Amibiasis vulvar: caso clínico / Vulvar amebiasis: clinical case

La amibiasis genital causada por Entamoeba histolytica es una entidad clínica poco frecuente, aun en zonas donde la enfermedad es endémica, es por ello que informamos el caso de una mujer de 74 años de edad ingresada en el servicio de Ginecología de nuestro centro con lesión exofítica ulcerada cubierta por una secreción amarillo verdosa fétida que afectaba labios mayores, labios menores y pliegues genito crurales, con diagnóstico por biopsia de amibiasis vulvar. Recibió tratamiento con metronidazol con resolución completa de la lesión genital. El objetivo de la publicación de este caso es por lo poco frecuente de la patología y la escasa literatura sobre la misma que se puede encontrar(AU)

The genital amebiasis caused by histolytic Entamoeba is a rare clinical entity, even in areas where the disease is endemic, that is which is why report the case of a 74-year-old woman, admitted to the gynecology service medical center, ulcerated exophytic lesion, covered by a fetid greenish yellow discharge that affected labia majora, labia minora and genito crural folds with vulvar biopsy diagnosis of amebiasis. She was treated with metronidazole with complete resolution of genital injury. The aim of the publication is so little frequent of pathology and the scarce literature on it that can be found(AU)

Amebiasis: aspectos clínicos, terapéuticos y de diagnóstico de la infección / An update on amebiasis

The description of Entamoeba dispar, and the recovery of Entamoeba moshkovskii from humans had a major impact in the epidemiology and clinical management of amebiasis. Infections range from asymptomatic colonization to hemorrhagic colitis and extra-intestinal diseases. Only a minority of amebiasis patients progress to the development of disease. Recent studies suggest that susceptibility to infection, and its outcome is influenced by the host, parasite genotype, and environment. The identification of Entamoeba histolytica is based on the detection of specific antigens by ELISA and DNA in stool and other clinical samples. Several diagnostic tests have been developed, including polymerase chain reaction, the technique of choice, for the detection and differentiation of E. histolytica, E. dispar, and E. moshkovskii. Combination of serologic tests with detection of the parasite DNA by PCR or antigen by ELISA offers the best approach to diagnosis. However, these techniques are impractical for clinical laboratories of developing countries. Clinicians must follow the guidelines of the World Health Organization to avoid unnecessary treatments. This review describes and discusses recent advances in amebiasis with emphasis in the clinical aspects and management of infection.

Farmacoterapia actual de la amibiasis, avances en nuevas drogas y diseño de una vacuna / Current pharmacotherapy of amebiasis, advances in new drugs, and design of a vaccine

Aunque existe una gran cantidad de fármacos amebicidas que actúan en la luz intestinal, las drogas de acción tisular usadas para tratar la amibiasis invasiva son aún relativamente limitadas. El advenimiento del metronidazol (MTZ), que es el fármaco de elección para la amibiasis invasiva, y otros nitroimidazoles en el tratamiento de la amibiasis, ha simplificado enormemente la quimioterapia de la infección. No obstante, la erradicación de ésta después de la administración del MTZ requiere terapia adicional con un amebicida de acción luminal como la paramomicina. Después de décadas desde la introducción de estas drogas en la terapia de la infección, se han hecho pocas innovaciones. Mientras tanto, esta parasitosis continúa siendo una causa importante de morbilidad y mortalidad en el mundo contemporáneo. Debido a los efectos tóxicos y los recientes fracasos en el tratamiento de algunos protozoos intestinales con el MTZ, es necesaria la búsqueda de nuevos compuestos amebicidas. Un avance reciente es la nitazoxanida que tiene una actividad de amplio espectro contra diversos agentes infecciosos y se ha demostrado recientemente su acción contra E. histolytica. Este fármaco podría ser clave como amebicida por su efectividad contra el parásito en la luz intestinal y en los tejidos. Sin embargo, el diseño de una vacuna protectora contra la infección sigue siendo deseable. Los estudios experimentales recientes en animales modelo son alentadores. El objetivo de esta revisión es examinar y discutir los aspectos más importantes de la farmacoterapia actual de la amibiasis, así como de los prospectos para el desarrollo de nuevas drogas y una vacuna protectora contra la infección.

Although many drugs destroy Entamoeba histolytica within the colonic lumen, the number of tissue amebicides used to treat invasive amebiasis is still relatively limited. Metronidazole (MTZ), which is the drug of choice for invasive amebiasis, and other nitroimidazoles have greatly simplified the chemotherapy of this disease. However, eradication of E. histolytica infection after completion of MTZ therapy requires additional treatment with luminal amebicides, such as paramomycin. After decades of the introduction of MTZ and other nitroimidazoles in the therapy of amebiasis, there have been few innovations in treating amebic infections. Meanwhile, amebiasis remains among the leading causes of morbidity and mortality in the contemporary world. The toxic effects of MTZ and recent failures in the treatment of several intestinal protozoan parasites, has led to a search for other amebicidal drugs. A recent advance is the demonstration of the effect of nitazoxanide, which has broad spectrum of antiparasitic activity, against E. histolytica. This compound could be the key in the therapy of amebiasis by its action against both luminal and invasive parasite forms. However, the design of an effective vaccine against the infection is still being desirable. Work is underway to develop a vaccine and recent experimental studies are promising. The aim of this review is to examine and discuss the most important aspects of current antiamebic pharmacotherapy and the prospects for development of new drugs and a vaccine.

Absceso esplénico amebiano / Amebic splenetic abscess

La localización extraintestinal es una complicación temible de la amebiasis intestinal, con una elevada mortalidad, que oscila entre el 4 al 14 por ciento de los casos diagnosticados. La forma de presentación más común es el absceso hepático amebiano, y aunque se han reportado localizaciones pulmonares, peritoneales, y hasta cerebrales, la localización esplénica es extremadamente infrecuente. Se reporta un caso de amebiasis esplénica que evolucionó tórpidamente, a pesar del tratamiento específico con metronidazol desde su admisión al Departamento de Emergencia, y que fue intervenido quirúrgicamente al séptimo día, con evolución favorable después de la resección del bazo. Se realiza una revisión de la literatura actualizada sobre el tema(AU)

The extraintestinal location is a fearsome complication of the intestinal amebiasis, with a high mortality fluctuating between the 4 and the 14 percent of cases diagnosed. The commonest presentation way is the amebic hepatic abscess and although others have reported pulmonary, peritoneal and up to cerebral locations, the splenetic one is extremely infrequent. A case of splenetic amebiasis is reported which evolved in a torpid way despite the specific treatment with metronidazole from its admission to Emergence Department and that was operated on at seventh day with a favorable evolution after spleen resection. Authors made a review of the updated literature on this subject(AU)

Bioavailability of two oral formulas of secnidazole in healthy volunteers / Biodisponibilidade de duas fórmulas de secnidazol oral em voluntários saudáveis

Secnidazole is an antimicrobial agent used primarily in the treatment of amoebiasis. For this bioequivalence study of secnidazole, twenty-eight healthy female volunteers were enrolled in a randomized crossover study. Each volunteer was given a single oral dose of secnidazole test preparation and then the reference preparation, or vice versa, with a wash out interval of two weeks. The plasma concentrations of secnidazole were determined by HPLC, and the samples were extracted with tert-butyl-methyl-ether: dicloromethane (60:40, v/v). Secnidazole and its parent compound metronidazole were separated on a C18 column with water:acetonitrile (85:15, v/v) as the mobile phase, and monitored at 310 nm. The ratio of mean Cmax, AUC0-t and AUC0-∞ values for the test and reference products were within the predetermined range established by ANVISA, demonstrating that the two formulations are bioequivalent in rate and extent of absorption.

Secnidazol é um agente antimicrobiano utilizado principalmente no tratamento da amebíase. Para este estudo de bioequivalência de secnidazol em voluntários saudáveis, foram incluídos vinte e oito voluntárias mulheres no estudo randomizado cruzado. Cada voluntária recebeu uma única dose oral de secnidazol do produto teste e referência para comparação, com um intervalo de wash-out de duas semanas. As concentrações plasmáticas de secnidazol foram determinados por CLAE, as amostras foram extraídas com terc-butil-metil-éter: dicloromethano (60:40, v/v). O secnidazol e seu padrão interno metronidazol foram separados em uma coluna (C18 ) com fase móvel água ultra-pura:acetonitrila (85:15, v/v) e monitorado em 310 nm. As razões entre as médias geométricas de Cmáx, ASC0-t e ASC0-∞, encontraram-se dentro do estabelecido pela ANVISA, demonstrando que as formulações são bioequivalentes quanto à taxa e extensão de absorção.

Acanthameba meningitis with successful outcome.

We report a rare cause of sub acute meningitis in a 15-yr-old immunocompetent female child with successful outcome. The etiological agent was Acanthameba. The child was sucessfully treat with combination of Ketoconazole. Rifampicin, cotrimoxa zole and for a period of 9 month.

Review of epidemiological features, microbiological diagnosis and treatment outcome of microbial keratitis: Experience of over a decade.

Purpose: To review the epidemiological characteristics, microbiological profile, and treatment outcome of patients with suspected microbial keratitis. Materials and Methods: Retrospective analysis of a non-comparative series from the database was done. All the patients presenting with corneal stromal infiltrate underwent standard microbiologic evaluation of their corneal scrapings, and smear and culture-guided antimicrobial therapy. Results: Out of 5897 suspected cases of microbial keratitis 3563 (60.4%) were culture-proven (bacterial – 1849, 51.9%; fungal – 1360, 38.2%; Acanthamoeba – 86, 2.4%; mixed – 268, 7.5%). Patients with agriculture-based activities were at 1.33 times (CI 1.16–1.51) greater risk of developing microbial keratitis and patients with ocular trauma were 5.33 times (CI 6.41–6.44) more likely to develop microbial keratitis. Potassium hydroxide with calcofluor white was most sensitive for detecting fungi (90.6%) and Acanthamoeba (84.0%) in corneal scrapings, however, Gram stain had a low sensitivity of 56.6% in detection of bacteria. Majority of the bacterial infections were caused by Staphylococcus epidermidis (42.3%) and Fusarium species (36.6%) was the leading cause of fungal infections. A significantly larger number of patients (691/1360, 50.8%) with fungal keratitis required surgical intervention compared to bacterial (799/1849, 43.2%) and Acanthamoeba (15/86, 17.4%) keratitis. Corneal healed scar was achieved in 75.5%, 64.8%, and 90.0% of patients with bacterial, fungal, and Acanthamoeba keratitis respectively. Conclusions: While diagnostic and treatment modalities are well in place the final outcome is suboptimal in fungal keratitis. With more effective treatment available for bacterial and Acanthamoeba keratitis, the treatment of fungal keratitis is truly a challenge.

Development of time and pH dependent controlled release colon specific delivery of tinidazole

Tinidazole is used in treatment of amoebiasis and other protozoal infections in doses of 2.0 g/ day [60 mg/kg] for three days. In the present paper, controlled release formulation of tinidazole was developed with an objective to achieve colon specific drug delivery with reduced frequency of dosing, to minimize gastric side effects and thus to increase patient compliance. Matrix systems of tinidazole [500 mg] were prepared by using swellable and pH dependent polymers like hydroxypropyl methylcellulose [HPMC K4M and K15M] and eudragit [eudragit L-100 and S-100]. Prepared tablets were enteric coated in order to overcome variability in gastric emptying time and delay in the release, to reduce gastric side effects and to provide prolonged localized action in colon. Process of manufacture was optimized during the scale up studies. Bioavailability study [using parallel group design] was carried of on conventional marketed, developed uncoated and enteric coated tablets in healthy human volunteers. Bioavailability study showed that greater portion of tinidazole was released in the large intestine and drug level in plasma was above 4 micro g/mL in blood for 24 hours. From the results of this study it appears that, the proposed single enteric coated tinidazole [500 mg] tablet per day could be used in place of 3-4 doses of 500 mg tinidazole conventional tablet with better control of drug release for targeted drug delivery. In addition developed colon-specific drug delivery system [CDDS] was relatively inexpensive and easy to manufacture using conventional pharmaceutical coating technique

Encefalitis amebiana granulomatosa por Balamuthia mandrillaris. Primer caso diagnosticado en Chile / Granulomatous amebic encephalitis caused by Balamuthia mandrillaris: first case diagnosed in Chile

Se presenta el caso de un lactante de sexo masculino de 7 meses de vida con una historia de varias semanas de evolución caracterizada por convulsiones, fiebre y cambios conductuales. Hospitalizado, la tomografía axial computada de cerebro mostró lesiones multifocales de algunos mm a 4 cm de diámetro, sin efecto de masa, y una biopsia de las mismas reveló una encefalitis necrotizante con arteritis necrótica fibrinoide. A pesar del tratamiento, las lesiones progresaron y el niño falleció. La necropsia demostró una extensa encefalitis necrotizante, multifocal, con arteritis necrótica fibrinoide, algunos signos de organización, y la presencia de elementos parasitarios con caracteres de trofozoitos y quistes de amebas de vida libre del género Acanthamoeba o Balamuthia. Además, se constató una hipoplasia- displasia del timo y signos de schok. Los elementos encontrados corresponden al cuadro descrito como encefalitis amebiana granulomatosa y el agente encontrado fue tipificado, (Centers for Disease Control and Prevention, Atlanta, USA) correspondiendo a la especie Balamuthia mandrillaris.

Meningoencefalitis granulomatosa por Balamuthia mandrillaris: Reporte de un caso y revisión de la literatura / Granulomatous amoebic meningoencephalitis by Balamuthia mandrillaris: case report and literature review

Durante los últimos años, otra ameba de vida libre, Balamuthia mandrillaris, ha sido identificada como agente etiológico de meningoencefalitis granulomatosa amebiana (MGA) en humanos. Presentamos el caso de una escolar de sexo femenino, inmunocompetente en quien se realizó el diagnóstico post mortem de MGA por este agente. Consultó por aparición de lesiones eritematosas e induradas que comprometían la zona centro-facial. En biopsia cutánea se evidenció una lesión granulomatosa con RPC positiva para secuencias génicas de Mycobacterium atípico, por lo que se inició tratamiento para micobacteriosis atípica extrapulmonar. Evolucionó con compromiso neurológico progresivo, falleciendo aproximadamente un año después de iniciar los síntomas. La necropsia reveló una MGA, cuyo estudio posterior demostró la presencia de B. mandrillaris. La infección por B. mandrillaris debe ser considerada en el diagnóstico diferencial de una enfermedad granulomatosa crónica que evoluciona con compromiso neurológico.

Amoebiasis cutis in HIV positive patient.

Protozoan infections of the skin, particularly cutaneous amoebiasis, are rare in HIV-positive patients. We report a case of amoebiasis cutis in an HIV-positive truck driver with a history of frequent unprotected sexual exposures. He presented with multiple painful ulcers and sinuses with purulent discharge, necrotic slough and scarring in the perianal and gluteal region for the last 2 years. He was positive for HIV-1 and -2. Cutaneous biopsy revealed numerous Entamoeba histolytica in the trophozoite form, in addition to an inflammatory infiltrate and necrotic debris. He responded well to oral metronidazole and chloroquine. Amoebiasis cutis should be considered in the differential diagnosis of perianal ulcers, particularly in HIV-positive patients.

Comparative study of the efficacy and tolerability of Secnidazole suspension (single dose) and Tinidazole suspension (two days dosage) in the treatment of amebiasis in children

Amebiasis caused by Entamoeba histolytica may be considered the most aggressive parasitic disease affecting human intestine, causing acute amoebic colitis and extra-intestinal diseases of high morbidity and mortality. 5-nitroimidazoles are the drugs of choice. In this multicenter, open and randon clinical trial, the efficacy and tolerability of secnidazole suspension in a single oral dose of 1ml/kg was compared with 0.5ml/kg doses of tinidazole suspension given for 2 consecutive days to 303 Entamoeba histolytica-positive children aged 2 to 13. Patients with extra-intestinal complications were excluded from the study. Clinical and parasitological follow-up using the Faus and Kato-Katz method were carried out 7, 14, and 21 days after treatment. Clinical improvement/cure was observed in 93 percent of the patients in the secnidazole group and 91 percent in the tinidaloze group. Parasitological sucess was reported for 77 percent and 63 percent of the secnidazole and tinidazole patients, respectively, showing a significant statistical difference between the two groups (p=0.007). Both drugs were well tolerated, and the adverse effects reported were mild, consisting mainly of digestive disturbances. This comparative study showed that a single oral dose of 1ml/kg of secnidazole produced a significantly higher parasitological cure rate than 2 doses of tinidazole. Secnidazole is a safe and effective drug for the treatment of uncomplicated intestinal amebiasis.

Effect of alpha,beta-arteether against primary amoebic meningoencephalitis in Swiss mice.

Artemisinin and its derivative alpha, beta-arteether have been evaluated for activity against experimental primary amoebic meningoencephalitis. In vivo experiments have shown that amphotericin B at dose of 2.5 mg/kg for 5 days produced 100% protection. Artemisinin and alpha, beta-arteether, even when tested at a high doses (60-120 mg/kg x 5 days and 90-180 mg/x 5 days) respectively, were not curative and showed only slight protection as indicated by extension of mean survival time.

Antiamoebic activity of 3,3'-fluro-4,4'-di-(pyrrolidine-2-ylidene amino)-diphenyl (liroldine), against experimentally infected intestinal and hepatic amoebiasis.

HL 707, Liroldine, a novel synthetic compound, was found effective against both extraintestinal and intestinal amoebiasis in animal models. Its activity against hepatic infection in golden hamsters is comparable with that of different derivatives of nitroimidazoles used for human treatment. Against intestinal amoebiasis in Wistar rats, the activity was superior to nitroimidazoles and chloroquine. Paramomycin was comparable and diloxanide furoate was marginally superior. The comparative in vitro and in vivo studies with standard marketed drugs and Liroldine indicate an excellent profile of the compound against experimental amoebiasis. LD50 of Liroldine determined in mice is 910 mg/kg x 1, po and 940 mg/kg x 1 ip).