebic proteins stimulated) effector cells. The effector cells from animals recovered from infection showed enhanced cytotoxic responses against trophozoites of E histolytica. The suppressed cytotoxic response was accompanied by impairment of cytotoxic cell activities and lack, or very low level of anti-FI antibodies in the sera of animals during the establishment phase of infection. With the rise in anti-FI antibodies in the sera of animals ADCC could be induced effectively against trophozoites of E histolytica, which seem to result in clearance of amoebic infection.
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Amibiasis is the third leading cause of death due to parasitic infections in the world. Amibiasis is endemic in the warm regions of the world with deficient hygiene and socio-economic situations. Entamoeba histolytica is the causal agent of invasive amibiasis, unlike Entamoeba dispar which is not a pathogen for humans. Amibian colitis and amibian abscess of the liver are the most frequent intestinal and extra-intestinal manifestations. Pleuropulmonary complications almost always occur in patients with a liver abscess, the intrathoracic contamination via transphrenic dissemination predominating. Respiratory signs are inaugural in 80% of the cases. Pleuropulmonary ambiasis designates the localization of the amibian infestation, but the clinical expression may vary: pneumonia, lung abscess, pleurisy, hepatobronchial fistulization and more infrequently pulmonary embolism. The preferential localization is the right hemithorax related to abscess in the right lobe of the liver. Left lobe abscesses lead to left-sided pleuropulmonary complications with the risk of rupture into the pericardium. Chocolate-colored pus from a pleural or abscess puncture or vomitus strongly suggests the diagnosis, which is confirmed by highly-positive serology. Metronidazole is the treatment of choice, providing cure without sequellae. In Africa, mortality and morbidity due to ambiasis are high. In Abidjan, 92% of cured patients have sequella, and mortality reaches 15%, the consequence of late diagnosis.